Journal of Blood Medicine

Dovepress
open access to scientific and medical research

Review

Open Access Full Text Article

Deep vein thrombosis: a clinical review

This article was published in the following Dove Press journal:

Journal of Blood Medicine
26 April 2011
Number of times this article has been viewed

Emeka Kesieme 1
Chinenye Kesieme 2
Nze Jebbin 3
Eshiobo Irekpita 1
Andrew Dongo 1
1
Department of Surgery, Irrua
Specialist Teaching Hospital, Irrua,
Nigeria; 2Department of Paediatrics,
Irrua Specialist Teaching Hospital,
Irrua, Nigeria; 3Department of
Surgery, University of Port Harcourt
Teaching Hospital, Port-Harcourt,
Nigeria

Background: Deep vein thrombosis (DVT) is the formation of blood clots (thrombi) in the
deep veins. It commonly affects the deep leg veins (such as the calf veins, femoral vein, or
popliteal vein) or the deep veins of the pelvis. It is a potentially dangerous condition that can
lead to preventable morbidity and mortality.
Aim: To present an update on the causes and management of DVT.
Methods: A review of publications obtained from Medline search, medical libraries, and
Google.
Results: DVT affects 0.1% of persons per year. It is predominantly a disease of the elderly and
has a slight male preponderance. The approach to making a diagnosis currently involves an algorithm combining pretest probability, D-dimer testing, and compression ultrasonography. This will
guide further investigations if necessary. Prophylaxis is both mechanical and pharmacological.
The goals of treatment are to prevent extension of thrombi, pulmonary embolism, recurrence
of thrombi, and the development of complications such as pulmonary hypertension and postthrombotic syndrome.
Conclusion: DVT is a potentially dangerous condition with a myriad of risk factors. Prophylaxis
is very important and can be mechanical and pharmacological. The mainstay of treatment is
anticoagulant therapy. Low-molecular-weight heparin, unfractionated heparin, and vitamin K
antagonists have been the treatment of choice. Currently anticoagulants specifically targeting
components of the common pathway have been recommended for prophylaxis. These include
fondaparinux, a selective indirect factor Xa inhibitor and the new oral selective direct thrombin
inhibitors (dabigatran) and selective factor Xa inhibitors (rivaroxaban and apixaban). Others
are currently undergoing trials. Thrombolytics and vena caval filters are very rarely indicated
in special circumstances.
Keywords: deep vein thrombosis, pulmonary embolism, venous thromboembolism, prophylaxis,
treatment

Introduction

Correspondence: Emeka Kesieme

Department of Surgery, Irrua Specialist
Teaching Hospital, Irrua, PMB 8, Irrua,
Edo State, Nigeria
Tel +234 8080881312
Email ekesieme@gmail.com

submit your manuscript | www.dovepress.com

Dovepress
DOI: 10.2147/JBM.S19009

The term thrombosis refers to the formation, from constituents of blood, of an abnormal
mass within the vascular system of a living animal. When this process occurs within
the deep veins, it is referred to as deep vein thrombosis (DVT).
An accurate diagnosis of DVT is extremely important to prevent potentially fatal
acute complication of pulmonary embolism (PE) and long-term complications of
postphlebitis syndrome and pulmonary hypertension. It is also important to avoid
unjustified therapy with anticoagulants with associated high risk of bleeding in patients
misdiagnosed with the condition.1

Journal of Blood Medicine 2011:2 5969

2011 Kesieme et al, publisher and licensee Dove Medical Press Ltd. This is an Open Access article
which permits unrestricted noncommercial use, provided the original work is properly cited.

59

Dovepress

Kesieme et al

Clinical features are nonspecific; hence new strategies

for diagnosing this condition have evolved.
We aim to critically review the current state of knowledge
on this subject, with a view to updating clinicians on the
prophylaxis and treatment of DVT.

Methods
A literature review of DVT was done from 1970 to date using
a manual library search, journal publications on the subject,
and Medline. Full texts of the materials, including those of
relevant references were collected and studied. Information
relating to the epidemiology, pathology, clinical presentation,
investigations, prophylaxis, treatment, and complications was
extracted from the materials.

Results
Epidemiology
DVT is a major and a common preventable cause of death
worldwide. It affects approximately 0.1% of persons per
year. The overall average age- and sex-adjusted annual
incidence of venous thromboembolism (VTE) is 117 per
100,000 (DVT, 48 per 100,000; PE, 69 per 100,000), with
higher age-adjusted rates among males than females (130
vs 110 per 100,000, respectively).2 Both sexes are equally
afflicted by a first VTE, men having a higher risk of recurrent
thrombosis.3,4 DVT is predominantly a disease of the elderly
with an incidence that rises markedly with age.2
A study by Keenan and White revealed that AfricanAmerican patients are the highest risk group for first-time
VTE. Hispanic patients risk is about half that of Caucasians.
The risk of recurrence in Caucasians is lower than that of
African-Americans and Hispanics.5
The incidence of VTE is low in children. Annual incidences of 0.07 to 0.14 per 10,000 children and 5.3 per
10,000 hospital admissions have been reported in Caucasian studies.6,7 This low incidence may be due to decreased
capacity to generate thrombin, increased capacity of
alpha-2-macroglobulin to inhibit thrombin, and enhanced
antithrombin potential of vessel walls. The highest incidence
in childhood is during the neonatal period, followed by
another peak in adolescence.8 The incidence rate is comparatively higher in adolescent females because of pregnancy and
use of oral contraceptive agents.9
Pregnant women have a much higher risk of VTE than
nonpregnant women of similar age and the risk has been
shown to be higher after cesarian section than after vaginal
delivery.10 In a study conducted in an African population, the
documented rate was 48 DVT per 100,000 births per year.11

60

submit your manuscript | www.dovepress.com

Dovepress

The incidence appears to be highest in the postpartum

period.11,12
The approximate risk for DVT following general surgery
procedures is 15% to 40%. It nearly doubles after hip or
knee replacement surgery or hip fracture surgery (40% to
60%).13 Geerts etal revealed that without prophylaxis, fatal
PE occurs in 0.2% to 0.9% of patients undergoing elective
general surgery, 0.1% to 2% of those undergoing elective
hip replacement and up to 2.5% to 7.5% of those undergoing
surgery for hip fracture.14 Though regarded mainly as a surgical complication, most symptomatic VTE events and fatal
PE occur in medical patients.15

Pathogenesis/classification
Thrombus formation preferentially starts in the valve pockets
of the veins of the calf and extends proximally. This is especially true for those that occur following surgery.16 Though
most thrombi begin intraoperatively, some start a few days,
weeks, or months after surgery. Lending its support to the
origin of thrombus in valve pockets is a recent hypothesis
of an increased expression of endothelial protein C receptor
(EPCR) and thrombomodulin (TM) and a decreased expression of Von Willebrand factor (vWF) noted in valve sinus
endothelium compared with vein luminal endothelium. This
means an upregulation of anticoagulants (EPCR, TM) and
a downregulation of procoagulant (vWF) properties of the
valvular sinus endothelium.17
Thrombus is composed predominantly of fibrin and red
cells (red or static thrombus). Venous thrombus must be
differentiated from postmortem clot at autopsy. Postmortem
clots are gelatinous and have a dark red dependent portion
(formed by red cells that have settled by gravity and a yellow
chicken fat supernatant resembling melted and clotted
chicken fat). They are usually not attached to the underlying wall. This is in contrast to the venous thrombi which are
firmer. They almost always have a point of attachment to
the wall and transection reveals vague strands of pale gray
fibrin.18
DVT in the lower limb can be classified as a) proximal,
when the popliteal vein or thigh veins are involved or b)
distal, when the calf veins are involved. Clinically, proximal
vein thrombosis is of greater importance and is associated
with serious chronic diseases such as active cancer, congestive cardiac failure, respiratory insufficiency, or age above
75 years, whereas distal thrombosis is more often associated
with risk factors such as recent surgery and immobilization.
Fatal PE is far more likely to result from proximal DVT.19
Post-thrombotic syndrome, a chronic, potentially disabling

Journal of Blood Medicine 2011:2

Dovepress

condition characterized by leg swelling, pain, venous ectasia,

and skin induration, is established by 1 year after DVT in
17% to 50% of cases.20
Uncommon presentations of VTE are forms of acute
massive venous thrombosis with obstruction of venous
drainage to the extremity. These include phlegmasia alba
dolens, phlegmasia cerulea dolens, and venous gangrene.
In phlegmasia alba dolens, the thrombosis involves only
the major deep venous channels of the extremity, sparing
collateral veins. However, in phlegmasia cerulea dolens, the
thrombosis extends to the collateral vein, resulting in massive
fluid sequestration and more significant edema.

Clinical features
History and clinical examination are not reliable ways of
diagnosing DVT.21 Lower extremity DVT can be symptomatic
or asymptomatic. Patients with lower extremity DVT often
do not present with erythema, pain, warmth, swelling, or
tenderness. Symptomatic patients with proximal DVT may
present with lower extremity pain, calf tenderness, and lower
extremity swelling.22,23 Homans sign may be demonstrable in
DVT. Most of these features lack specificity; hence clinical
evaluation usually implies the need for further evaluation.
The left leg is the commonest site for venous thrombosis in
pregnancy11 and in acute massive venous thrombosis. This
may be due to compression of the left iliac vein by the right
iliac artery (MayThurner syndrome).24
Phlegmasia alba dolens is characterized by edema, pain,
and blanching without cyanosis while phlegmasia cerulea
dolens is characterized by these features in addition to
cyanosis, which characteristically progresses from distal to
proximal areas and bleb/bulla formation.

Risk factors
Rudolph Virchow described three conditions that predispose
to thrombus, the so-called Virchows triad. This triad includes
endothelial injury, stasis or turbulence of blood flow, and
blood hypercoagulability.
Stasis and endothelial injury are important in DVT
following trauma or surgery while hypercoagulability is
responsible for most cases of spontaneous DVT. At least
96% of patients treated for VTE have been shown to have
at least one risk factor.25
Risk can be classified as acquired or genetic. When
genetic defects are combined with one or more acquired risk
factors, or in combined genetic defects or combination of two
acquired defects, it results in a risk of VTE that exceeds the
separate effects of a single factor.26

Journal of Blood Medicine 2011:2

DVT clinical review

In adults, the clinical conditions that predispose to VTE

are increasing age, cancer and its treatment, prolonged
immobility, stroke or paralysis, previous VTE, congestive
heart failure, acute infection, pregnancy or puerperium,
dehydration, hormonal treatment, varicose veins, long air
travel, acute inflammatory bowel disease, rheumatological
disease, and nephrotic syndrome. Other acquired factors
that have recently been associated with increased risk of
VTE disorders include persistent elevation of D-dimer and
atherosclerotic disease.27
Oral contraceptive pills, especially those that contain
third-generation progestins increase the risk of VTE.28 Risk
of DVT associated with long-duration air travel is called
economy class syndrome.29 It is 3% to 12% in a long-haul
flight with stasis, hypoxia, and dehydration being pathophysiological changes that increase the risk.30 van Aken etal demonstrated that subjects with elevated levels of interleukin-8
have increased risk of venous thrombosis, supporting an
important role of inflammation in etiopathogenesis of venous
thrombosis.31
Clayton etal have described a strong association between
recent respiratory infection and VTE. They demonstrated
an increased risk of DVT in the month following infection
and PE in 3months following infection, both persisting up
to a year.32
In the pediatric age group, the most important triggering
risk factors for development of thromboembolism are the
presence of central venous lines, cancer, and chemotherapy.
Severe infection, sickle cell disease, trauma, and antiphospholipid syndromes are clinical conditions associated with
hypercoagulability states.33
Genetic risk factors can be divided into strong, moderate,
and weak factors.34 Strong factors are deficiencies of antithrombin, protein C and protein S. Moderately strong factors
include factor V Leiden, prothrombin 20210A, non-O blood
group, and fibrinogen 10034T. Weak genetic risk factors
include fibrinogen, factor XIII and factor XI variants.

Clinical prediction rules

A commonly accepted evidence-based approach to diagnosis of VTE is the use of a clinical model that standardizes
the clinical assessment (combining risk factors, signs and
symptoms) and subsequently stratifies patients suspected
of DVT.
Though this model has been used for both primary care
patients and secondary settings, there is no doubt that it does
not guarantee accurate estimation of risk in primary care
patients in whom DVT is suspected.35

submit your manuscript | www.dovepress.com

Dovepress

61

Dovepress

Kesieme et al

The most commonly recommended model is that

developed by Wells and colleagues. Based on clinical presentation and risk factors, an initial model was developed
to group patients into low-, moderate-, and high-probability
groups. The high-probability group has an 85% risk of
DVT, the moderate-probability group a 33% risk, and the
low-probability group a 5% risk.36 However, in a later study,
Wells and colleagues further streamlined the diagnostic process by stratifying patients into two risk categories: DVT
unlikely if the clinical score is #1 and DVT likely if the
clinical score is .1 (Table 1).37

D-dimer assay
D-dimer is a degradation product of cross-linked fibrin that
is formed immediately after thrombin-generated fibrin clots
are degraded by plasmin. It reflects a global activation of
blood coagulation and fibrinolysis.38 It is the best recognized
biomarker for the initial assessment of suspected VTE. The
combination of clinical risk stratification and a D-dimer test
can exclude VTE in more than 25% of patients presenting
with symptoms suggestive of VTE without the need for
additional investigations.39 Even in patients with clinically
suspected recurrent DVT, this combination (clinical evaluation and D-dimer) has proved to be useful for excluding
DVT, especially in patients included in the lower clinical
pretest probability group.40
Levels of D-dimer can be popularly measured using three
types of assay:
Enzyme linked immunosorbent assay (ELISA).
Latex agglutination assay.
Red blood cell whole blood agglutination assay
(simpliRED).
These assays differ in sensitivity, specificity, likelihood
ratio, and variability among patients with suspected VTE.
ELISAs dominate the comparative ranking among D-dimer
assays for sensitivity and negative likelihood ratio.
D-dimer assays are highly sensitive (values up to 95%),
but have poor specificity to prove VTE. The negative predictive value for patients with a negative D-dimer blood test is
nearly 100%. Hence a negative value of D-dimer may safely
rule out both DVT and PE. False positive D-dimer results
have been noted in inflammation,41 pregnancy,42 malignancy,43
and the elderly.44 Clinical usefulness of the measurement of
D-dimer has been shown to decrease with age.45 The use
of age-dependent cut-off values of D-dimer assays is still a
matter of controversy. Several studies have shown that the
levels of D-dimer assays increase with gestational age and
in complicated pregnancies as observed in preterm labor,

62

submit your manuscript | www.dovepress.com

Dovepress

abruptio placenta, and gestational hypertension.4648 Elevated

D-dimer was found to be predictive of poor outcome (persistent thrombosis, recurrence or post-thrombotic syndrome)
in children with an acute thrombotic event.49 False negative
D-dimer results have been noted after heparin use; hence it
has been recommended that D-dimer assay should be done
prior to administering heparin to a patient.43 Other causes of
false negative D-dimer results are late presentation (symptoms longer than 2 weeks) and small below-knee DVT.

Venous ultrasonography
Venous ultrasonography is the investigation of choice in
patients stratified as DVT likely.50 It is noninvasive, safe,
available, and relatively inexpensive. There are three types
of venous ultrasonography: compression ultrasound (B-mode
imaging only), duplex ultrasound (B-mode imaging and
Doppler waveform analysis), and color Doppler imaging
alone. In duplex ultrasonography, blood flow in normal vein
is spontaneous, phasic with respiration, and can be augmented
by manual pressure. In color flow sonography, pulsed Doppler
signal is used to produce images.51 Compression ultrasound is
typically performed on the proximal deep veins, specifically
the common femoral, femoral, and popliteal veins, whereas
a combination of duplex ultrasound and color duplex is more
often used to investigate the calf and iliac veins.52
The major ultrasonographic criterion for detecting venous
thrombosis is failure to compress the vein lumen under gentle
probe pressure. Other criteria for ultrasonographic diagnosis
of venous thrombosis include loss of phasic pattern in which
flow is defined as continuous, response to valsava or augmentation (Duplex ultrasound), and complete absence of spectral
or color Doppler signals from the vein lumen.53
The other advantages of venous ultrasound are its ability to
diagnose other pathologies (Bakers cysts, superficial or intramuscular hematomas, lymphadenopathy, femoral aneurysm,
superficial thrombophlebitis, and abscess), and the fact that
there is no risk of exposure to irradiation, while its major limitation is its reduced ability to diagnose distal thrombus.22 Venous
compressibility may be limited by a patients characteristics
such as obesity, edema, and tenderness as well as by casts or
immobilization devices that limit access to the extremity. Compression B-mode ultrasonography with or without color Duplex
imaging has a sensitivity of 95% and a specificity of 96% for
diagnosing symptomatic, proximal DVT.54 For DVT in the calf
vein, the sensitivity of venous ultrasound is only 73%.55
Repeat or serial venous ultrasound examination is
indicated for initial negative examination in symptomatic
patients who are highly suspicious for DVT and in whom

Journal of Blood Medicine 2011:2

Dovepress

an alternative form of imaging is contraindicated or not

available. Serial testing has been found unnecessary for those
in whom DVT is unlikely by Wells score and has a negative
D-dimer test.

Contrast venography
Venography is the definitive diagnostic test for DVT, but it
is rarely done because the noninvasive tests (D-dimer and
venous ultrasound) are more appropriate and accurate to
perform in acute DVT episodes. It involves cannulation of
a pedal vein with injection of a contrast medium, usually
noniodinated, eg, Omnipaque. A large volume of Omnipaque
diluted with normal saline results in better deep venous filling
and improved image quality.56
The most reliable cardinal sign for the diagnosis of
phlebothrombosis using venogram is a constant intraluminal
filling defect evident in two or more views.56 Another reliable
criterion is an abrupt cutoff of a deep vein, a sign difficult to
interpret in patients with previous DVT.57 It is highly sensitive
especially in identifying the location, extent and attachment
of a clot and also highly specific.
Being invasive and painful remains its major setback. The
patient is exposed to irradiation and there is also an additional
risk of allergic reaction and renal dysfunction. Occasionally
a new DVT may be induced by venography,58 probably due
to venous wall irritation and endothelial damage. The use of
nonionic contrast medium has reduced considerably risks of
anaphylactic reaction and thrombogenecity or may have even
eliminated them.59,60

Impedance plethysmography
The technique is based on measurement of the rate of change
in impedance between two electrodes on the calf when a
venous occlusion cuff is deflated. Free outflow of venous
blood produces a rapid change in impedance while delay in
outflow, in the presence of a DVT, leads to a more gradual
change.61 It is portable, safe, and noninvasive but its main
drawback remains an apparent insensitivity to calf thrombi
and small, nonobstructing proximal vein thrombi.

Magnetic resonance imaging (MRI)

This investigative modality has high sensitivity in detecting calf and pelvic DVTs,62 and upper extremity venous
thromboses.63 It is also relevant in ruling out differential
diagnoses in patients suspected of DVT. MRI is the diagnostic test of choice for suspected iliac vein or inferior vena
caval thrombosis when computed tomography venography
is contraindicated or technically inadequate. There is no

Journal of Blood Medicine 2011:2

DVT clinical review

risk of ionizing radiation but it is costly, scarce, and reader

expertise is required.

Algorithm for the diagnosis of DVT

The first step is the pretest probability assessment using an
established model such as the Wells score (Figure 1). If score
is #1 (DVT unlikely), D-dimer assay is done. If assay is
negative, DVT is excluded and the patient can be discharged
without further investigations. If assay is positive, a venous
ultrasound is indicated. Negative venous ultrasound scan
excludes the diagnosis of DVT. Diagnosis of DVT is made
if venous ultrasonography is positive.
If the DVT is likely (probability score $2), venous
ultrasonography is indicated. DVT is diagnosed and treated
if venous ultrasound is positive. If negative, D-dimer assay
should be done. Negative D-dimer excludes the diagnosis
of DVT while a positive result is an indication for follow-up
studies; repeat ultrasound in 6 to 8days or do venography.
This algorithm is not used in pregnancy because D-dimer is
falsely elevated.

Prophylaxis
Mechanical

Mechanical methods of prophylaxis against DVT include

intermittent pneumatic compression (IPC) device, graduated
compression stocking (GCS), and the venous foot pump.
Intermittent pneumatic compression enhances blood flow
in the deep veins of the leg, preventing venous stasis and
hence preventing venous thrombosis.64 Agu etal have shown
that these mechanical methods reduce postoperative venous
thrombosis.65 A Cochrane review showed a reduction of
Table 1 Pretest probability assessment (Wells score)
Points
Active cancer (treatment ongoing or within previous
6 months or palliative)
Paralysis, paresis, or recent plaster immobilization of the
lower extremities
Recently bedridden for 3 days or major surgery within
12 weeks requiring general or regional anesthesia
Localized tenderness along the distribution of the deep
veins
Entire leg swollen
Calf swelling 3 cm . asymptomatic side (measured 10 cm
below tibial tuberosity)
Pitting edema limited to the symptomatic leg
Collateral superficial veins (nonvaricose)
Previous DVT
Alternative diagnosis as likely as or more likely than DVT

1
1
1
1
1
1
1
1
1
2

Notes: DVT unlikely: #1; DVT likely: $2

submit your manuscript | www.dovepress.com

Dovepress

63

Dovepress

Kesieme et al

Table 2 Advantages of low-molecular-weight heparin over

unfractionated heparin
Greater bioavailability
Predictability and dose-dependent plasma level
Less risk of bleeding
Lower incidence of heparin-induced thrombocytopenia
Lower risk of heparin-induced osteoporosis
No need for laboratory monitoring
Can be safely administered in outpatient
Duration of anticoagulant effect is longer, permitting once- or
twice-daily administration

VTE by about 50% with the use of graduated compression

stockings.66 Intermittent pneumatic compression, in addition
to preventing venous thrombosis, has been shown to reduce
plasminogen activator inhibitor-1, thereby increasing endogenous fibrinolytic activity.67
Compared with compression alone, combined prophylactic modalities decrease significantly the incidence of
VTE. Compared with pharmacological prophylaxis alone,
combined modalities reduce significantly the incidence of
DVT, but the effect on PE is unknown. This is recommended
especially for high-risk patients.68
A mechanical method of DVT prophylaxis is indicated
in patients at high risk of bleeding with anticoagulation prophylaxis. These includes patients with active or
recent gastrointestinal bleeding, patients with hemorrhagic stroke, and those with hemostatic defects such as

severe thrombocytopenia.69 It is contraindicated in patients

with evidence of leg ischemia due to peripheral vascular disease. There is a theoretical risk of fibrinolysis and
clot dislodgement.70 Leg wrappings and stockings with no
pressure gradient are ineffective in the prevention of DVT.71
Hilleren-Listerud demonstrated that knee-length GCS and
IPC devices are as effective as thigh-length GCS and IPC
devices. They are also more comfortable, cheaper and more
user-friendly for the patient.72
Chin et al compared the efficacy and safety of different modes of thromboembolic prophylaxis (IPC, GCS, and
enoxaparin) for elective total knee arthroplasty (TKA) in
Asian patient and recommended IPC as the preferred method
of thromboprophylaxis for TKA.73 However no meaningful
difference in performance between GCS and IPC was demonstrated by Morris and Woodcock.74
Daily use of elastic compression stockings after proximal DVT reduced the incidence of postphlebitis syndrome
by 50%.20
Other mechanical means in both medical and surgical
patients include ambulation and exercises involving foot extension. They improve venous flow and should be encouraged.

Pharmacological
Unfractionated heparin (UFH), low-molecular-weight
heparins (LMWH), fondaparinux, and the new oral direct
selective thrombin inhibitors and factor Xa inhibitors are

Clinical features and risk factors (DVT)

Clinical probability

DVT unlikely
(probability score 1)

DVT likely
(probability score 2)

D-dimer assay

Venous USS

Negative

Positive

Positive

Negative

DVT excluded

Venous USS

Diagnose/treat
DVT

D-dimer assay

Positive

Negative

Negative

Positive

DVD diagnose/treat

DVT excluded

DVT excluded

DVT Follow up studies

(repeat venous USS in
a week or venography)

Figure 1 Algorithm for diagnosing DVT using clinical assessment, D-dimer testing, and venous ultrasonography.
Abbreviation: USS, ultrasound.

64

submit your manuscript | www.dovepress.com

Dovepress

Journal of Blood Medicine 2011:2

Dovepress

effective pharmacological agents for prophylaxis of DVT.

Studies have shown that the incidence of all DVTs, proximal
DVT, and all PE including fatal PE has been reduced by
low-dose UFH.75,76
LMWH has additional advantages over unfractionated
heparin (Table 2). It can be given once or twice daily without
laboratory monitoring. Other advantages are predictability,
dose-dependent plasma levels, a long half-life, less bleeding
for a given antithrombotic effect, and a lower incidence of
heparin-induced thrombocytopenia than with UFH.77
The risk of heparin-induced osteoporosis is lower with
LMWH than with UFH as it does not increase osteoclast
number and activity.78 It has a far greater effect on inhibition of factor Xa and a lesser effect on antithrombin III by
inhibiting thrombin to a lesser extent than UFH.79 Current
contraindications to the early initiation of LMWH thromboprophylaxis include the presence of intracranial bleeding,
ongoing and uncontrolled bleeding elsewhere, and incomplete spinal cord injury associated with suspected or proven
spinal hematoma.
Fondaparinux, a synthetic pentasaccharide, has been
approved for prophylaxis of DVT. It is an indirect selective
inhibitor of factor Xa which binds to antithrombin with high
affinity in a reversible manner. Heparin-induced thrombocytopenia has not been reported with fondaparinux as it does
not interact with platelet function and aggregation, and has
a predictable response.80 Monitoring of prothrombin time
or partial thromboplastin time is also not required. In summary, it has an equal or better effectiveness than currently
available agents, a low bleeding risk, no need for laboratory
monitoring, and once daily administration.
Dabigatran is a new oral univalent direct thrombin
inhibitor. Dabigatran etexilate is the prodrug of dabigatran.
It is rapidly absorbed from the gastrointestinal tract with a
bioavailability of 5% to 6%. It has a half-life of 8hours after
single-dose administration and up to 17hours after multiple
doses with plasma levels that peak at 2hours.81 The drug
is excreted largely unchanged via the kidneys. It has a low
bioavailability (6%), produces a predictable anticoagulant
effect, and requires no coagulation monitoring.81 Dabigatran
has been approved in Canada and Europe for VTE prevention
after orthopedic surgery.
The RE-COVER trial compared dabigatran etexilate with
warfarin for 6months in patients with acute VTE; dabigatran
was as effective as warfarin in preventing recurrent VTE,
with comparable major bleeding and significantly lower total
bleeding rates.82,83 Another study (The RE-NOVATE II trial)
compared the efficacy and safety of oral dabigatran with

Journal of Blood Medicine 2011:2

DVT clinical review

subcutaneous enoxaparin for extended thromboprophylaxis

in patients undergoing total hip arthroplasty.82 Extended
prophylaxis with oral dabigatran 220mg once daily was as
effective as subcutaneous enoxaparin 40mg once daily in
reducing the risk of VTE after total hip arthroplasty, and
superior to enoxaparin for reducing the risk of major VTE.
The risk of bleeding and safety profiles were similar.84
Rivaroxaban is a potent and selective oral factor Xa
inhibitor. It has a rapid onset of action, a high bioavailability
(80%), and a half-life of 4 to 12hours.81 EINSTIEN-DVT
trial has shown that oral rivaroxaban is as effective in preventing recurrence of symptomatic VTE as the current standard
therapy of injectable LMWH, enoxaparin, or fondaparinux,
and an oral vitamin K antagonist in well-managed patients.85
The results of RECORD phase III trials have also shown
that rivaroxaban 10mg once daily is superior to the LMWH
enoxaparin, when used for prophylaxis of VTE in orthopedic
surgeries.86 The drug also has the major advantages of once
daily oral dosing and no required laboratory monitoring.
Other drugs in this group such as apixaban and edoxaban
are currently undergoing clinical trials.
Oral anticoagulation with vitamin Kantagonists such as
warfarincan be commenced preoperatively, at the time of surgery, or postoperatively for the prevention of VTE.87 Warfarin
is contraindicated in antepartum thromboprophylaxis because
it crosses the placenta and can result in unwanted teratogenicity and bleeding in the fetus.88 However the drug is safe
during lactation as it does not accumulate in the breast milk
to a substantial extent.89 Unlike warfarin, heparin is safe and
it is recommended both in pregnancy and lactation.90
The use of aspirin alone is not recommended for thromboprophylaxis against VTE for any patient group. Some
studies on the use of aspirin as prophylactic agent for DVT
have shown some degree of protection against VTE in hospitalized patients,91,92 while other studies have either shown
no benefit,93,94 or have proven to be less effective to other
thromboprophylactic agents.95,96
The duration of thromboprophylaxis depends on the level
of risk of VTE. For patients undergoing total hip replacement
or hip fracture surgery, prolonged thromboprophylaxis beyond
10days and up to 35days is recommended especially for patients
who are considered to be at high risk for VTE, while in patients
admitted with acute medical illness thromboprophylaxis should
be continued until discharge for the majority of the patients.87

Treatment
The goal of therapy for DVT is to prevent the extension
of thrombus, acute PE, recurrence of thrombosis, and the

submit your manuscript | www.dovepress.com

Dovepress

65

Dovepress

Kesieme et al

development of late complications such as pulmonary

hypertension and post-thrombotic syndromes. The initial
treatment usually involves achieving a therapeutic dose of
UFH or LMWH, or with fondaparinux.
Studies have shown that the efficacy of treatment with
heparin largely depends on the ability to achieve a critical
therapeutic ratio within the first 24hours of treatment,97,98
ie, achieving an activated partial thromboplastin time (aPTT)
that is 1.5 times the mean of control value or the upper limit
of normal aPTT range (aPTT ratio) of 1.5 to 2.5. This level
corresponds to a heparin blood level of 0.3 to 0.7U/mL by
amidolytic antifactor Xa assay.99
Because of the advantages of LMWH, it is recommended
over unfractionated UFH for treatment of acute DVT. UFH
is, however, preferred in patients with severe renal failure
as LMWH is mainly excreted via the kidneys. Heparin is
initially given with warfarin and stopped after a minimum
of 4 to 5days, at which time the international normalized
ratio (INR) should be within 2.0 to 3.0 (therapeutic range).
This overlap with warfarin is essential because factors II, IX,
X will not be affected until after 5days, hence the intrinsic
clotting pathway is intact. The initial prolongation of INR
is mainly due to the effect of depression of factor VII which
has a half-life of 5 to 7hours.
Warfarin remains the drug of choice for long-term
therapy to prevent clot formation once acute anticoagulation is achieved. LMWH is, however, preferred after longterm therapy of DVT in pregnancy as warfarin therapy is
contraindicated,100 and in patients with cancer. Long-term
anticoagulant therapy with LMWH is more effective than
warfarin at preventing recurrent venous thrombosis in
cancer patients without a statistically significant bleeding
risk.101
The duration of anticoagulation depends on whether the
patient has a first episode of DVT, ongoing risk factors for
VTE disease, and known thrombophlebitis.102 In patients
with first proximal DVT occurring in the context of a
transient risk factor such as surgery or trauma, the risk of
recurrence is very low and a limited duration of treatment
(3 months) is adequate.103,104 Long-term anticoagulation
therapy should be considered for recurrent thromboses,
patients with ongoing risk such as active cancer and a first
unprovoked proximal DVT or PE where no risk factors for
bleeding are present, and where anticoagulation control is
good. This may be particularly the case if D-dimer is raised
after discontinuing anticoagulation, in males, in those with
post-thrombotic syndrome, and in those with antiphospholipid antibodies.43,105

66

submit your manuscript | www.dovepress.com

Dovepress

Thrombolytic therapy
This is rarely indicated. The risk of major bleeding, including
intracranial hemorrhage, should be weighed against the
benefits of a complete and rapid lysis of thrombi. It is indicated in massive DVT which leads to phlegmasia cerulean
dolens and threatened limb loss. The available thrombolytic
agents include tissue plasminogen activator, streptokinase,
and urokinase.
Endovascular thrombolytic methods have evolved considerably in recent years. Catheter-directed thrombolysis (CDT)
can be used to treat DVTs as an adjunct to medical therapy.106
Current evidence suggests that CDT can reduce clot burden
and DVT recurrence and consequently prevent the formation of
post-thrombotic syndrome compared with systemic anticoagulation.106 Pharmacomechanical CDT is now routinely used in
some centers for the treatment of acute iliofemoral DVT.107
Appropriate indications may include younger individuals
with acute proximal thromboses, a long life expectancy, and
relatively few comorbidities. Limb-threatening thromboses
may also be treated with CDT, although the subsequent mortality remains high.106 A number of randomized controlled
trials are currently underway comparing the longer-term
outcomes of CDT compared with anticoagulation alone.

Vena cava filters

Vena cava filters are indicated in very few circumstances. They
include absolute contraindication to anticoagulation, life-threatening hemorrhage on anticoagulation, and failure of adequate
anticoagulation.108 Absolute contraindications to anticoagulation include central nervous system (CNS) hemorrhage, overt
gastrointestinal bleeding, retroperitoneal hemorrhage, massive
hemoptysis, cerebral metastases, massive cerebrovascular accident, CNS trauma, and significant thrombocytopenia (,50,000/
L).108 They may be retrievable or nonretrievable, most of the
newly developed ones being retrievable.
Studies to assess the effectiveness of filters revealed
significantly fewer patients suffering PE in the short term,
but no significant effect on PE. There was a higher rate of
recurrent DVT in the long term.109 Complications of inferior
vena cava filters include hematoma over the insertion site,
DVT at the site of insertion, filter migration, filter erosion
through the inferior vena cava wall, filter embolization, and
inferior vena cava thrombosis/obstruction.110

Conclusion
DVT is a potentially dangerous clinical condition that can lead
to preventable morbidity and mortality. A diagnostic pathway
involving pretest probability, D-dimer assay, and venous

Journal of Blood Medicine 2011:2

Dovepress

ultrasound serves as a more reliable way of diagnosing DVT.

Prevention consists of both mechanical and pharmacological
modalities and is encouraged in both inpatients and outpatients
who are at risk of this condition. The goal of therapy for DVT
is to prevent the extension of thrombus, acute PE, recurrence
of thrombosis, and the development of late complication such
as pulmonary hypertension and post-thrombotic syndrome.

Disclosure
The authors report no conflicts of interest and did not request
or receive any form of financial support for this project.

References

1. Hirsh J, Hoak J. Management of deep vein thrombosis and pulmonary

embolism. A statement for healthcare professionals. Council on Thrombosis (in consultation with the Council on Cardiovascular Radiology),
American Heart Association. Circulation. 1996;93(12):22122245.
2. Silverstein MD, Heit JA, Mohr DN, etal. Trends in the incidence of
deep vein thrombosis and pulmonary embolism: a 25-year populationbased study. Arch Intern Med. 1998;158(6):585593.
3. Naess IA, Christiansen SC, Romundstad P, Cannegieter SC, Rosendaal FR,
Hammerstrm J. Incidence and mortality of venous thrombosis: a
population-based study. J Thromb Haemost. 2007;5(4):692699.
4. Kyrle PA, Minar E, Bialonczyk C, Hirschl M, Weltermann A,
Eichinger S. The risk of recurrent venous thromboembolism in men
and women. N Engl J Med. 2004;350(25):25582563.
5. Keenan CR, White RH. The effects of race/ethnicity and sex on the
risk of venous thromboembolism. Curr Opin Pulm Med. 2007;13(5):
377383.
6. Andrew M, David M, Adams M, etal. Venous thromboembolic complications (VTE) in children: first analyses of the Canadian Registry
of VTE. Blood. 1994;83(5):12511257.
7. Van Ommen CH, Heijboer H, Buller HR, Hirasing RA, Heijmans HS,
Peters M. Venous thromboembolism in childhood: a prospective twoyear registry in the Netherlands. J Pediatr. 2001;139(5):676681.
8. Parasuraman S, Goldhaber SZ. Venous thromboembolism in children.
Circulation. 2006;113:e12e16.
9. Stein PD, Kayali F, Olson RE. Incidence of venous thromboembolism
in infants and children: data from the National Hospital Discharge
Survey. J Pediatr. 2004;145(4):563565.
10. Bates SM, Ginsberg JS. Pregnancy and deep vein thrombosis. Semin
Vasc Med. 2001;1(1):97104.
11. Gader AA, Haggaz A, Adam I. Epidemiology of deep venous thrombosis
during pregnancy and puerperium in Sudanese women. Vasc Health
Risk Manag. 2009;5(1):8587.
12. Simpson EL, Lawrenson RA, Nightingale AL, Farmer RD. Venous
thromboembolism in pregnancy and the puerperium: incidence and
additional risk factors from a London perinatal database. BJOG.
2001;108(1):5660.
13. Hirsh J, Guyatt G, Albers GW, Harrington R, Schunemann HJ; the
American College of Chest Physicians.Antithrombotic and thrombolytic therapy: American College of Chest Physicians evidencebased clinical practice guidelines, 8th ed. Chest. 2008;133(6 Suppl):
110S112S.
14. Geerts WH, Heit JA, Clagett GP, et al. Prevention of venous
thromboembolism.Chest. 2001;119(1 Suppl):132S175S.
15. Sandler DA, Martin JF. Autopsy proven pulmonary embolism in hospital patients: are we detecting enough deep vein thrombosis? J R Soc
Med. 1989;82(4):203205.
16. Nicolaides AN, Kakkar VV, Field ES, Renney JT. The origin of deep
vein thrombosis: a venographic study. Br J Radiol. 1971;44(525):
653663.

Journal of Blood Medicine 2011:2

DVT clinical review

17. Brooks EG, Trotman W, Wadsworth MP, etal. Valves of the deep venous
system: an overlooked risk factor. Blood. 2009;114(6):12761279.
18. Mitchell RN. Hemodynamic disorders, thromboembolic disease
and shock. In Kumar V, Abbas AK, Fausto N. Robbins and Cotran
Pathologic Basis of Disease. 7th ed. India: Elsevier; 2009:133.
19. Kearon C. Natural history of venous thromboembolism. Circulation.
2003;107(23 Suppl 1):122130.
20. Kahn SR, Solymoss S. Lamping DL, Abenhaim L. Long-term outcomes
after deep vein thrombosis: postphlebitic syndrome and quality of life.
J Gen Intern Med. 2000;15(6):425429.
21. Oudega R, Moons KGM, Hoes AW. Limited value of patient history and
physical examination in diagnosing deep vein thrombosis in primary
care. Family Practice. 2005;22(1):8691.
22. Tapson VF, Carroll BA, Davidson BL, etal. The Diagnostic Approach
to Acute Venous Thromboembolism. Clinical Practice Guideline.
American Thoracic Society. Am J Respir Crit Care Med. 1999;160(3):
10431066.
23. Kahn SR. The clinical diagnosis of deep vein thrombosis: integrating
incidence, risk factors and symptoms and signs. Arch Intern Med. 1998;
158(21):23152323.
24. Ikard RW, Ueland K, Folse R. Lower limb venous dynamics in pregnant
women. Surg Gynecol Obstet. 1971;132(3):483488.
25. Anderson FA, Wheeler HB. Physicians practices in the management
of venous thromboembolism: a communitywide survey. J Vasc Surg.
1992;16(5):707714.
26. Rosendaal FR. Risk factors for venous thrombosis: prevalence, risk,
and interaction. Semin Hematol. 1997;34(3):171187.
27. Prandoni P. Acquired risk factors for venous thromboembolism in medical patients. Pathophysiol Haemost Thromb. 2006;35(12):128132.
28. Vandenbroucke JP, Rosing J, Bloemenkamp KW, et al. Oral contraceptives and the risk of venous thrombosis. N Engl J Med. 2001;344:
15271535.
29. Anderson FA, Spencer FA. Risk factors for venous thromboembolism.
Circulation. 2003;107(Suppl 1):916.
30. Gavish I, Brenner B. Air travel and the risk of thromboembolism. Intern
Emerg Med. 2010Nov 6. [Epub ahead of print].
31. van Aken BE, Reitsma PH, Rosendaal FR. Interleukin 8 and venous
thrombosis: evidence for a role of inflammation in thrombosis. Br J
Haematol. 2002;116:173177.
32. Clayton TC, Gaskin M, Meade TW. Recent respiratory infection and
risk of venous thromboembolism: casecontrol study through a general
practice database. Int J Epidemiol. 2011. [Epub ahead of print].
33. Gertziafas GT. Risk factors for venous embolism in children. Int Angiol.
2004;23(3):195205.
34. Rosendaal FR, Reitsma PH. Genetics of venous thrombosis. J Thromb
Haemost. 2009;7 Suppl 1:301304.
35. Oudega R, Hoes AW, Moons KG. The Wells rule does not adequately
rule out deep venous thrombosis in primary care patients. Ann Intern
Med. 2005;143(2):100107.
36. Wells PS, Hirsh J, Anderson DR, etal. Accuracy of clinical assessment
of deep-vein thrombosis. Lancet. 1995;345(8961):13261330.
37. Wells PS, Anderson DR, Bormanis J, et al. Value of assessment of
pretest probability of deep-vein thrombosis in clinical management.
Lancet. 1997;350(9094):17951798.
38. Pabinger I, Ay C. Biomarkers and venous thromboembolism.
Arterioscler Thromb Vasc Biol. 2009;29:332336.
39. Wells PS, Anderson DR, Rodger M, etal. Evaluation of D-dimer in the
diagnosis of suspected deep-vein thrombosis. N Engl J Med. 2003;349:
12271235.
40. Aguilar C, del Villar V. Combined D-dimer and clinical probability
are useful for exclusion of recurrent deep venous thrombosis. Am J
Hematol. 2007;82(1):4144.
41. Brotman DJ, Segal JB, Jani JT, Petty BG, Kickler TS. Limitations
of D-dimer testing in unselected inpatients with suspected venous
thromboembolism. Am J Med. 2003;114(4):276282.
42. Eichinger S. D-dimer testing in pregnancy. Pathophysiol Haemost
Thromb. 2003;33:327329.

submit your manuscript | www.dovepress.com

Dovepress

67

Kesieme et al
43. Curry N, Keeling D. Venous thromboembolism: the role of the clinician.
J R Coll Phys Edinb. 2009;39:243246.
44. Antonelli F, Villani L, Masotti L, Landini G. Ruling out the diagnosis
of venous thromboembolism in the elderly: is it time to revise the role
of D-dimer? Am J Emerg Med. 2007;25(6):727728.
45. Masotti L, Ray P, Righini M, etal. Pulmonary embolism in the elderly:
A review on clinical, instrumental and laboratory presentation. Vasc
Health Risk Manag. 2008;4(3):629636.
46. Nolan TE, Smith RP, Devoe LD. Maternal plasma D-dimer levels in
normal and complicated pregnancies. Obstet Gynecol. 1993;81(2):
235238.
47. Proietti AB, Johnson MJ, Proietti FA, Repke JT, Bell WR. Assessment
of fibrin(ogen) degradation products in preeclampsia using immunoblot
enzyme-linked immunosorbent assay and latex-based agglutination.
Obstet Gynecol. 1991;77(5):696700.
48. Francalanci I, Comeglio P, Liotta AA, etal. D-dimer concentrations
during normal pregnancy, as measured by ELISA. Thromb Res. 1995;
78(5):399405.
49. Goldenberg NA, Knapp-Clevenger R, Manco-Johnson MJ. Elevated
plasma factor VIII and D-dimer levels as predictors of poor outcomes
of thrombosis in children. N Engl J Med. 2004;351(11):10811088.
50. Hirsh J, Lee AY. How we diagnose and treat deep vein thrombosis.
Blood. 2002;99:31023110.
51. Tovey C, Wyatt S. Diagnosis, investigation, and management of deep
vein thrombosis Clinical review. BMJ. 2003;326:11801184.
52. Zierler BK. Ultrasonography and diagnosis of venous thromboembolism.
Circulation. 2004;109(12 Suppl 1):I9I14.
53. Kearon C, Ginsberg JS, Hirsh J. The role of venous ultrasonography
in the diagnosis of suspected deep venous thrombosis and pulmonary
embolism. Ann Intern Med. 1998;129(12):10441049.
54. Rose SC, Zwiebel WJ, Nelson BD, etal. Symptomatic lower extremity
deep venous thrombosis: accuracy, limitations, and role of color duplex
flow imaging in diagnosis. Radiology. 1990;175(3):639644.
55. Kearon C, Julian JA, Newman TE, Ginsberg JS. Noninvasive diagnosis of deep vein thrombosis. McMaster Diagnostic Imaging Practice
Guidelines Initiative. Ann Intern Med. 1998;128(8):663677.
56. Rabinov K, Paulin S. Roentgen diagnosis of venous thrombosis in the
leg. Arch Surg. 1972;104(2):134144.
57. Tapson VF, Carroll BA, Davidson BL, etal. The Diagnostic Approach
to Acute Venous Thromboembolism Clinical Practice Guideline.
American Thoracic Society. Am J Respir Crit Care Med. 1999;160(3):
10431066.
58. Ting AC, Cheng SW, Cheung GC, Wu LL, Hung KN, Fan YW.
Perioperative deep vein thrombosis in Chinese patients undergoing
craniotomy. Surg Neurol. 2002;58(34):274279.
59. Katayama H, Yamaguchi K, Kozuka T, Takashima T, Seez P,
Matsuura K. Adverse reactions to ionic and non-ionic contrast media.
A report from the Japanese Committee on the Safety of Contrast Media.
Radiology. 1990;175(3):621628.
60. Albrechtsson U, Olsson CG. Thrombotic side-effects of lower-limb
phlebography. Lancet. 1976;1:723724.
61. Glew D, Cooper T, Mitchelmore AE, Parsons D, Goddard PR, Hartog M.
Impedance plethysmography and thrombo-embolic disease. Br J Radiol.
1992;65(772):306308.
62. Fraser DG, Moody AR, Morgan PS, Martel AL, Davidson I. Diagnosis
of lower-limb deep venous thrombosis: a prospective blinded study of
magnetic resonance direct thrombus imaging. Ann Intern Med. 2002;
136(2):8998.
63. Erdman WA, Jayson HT, Redman HC, Miller GL, Parkey RW,
Peshock RW. Deep venous thrombosis of extremities: role of MR imaging in the diagnosis. Radiology. 1990;174(2):425431.
64. Roberts VC, Sabri S, Beeley AH, Cotton LT. The effect of intermittently
applied external pressure on the haemodynamics of the lower limb in
man. Br J Surg. 1972;59(3):223226.
65. Agu O, Hamilton G, Baker D. Graduated compression stockings in
the prevention of venous thromboembolism. Br J Surg. 1999;86(8):
9921004.

68

submit your manuscript | www.dovepress.com

Dovepress

Dovepress
66. Amaragiri SV, Lees TA. Elastic compression stockings for the prevention of deep vein thrombosis. Cochrane Database Syst Rev. 2000;3:
CD001484.
67. Hull RD, Delmore TJ, Hirsh J, et al. Effectiveness of intermittent
pulsatile elastic stockings for the prevention of calf and thigh vein
thrombosis in patients undergoing elective knee surgery. Thromb Res.
1979;16(12):3745.
68. Kakkos SK, Caprini JA, Geroulakos G, Nicolaides AN, Stansby GP,
Reddy DJ. Combined intermittent pneumatic leg compression and pharmacological prophylaxis for prevention of venous thromboembolism in
high-risk patients. Cochrane Database Syst Rev. 2008;4:CD005258.
69. Francis CW. Prophylaxis for thromboembolism in hospitalized medical
patients. N Engl J Med. 2007;356:14381444.
70. Comerota AJ, Chouhan V, Harada RN, et al. The fibrinolytic effects
of intermittent pneumatic compression: mechanism of enhanced
fibrinolysis. Ann Surg. 1997;226(3):306314.
71. Browse NL, Jackson BT, Mayo ME, Negus D. The value of mechanical
methods of preventing postoperative calf vein thrombosis. Br J Surg.
1974;61(3):219223.
72. Hilleren-Listerud AE. Graduated compression stocking and intermittent pneumatic compression device length selection. Clin Nurse Spec.
2009;23(1):2124.
73. Chin PL, Amin MS, Yang KY, Yeo SJ, Lo NN. Thromboembolic
prophylaxis for total knee arthroplasty in Asian patients: a randomised
controlled trial. J Orthop Surg. (Hong Kong). 2009;17(1):15.
74. Morris RJ, Woodcock JP. Intermittent pneumatic compression or
graduated compression stockings for deep vein thrombosis prophylaxis?
A systematic review of direct clinical comparisons. Ann Surg. 2010;
251(3):393396.
75. Collins R, Scrimgeour A, Yusuf S, Peto R. Reduction in fatal pulmonary
embolism and venous thrombosis by perioperative administration of
subcutaneous heparin. N Engl J Med. 1988;318(18):11621173.
76. Leonardi MJ, McGory ML, Ko CY. The rate of bleeding complications
after pharmacologic deep venous thrombosis prophylaxis: a systematic
review of 33 randomized controlled trials. Arch Surg. 2006;141(8):
790797.
77. Warkentin TE, Levine MN, Hirsch J, et al. Heparin-induced thrombocytopenia in patients treated with low-molecular-weight heparin or
unfractionated heparin. N Engl J Med. 1995;332(20):13301335.
78. Bhandari M, Hirsh J, Weitz JI, Young E, Venner TJ, Shaughnessy SG.
The effects of standard and low molecular weight heparin on bone
nodule formation in vitro. Thromb Haemost. 1998;80(3):413417.
79. Hirsch J, Raschke R, Warkentin TE, Dalen JE, Deykin D, Poller L.
Heparin: mechanism of action, pharmacokinetics, dosing considerations,
monitoring, efficacy and safety. Chest. 1995;108(4Suppl):258275.
80. Bauer KA. Fondaparinux sodium: a selective inhibitor of factor Xa.
Am J Health Syst Pharm. 2001;58Suppl 2:S14S17.
81. Weitz JI, Hirsh J, Samama MM. New Antithrombotic Drugs: American
College of Chest Physicians Evidence-Based Clinical Practice Guidelines, 8th ed. Chest. 2008;133:234S256S.
82. Schulman S, Kearon C, Kakkar AK, etal; RE-COVER Study Group.
Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med. 2009;361(24):23422352.
83. Dahl OE, Huisman MV. Dabigatran etexilate: advances in anticoagulation therapy. Expert Rev Cardiovasc Ther. 2010;8(6):771774.
84. Eriksson BI, Dahl OE, Huo MH, etal; the RE-NOVATE II Study Group.
Oral dabigatran versus enoxaparin for thromboprophylaxis after primary
total hip arthroplasty (RE-NOVATE II). A randomised, double-blind, noninferiority trial. Thromb Haemost. 2011;105(4). [Epub ahead of print].
85. Effective single-drug approach is welcomed for deep-vein thrombosis
treatment. Cardiovasc J Afr. 2010;21(5):301.
86. Chen T, Lam S. Rivaroxaban: an oral direct factor Xa inhibitor for the
prevention of thromboembolism. Cardiol Rev. 2009;17(4):192197.
87. Geerts WH, Bergqvist D, Pineo GF, et al. Prevention of venous
thromboembolism: American College of Chest Physicians EvidenceBased Clinical Practice Guidelines 8th ed. Chest. 2008;133(6Suppl):
381S453S.

Journal of Blood Medicine 2011:2

Dovepress
88. Hall JG, Pauli RM, Wilson KM. Maternal and fetal sequelae of
anticoagulants during pregnancy. Am J Med. 1980;68:122140.
89. Bates SM, Ginsberg JS. How we manage venous thromboembolism
during pregnancy. Blood. 2002;100(10):34703478.
90. Ginsberg JS, Greer I, Hirsh J. Use of antithrombotic agents during
pregnancy. Chest. 2001;119(1Suppl):122S131S.
91. Antiplatelet Trialists Collaboration. Collaborative overview of
randomised trials of antiplatelet therapy: III. Reduction in venous
thrombosis and pulmonary embolism by antiplatelet prophylaxis among
surgical and medical patients. BMJ. 1994;308(6923):235246.
92. Hovens MM, Snoep JD, Tamsma JT, Huisman MV. Aspirin in the
prevention and treatment of venous thromboembolism. J Thromb
Haemost. 2006;4(7):14701475.
93. McKenna R, Galante J, Bachmann F, Wallace DL, Kaushal PS, Meredith
P. Prevention of venous thromboembolism after total knee replacement
by high-dose aspirin or intermittent calf and thigh compression. Br Med
J. 1980;280(6213):514517.
94. Powers PJ, Gent M, Jay RM, etal. A randomized trial of less intense
postoperative warfarin or aspirin therapy in the prevention of venous
thromboembolism after surgery for fractured hip. Arch Intern Med.
1989;149(4):771774.
95. Graor RA, Stewart JH, Lotke PA, Davidson BL. RD heparin (ardeparin
sodium) vs aspirin to prevent deep venous thrombosis after hip or knee
replacement surgery [abstract]. Chest. 1992;102:118S.
96. Gent M, Hirsh J, Ginsberg JS, et al. Low-molecular-weight heparinoid orgaran is more effective than aspirin in the prevention of
venous thromboembolism after surgery for hip fracture. Circulation.
1996;93(1):8084.
97. Basu D, Gallus A, Hirsh J, Cade J. A prospective study of the value of
monitoring heparin treatment with the activated partial thromboplastin
time. N Engl J Med. 1972;287(7):324327.
98. Hull RD, Raskob GE, Brant RF, Pineo GF, Valentine KA. Relation
between the time to achieve the lower limit of the APTT therapeutic
range and recurrent venous thromboembolism during heparin treatment for deep venous thrombosis. Arch Intern Med. 1997;157(22):
25622568.
99. Hirsh J, Raschke R. Heparin and low-molecular-weight heparin the
Seventh ACCP Conference on Antithrombotic and Thrombolytic
Therapy. Chest. 2004;126(3Suppl):188S203S.

Journal of Blood Medicine

Publish your work in this journal

The Journal of Blood Medicine is an international, peer-reviewed, open
access, online journal publishing laboratory, experimental and clinical aspects
of all topics pertaining to blood based medicine including but not limited to:
Transfusion Medicine; Blood collection, Donor issues, Transmittable diseases,
and Blood banking logistics; Immunohematology; Artificial and alternative

DVT clinical review

100. Hyers TM, Agnelli G, Hull RD, et al. Antithrombotic therapy
for venous thromboembolic disease. Chest. 2001;119(1 Suppl):
176S193S.
101. Lee AY, Levine MN, Baker RI, etal. Low-molecular-weight heparin
versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med. 2003;349(2):146153.
102. Ramzi DW, Leeper KV. DVT and pulmonary embolism: Part II.
Treatment and prevention. Am Fam Physician. 2004;69:28412848.
103. Levine MN, Hirsh J, Gent M, etal. Optimal duration of oral anticoagulation therapy: a randomized trial comparing four weeks with three
months of Warfarin in patients with proximal deep vein thrombosis.
Thromb Haemost. 1995;74(2):606611.
104. Schulman S, Rhedin AS, Lindmarker P, etal. A comparison of six
weeks with six months of oral anticoagulant therapy after a first episode
of venous thromboembolism: Duration of Anticoagulation Trial Study
Group. N Engl J Med. 1995;332(25):16611665.
105. Kearon C, Kahn SR, Agnelli G, et al. Antithrombotic therapy for
venous thromboembolic disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines, 8th ed. Chest.
2008;133(Suppl 6):454S545S.
106. Patterson BO, Hinchliffe R, Loftus IM, Thompson MM, Holt PJ.
Indications for catheter-directed thrombolysis in the management of
acute proximal deep venous thrombosis. Arterioscler Thromb Vasc
Biol. 2010;30(4):669674.
107. Popuri RK, Vedantham S. The role of thrombolysis in the clinical
management of deep vein thrombosis. Arterioscler Thromb Vasc Biol.
2011;31(3):479484.
108. Streiff MB. Vena caval filters: a comprehensive review. Blood.
2000;95(12):36693677.
109. Decousus H, Leizorovicz A, Parent F, etal. A clinical trial of vena
caval filters in the prevention of pulmonary embolism in patients with
proximal deep-vein thrombosis. Prvention du Risque dEmbolie
Pulmonaire par Interruption Cave Study Group. N Engl J Med. 1998;
338(7):409415.
110. Joels CS, Sing RF, Heniford BT. Complications of inferior vena cava
filters. Am Surg. 2003;69(8):654659.

Dovepress
blood based therapeutics; Hematology; Biotechnology/nanotechnology of
blood related medicine; Legal aspects of blood medicine; Historical perspectives. The manuscript management system is completely online and includes
a very quick and fair peer-review system. Visit http://www.dovepress.com/
testimonials.php to read real quotes from published authors.

Submit your manuscript here: http://www.dovepress.com/Journal-of-blood-medicine-journal

Journal of Blood Medicine 2011:2

submit your manuscript | www.dovepress.com

Dovepress

69