Clsi H49 A

H49-A
Vol. 24 No. 23
Replaces H49-P
Vol. 23 No. 23
Point-of-Care Monitoring of
Anticoagulation Therapy; Approved
Guideline
This document provides guidance to users and manufacturers of point-of-care coagulation

devices for monitoring heparin and warfarin anticoagulant therapy, and to ensure reliable
results comparable to those obtained by routine clinical laboratory testing.
A guideline for global application developed through the NCCLS consensus process.
NCCLS...
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H49-A
ISBN 1-56238-540-2
Volume 24 Number 23 ISSN 0273-3099
Point-of-Care Monitoring of Anticoagulation Therapy; Approved
Guideline
J. Heinrich Joist, M.D., Ph.D.
Jack E. Ansell, M.D.
George G. Despotis, M.D.
Frank LaDuca, Ph.D.
Richard A. Marlar, Ph.D.
Ginette Y. Michaud, M.D.
David L. Phillips
Paula J. Santrach, M.D.
Abstract
Point-of-care coagulation testing (POC-CT), also known as “bedside testing” or “near-patient testing,” is intended to provide test
results more rapidly than can be achieved in hospital or reference laboratory settings. This is important in intensive care units,
emergency rooms, operating rooms, and outpatient clinics, where it may help to expedite treatment decisions. POCT allows
coagulation testing in the home environment, including patient self-testing (PST), thus providing increased access and
convenience for the patient and/or caregiver and improving quality of care.
The guideline provides users of POC-CT systems with information and suggestions for good clinical testing practice and for
producing reliable test results regardless of where or by whom the test is performed. This document deals with POC-CT
performed for monitoring heparin and warfarin therapy.
NCCLS. Point-of-Care Monitoring of Anticoagulation Therapy; Approved Guideline. NCCLS document H49-A (ISBN 1-56238-
540-2). NCCLS, 940 West Valley Road, Suite 1400, Wayne, Pennsylvania 19087-1898 USA, 2004.
THE NCCLS consensus process, which is the mechanism for moving a document through two or more levels of review by the
healthcare community, is an ongoing process. Users should expect revised editions of any given document. Because rapid
changes in technology may affect the procedures, methods, and protocols in a standard or guideline, users should replace
outdated editions with the current editions of NCCLS documents. Current editions are listed in the NCCLS Catalog, which is
distributed to member organizations, and to nonmembers on request. If your organization is not a member and would like to
become one, and to request a copy of the NCCLS Catalog, contact the NCCLS Executive Offices. Telephone: 610.688.0100;
Fax: 610.688.0700; E-Mail: exoffice@nccls.org; Website: www.nccls.org
Number 23 NCCLS
This publication is protected by copyright. No part of it may be reproduced, stored in a retrieval system,
transmitted, or made available in any form or by any means (electronic, mechanical, photocopying,
recording, or otherwise) without prior written permission from NCCLS, except as stated below.
NCCLS hereby grants permission to reproduce limited portions of this publication for use in laboratory
procedure manuals at a single site, for interlibrary loan, or for use in educational programs provided that
multiple copies of such reproduction shall include the following notice, be distributed without charge,
and, in no event, contain more than 20% of the document’s text.
Reproduced with permission, from NCCLS publication H49-A—Point-of-Care

Monitoring of Anticoagulation Therapy; Approved Guideline (ISBN 1-56238-540-2).
Copies of the current edition may be obtained from NCCLS, 940 West Valley Road,
Suite 1400, Wayne, Pennsylvania 19087-1898, USA.
Permission to reproduce or otherwise use the text of this document to an extent that exceeds the
exemptions granted here or under the Copyright Law must be obtained from NCCLS by written request.
To request such permission, address inquiries to the Executive Director, NCCLS, 940 West Valley Road,
Suite 1400, Wayne, Pennsylvania 19087-1898, USA.
Copyright ©2004. The National Committee for Clinical Laboratory Standards.
Suggested Citation
(NCCLS. Point-of-Care Monitoring of Anticoagulation Therapy; Approved Guideline. NCCLS

document H49-A [ISBN 1-56238-540-2]. NCCLS, 940 West Valley Road, Suite 1400, Wayne,
Pennsylvania 19087-1898 USA, 2004.)
Proposed Guideline
September 2003
Approved Guideline
July 2004
ISBN 1-56238-540-2
ISSN 0273-3099
ii
Volume 24 H49-A
Committee Membership
Area Committee on Hematology
Bruce H. Davis, M.D. Albert Rabinovitch, M.D., Ph.D. Dennis J. Ernst, M.T.(ASCP)
Chairholder Hematology Business Unit Center for Phlebotomy Education
Maine Medical Center Research Institute Abbott Diagnostics Division Ramsey, Indiana
Scarborough, Maine Santa Clara, California
John A. Koepke, M.D.
Samuel J. Machin, MB, Ch.B, Maryalice Stetler-Stevenson, M.D., Ph.D. Durham, North Carolina
FRCPath, FRCP National Institutes of Health
Vice-Chairholder Bethesda, Maryland Francis Lacombe, M.D., Ph.D.
The University College London Hospitals Hôpital Haut-Lévêque
London, United Kingdom Advisors Pessac, France
Dorothy M. Adcock, M.D. Charles F. Arkin, M.D. Richard A. Marlar, Ph.D.

Esoterix Coagulation Lahey Clinic Oklahoma City VA Medical Center
Aurora, Colorado Burlington, Massachusetts Oklahoma City, Oklahoma
Frank M. LaDuca, Ph.D. J. David Bessman, M.D. Diane I. Szamosi, M.A.,

International Technidyne Corporation University of Texas Medical Branch M.T.(ASCP)SH
Edison, New Jersey Galveston, Texas Greiner Bio-One,
VACUETTE North America, Inc.
Ginette Y. Michaud, M.D. Sheila Clover, CPT(ASCP)(NCA) Monroe, North Carolina
Center for Devices and Radiologic Health Phlebotomy West
Food and Drug Administration Brentwood, California Luc Van Hove, M.D., Ph.D.
Rockville, Maryland Abbott Laboratories
Abbott Park, Illinois
Subcommittee on Point-of-Care Coagulation Testing

Jack E. Ansell, M.D. Advisors Marilyn Lightfoote
Chairholder FDA Center for Devices/Rad. Health
Boston University Medical Center Sue S. Beglinger, M.S., M.T.(ASCP) Rockville, Maryland
Boston, Massachusetts University of Wisconsin
Madison, Wisconsin Janice Marks
George G. Despotis, M.D. Health Park Medical Center
Washington University School of J. David Bessman, M.D. Fort Myers, Florida
Medicine University of Texas Medical Branch
St. Louis, Missouri Galveston, Texas Valerie L. Ng, Ph.D., M.D.
San Francisco General Hospital
Frank M. LaDuca, Ph.D. Mary F. Cavin San Francisco, California
International Technidyne Corporation John L. McClellan Memorial VA Hospital
Edison, New Jersey Irvine, California John D. Olson, M.D.
University of Iowa Hospitals and Clinics
Richard A. Marlar, Ph.D. W. Gregory Cooper Iowa City, Iowa
Denver VA Medical Center Bio-Rad Laboratories, ECS Division
Denver, Colorado Indianapolis, Indiana Staff
Ginette Y. Michaud, M.D. Catherine Cox, M.D. David E. Sterry, M.T.(ASCP)

FDA Center for Devices/Rad. Health Methodist Hospital of Indiana Staff Liaison
Rockville, Maryland Indianapolis, Indiana NCCLS
Wayne, Pennsylvania
David L. Phillips Amando D’Angelo
i-Stat Corp. H.S. Raffaele Donna M. Wilhelm
East Windsor, New Jersey Milan, Italy Editor
NCCLS
Paula J. Santrach, M.D. Paul A. Foster, M.D. Wayne, Pennsylvania
Mayo Clinic Abbott Laboratories
Rochester, Minnesota Abbott Park, Illinois Melissa A. Lewis
Assistant Editor
Kenneth D. Levy NCCLS
Roche Diagnostics Corporation Wayne, Pennsylvania
Indianapolis, Indiana
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Number 23 NCCLS
Acknowledgement
NCCLS gratefully acknowledges the late Dr. J. Heinrich Joist, St. Louis University Health Sciences
Center, who served as the Chairholder from the development through the completion of the proposed-
level guideline.
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Volume 24 H49-A
Contents
Abstract ....................................................................................................................................................i
Committee Membership........................................................................................................................ iii
Foreword .............................................................................................................................................. vii
1 Scope..........................................................................................................................................1
2 Introduction................................................................................................................................1
3 Standard Precautions..................................................................................................................1
4 Definitions .................................................................................................................................1
5 Point-of-Care Coagulation Testing (POC-CT)—General Considerations.................................6
6 Quality Management: General Considerations for Point-of-Care Coagulation Testing ............6

6.1 Operators, Materials, and Performance of POC-CT .....................................................6
6.2 Training.........................................................................................................................7
6.3 Quality Control and Proficiency Testing ......................................................................8
6.4 Result Recording and Reporting...................................................................................9
7 Monitoring Heparin Therapy ...................................................................................................10
7.1 Introduction.................................................................................................................10
7.2 Blood Specimen Collection and Handling..................................................................11
7.3 POC-CT Systems Used for Monitoring Heparin Therapy..........................................11
7.4 Specific Applications ..................................................................................................14
8 Monitoring Warfarin Therapy..................................................................................................15
8.1 Introduction.................................................................................................................15
8.2 Blood Specimen Collection and Handling..................................................................15
8.3 Test Systems Used for Monitoring Warfarin Therapy................................................16
8.4 Specific Applications ..................................................................................................18
8.5 Result Recording and Reporting.................................................................................19
References.............................................................................................................................................20
Summary of Delegate Comments and Subcommittee Responses.........................................................22
The Quality System Approach..............................................................................................................26
Related NCCLS Publications................................................................................................................27
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Volume 24 H49-A
Foreword
Medical conditions, physical location of the patient, and treatment regimens often require test results to be
obtained quickly, so appropriate medical care can be administered expeditiously. Laboratory medicine
professionals are challenged by the increasing demands for providing faster turnaround of test results,
without compromising accuracy. The need to provide test results at greater convenience to, and increased
efficiency for, the patient/caregiver without compromising cost-effectiveness is also recognized.
With the introduction of portable devices capable of producing results within seconds or minutes, point-
of-care testing (POC—also referred to as “near-patient testing” or “bedside testing”), has been evolving
as one way to meet these demands. Because of the potentially serious consequences of inaccurate test
results, it is essential that results are accurate and reliable.
One of the challenges facing the healthcare community is acceptance of the idea that clinical coagulation
testing, traditionally performed by and under the supervision of trained laboratory professionals, may be
performed by personnel not trained in clinical laboratory practice or by patients/caregivers in the home.
However, it is the responsibility of the manufacturer to provide test systems capable of delivering
accurate results when used properly. Professionals in laboratory medicine should support high-quality
point-of-care coagulation testing (POC-CT) services. POC-CT has been, and will continue to be
implemented in different sites within the hospital, e.g., operating room, emergency room, intensive care
unit, postsurgical recovery room, hemodialysis unit, ambulatory care site, and the patient’s home. The
selection of patients for patient self-testing (PST) is the responsibility of the treating physician.
This document provides information to users on how to proceed in the evaluation, implementation, and
monitoring of POC-CT, and deals only with the use of POC-CT in monitoring of anticoagulant therapy. It
does not address issues related to the use of POC-CT in the evaluation of patients with suspected bleeding
disorders. The guideline was written under the assumption that most users may not be laboratory
professionals and provides important definitions, procedures, and recommendations. The format is
designed to be easy to follow for the lay user.
This document relates closely to NCCLS documents EP18—Quality Management for Unit-Use Testing
and AST2—Point-of-Care In Vitro Diagnostic (IVD) Testing. Please refer to these documents for
additional information.
A Note on Terminology
NCCLS, as a global leader in standardization and harmonization, is firmly committed to achieving global
harmonization wherever possible. Harmonization is a process of recognizing, understanding, and
explaining differences while taking steps to achieve worldwide uniformity. NCCLS recognizes that
medical conventions in the global metrological community have evolved differently in the United States,
Europe, and elsewhere; that these differences are reflected in NCCLS, ISO, and CEN documents; and that
legally required use of terms, regional usage, and different consensus timelines are all obstacles to
harmonization. In light of this, NCCLS recognizes that harmonization of terms facilitates the global
application of standards and is an area of immediate attention. Implementation of this policy must be an
evolutionary and educational process that begins with new projects and revisions of existing documents.
In order to align the terminology used in H49-A with ISO, the term “trueness” is used in this document
when referring to the closeness of the agreement between the average value from a large series of
measurements to a true value of a measurand. The term “accuracy,” in its metrological sense, refers to the
closeness of the agreement between the result of a (single) measurement and a true value of a measurand,
thus comprising both random and systematic effects.
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Number 23 NCCLS
All terms and definitions will be reviewed again for consistency with international use, and revised
appropriately during the next scheduled revision of this document.
The Subcommittee on Point-of-Care Coagulation Testing appreciates the opinions of manufacturers and
users of POC-CT devices. We encourage all to participate in the consensus process by submitting written
comments on content and format to the NCCLS Executive Offices. The subcommittee will consider all
comments when it revises this guideline for the next edition.
Key Words
Calibration, point-of-care testing, quality assurance, quality control, safety
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Volume 24 H49-A
Point-of-Care Monitoring of Anticoagulation Therapy; Approved Guideline
1 Scope
This document deals only with the use of POC-CT in monitoring of anticoagulant therapy with
unfractionated heparin (hereafter called “heparin”) and warfarin. It does not address issues related to the
use of POC-CT in the evaluation of patients with suspected hemostatic disorders or use of other
anticoagulants. There are many potential sites for POC-CT, such as hospitals, physicians’ offices, and
patients’ homes. Those performing POC-CT may include healthcare professionals and patient caregivers,
as well as patients.
2 Introduction
Advances in technology and the development of microtechniques and portable test instruments have made
it possible to move medical testing closer to the patient. Point-of-care coagulation testing (POC-CT), is
intended to provide test results more rapidly, efficiently, and conveniently than can be achieved in the
clinical laboratory. This is particularly important in intensive care units, emergency rooms, operating
rooms, and outpatient clinics where it may help expedite treatment decisions. POC-CT may also provide
greater access to testing for the patient and/or caregiver, whether in the clinic or home setting. POC-CT
may also reduce errors due to incorrect or delayed test result transmission to the patient/caregiver and thus
improve overall quality of care. The guideline provides information and suggestions for good medical
testing practice to produce accurate test results regardless of where, and by whom, testing is performed.
3 Standard Precautions
Because it is often impossible to know what might be infectious, all patient and laboratory specimens are
treated as infectious and handled according to “standard precautions.” Standard precautions are guidelines
that combine the major features of “universal precautions and body substance isolation” practices.
Standard precautions cover the transmission of all infectious agents and thus are more comprehensive
than universal precautions which are intended to apply only to transmission of blood-borne pathogens.
Standard and universal precaution guidelines are available from the U.S. Centers for Disease Control and
Prevention (Guideline for Isolation Precautions in Hospitals. Infection Control and Hospital
Epidemiology. CDC. 1996;17(1):53-80 and MMWR 1988;37:377-388). For specific precautions for
preventing the laboratory transmission of all infectious agents from laboratory instruments and materials
and for recommendations for the management of exposure to all infectious disease, refer to the most
current edition of NCCLS document M29—Protection of Laboratory Workers from Occupationally
Acquired Infections.
4 Definitions
Accuracy (of measurement) – Closeness of the agreement between the result of a measurement and a
true value of the measurand (VIM93)1; NOTE: See Measurand.
Activated clotting time, ACT – A global coagulation test which is particularly sensitive to abnormalities
in the intrinsic blood coagulation pathway and the anticoagulant activity of heparin; NOTE: The ACT is
a measurement of the time in seconds required for a clot to form in a native (i.e., nonanticoagulated)
blood specimen which has been exposed to a contact activator of the intrinsic phase blood coagulation
pathway.
An NCCLS global consensus guideline. ©NCCLS. All rights reserved. 1

Number 23 NCCLS
Activated partial thromboplastin time, APTT – A global coagulation test used for the evaluation of the
intrinsic and common coagulation pathway and for monitoring therapy with unfractionated heparin and
certain other anticoagulants; NOTE: The APTT is the time in seconds required for a fibrin clot to form in
a plasma sample after an optimal amount of calcium chloride, a partial thromboplastin reagent
(phospholipid), and a contact factor activating agent have been added to the sample.
Anticoagulant – An agent, natural or pharmacological, that inhibits clotting of blood or plasma.
Antithrombin, AT (formerly Antithrombin III) – A plasma protein which, when activated by heparin
or heparin-like molecules containing a specific pentasaccharide sequence such as glucosaminoglycans on
endothelial cells, is a potent, irreversible inhibitor of activated, procoagulant serine proteases such as
thrombin and Factor Xa.
APTT (POC) – The APTT performed using a point-of-care (POC) test system.
Bias – The difference between the expectation of the test results and an accepted reference value (ISO
3534-1).2
Blood specimen – The discrete portion of blood taken for examination, study, or analysis of one or more
quantities or characteristics to determine the character of the whole.
Arterial – Blood obtained by arterial puncture or from an individual arterial line, catheter, or
extracorporeal circuit.
Capillary – Blood obtained by skin puncture.
Venous – Blood obtained by venipuncture or from an indwelling line or catheter.
Calibration – Set of operations that establish, under specified conditions, the relationship between values
of quantities indicated by a measuring instrument or measuring system, or values represented by a
material measure or a reference material, and the corresponding values realized by standards (VIM93)1;
NOTE: According to the U.S. Code of Federal Regulations, calibration is the process of testing and
adjustment of an instrument, kit, or test system, to provide a known relationship between the
measurement response and the value of the substance being measured by the test procedure (US CFR 493
February 28, 1992).3
Cardiopulmonary bypass, CPB – A procedure used to sustain organ perfusion with oxygenated blood
during cardiac surgery.
Coagulation test system – A device used to measure the rate of clotting of blood or plasma.
Common blood coagulation pathway – The activation of Factor X by Tissue Factor/VIIa complex
and/or Factor IXa, followed by activation of Factor II and conversion of fibrinogen to fibrin.
Competency assessment – Evaluation of a person’s ability to perform a test including all aspects of
testing, from specimen collection to result reporting.
Contact activator – A particulate (e.g., kaolin, celite, silica) or soluble (e.g., ellagic acid) substance
which activates the “contact phase of coagulation,” involving Hageman Factor (Factor XII), Prekallikrein,
and HMW Kininogen, thereby initiating the intrinsic phase blood coagulation pathway (i.e., activation of
Factors XI and IX).
2 An NCCLS global consensus guideline. ©NCCLS. All rights reserved.

Volume 24 H49-A
Control/control material – A device, solution, or lyophilized preparation intended for use in the quality
control process to monitor the reliability of a test system and to maintain its performance within
established limits; NOTE: The expected reaction or concentration of analytes of interest are known
within limits ascertained during preparation and confirmed in use.
Correlation – The degree to which two variables are proportionally related to each other; NOTE: High
method correlation does not imply high numeric agreement of analytic results, but only the predictability
of one method’s results by the other method.
Extrinsic blood coagulation pathway – The activation of Factor X by Tissue Factor/VIIa complex.
Hemodialysis – A procedure used to remove toxic substances from blood in patients with severe renal
failure.
Heparin (unfractionated) – A mixture of complex glycosaminoglycans (mucopolysaccharides) of

widely varying molecular weight (5000 – 50 000 d) derived from animal tissues, used for prevention and
treatment of venous and arterial thrombosis.
Imprecision – Dispersion of independent results of measurements obtained under specified conditions;

NOTE: It is expressed numerically as standard deviation or coefficient of variation.
International normalized ratio, INR – Expression of the patient’s prothrombin time (PT) test result
expressed as a ratio to a normal population control which has been standardized (or normalized) for the
potency to the thromboplastin used in the assay; NOTES: a) The INR is determined by using the
equation: INR = RISI, where R is the PT ratio obtained with the working thromboplastin; b) The ISI
should be determined by standard protocols according to WHO guidelines and provided by the
manufacturer to the user for a particular reagent/instrument combination or POC-CT system.
International sensitivity index, ISI – A mathematical indicator of the responsiveness of a PT testing

system to deficiencies of the vitamin K coagulation factors; NOTES: a) It is the comparative slope used
to calculate the INR; b) A low ISI indicates a highly responsive PT system and a high ISI indicates a
poorly responsive system; c) It is determined by standard protocols according to WHO guidelines and
provided by the manufacturer to the user for a particular reagent/instrument combination.
Intrinsic phase blood coagulation pathway – The sequential activation of Factors XII, XI, and IX in the
presence of Prekallikrein and co-factors HMW-Kininogen and Factor VIII triggered by contact factor.
Measurand – Particular quantity subject to measurement; (VIM93-2.6). NOTE 1: [VIM93-2.6] For

example, vapour pressure of a given sample of water at 20 °C; NOTE 2: [VIM93-2.6] The specification
of a measurand may require statements about quantities such as time, temperature and pressure; NOTE 3:
[NRSCL8] This term and definition encompass all quantities, while the commonly used term “analyte”
refers to a tangible entity subject to measurement. For example, “substance” concentration is a quantity
that may be related to a particular analyte.
Native whole blood – Blood withdrawn into a syringe or tube to which no additives, such as
anticoagulants, are added.
Patient self-testing, PST – The testing by a patient or caregiver on blood or body fluid obtained from the
patient.
Percutaneous coronary intervention, PCI – Any one of a number of intervention procedures in which a
catheter is inserted into a coronary artery for the purpose of removing obstruction by an atherosclerotic

Number 23 NCCLS
plaque; these include percutaneous transluminal coronary angioplasty (PTCA), atherectomy, and coronary
stent placement.
Plasma – In vivo, the liquid portion of whole blood that does not contains cells; in vitro, the liquid portion
of anticoagulated whole blood that does not contain cells.
POC-APTT – See APTT (POC).
POC-PT – See PT (POC).
Point-of-care (POC) testing//bedside, near-patient testing – Testing performed in an alternate site,

outside a central laboratory environment, generally nearer to, or at the site of, the patient.
Precision – The closeness of agreement between independent measurement results obtained under
stipulated conditions (ISO 3534-1)2; NOTE: Precision is not typically represented as a numerical value
but is expressed quantitatively in terms of imprecision—the standard deviation (SD) or the coefficient of
variation (CV) of the results in a set of replicate measurements (ISO 3534-1).2
Proficiency testing (quality assessment scheme) – Determination of laboratory testing performance by

means of interlaboratory comparisons; NOTES: a) Commonly, a program periodically sends multiple
specimens to members of a group of laboratories for analysis and/or identification; the program then
compares each laboratory’s results with those of other laboratories in the group and/or with an assigned
value, and reports the results to the participating laboratory and others; b) The results are summarized,
analyzed, and, with some tests, graded by the program and provided to the participating site which can
compare its results with those of other sites that use a similar method; c) Other forms of PT/EQA include:
data transformation exercises, single-item testing (where one item is sent to a number of laboratories
sequentially and returned to the program at intervals), and one-off exercises (where laboratories are
provided with a test item on a single occasion).
Prothrombin time, PT – The time in seconds required for a fibrin clot to form after tissue
thromboplastin and an optimal amount of calcium chloride have been added to a plasma sample.
Prothrombin time test – A coagulation test sensitive to abnormalities of the extrinsic and common
coagulation pathway;
PT (POC) – The PT performed using a point-of-care test system.
PT ratio – The PT of a test plasma divided by the geometric mean of the normal PT reference range;
NOTE: The PT ratio is used to calculate the international normalized ratio (INR).
Quality assurance, QA – All the planned and systematic activities implemented within the quality
system and demonstrated as needed, to provide adequate confidence that an entity will fulfill
requirements for quality (ISO8402:94-3.5); NOTE: QA includes monitoring, evaluating, taking
corrective actions, if necessary and monitoring the corrective actions for preanalytical, analytical, and
post-analytical activities; these activities include, but are not limited to, recordkeeping, calibration and
maintenance of equipment, quality control, proficiency testing, and training.
Quality control, QC – In healthcare testing, a set of procedures designed to monitor the test method, and
the results to assure optimal test system performance; NOTE: QC includes testing of normal and
abnormal control materials, recording the results, identifying sources of error, and evaluating and
documenting any corrective action taken.

Volume 24 H49-A
Reagent – A substance that produces a chemical reaction in a sample that allows an analyte to be detected
and/or measured.
Sample – In this document, a sample taken from the patient specimen and used to obtain information by
means of a specific laboratory test.
Sensitivity (analytical) – The change in response of a measuring system or instrument divided by the
corresponding change in the stimulus (modified from VIM93)1; NOTES: a) The sensitivity may depend
on the value of the stimulus (VIM93)1; b) The sensitivity depends on the imprecision of the measurements
of the sample.
Skin puncture – Breakage of skin with a needle or lancet to produce blood for collection and testing.
Stability – The capacity of a product to retain its composition, characteristics, and properties during
specified conditions.
Testing site – The physical location where testing is performed.
Tilt tube – A means of determining the clotting endpoint of an in vitro coagulation assay; NOTES: a)
The determination is usually performed by the visual observation of the back-and-forth movement of
plasma in a test tube to which reagents have been added to stimulate coagulation; b) The endpoint of the
tilt tube assay is the appearance of a fibrin clot.
Time-in-therapeutic range, TTR – A quality measure of therapeutic effectiveness for patients on oral
anticoagulants; NOTE: Depending on the methodology used to measure it, it represents either estimated
time (days) spent in a patient-specific therapeutic range or the percent of INRs in therapeutic range.
Trueness – The closeness of agreement between the average value obtained from a large series of test
results and an accepted reference value; (ISO 3534-1)2; NOTES: a) Trueness is usually expressed
numerically by the statistical measure bias that is inversely related to trueness; b) See also Accuracy and
Bias.
Validation – Confirmation through the provision of objective evidence, that requirements for a specific
intended use or application have been fulfilled (ISO 9000)4; NOTES: a) WHO defines validation as the
action {or process} of proving that a procedure, process, system, equipment, or method used works as
expected and achieves the intended result (WHO-BS/95.1793)5; b) The components of validation are
quality control, proficiency testing, validation of employee competency, instrument calibration, and
correlation with clinical findings.
Venipuncture – The puncture of a vein for surgical or therapeutic, purposes, or for collecting blood
specimens for analysis (RHUD1.7CD) (Cf. H3).
Venous thromboembolism, VTE – A term commonly used for the closely linked conditions of deep
vein thrombosis and pulmonary embolism.
Verification – Confirmation through the provision of objective evidence that specified requirements have
been fulfilled (ISO 9000)4; NOTE: A one-time process completed to determine or confirm test
performance characteristics before the test system is used for patient testing.
Whole blood – Blood that contains all of its cellular and plasma components; NOTES: a) It may be
collected in an anticoagulant solution, with or without the addition of nutrients,5 or it may be derived
directly from a fingerstick sample; b) In the context of this document, whole blood refers primarily to
blood derived from a fingerstick.

Number 23 NCCLS
5 Point-of-Care Coagulation Testing (POC-CT)—General Considerations

Justification for using POC-CT in a given clinical setting involves a careful “needs assessment,” which
includes the needs of the patient, the provider, the payer, and the institution. The following list includes
many of the questions that should be asked before selecting the tests and instruments for each POC-CT
setting. Many of these questions are addressed in detail in NCCLS document AST2—Point-of-Care In
Vitro Diagnostic (IVD) Testing.
• Rationale for Selection of the System:
− What is the specific clinical need for POC-CT?

− What is the purpose of the test (i.e., to monitor heparin/warfarin therapy)?
− What is the patient population and testing environment?
− Will POC-CT improve patient care/patient outcome?
− How will cost be affected?
− What is the cost benefit ratio?
• General Administrative Issues:
− Who will select, purchase, and maintain the system?

− Who is responsible for direction and supervision of testing?
− Who holds the license or certificate for testing?
− How will inventory be controlled?
− How will the test be billed?
− How will the expense of training be incorporated into the test charge?
• Logistical and Technical Issues:
− Who will perform the testing?

− Who will train individuals to perform testing?
− What are the specimen requirements?
− How will the method of test ordering be developed?
− How will results be recorded?
− How will results be reported?
− How will results be managed and stored?
− Who is responsible for troubleshooting and assuring availability of a backup procedure?
6 Quality Management: General Considerations for Point-of-Care Coagulation

Testing
A quality management system should be implemented to provide consistently reliable results that can be
used to guide patient therapy. The basic elements of such a system include a defined organizational
structure, standard operating procedures for all aspects of the testing program, periodic training and
competency assessment for all test operators, process control procedures (quality control, external
proficiency testing, split samples, etc.), incident management, and auditing. (See NCCLS document
EP18—Quality Management of Unit-Use Testing for further information.)
6.1 Operators, Materials, and Performance of POC-CT
POC-CT should be performed by trained healthcare providers. Before performing the test, the following
should be assessed:

Volume 24 H49-A
• quality control tests have been performed with acceptable results according to the manufacturer’s and
institutional recommendations;
• disposables are within the expiration date;
• disposables and instruments are devoid of any contaminants (e.g., blood); and
• other specified manufacturer’s recommendations have been followed.
6.2 Training
Operators performing point-of-care unit-use tests should have formal training in the systems involved or
have worked under the supervision of an experienced laboratorian until they have satisfactorily
demonstrated proficiency for each procedure. The degree of training depends upon both the background
of the individual who will be performing the testing and the analytical systems being employed (e.g., the
complexity of the system, the degree of technique dependence, etc.). When selecting a system, the level
of training that is required to implement a new method or instrument should be considered.
Training of individuals who perform the tests should include the following:
• theory of instrument/device/test system;

• specimen collection/preservation/transport;
• instrument calibration;
• instrument maintenance;
• quality control principles and procedures;
• testing procedure;
• sources and degree of error (preanalytic, analytic, and postanalytic); and
• clinical significance.
Sources of training include:
• manufacturer’s on-site training and telephone technical assistance;

• local hospital laboratory or commercial laboratory;
• medical technologists or other trained personnel available as consultants; and
• workshops and training seminars.
Evaluating the competency of all testing personnel and ensuring the staff’s continuing competency to
perform tests and report tests promptly, accurately, and proficiently are essential components of a quality
testing system. Individuals must demonstrate competency in performing the procedure, and evidence of
this competency must be documented. Competency assessment should be performed annually or/as per
institutional policies and procedures. Evaluation of the competency of the staff may include, among other
procedures, the following:
• direct observation of routine patient test performance, including patient preparation (if applicable),
specimen handling, specimen processing, and testing;
• monitoring the recording and reporting of test results;
• review of intermediate test results or worksheets, QC records, proficiency testing results, and
preventive maintenance records;
• direct observation of QC testing;
• direct observation of instrument maintenance and function check performance;
• assessment of test performance through testing of previously analyzed specimens, internal blind
testing samples, or external proficiency testing samples;
• assessment of problem-solving skills;
• use of corrective action logs for failed QC; and

Number 23 NCCLS
• evaluation and documentation of the performance of persons responsible for testing, and providing
such documentation to the testing personnel manager.
6.3 Quality Control and Proficiency Testing
The goal of process control is to confirm that all system components are performing as specified by the
manufacturer and at a quality level acceptable to the user. System components include the operator, the
instrument, the reagents, the sample, and the environment. Various forms of controls test different parts
of the process. (For additional procedures for test validation, refer to the most recent version of NCCLS
document GP29—Assessment of Laboratory Tests When Proficiency Testing is Not Available.)
Process controls should comply with all institutional or jurisdictional requirements. At a minimum,
process controls should be performed as specified by the manufacturer. Users may implement additional
controls. The types selected should check the components most vulnerable to failure. Periodically,
material should be used that verifies all system components at one time under usual testing conditions.
The composition and frequency of such testing should be defined by considering the following
characteristics:
• variability in storage conditions;

• availability of alternate or simulated testing (i.e., electronic QC);
• duplicate testing;
• ability to utilize split patient samples;
• anticipated failures and likelihood of occurrence;
• available control materials;
• operator experience with the test system;
• institutional experience with the test system;
• the medical impact of the test results; and
• occurrence of improper handling (e.g., dropped device, excess heat).
Users of POC-CT systems are encouraged to refer to NCCLS document EP18—Quality Management for
Unit-Use Testing.
6.3.1 Quality Control
The manufacturer should develop system-specific QC recommendations that are consistent with the
robustness and stability of the test system, its intended use, and with the device’s process controls and
available QC modalities. When designing a quality control approach, it is important to consider the
specific characteristics of a test system. Recommendations should be based on the findings of a hazard
analysis, and supported by valid scientific evidence.a The manufacturer may provide additional
recommendations for corrective action when QC fails. Users of POC-PT systems are encouraged to refer
to NCCLS document EP18—Quality Management for Unit-Use Testing.
6.3.1.1 Specific Recommendations for Manufacturers of POC-CT
Manufacturers must provide minimum quality control testing recommendations. It is also advisable for
the manufacturer to provide practical information for users regarding the types of quality control
procedures which may be employed and the value of each system. Manufacturers should address the
following:
a
In the U.S., users of POC-PT systems must work with the local holder of the laboratory license to develop an appropriate QC
program. Requirements will vary depending upon the test CLIA (Clinical Laboratory Improvement Amendments) complexity
category and relevant local accreditation rules.

Volume 24 H49-A
• Target of the quality control material/modality. Clearly define and communicate to the user the
process, analytic procedure, or portion of the assay controlled by each QC material/modality.
• Quality control material/modality levels. Ensure that the QC materials/modalities span the medical
decision range of the assay and target medically relevant decision points.
• Tolerances for quality control materials. Ensure that tolerances for wet quality control materials
are relevant in terms of total allowable error. Ranges that are too broad may be incapable of reliably
detecting unacceptable levels of imprecision or bias. Account for matrix effects in relating the
tolerance ranges to the total allowable error.
Establish tolerance ranges that provide meaningful quality control without the use of statistical tools
(e.g., Westgard rules). Alternatively, incorporate statistical methods in the device software to provide
access by nonlaboratory professionals to statistical quality control.
• Sensitivity of the quality control material/modality to detect analytical problems. Conduct a

hazard analysis to identify potential test system failures. Using valid scientific evidence, demonstrate
that the proposed QC protocol is capable of detecting these failures at an acceptable rate. This may be
accomplished by experimentally challenging the system (e.g., accelerated degradation of the reagent,
etc.) and verifying the ability of the QC method to detect the system failure.
Identify significant matrix bias. QC testing may be run in parallel with actual patient samples to
determine the sensitivity of the QC material to deviations in test system performance or operator
error.
6.3.2 Proficiency Testing
Proficiency testing is an important tool for the ongoing validation of adequate test system performance.b
This should be taken into consideration for instrument users in professional settings. Whenever possible,
users of these devices should enroll and regularly participate in proficiency testing programs.
6.4 Result Recording and Reporting
All patient test results should be reported in a timely fashion to the appropriate healthcare provider and
recorded in the patient’s medical record in a consistent, predictable place so that all members of the
healthcare team may access them easily. It is recommended that results are tracked in such a fashion that
they can be easily correlated with anticoagulant dose adjustments and changes in other medications.
Results may be entered into the laboratory information system (LIS) or clinic records; they may also be
part of the general summary of all laboratory tests. Access to results should be password-oriented with
graded access to the information when applicable.c With sequential testing, healthcare providers should be
able to easily review results over time. Normal reference and target therapeutic ranges should be clearly
stated to facilitate correct interpretation of patient results. If transcription is the primary method of result
recording, periodic auditing should be performed to assess the incidence of transcription errors. The
potential for such errors can be significantly reduced through the use of computerized data management
systems. These systems typically allow both downloading of results from the analyzer to the data
manager and bidirectional interfacing from the data manager to the LIS. A method should be established
for rejection-verification of test results before transfer to the LIS. Results of quality control tests and
other quality assurance activities must be documented and readily available for regulatory and
accreditation purposes. Records of other test-related information (e.g., ordering physician, test operator,
b
In the U.S., proficiency testing is mandated by CLIA certification.
c
In the U.S., access to results should comply with HIPPA requirements.
Number 23 NCCLS
lot numbers, expiration dates for consumables, maintenance, testing difficulties, etc.) must also be
maintained. Either paper- or electronic-based systems are acceptable.
7 Monitoring Heparin Therapy
7.1 Introduction
Unfractionated heparin is routinely used in the treatment of thrombosis and thromboembolic

complications, because it is instantly effective, immediately reversible, generally well tolerated, and
inexpensive. However, bioavailability and anticoagulant effect of heparin vary considerably among
normal subjects and patients with different conditions. Thus, frequent monitoring of anticoagulant effect
and appropriate dose adjustment are required in patients treated with heparin.6 Selection of POC-CT
systems for the monitoring of heparin anticoagulation should be based on the intended clinical
application, i.e., the range of heparin concentrations to be targeted in a particular clinical condition and
patient population. Heparin doses may be classified as shown in Table 1. Thus, standard or intermediate-
dose heparin therapy is generally used for treatment of low- to moderate-level thrombosis/thrombotic risk,
i.e., venous thromboembolism (VTE) (including deep vein thrombosis (DVT) and pulmonary embolism
(PE)), hemodialysis, diagnostic (e.g., cardiac catheterization) and interventional cardiology (PCI),
interventional radiology (e.g., catheter-directed thrombolytic therapy), long-term extracorporeal support
such as extracorporeal membrane oxygenation (ECMO) and ventricular assistance device (VAD), and
surgical interventions where thrombotic complications are common (e.g., orthopedic surgery). In contrast,
high-dose heparin therapy is generally employed in cardiac surgery involving cardiopulmonary bypass
(CPB). All of the available POC-CT systems use whole blood specimens. Test systems vary with regard
to specimen volume requirements, activators (e.g., kaolin, celite), and clot detection methods, but have in
common the use of “unit” use cartridges, which are discarded after testing. The most commonly used
POC-CT for heparin monitoring (which are described below) are the activated clotting time (ACT),7
activated partial thromboplastin time (APTT),8 and heparin concentration measurements. For the
commonly used test systems, the applicable therapeutic heparin ranges are indicated by the manufacturer.
Table 1. Classification of Heparin Dose Regimens Used in the Prevention and Treatment of Venous
and Arterial Thromboembolic Complications
Heparin Dose Heparin Clinical Use Methods for Monitoring
Concentration,
U/mL
Standard 0.2 - 0.5 Venous thromboembolism APTT; Heparin Concentration
Intermediate 0.5 - 3.0 Hemodialysis ACT; APTT; Heparin
ECMO/VADs Concentration
Diagnostic Catheterization
PCI
High 3.0 - 8.0 Cardiac surgery (CPB) ACT; Heparin Concentration
In patients requiring extended anticoagulant therapy, anticoagulation is changed from heparin to another
agent which can be administered more conveniently by mouth, such as warfarin. Warfarin anticoagulant
effect is not instantaneous but depends on moderate reduction of plasma levels of vitamin K-dependent
procoagulant factors II and X, which takes two to three days. Thus, heparin administration must be
continued until the prothrombin time (PT)9 or its commonly used expression PT-INR (used to monitor
warfarin anticoagulation) has been in the desired therapeutic range for two days.10 During the overlap
period the results of tests used to monitor heparin therapy may be prolonged by the effects of warfarin and
thus should be interpreted with caution.

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7.2 Blood Specimen Collection and Handling
7.2.1 Blood Specimen Type
Arterial or venous blood specimens are frequently used. Whether there are clinically significant
differences between arterial and venous blood measurements has not been adequately studied. Preferably,
venous specimens should not be obtained from heparin-coated central venous lines or pulmonary artery
catheters. Capillary specimens are generally not used with tests that require volumes of blood ≥0.4 mL.
Follow the manufacturer’s directions for obtaining the correct specimen type.
7.2.2 Blood Specimen Collection
General blood specimen collection and handling procedures should be followed as described in NCCLS
documents H3—Procedures for Collection of Diagnostic Blood Specimens by Venipuncture; H11—
Procedures for the Collection of Arterial Blood Specimens; and H4—Procedures and Devices for the
Collection of Diagnostic Capillary Blood Specimens. Specimens may be collected by venipuncture,
capillary puncture or from indwelling lines as specified by the POC-CT system manufacturer. Only
specimen types for which the performance of the system has been characterized should be used. In
obtaining specimens by venipuncture, sterile collection procedures should be used and the manufacturer’s
instructions regarding collection vehicle (e.g., test tube, syringe, capillary tube) should be followed. For
indwelling catheters, the line should be flushed11 with 5 mL saline; separate, single-use syringes should be
used to collect at least 5 mL or 6 dead space volumes of blood (to be discarded) prior to collection of
blood specimens for testing, to minimize effects of hemodilution (e.g., crystalloid fluid in line) or heparin
in solutions used for flushing indwelling lines. Institutional policies and procedures should be followed.
7.2.3 Blood Specimen Handling and Testing
Free flowing blood specimens may be collected without the use of anticoagulant or they can be drawn
into anticoagulant (e.g., citrate), depending on the specifications of the POC-CT system used. Most test
systems require native whole blood. Nonanticoagulated blood collected into a plastic syringe should be
transferred to the test unit without delay according to the manufacturer’s recommendation. Citrated blood
specimens should be tested within one hour according to NCCLS document H21—Collection, Transport,
and Processing of Blood Specimens for Testing Plasma-Based Coagulation Assays.
7.3 POC-CT Systems Used for Monitoring Heparin Therapy
7.3.1 Activated Partial Thromboplastin Time (APTT)
The APTT was first described in 1961 as a global, two-stage coagulation screening test,8 which is
particularly sensitive to deficiencies of or inhibitors to intrinsic phase blood coagulation factors, lupus
anticoagulants, and heparin.8,12,13 An aliquot of citrated, platelet-poor test plasma is incubated with an
activator of the coagulation contact system (e.g., kaolin, silica, celite, ellagic acid) for a standard period of
time (three to five minutes), calcium chloride is added, and the time required for clot formation is
recorded.
7.3.1.1 Description of POC-APTT
The POC-APTT is a one-stage assay based on the same principles as the routine APTT performed in the
clinical laboratory (see the current edition of NCCLS document H47—One-Stage Prothrombin Time (PT)
Test and Activated Partial Thromboplastin Time (APTT) Test). Native or citrated blood is added to a
cartridge containing a contact activator such as celite, and phospholipid, and the time required for clot
formation is recorded (for citrated blood after addition of calcium chloride). Different activators and
phospholipid preparations are used with various POC-APTT systems. Systems vary with regard to
Number 23 NCCLS
required specimen volume, use of citrate anticoagulant, and method of clot detection. POC-APTT systems
are single-use or unit-use systems. With most POC-APTT systems the manufacturer specifies the
system’s ability to detect changes in heparin and coagulation factor concentration. The most common
POC-APTT clinical application is monitoring of low- to intermediate-dose heparin therapy yielding
plasma heparin concentrations of 0.2 to 1 U/mL. Some POC-APTT systems may not be suitable for
monitoring of anticoagulant effects of target heparin concentrations >1.0 U/mL.
7.3.1.2 Test Performance
Tests should be performed according to the system manufacturer’s directions. The correlation between
POC-APTT and laboratory-based APTT should be evaluated.
7.3.1.3 Test Result Interpretation and Limitations
Knowledge of a POC-APTT system’s ability to detect changes in heparin concentration in the desired
therapeutic range is important. Before instituting clinical use of POC-APTT, the user should establish the
system normal reference range using blood specimens from at least 20 normal, apparently healthy male
and female subjects. There is relatively high variability of both laboratory-based and POC-APTT results
in normal subjects and especially in patients on heparin therapy due in part to the current lack of
laboratory APTT reagent standardization and variably extensive binding of heparin to endothelial cells
and cellular and soluble blood components.9,12 It is therefore generally difficult to assess trueness of
POC-APTT by comparing individual POC-APTT results with laboratory-based APTT results.
Users must therefore establish normal and therapeutic reference ranges for each test system
independently. The therapeutic reference range for each POC-APTT system may be established using
normal blood to which therapeutic concentrations of heparin have been added. Alternatively, blood
specimens from patients on heparin therapy may be used.14 Heparin concentrations in those specimens
may be determined by anti-Xa, anti-IIa chromogenic assays, protamine sulfate titration, or heparin
response measurements. The preanalytic factors affecting POC-APTT test results are largely those
affecting the results of laboratory-based APTT (see the current edition of NCCLS document H47—One-
Stage Prothrombin Time (PT) Test and Activated Partial Thromboplastin Time (APTT) Test).12,13 Even
without anticoagulation therapy, patients with antiphospholipid antibodies (like lupus anticoagulant) may
have prolonged POC-APTT test results. The usefulness of POC-APTT in routine monitoring of heparin
therapy has been evaluated in only a limited number of studies. Use of the POC-APTT may decrease
turnaround time, time for clinical decision making, and time to yield target therapeutic range heparin
levels.15
7.3.2 Activated Clotting Time (ACT)
The ACT has been used as a POC-CT for high-dose heparin activity monitoring with CPB since its
description in 1966.7 However, more recently, ACT systems have become available which allow
monitoring of intermediate dose heparin therapy (0.5 to 3.0 U/mL) in clinical settings such as
hemodialysis, intensive care units, diagnostic cardiac catheterization, and PCI.9,12,16
7.3.2.1 Description of ACT
Native whole blood is added to a cartridge containing a contact activator, which triggers a clot detection
system, and the time in seconds to yield a clot is determined. The ACT is a global coagulation test
potentially affected by abnormalities of the intrinsic and common phase of blood coagulation that can be
used to measure heparin anticoagulant activity. With ACT or ACT-like systems, a linear relationship
between heparin concentrations and clotting times is observed in individual patients over specified
heparin concentration ranges. ACT test systems vary with regard to specimen volume and collection
requirements, type of contact activator, and clot detection methods. All available ACT tests are single-
use or unit-use systems. Some ACT test systems also include a heparin neutralization component, such as

Volume 24 H49-A
heparinase or protamine, to test for residual heparin following heparin neutralization post-CPB or use of
plasma-mixing to assess potential factors other than heparin, such as clotting factor deficiencies or lupus
anticoagulants which may prolong the clotting time.
Tests should be performed according to the manufacturer’s directions.
Before instituting use of an ACT test system, the users must establish the normal reference range using
blood obtained from at least 20 normal, apparently healthy male and female subjects. Since there is no
“standard” ACT against which individual systems can be referenced, it is necessary to establish normal
and therapeutic ranges for each system and activator used. ACT systems are designed to achieve linear
responsiveness over a specific, desired range of heparin concentrations. Users must select the test system
appropriate for the intended clinical application and target heparin ranges (e.g., intermediate-dose heparin
therapy in hemodialysis (0.5 to 1.5 U/mL) or PCI (2 to 3 U/mL), or high-dose heparin therapy in cardiac
surgery with CPB (3 to 8 U/mL)). It is the responsibility of the manufacturer to specify the range of
heparin concentration, which can be reliably measured with a particular ACT system, and assure linear
responsiveness of ACT values within the specified range of heparin concentrations.
ACT or ACT-like tests may be frequently affected by a number of preanalytic, patient-related,17 and
clinical18,19 variables such as the effects of hypothermia and/or hemodilution. The ACT may also be
affected by platelet concentration, impaired platelet function, and the effects of certain antiplatelet agents. 20,21
Serine protease inhibitors (e.g., aprotinin) can substantially prolong the ACT by binding and/or inhibiting
contact activators, such as celite,22,23 while ACT systems using kaolin are not affected at low to moderate
concentrations of aprotinin.24 Reductions in coagulation factors secondary to presurgery warfarin
therapy,19 lupus anticoagulants,25,26 and inherited deficiencies of contact system factors17 may prolong the
ACT and thus may make adequate monitoring of heparin therapy with ACT difficult or impossible.
Analytical variables that should be considered as possible causes for ACT variability are differences
among different ACT systems with regard to endpoint detection, automation, deviation from the
manufacturer’s instructions for storage of cartridges, and conditions such as instrument temperature and
humidity.
7.3.3 POC Heparin Concentration Measurements
Heparin concentration may be determined with an automated whole blood POC system based on
neutralization of heparin by protamine sulfate (PS) (automated PS titration system).27,28 Measurement of
heparin concentration by POC-PS titration may be particularly useful in patients with suspected heparin
resistance19,29,30 and patients undergoing cardiac surgery to more effectively suppress excessive
intravascular coagulation,31 or when functional tests like the ACT may give inaccurate results due to
contact factor deficiencies or lupus anticoagulants.19
7.3.3.1 Description of Test
Blood containing heparin is added to cartridges containing tissue thromboplastin reagent and different
amounts of PS, and the clotting times are determined. The heparin concentration in blood is calculated by
determining the amount of PS causing maximal shortening of the clotting time (equivalent to complete
neutralization of heparin) and taking into account the predetermined PS/heparin equivalency.

Number 23 NCCLS
Tests should be performed according to the system manufacturer’s directions.
Heparin levels determined by this system have been shown to correlate reasonably well with those
determined by anti-Xa chromogenic assay in plasma, even in the presence of aprotinin.19,20 PS titration-
based POC-test systems may yield lower heparin levels than laboratory-based anti-Xa or anti-IIa-based
systems, particularly with low- and intermediate-dose heparin monitoring (e.g., <1 U/mL).19 A major
potential advantage of heparin concentration monitoring by POC system is related to the fact that the
results are less affected by factors such as hemodilution, hypothermia, and pharmacologic agents (e.g.,
antiplatelet agents, aprotinin), and not at all affected by lupus anticoagulants or inherited deficiencies of
contact factors.19 However, on the other hand, heparin concentration measurements do not allow
assessment of anticoagulant effects (intensity of anticoagulation) and may be misleading in certain
patients with low levels of AT due to excessive consumption (e.g., DIC or preoperative heparin infusion
for several days), and/or decreased production (e.g., liver failure).30
7.4 Specific Applications
7.4.1 Cardiac Surgery
High-dose heparin anticoagulation (to yield heparin levels of 3 to 8 U/mL and ACT values between 350
to 800 seconds) is required during cardiac surgery with CPB to prevent clot formation in the
extracorporeal circuit and to minimize excessive CPB-related activation of the hemostatic system.19 There
is substantial variability of heparin anticoagulant responses even with high-dose therapy as illustrated by a
wide range of heparin response slope values (expressed as the increase in clotting time in seconds per unit
of heparin per mL of blood) in patients undergoing cardiac surgery, and this variability seems to be
greater than that observed in normal volunteers.30 This variability in heparin responsiveness is related to
substantial variation in the extent of heparin binding to endothelial cells and cellular (e.g., platelets,
monocytes, polymorphonuclear leukocytes) and soluble blood components (e.g., AT, fibrinogen, platelet
factor 4, Factor VIII).19 Therefore, it is imperative to monitor heparin closely during cardiac surgery to
minimize bleeding and thrombotic complications.
In cardiac surgery with CPB, most heparin monitoring protocols include measuring a preheparin, baseline
ACT, administering a weight-based (300 to 400 U/kg) heparin loading bolus, and repeating an ACT every
30 to 60 minutes, to allow further adjusting of the heparin dose by giving additional heparin boluses to
achieve and maintain either an ACT within the targeted range (typically 400 to 600 seconds) or maintain
heparin concentration within a targeted range (3 to 8 U/mL).28,32 Alternatively, the initially required
heparin dose may be estimated by measuring the ex vivo anticoagulant response of the patient’s blood to
heparin before administering the initial heparin bolus.28,33 An alternative approach to monitoring
anticoagulation during CPB may be achieved by using measurements of heparin concentration in addition
to ACT values to maintain a specific target heparin concentration (see Section 7.3.3).
At the end of CPB, heparin must be effectively neutralized to prevent excessive postoperative bleeding.
This is usually accomplished by administration of PS, which forms relatively stable complexes with
heparin that are cleared from the circulation.19 The methods used for heparin neutralization by PS will not
be discussed here.19
7.4.2 Interventional Cardiology/Radiology
Heparin is required to prevent excessive coagulation and thrombus formation during diagnostic
catheterizations or PCI. The level of heparin required is based upon the procedure; low dose (0.1 to 1.0

Volume 24 H49-A
U/mL) during diagnostic cardiology or radiology, and intermediate dose for more aggressive PCI
procedures including PTCA, and coronary stent placement (1.0 to 3.0 U/mL). Appropriate monitoring
tests, such as the POC-APTT, ACT, or heparin measurement, must be selected based upon the target
heparin concentration range.34,35 With any of these procedures the end user should be aware of potential
effects of contrast agents on coagulation measurements.
7.4.3 Intensive Care Units
Heparin is commonly administered in the intensive care unit for prophylaxis and/or treatment of
thromboembolic complication. The targeted heparin levels are usually below 1.0 U/mL. The selection of
POC test systems for monitoring heparin therapy should be based on the target heparin concentration
range. A POC-APTT or ACT system or heparin concentration assay may be used as long as the system
has adequate responsiveness to reliably determine anticoagulation intensity within the target range.36,37
7.4.4 Hemodialysis
Monitoring of heparin therapy for hemodialysis using target peak concentrations usually not exceeding
1.5 U/mL may be accomplished with an appropriate ACT system, or POC-APTT system, or heparin
concentration assay as long as the system has adequate responsiveness to reliably determine
anticoagulation intensity within the targeted range.
7.4.5 Standard Intermediate Dose Heparin Therapy (e.g., for venous thromboembolism)
Monitoring of heparin in the treatment of venous thrombosis and pulmonary embolism (target heparin
concentration of 0.2 to 0.4 U/mL by PS titration or anti-Xa measurements corresponding to 0.2 to 0.4
U/mL by PS titration)6,15 is generally performed using laboratory-based APTT but may be performed
using a POC-APTT system as appropriate. The normal and therapeutic ranges for each system must be
established independently. The correlation between POC-APTT system results and laboratory-based
APTT results must be initially established and periodically monitored.
8 Monitoring Warfarin Therapy
8.1 Introduction
An important advancement in oral anticoagulation therapy management has been the development of
systems that allow POC performance of the prothrombin time (POC-PT). POC-PT systems measure the
clotting time using native whole blood, citrated whole blood, or citrated plasma. The test result is
available in a few minutes and is expressed as a PT in seconds, or an international normalized ratio (INR).
The latter expression is recommended, because it reduces intersystem variation in test results. POC-PT
systems are available for professional use in hospitals, clinics or office settings, and for home use
allowing patients to perform their own INR monitoring. Major advantages of POC-PT testing include
decreased need for venous access; increased patient and care provider convenience; facilitation of more
frequent PT-INR monitoring and warfarin dose adjustment likely resulting in greater time in therapeutic
range38; more timely, direct, and clear physician/caregiver/patient communication; improved efficacy and
safety39; and decreased cost of long-term anticoagulant therapy.40
8.2 Blood Specimen Collection and Handling
POC-PT systems are typically intended for use with capillary whole blood obtained by a fresh fingerstick.
The blood is applied immediately to a test strip or cartridge. The volume of blood required differs with
each instrument. The recommended method for acquisition of the blood specimen is described in the
package insert of each system. Alternatively, guidelines for specimen collection are available in NCCLS
document H4—Procedures and Devices for the Collection of Diagnostic Capillary Blood Specimens.
Number 23 NCCLS
Depending on the test system, blood specimens other than capillary blood may be used. The manufacturer
is responsible for establishing the suitability of recommended specimen types, whether capillary, citrated,
or native venous whole blood or plasma. Only blood specimen types for which the performance of the
system has been characterized should be used. When using native venous whole blood, the specimen can
be drawn in an anticoagulant-free plastic syringe and rapidly expressed from the syringe before
coagulation begins. Since test systems are primarily designed for use of native whole blood, specimen
storage is generally not applicable. When using citrated specimens, standard blood specimen collection,
processing, and storage recommendations apply (see NCCLS documents H3—Procedures for the
Collection of Diagnostic Blood Specimens by Venipuncture; H18—Procedures for the Handling and
Processing of Blood Specimens; and H21—Collection, Transport, and Processing of Blood Specimens for
Testing Plasma-Based Coagulation Assays) unless otherwise stated by the manufacturer.
8.3 Test Systems Used for Monitoring Warfarin Therapy
8.3.1 PT Test Systems
8.3.1.1 Descriptions of Tests
Different types of technologies are employed in currently available POC-PT test systems. In addition,
several systems are also approved for patient self-testing. Each system uses a tissue thromboplastin
reagent contained within a disposable test unit. The whole blood or plasma blood specimen is added, and
the time to clot formation is measured and converted to a plasma-equivalent PT and/or INR. The method
for detection of the endpoint differs from system to system and from that of a conventional laboratory
plasma-based PT. When the endpoint is reached, the device software converts the observed time to an
INR and/or plasma-equivalent PT. The time at endpoint is converted using a formula established by the
manufacturer to make the test result traceable to the reference World Health Organization (WHO) tilt-
tube/international reference preparation (IRP) method. This calibration is achieved by simultaneously
testing blood specimens with the POC system and with a predefined instrument/thromboplastin
combination, traceable to the reference WHO tilt-tube/IRP method. The conversion equation thus
obtained is embedded in the device software. Results are customarily displayed on the instrument
monitor. Users of POC systems should have a basic understanding of the POC-PT test system and
technologies available and the particular system to be used before instituting POC-PT testing.
Tests should be performed according to the system manufacturer’s directions. The first or second drop of
blood is directly applied to a target area on the test unit. The test is initiated immediately and
automatically after specimen application. The correlation between the POC-PT/POC-INR and the
laboratory method should be known.
The systems are calibrated to determine a PT/INR from whole blood within a defined range of
hematocrits and platelet concentrations as defined by the manufacturer. The manufacturer also identifies
other variables impacting on the trueness and precision of test results.
Use of the INR is essential for correct interpretation of PT results and proper management of oral
anticoagulation. INR corrects for differences in thromboplastin reagent sensitivity to warfarin-induced
reductions in vitamin K-dependent, procoagulant coagulation factors. The INR is a product of the WHO
standardization scheme through which different thromboplastin reagents are calibrated against an IRP
thromboplastin. The WHO reference method widely used for calibration of commercial thromboplastin
preparations consists of simultaneously testing normal plasmas and plasmas from warfarin-anticoagulated

Volume 24 H49-A
patients with the IRP and a specific thromboplastin to be used in PT testing. The new thromboplastin is
assigned an international sensitivity index (ISI) based on its comparison to the IRP. The ISI is then used
to compute the INR results. Since ISI values of thromboplastins vary with use of different clot timers,
manufacturers of thromboplastins provide ISI values for a specific thromboplastin/clot timer combination.
An identical standardization approach cannot be used with POC systems, since the WHO reference
procedure determines PT results on citrated plasma samples using a manual tilt-tube method. POC
instruments (with their own specific thromboplastin reagents) are generally calibrated by comparing POC
test results to those obtained with a predefined thromboplastin/clot timer combination (i.e., secondary
reference) that is traceable to the WHO IRP/tilt-tube method.
INR standardization considerably improves comparability of results obtained with different test
systems. However, it does not correct for all potential variables. This is true for both laboratory-
based and POC-PT test systems. Moreover, poor correlation of INRs obtained with highly sensitive
(low-ISI) thromboplastins and less sensitive (high-ISI) thromboplastins may be observed.
The INR system is very useful but imperfect, and clinically important discrepancies of INR are
often observed among different laboratory-based PT test systems as well as point-of-care test
systems. In a study of laboratory-based PT systems, a 20% INR nonagreement was noted using 12
different reagent/instrument combinations which represented only a fraction of the 300 possible
reagent/instrument combinations.41 Similar results were reported in another recent study of variability of
laboratory-based INR.42 Similarly, extensive INR variability has been reported for different POC-PT
systems.43,44 The likelihood of observing clinically important system differences increases as the INR
rises above 3.0. Clinicians and laboratorians must recognize INR differences that have clinical decision
impact. In this regard, others45 noted that when looking at repeated measurements, statistically there is an
equivalence of INRs that are within 0.4 at a target INR of 2.5 and 0.7 at a target INR of 3.5. In a large
comparison study,46 the percentage of INR agreement between a POC system and a reference laboratory
system was similar to that observed between a local hospital laboratory and the reference laboratory.
When attempting to establish the trueness of a POC system, the required comparative data analysis must
include traditional correlation analysis, mean versus difference plots, and assessment of the incidence of
clinically important INR differences.
Results exceeding an INR of 5.0 generally have reduced trueness, precision, and linearity, both in POC-
and laboratory-based PT testing. These results should be interpreted accordingly. Appreciation of the
general agreement between INR results obtained at POC and different laboratory-based systems is
essential for optimal patient management. Although there has been considerable concern about the
reliability and safety of POC-PT testing (particularly when performed by patients themselves), published
evidence47 seems to support the notion that POC-PT testing is as reliable as laboratory-based testing.
Furthermore, it has been shown in a number of comparative studies that percent time in therapeutic range
(TTR) may be considerably increased in patients monitored by POC-PT testing as compared to patients
monitored by laboratory-based PT testing, possibly in part related to more frequent testing in POC-PT
monitored patients.47 It would clearly be desirable to have definitive evidence that monitoring by POC-PT
testing is as good or better than laboratory-based PT monitoring in terms of long-term outcome (i.e.,
prevention of recurrent thromboembolic complications and minimization of warfarin side effects; in
particular, serious abnormal bleeding). However, the cost of such studies, which would require enrollment
of tens of thousands of patients, is likely to be prohibitive.

Number 23 NCCLS
8.4 Specific Applications
8.4.1 Healthcare Provider Use
POC-PT tests are used in a variety of outpatient and inpatient settings, primarily for monitoring oral
anticoagulant therapy. These settings include emergency rooms, outpatient clinics, physicians’ offices,
hospital wards, surgical suites, and intensive care units.
POC-PT tests offer several advantages over conventional laboratory tests such as:
• ease of use (systems may be operated by trained, nonlaboratory healthcare providers);

• suitability for various blood or plasma specimen types;
• rapid availability of results;
• ability to immediately repeat testing if initial results are questionable; and
• convenience for the patient in terms of access to testing.
8.4.2 Patient Self-Testing (PST)
POC-PT systems intended for use in the home environment are designed to perform reliably in multiple
settings and under varying conditions of temperature, humidity, light, and physical handling. These
instruments provide simple prompts to the user and generally require minimal maintenance and
calibration. They are lightweight and highly portable.
8.4.2.1 Patient Selection
Not all patients requiring oral anticoagulant therapy are candidates for PST. Careful selection of patients
is essential. Criteria for selection of patients for PST include:
• adequate understanding of indication for and potential benefits and risks of warfarin anticoagulation;
• physical/mental ability to perform PST;
• willingness to perform PST;
• willingness to comply with requirements for procedures, recording of QC data and timely
communication with caregiver in case of test system malfunction or out-of-range QC results;
• history of compliance with medical recommendations; and
• adequate insurance coverage for PST or willingness and ability for self-pay.
8.4.2.2 Training
Participants in a PST program require unique and comprehensive training beyond that traditionally
required for professional users of POC-CT systems. POC-CT systems which are intended to be used for
PST must have an accompanying manufacturer-recommended training guideline that professionals can
reference when selecting and training PST candidates. A proper training program should encompass the
following categories:
• Basic disease and anticoagulation information

— indication for and duration of anticoagulation therapy;
— mechanism of warfarin anticoagulant effect;
— prothrombin time and INR;
— desired therapeutic INR range;
— rationale for monitoring;

Volume 24 H49-A
— side effects/complications of warfarin anticoagulation;

— impact of diet, drugs, illness, liver function, etc., on INR; and
— relationship between antithrombolic efficacy and bleeding complications.
• Blood collection technique

— operation of device for fingerstick;
— fingerstick puncture and aseptic technique;
— storage, handling, and disposal of supplies and contaminated materials; and
— care of device.
• Performance of POC-PT test

— preparation for testing;
— purpose, and performance of quality control procedures; and
— storage, handling of test system and cartridges, and disposal of supplies and contaminated
material.
• Data management and transmission of results to healthcare provider

— recording and reporting of results;
— troubleshooting system errors;
— maintaining QC data; and
— communicating with healthcare provider (indication of mechanism - telephone, fax, e-mail).
8.4.2.3 Quality Control Management for PST
Patient self-testers should be instructed regarding the specific manufacturer’s guidelines for quality
control and quality assurance. Manufacturers should provide written quality control recommendations,
which are consistent with the guidelines found in Section 6. Patient training before starting PST should
include details of the required quality control procedures. The healthcare professional responsible for the
patient’s care should document routine verification of patient compliance with quality control
requirements. The healthcare provider should additionally verify the patient’s technique through direct
observation, at regular intervals. Split-sample testing should also be performed, according to an
established schedule, to verify that the relationship between the patient’s device and the clinical
laboratory assay is unchanged and to ensure continued acceptable performance of the patient’s device.
8.5 Result Recording and Reporting
The optimal use of POC-CT for patient self-testing requires that the patient effectively communicate
reliable test results to the healthcare provider. Reliability of results is determined not only by the
performance of the test system but also by the user’s testing proficiency, and the patient’s compliance in
terms of quality control and maintenance of the instrument.

Number 23 NCCLS
References
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ISO. Quality management systems – Fundamentals and vocabulary. ISO 9000. Geneva: International Organization for Standardization; 2000.
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WHO. Expert Committee on Biological Standardization. Glossary of Terms for Biological Substances Used for Texts of the Requirements.
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Hirsh J, Anand SS, Halperin JL, Fuster V. Guide to anticoagulant therapy: Heparin. Circulation. 2001;103:2994-3018.
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Hattersley PG. Activated coagulation time of whole blood. JAMA. 1966;196:436-440.
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Hirsh J, Dalen JE, Anderson DR, et al. Oral anticoagulants: Mechanism of action, clinical effectiveness and optimal therapeutic range. Chest.
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Laxson CJ, Titler MG. Drawing coagulation studies from arterial lines: An integrative literature review. Am J Crit Care. 1994;1:16-24.
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Olson JD, Arkin CF, Brandt JT, et al. College of American Pathologists Conference XXI on Laboratory Monitoring of Anticoagulant
Therapy. Laboratory monitoring of unfractionated heparin therapy. Arch Pathol Lab Med. 1998;122:782-798.
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Bajaj SP, Joist JH. New insights into how blood clots: Implications for the use of APTT and PT as coagulation screening tests and in
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Brill-Edwards P, Ginsberg JS, Johnston M, Hirsh J. Establishing a therapeutic range for heparin therapy. Ann Intern Med. 1993;119:104-109.
15
Becker RC, Cyr J, Corrao JM, Ball SP. Bedside coagulation monitoring in heparin treated patients with active thromboembolic disease: A
coronary care unit experience. Am Heart J. 1994;120:719-723.
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Zucker ML, LaDuca FM. Activated clotting time: How to select the right assay for the right clinical application. Clin Lab News. 2002:10-12.
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Moorman RM, Reynolds DS, Comunale ME. Management of cardiopulmonary bypass in a patient with congenital factor XII deficiency. J
Cardiothor Vasc Anesthesia. 1993;7:452-454.
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Despotis GJ, Summerfield AL, Joist JH, et al. Comparison of activated coagulation time and whole blood heparin measurements with
laboratory plasma anti-Xa heparin concentration in patients having cardiac operations. J Thorac Cardiovasc Surg. 1994;108:1076-1082.
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Despotis GJ, Gravlee G, Filos KS, Levy JH. Anticoagulation monitoring during cardiac surgery: A review of current and emerging techniques.
Anesthesiology. 1999;91:1122-1151.
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The EPILOG Investigators: Platelet glycoprotein IIb/IIIa receptor blockade and low dose heparin during percutaneous coronary
revascularization. NEJM. 1997;336:1689-1696.
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Amar T, Scudder L, Coller B. In vitro effects of platelet glycoprotein IIb/IIIa receptor antagonist c7E3 Fab on the activated clotting time.
Circulation. 1997;95:614-614.
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Feindt P, Volkmer I, Seijfert U, et al. Activated clotting time anticoagulation, use of heparin and thrombin activation during extracorporeal
circulation: Changes under aprotinin therapy. Thorac Cardiovasc Surg. 1993;41:9-15.
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Hunt BS, Segal HC, Yacoub M. Guidelines for monitoring heparin by the activated clotting time when aprotinin is used during
cardiopulmonary bypass. (Letter). J Thorac Cardiovasc Surg. 1992;104:211-212.
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Despotis GJ, Joist JH, Joiner-Maier D, et al. Effect of aprotinin on activated clotting time, whole blood and plasma heparin measurements.
Ann Thorac Surg. 1995;59:106-111.
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Sheikh F, Lechowicz A, Seflur R, et al. Recognition and management of patients with antiphospholipid antibody syndrome undergoing
cardiac surgery. J Cardiothor Vasc Anesthesia. 1997;11:764-766.
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Ducart AR, Collard EL, Osselaer JC, et al. Management of anticoagulation during cardiopulmonary bypass in a patient with a circulating lupus
anticoagulant. J Cardiothor Vasc Anesthesia. 1997;11:878-879.

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27
Jobes DR, Schwartz AJ, Ellisson N, et al. Monitoring heparin anticoagulation and its neutralization. Am Thorac Surg. 1980;31:161-166.
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Gravlee GP, Hadon WS, Rothberger HK, et al. Heparin dosing and monitoring for cardiopulmonary bypass: A comparison of techniques with
measurement of subclinical plasma coagulation. J Thorac Cardiovasc Surg. 1990;99:518-527.
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Levine MN, Hirsh J, Gent M, et al. A randomized trial comparing activated thromboplastin time with heparin assay in patients with acute
venous thromboembolism requiring large daily doses of heparin. Arch Intern Med. 1996;154:49-56.
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Despotis GJ, Levine V, Joist JH, et al. Antithrombin III during cardiac surgery: Effect on response of activated clotting time to heparin and
relationship to markers of hemostatic activation. Anesth Analg. 1997;85(3):498-506.
31
Despotis GJ, Joist JH, Hogue CW Jr., et al. More effective suppression of hemostatic system activation in patients undergoing cardiac surgery
by heparin dosing based on heparin blood concentrations rather than ACT. Thromb Haemostasis. 1996;76(6):902-908.
32
Bull B, Korpman R, Huse W, Briggs B. Heparin therapy during extracorporeal circulation. I. Problems inherent in existing heparin protocols. J
Thorac Cardiovasc Surg. 1975:69;674-684.
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Bull B, Huse W, Brauer F, Korpman R. Heparin therapy during extracorporeal circulation. II. The use of the dose-response curve to
individualize heparin and protamine dose. heparin protocols. J Thorac Cardiovasc Surg. 1975;69:685-689.
34
Ogilby J, Kopelman H, Klein L, Agarwal J. Adequate heparinization during PTCA: Assessment using activated clotting times. Cath and
Cardiovasc Diag. 1989:18;206-209.
35
Chew D, Bhatt D, Lincoff M, et. al. Defining activated clotting time during percutaneous coronary intervention. Circulation. 2001;103:961-
966.
36
Blumenthal R, Carter A, Resar J, et al. Comparison of bedside and hospital laboratory coagulation studies during and after coronary
intervention. Cath and Cardiovasc Diag. 1995;35:9-17.
37
Siskin G, Reiner E, Stainken B, et al. Activated clotting time as a screening test prior to catheter-based cardiovascular procedures. Cath and
Cardiovasc Diag. 2001;54:191-195.
38
Samsa GP, Matchar DB. Relationship between test frequency and outcomes of anticoagulation: A literature review and commentary with
implications for the design of randomized trials of patient self-management. J Thrombosis Thrombolysis. 2000;9:283-292.
39
Ansell J, Hirsch J, Dalen J, et al. Managing oral anticoagulant therapy. Chest. 2001;119-22S-382.
40
Muller E, Bergemann R, GELIA Study Group. Economic analysis of bleeding and thromboembolic sequelae after heart valve replacement
(GELIA 7). Euro Heart J. 2001;3(Suppl Q):Q65-Q69.
41
McGlasson DL. A comparison of INR after local calibration of thromboplastin international sensitivity indexes. Clin Lab Sci. 2002:15;91-95.
42
Jacobson AK, Ruybalid RL, Johnston M, Westengard J. Significant variation in the reporting of prothrombin time results despite utilization of
the INR method of reporting. Circulation. 1999;100:I-620.
43
Jacobson AK, Peterson M, Gunneman T, et al. Magnitude of INR variation attributable to differences between point-of-care testing devices. J
Am College of Cardiology. 2002:39:5, 234A.
44
Gosselin R, Owings JT, White RH, et al. A comparison of point-of-care instruments designed for monitoring oral anticoagulation with
standard laboratory methods. Thromb Haemostas. 2002;83:698-703.
45
Lassen JF, Brandslund I, Antonsen S, et al. International normalized ratio for prothrombin times in patients taking oral anticoagulants: Critical
difference and probability of significant change in consecutive measurements. Clin Chem. 1995;41:444-447.
46
Oral Anticoagulation Monitoring Study Group. Point-of-care prothrombin time measurement for professional and patient self-testing use. Am J
Clin Path. 2001;115:288-296.
47
Ansel J, Hirsh J, Dalen J, et al. Managing oral anticoagulant therapy. Chest. 2001;22S-38S.

Number 23 NCCLS
NCCLS consensus procedures include an appeals process that is described in detail in Section 8 of
the Administrative Procedures. For further information, contact the Executive Offices or visit our
website at www.nccls.org.
Summary of Delegate Comments and Subcommittee Responses

H49-P: Point-of-Care Monitoring of Anticoagulation Therapy; Proposed Guideline
General
1. This is a valuable document for anyone setting up a POC-CT laboratory. Because it is a “global” document, in
some areas it may be vague and excessively general.
• The subcommittee appreciates the input.
2. This well-scoped document forms a foundation for more specific guideline(s) for the rapidly diversifying field
of POC coagulation.
• The subcommittee appreciates the positive comment.
3. This is an important document. A few small comments: Since this is about “Point of Care,” I wish the authors
would use only THAT term in the document. We need standardization on this term, and to continue the habit of
“also referred to as ...” is not helping. I noted this specifically on pages vii,1, and 3.
• The phrase “also referred to as near-patient testing or bedside testing” has been deleted from page 1.
However, the phrase has been retained in the Abstract and the Definitions. POC is used exclusively
throughout the rest of the text without mention of the alternative terms. The other terms were retained in
the Abstract and Definitions, since this document will be read by others throughout the world where such
terms are in common use, and the subcommittee believes it is reasonable to indicate for such readers
(especially in the definition) that POC indicates the same process as the other terms denote.
Section 4, Definitions (Formerly Section 3)
4. “Sample” definition – the last word of the 1st sentence should be “test” instead of “rest.”
• The text has been corrected.
5. Add “native” and “tilt-tube” to the list of definitions.
• The suggested definitions have been added to the document.
Section 6.2, Training (Formerly Section 5.2)
6. Calibrations need to be added to the list of training for users.
• Instrument calibration has been added to the training list for users.
7. Evaluating competency should include the use of corrective action logs for failed QC.
• The use of corrective action logs for failed QC has been added to Section 6.2.
8. At the top of Page 7 – “medical technologists or other trained personnel available as part-time consultants.”
Why “part-time”?
• The term “part-time” has been deleted.

Volume 24 H49-A
Section 6.3.1, Quality Control (Formerly Section 5.3.1)
9. Sensitivity of quality control to detect analytical problems should include recommendations of what to do when
QC fails.
• The following text has been added: “The manufacturer may provide additional recommendations for
corrective action when QC fails.”
Section 6.3.2, Proficiency Testing (Formerly Section 5.3.2)
10. Proficiency testing is also mandated by CLIA certification; since many nonlaboratory folks are liable to use this
document, this should be mentioned.
• The text has been revised to include that proficiency testing is mandated by CLIA.
Section 6.4, Result Recording and Reporting (Formerly Section 5.4)
11. A record of expiry dates for consumables should also be kept.
• The recording of expiration dates for consumables has been added to the text.
12. Confidentiality has worldwide importance and should be more emphasized with password-oriented, graded
access to the information system when applicable.
• The following text has been added: “Access to results should be password-oriented with graded access to
the information when applicable.”
Section 7.2.3, Blood Specimen Handling and Testing (Formerly Section 6.2.3)
13. A statement should be included about “free flowing blood collection.”
• The text has been revised as suggested.
Section 7.3.1.3, Test Result Interpretation and Limitations (Formerly Section 6.3.1.3)
14. A statement about the effect of phospholipid antibodies on POC-APTT results may be needed.
• The following text has been added: “Even without anticoagulation therapy, patients with
antiphospholipid antibodies (like lupus anticoagulant) may have prolonged POC-APTT test results.”
15. The lack of comparability between laboratory aPTT and POC-CT aPTT should be boldfaced or italicized
because of its importance.
• The text has been boldfaced as suggested.
Section 7.3.2.1, Description of ACT (Formerly Section 6.3.2.1)
16. “Non-anticoagulated blood” is an ambiguous term, especially if the ACT is used to monitor heparin therapy.
Anticoagulant might be present, but it is not added to the specimen/sample after the blood is withdrawn from
the patient. This issue should be clarified.
• The phrase “non-anticoagulated” has been replaced by “native whole.”
Section 7.4.1, Cardiac Surgery (Formerly Section 6.4.1)
17. “The methods used for heparin neutralization by PS will not be discussed here.” A reference would be nice.
• A reference has been added to the end of Section 7.4.1 as suggested.

Number 23 NCCLS
Section 7.4.2, Interventional Cardiology/Radiology (Formerly 6.4.2)
18. The potential effects of contrast agents on coagulation measurement should be considered. It is unclear if this is
a recommendation to the end user or the manufacturer.
• The text has been revised for clarification. The following phrase has been added to the last sentence:
“…end user should be aware of…”
Section 8.1, Introduction (Formerly Section 7.1)
19. “Non-anticoagulated (native) whole blood.” “Native” should be defined.
• The term “non-anticoagulated” has been replaced with “native.” The term “native” has been added to
the definitions.
Section 8.2, Blood Specimen Collection and Handling (Formerly Section 7.2)
20. “Non-anticoagulated” recurs. It’s an issue with in vivo vs in vitro anticoagulation as above.
• The term “non-anticoagulated” has been replaced with “native.”
Section 8.3.1.1, Description of Tests (Formerly Section 7.3.1.1)
21. The term “tilt-tube” should be defined.
• The suggested term has been added to the definitions.
Section 8.3.1.3, Test Result Interpretation and Limitations (Formerly Section 7.3.1.3)
22. The term “tilt-tube” should be defined.
• The suggested term has been added to the definitions.
23. Some of the commentary concerning the lack of comparability, “normalization” or “harmonization” of the
laboratory and POC-CT INR should be in bold or italics because of the importance of this issue. Because the PT
ratio is multiplied by the ISI power, differences between the laboratory and POC-CT PT ratios will be
magnified (vs. mere factoring by the ISI if it were not a power).
• The text has been boldfaced as suggested.
Section 8.4.2.2, Training (Formerly Section 7.4.2.2)
24. Why would anyone consider it important to train a patient in “mechanism of warfarin anticoagulant effect” as
part of teaching them how to do self-testing? And, in that same section, “impact of diet, drugs, illness, liver
function, etc., on INR” - no patient is going to know their liver function. Why not say “laboratory test results”?
• Education of the patient (who does self-testing) about mechanism of action of warfarin, or liver function,
drug interactions, etc., does not imply that detailed, basic science education is provided, but only the bare
essentials. For example: warfarin mechanism of action means that warfarin interferes with the ability of
the blood to form a clot. It does not “thin out” the blood. The patient must understand that drugs can
interact with warfarin (mechanism is not necessary), and thus be alert to tell his/her physician anytime a
drug is initiated or discontinued. We realize that patients will not know their liver function, but to
understand that impairment of liver function can effect the INR (e.g., too much alcohol intake) is
important. We strongly believe that an educated patient is best able to deal with the vicissitudes of INR
monitoring. This rudimentary education is really basic to all anticoagulation therapy.

Volume 24 H49-A
NOTES

Number 23 NCCLS
The Quality System Approach

NCCLS subscribes to a quality system approach in the development of standards and guidelines, which facilitates
project management; defines a document structure via a template; and provides a process to identify needed
documents through a gap analysis. The approach is based on the model presented in the most current edition of
NCCLS HS1—A Quality System Model for Health Care. The quality system approach applies a core set of “quality
system essentials (QSEs),” basic to any organization, to all operations in any healthcare service’s path of workflow.
The QSEs provide the framework for delivery of any type of product or service, serving as a manager’s guide. The
quality system essentials (QSEs) are:
Documents & Records Equipment Information Management Process Improvement

Organization Purchasing & Inventory Occurrence Management Service & Satisfaction
Personnel Process Control Assessment Facilities & Safety
H49-A addresses the quality system essentials (QSEs) indicated by an “X.” For a description of the other NCCLS
documents listed in the grid, please refer to the Related NCCLS Publications section on the following page.
Purchasing &
Improvement
Organization
Management
Management
Information
Satisfaction
Assessment
Facilities &
Occurrence
Documents
Equipment
& Records
Service &
Personnel
Inventory
Control
Process
Process
Safety
X
GP29
AST2
EP18
Adapted from NCCLS document HS1—A Quality System Model for Health Care.
Path of Workflow
A path of workflow is the description of the necessary steps to deliver the particular product or service that the
organization or entity provides. For example, GP26-A2 defines a clinical laboratory path of workflow which
consists of three sequential processes: preanalytic, analytic, and postanalytic. All clinical laboratories follow these
processes to deliver the laboratory’s services, namely quality laboratory information.
H49-A addresses the clinical laboratory path of workflow steps indicated by an “X.” For a description of the other
NCCLS documents listed in the grid, please refer to the Related NCCLS Publications section on the following page.
Preanalytic Analytic Postanalytic

Interpretation
Management
Test Request
Assessment
Laboratory
Collection
Specimen
Specimen
Specimen
Specimen
Transport
Post-test
Receipt
Review
Testing
Results
Patient
Report
X X X X
H3 H47
H4
H21
Adapted from NCCLS document HS1—A Quality System Model for Health Care.

Volume 24 H49-A
Related NCCLS Publications*

AST2-A Point-of-Care In Vitro Diagnostic (IVD) Testing; Approved Guideline (1999). This document contains
guidelines for users of in vitro diagnostic (IVD) devices outside the clinical laboratory to produce reliable
results comparable to those obtained in the clinical laboratory.
EP18-A Quality Management for Unit-Use Testing; Approved Guideline (2002). This guideline recommends a
quality management system for unit-use devices that will aid in the identification, understanding, and
management of sources of error and help to ensure correct results. It is targeted for those involved in the
supervision of laboratory-testing quality management, and it addresses issues related to specimen collection
through reporting of test results.
GP29-A Assessment of Laboratory Tests When Proficiency Testing is Not Available; Approved Guideline
(2002). This document offers methods to assess test performance when proficiency testing (PT) is not
available; these methods include examples with statistical analyses. This document is intended for use by
laboratory managers and testing personnel in traditional clinical laboratories as well as in point-of-care and
bedside testing environments.
H3-A5 Procedure for the Collection of Diagnostic Blood Specimens by Venipuncture; Approved Standard—
Fifth Edition (2003). This document provides procedures for the collection of diagnostic specimens by
venipuncture, including line draws, blood culture collection, and venipuncture in children. It also includes
recommendations on order of draw.
H4-A5 Procedures and Devices for the Collection of Diagnostic Capillary Blood Specimens; Approved
Standard—Fifth Edition (2004). This document provides a technique for the collection of diagnostic blood
specimens by skin puncture, including recommendations for collection sites and specimen handling and
identification. Specifications for disposable devices used to collect, process, and transfer diagnostic blood
specimens obtained by skin puncture are also included.
H21-A4 Collection, Transport, and Processing of Blood Specimens for Testing Plasma-Based Coagulation
Assays; Approved Guideline—Fourth Edition (2003). This document provides procedures for collecting,
transporting, and storing blood; processing blood specimens; storage of plasma for coagulation testing; and
general recommendations for performing the tests.
H47-A One-Stage Prothrombin Time (PT) Test and Activated Partial Thromboplastin Time (APTT) Test;
Approved Guideline (1996). This document provides guidelines for performing the PT and APTT tests in
the clinical laboratory, for reporting results, and for identifying sources of error.
*
Proposed- and tentative-level documents are being advanced through the NCCLS consensus process; therefore, readers should
refer to the most recent editions.
Number 23 NCCLS
NOTES

Volume 24 H49-A
NOTES

Number 23 NCCLS
NOTES

Volume 24 H49-A
NOTES

Active Membership
(as of 1 July 2004)
Sustaining Members Chinese Committee for Clinical EXPERTech Associates, Inc. Atlantic Health System (NJ)
Laboratory Standards F. Hoffman-La Roche AG Aurora Consolidated Laboratories
Abbott Laboratories Commonwealth of Pennsylvania Fort Dodge Animal Health (WI)
American Association for Clinical Bureau of Laboratories Gen-Probe AZ Sint-Jan (Belgium)
Chemistry Department of Veterans Affairs GenVault Azienda Ospedale Di Lecco (Italy)
Bayer Corporation Deutsches Institut für Normung GlaxoSmithKline Barnes-Jewish Hospital (MO)
BD (DIN) Greiner Bio-One Inc. Baxter Regional Medical Center
Beckman Coulter, Inc. FDA Center for Devices and Immunicon Corporation (AR)
bioMérieux, Inc. Radiological Health ImmunoSite, Inc. Baystate Medical Center (MA)
CLMA FDA Center for Veterinary Medicine Instrumentation Laboratory Bbaguas Duzen Laboratories
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GlaxoSmithKline Drug Products Corporation BC Biomedical Laboratories (Surrey,
Ortho-Clinical Diagnostics, Inc. Iowa State Hygienic Laboratory I-STAT Corporation BC, Canada)
Pfizer Inc Massachusetts Department of Public Johnson and Johnson Pharmaceutical Bermuda Hospitals Board
Roche Diagnostics, Inc. Health Laboratories Research and Development, L.L.C. Boulder Community Hospital (CO)
National Center of Infectious and K.C.J. Enterprises Brazosport Memorial Hospital (TX)
Professional Members Parasitic Diseases (Bulgaria) LAB-Interlink, Inc. Broward General Medical Center
National Health Laboratory Service LifeScan, Inc. (a Johnson & Johnson (FL)
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Physicians National Institute of Standards and LUZ, Inc. (Winnipeg, MB, Canada)
American Association for Clinical Technology Machaon Diagnostics Calgary Laboratory Services
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American Society for Clinical Pennsylvania Dept. of Health Advisory Council (Australia) (Nova Scotia, Canada)
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American Type Culture Collection, Belgium Ministry of Social Novartis Pharmaceuticals Cathay General Hospital (Taiwan)
Inc. Affairs, Public Health and the Corporation Central Texas Veterans Health Care
Asociacion Mexicana de Bioquimica Environment Olympus America, Inc. System
Clinica A.C. Swedish Institute for Infectious Ortho-Clinical Diagnostics, Inc. Centro Diagnostico Italiano (Milano,
Assn. of Public Health Laboratories Disease Control (Rochester, NY) Italy)
Assoc. Micro. Clinici Italiani- Ortho-McNeil Pharmaceutical Champlain Valley Physicians
A.M.C.L.I. Industry Members (Raritan, NJ) Hospital (NY)
British Society for Antimicrobial Oxoid Inc. Chang Gung Memorial Hospital
Chemotherapy AB Biodisk Paratek Pharmaceuticals (Taiwan)
Canadian Society for Medical Abbott Laboratories Pfizer Animal Health Changi General Hospital
Laboratory Science - Société Abbott Diabetes Care Pfizer Inc (Singapore)
Canadienne de Science de Acrometrix Corporation Pfizer Italia Srl Children’s Hospital (NE)
Laboratoire Médical Advancis Pharmaceutical Powers Consulting Services Children’s Hospital & Clinics (MN)
Canadian Standards Association Corporation Premier Inc. Children’s Hospital Medical Center
Clinical Laboratory Management Affymetrix, Inc. Procter & Gamble Pharmaceuticals, (Akron, OH)
Association Alifax S.P.A. Inc. Children’s Medical Center of Dallas
COLA Ammirati Regulatory Consulting QSE Consulting (TX)
College of American Pathologists Anna Longwell, PC Quintiles, Inc. CHR St. Joseph Warquignies
College of Medical Laboratory A/S ROSCO Radiometer America, Inc. (Belgium)
Technologists of Ontario AstraZeneca Pharmaceuticals Radiometer Medical A/S Christus St. John Hospital (TX)
College of Physicians and Surgeons Aventis Replidyne Clarian Health - Methodist Hospital
of Saskatchewan Axis-Shield POC AS Roche Diagnostics GmbH (IN)
ESCMID Bayer Corporation - Elkhart, IN Roche Diagnostics, Inc. CLSI Laboratories (PA)
International Council for Bayer Corporation - Tarrytown, NY Roche Laboratories (Div. Hoffmann- Community Hospital of Lancaster
Standardization in Haematology Bayer Corporation - West Haven, La Roche Inc.) (PA)
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Biomedical Laboratory Science BD Schering Corporation Monterey Peninsula (CA)
International Federation of Clinical BD Consumer Products Schleicher & Schuell, Inc. CompuNet Clinical Laboratories
Chemistry BD Diagnostic Systems Second Opinion (OH)
Italian Society of Clinical BD Thailand Ltd. Seraphim Life Sciences Consulting Cook Children’s Medical Center
Biochemistry and Clinical BD VACUTAINER Systems LLC (TX)
Molecular Biology Beckman Coulter, Inc. SFBC Anapharm Cook County Hospital (IL)
Japan Society of Clinical Chemistry Beckman Coulter K.K. (Japan) Streck Laboratories, Inc. Covance Central Laboratory
Japanese Committee for Clinical Bio-Development SRL SYN X Pharma Inc. Services (IN)
Laboratory Standards Bio-Inova Life Sciences Sysmex Corporation (Japan) Creighton University Medical Center
Joint Commission on Accreditation International Sysmex Corporation (Long Grove, (NE)
of Healthcare Organizations Biomedia Laboratories SDN BHD IL) Danish Veterinary Laboratory
National Academy of Clinical bioMérieux, Inc. (MO) TheraDoc (Denmark)
Biochemistry Biometrology Consultants Theravance Inc. Detroit Health Department (MI)
National Association of Testing Bio-Rad Laboratories, Inc. THYMED GmbH DFS/CLIA Certification (NC)
Authorities - Australia Bio-Rad Laboratories, Inc. – France Transasia Engineers Diagnósticos da América S/A
National Society for Bio-Rad Laboratories, Inc. – Plano, Trek Diagnostic Systems, Inc. (Brazil)
Histotechnology, Inc. TX Tyco Kendall Healthcare Dr. Everett Chalmers Hospital (New
New Zealand Association of BioVeris Corporation Vetoquinol S.A. Brunswick, Canada)
Phlebotomy Blaine Healthcare Associates, Inc. Vicuron Pharmaceuticals Inc. Duke University Medical Center
Ontario Medical Association Quality Bristol-Myers Squibb Company Vysis, Inc. (NC)
Management Program-Laboratory Canadian External Quality Wyeth Research Dwight David Eisenhower Army
Service Assessment Laboratory XDX, Inc. Medical Center (GA)
RCPA Quality Assurance Programs Cepheid YD Consultant Eastern Health Pathology (Australia)
PTY Limited Chen & Chen, LLC YD Diagnostics (Seoul, Korea) EMH Regional Medical Center (OH)
Sociedad Espanola de Bioquimica Chiron Corporation Emory University Hospital (GA)
Clinica y Patologia Molecular ChromaVision Medical Systems, Trade Associations Enzo Clinical Labs (NY)
Sociedade Brasileira de Analises Inc. Evangelical Community Hospital
Clinicas Clinical Micro Sensors AdvaMed (PA)
Taiwanese Committee for Clinical The Clinical Microbiology Institute Japan Association of Clinical Fairview-University Medical Center
Laboratory Standards (TCCLS) Cognigen Reagents Industries (Tokyo, Japan) (MN)
Turkish Society of Microbiology CONOSCO Florida Hospital East Orlando
Copan Diagnostics Inc. Associate Active Members Focus Technologies (CA)
Government Members Cosmetic Ingredient Review Focus Technologies (VA)
Cubist Pharmaceuticals Academisch Ziekenhuis -VUB Foothills Hospital (Calgary, AB,
Armed Forces Institute of Pathology Dade Behring Inc. - Cupertino, CA (Belgium) Canada)
Association of Public Health Dade Behring Inc. - Deerfield, IL Alfred I. duPont Hospital for Franciscan Shared Laboratory (WI)
Laboratories Dade Behring Inc. - Glasgow, DE Children (DE) Fresno Community Hospital and
BC Centre for Disease Control Dade Behring Inc. - Marburg, Allina Health System (MN) Medical Center
Caribbean Epidemiology Centre Germany American University of Beirut Gamma Dynacare Medical
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Canada) Center (CA) (CA) UCLA Medical Center (CA)
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(Montreal, Canada) (Microbiology Laboratory) Regions Hospital UNC Hospitals (NC)
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Quebec, Canada) (Burnaby, BC, Canada) Rhode Island Department of Health (Mexico)
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(MI) Hospital Riverside Medical Center (IL) Universita Campus Bio-Medico
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ON, Canada) (Napoleon Avenue, New Orleans, Hospital (NJ) University College Hospital
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ON, Canada) Davis Pkwy., New Orleans, LA) Sahlgrenska Universitetssjukhuset (OH)
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(Sweden) Michigan Department of St. Alexius Medical Center (ND) Hospital
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(Australia) Mid America Clinical Laboratories, St. Anthony’s Hospital (FL) (IL)
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Science (Australia) Montreal Children’s Hospital St. Francis Medical Ctr. (CA) (Hungary)
International Health Management (Canada) St. John Hospital and Medical University of Illinois Medical Center
Associates, Inc. (IL) Montreal General Hospital (Canada) Center (MI) University of the Ryukyus (Japan)
Jackson Memorial Hospital (FL) National Serology Reference St. John’s Hospital & Health Center The University of Texas Medical
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(MD) Canada) Clinic (WI) Center
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Canada) North Carolina State Laboratory of ON, Canada) Vejle Hospital (Denmark)
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(NJ) technologists médicaux du (IN) (Ireland)
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(FL) Ospedali Riuniti (Italy) Southwest Texas Methodist Hospital William Beaumont Army Medical
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(APO AE) (Ottawa, ON, Canada) Center (SC) William Beaumont Hospital (MI)
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(CA)
OFFICERS BOARD OF DIRECTORS
Thomas L. Hearn, Ph.D., Susan Blonshine, RRT, RPFT, FAARC Willie E. May, Ph.D.
President TechEd National Institute of Standards and Technology
Centers for Disease Control and Prevention
Kurt H. Davis, FCSMLS, CAE Gary L. Myers, Ph.D.
Robert L. Habig, Ph.D., Canadian Society for Medical Laboratory Science Centers for Disease Control and Prevention
President Elect
Abbott Laboratories Mary Lou Gantzer, Ph.D. Klaus E. Stinshoff, Dr.rer.nat.
Dade Behring Inc. Digene (Switzerland) Sàrl
Wayne Brinster,
Secretary Lillian J. Gill, M.S. Kiyoaki Watanabe, M.D.
BD FDA Center for Devices and Radiological Health Keio University School of Medicine
Gerald A. Hoeltge, M.D., Carolyn D. Jones, J.D., M.P.H. Judith A. Yost, M.A., M.T.(ASCP)
Treasurer AdvaMed Centers for Medicare & Medicaid Services
The Cleveland Clinic Foundation
J. Stephen Kroger, M.D., MACP
Donna M. Meyer, Ph.D., COLA
Immediate Past President
CHRISTUS Health
John V. Bergen, Ph.D.,

Executive Vice President
NCCLS T 940 West Valley Road T Suite 1400 T Wayne, PA 19087 T USA T PHONE 610.688.0100
FAX 610.688.0700 T E-MAIL: exoffice@nccls.org T WEBSITE: www.nccls.org T ISBN 1-56238-540-2

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H49-A

This document provides guidance to users and manufacturers of point-of-care coagulation

Reproduced with permission, from NCCLS publication H49-A—Point-of-Care

Copyright ©2004. The National Committee for Clinical Laboratory Standards.

(NCCLS. Point-of-Care Monitoring of Anticoagulation Therapy; Approved Guideline. NCCLS

Dorothy M. Adcock, M.D. Charles F. Arkin, M.D. Richard A. Marlar, Ph.D.

Frank M. LaDuca, Ph.D. J. David Bessman, M.D. Diane I. Szamosi, M.A.,

Subcommittee on Point-of-Care Coagulation Testing

Ginette Y. Michaud, M.D. Catherine Cox, M.D. David E. Sterry, M.T.(ASCP)

Committee Membership........................................................................................................................ iii

Foreword .............................................................................................................................................. vii

5 Point-of-Care Coagulation Testing (POC-CT)—General Considerations.................................6

6 Quality Management: General Considerations for Point-of-Care Coagulation Testing ............6

Summary of Delegate Comments and Subcommittee Responses.........................................................22

The Quality System Approach..............................................................................................................26

Related NCCLS Publications................................................................................................................27

Calibration, point-of-care testing, quality assurance, quality control, safety

Point-of-Care Monitoring of Anticoagulation Therapy; Approved Guideline

An NCCLS global consensus guideline. ©NCCLS. All rights reserved. 1

Anticoagulant – An agent, natural or pharmacological, that inhibits clotting of blood or plasma.

Capillary – Blood obtained by skin puncture.

Venous – Blood obtained by venipuncture or from an indwelling line or catheter.

2 An NCCLS global consensus guideline. ©NCCLS. All rights reserved.

Heparin (unfractionated) – A mixture of complex glycosaminoglycans (mucopolysaccharides) of

Imprecision – Dispersion of independent results of measurements obtained under specified conditions;

International sensitivity index, ISI – A mathematical indicator of the responsiveness of a PT testing

Measurand – Particular quantity subject to measurement; (VIM93-2.6). NOTE 1: [VIM93-2.6] For

An NCCLS global consensus guideline. ©NCCLS. All rights reserved. 3

POC-APTT – See APTT (POC).

POC-PT – See PT (POC).

Point-of-care (POC) testing//bedside, near-patient testing – Testing performed in an alternate site,

Proficiency testing (quality assessment scheme) – Determination of laboratory testing performance by

PT (POC) – The PT performed using a point-of-care test system.

4 An NCCLS global consensus guideline. ©NCCLS. All rights reserved.

Testing site – The physical location where testing is performed.

An NCCLS global consensus guideline. ©NCCLS. All rights reserved. 5

5 Point-of-Care Coagulation Testing (POC-CT)—General Considerations

• Rationale for Selection of the System:

− What is the specific clinical need for POC-CT?

• General Administrative Issues:

− Who will select, purchase, and maintain the system?

• Logistical and Technical Issues:

− Who will perform the testing?

6 Quality Management: General Considerations for Point-of-Care Coagulation

6.1 Operators, Materials, and Performance of POC-CT

6 An NCCLS global consensus guideline. ©NCCLS. All rights reserved.

• theory of instrument/device/test system;

Sources of training include:

• manufacturer’s on-site training and telephone technical assistance;

An NCCLS global consensus guideline. ©NCCLS. All rights reserved. 7

6.3 Quality Control and Proficiency Testing

• variability in storage conditions;

6.3.1 Quality Control

6.3.1.1 Specific Recommendations for Manufacturers of POC-CT

8 An NCCLS global consensus guideline. ©NCCLS. All rights reserved.

• Sensitivity of the quality control material/modality to detect analytical problems. Conduct a

6.3.2 Proficiency Testing

6.4 Result Recording and Reporting

7 Monitoring Heparin Therapy