Hemostatic & Fibrinolytic sys .

. Platelet
Overview
Life-span =
7-10 days
Structure Areas 1. Peripheral zone =
Plasma membrane (Phospholipid bi-layer)
2 .
Membrane sys .: Opencanalicular & Dense tubular
sys.
3 . Structural zone =
Cytoskeleton : Microtubule Actin , , Myosin, Submembranous cytoskeleton
4.
Organelle zone : Low Dense
body (ATP, ADP Serotonin Ca)
, , ,
-Granules , Lysosome (Collagenase Cathepsin Elastase)
, ,

·
Endothelial :

· Function =
platelet a in Collagen to subendothelial + 8 Platelet activation &
aggregation * Clot (Prition
1. Antiplatelet : CD39 (ADPase)

.
2 Anticoagulant (Antithrombin)
3 .

Profibrinolytic : Plasmin

Primary hemostasis· vin Platelet & Blood uss .

Platelet plug
·
STEP
-
i wa (Thromboplastin >
- Clot)

① Vasoconstriction : Gina Endothelial - No >

-
Vasoconstriction
h - - - - -

-
- - - - - -

>
-
GP Ib V (b95) VWF Collagen & subendothelial
I
-

② Platelet adhesion : Platelet

- Integrin
·
G (6)

22b1
-

(GP [a/la)
↓ PLC gramma 11 - Ca ↑
+

③ Platelet activation :
shape change
④ Platelet secretion : Ca** >
-
Exocytosis a & Dense granules & Diffusion

= Platelet aggregation : Platelet-GP Iba

(2b32/XbB3) -

Fibrinogen-2b3a-Platelet
·
Inside-out x Outside-in signaling
↑
t
Platelet rowin
Fibrinogen Secretion >
- >
-
Aggregation
↳
Phosphorelation moto-Secretion Aggregation >
-

Secondary hemostasis· rniu Coagulation factor :

Fibrinogen >
- Fibrin Blood clot : 2 got
↳again Koson

I
Liver arrin VI & VNF Reticuloendothelial (RES)
L key :# (Prothrombin) & mossi !!
L Half-live n : V
L vit / dependent : II
,
VII I E (2 ,
7 9
, ,
10)
, ,

model
Waterfall cascade

Cell-based
1. c .
①+2 +
3 =
Initiation >
- 2a

Tissue >
- =

Priming >
- Activated platelet (5a 82
, a)
,

Prothrombinase complex
bearing ( 0 Blood clot
④ 5
Propagation Thrombin BURST
+ + =
2a

,
>
-
5a I
>
-
L

↳-e L
L!

Y ↑
Tenase

!
Complex
L
7a
① L
10 a
(III) = Tissue =
Injury
Tenase 2

Prothrombinase complex
complex 10

(II) ([a)
M9a O
M O O
4
5 10
a

L
6

837
(I) (a)
5a BURST !!
a Thrombin 17 & A

-#
fo /MW/PK Activated platelet platelet
1. >
- No bleeding - - Fibrin
* desi ir 2
=

2 .
01 &VII (OW Hemophilia >
-
Bleed :800 7

3
. 80 -2 Hemostasis sita

Fibrinolytic system
s Gesintstatin dot insert norems clot
FA12PK- >
Plasminogen

&
Endothelial >
-

*
+-PA U-PA - Crosslink-fibrin

PAI1 &2 <

Plasmin -
L # FDP

Natural anticoagulant system ·

Totalin Clot madras pathway nainosinsitu datanu ->
22-Antiplasmin
(Clotb)

1.

2 .
Tissue factor pathway inhibitor (TFPI)

Protein C Inhibitor pathway : X

: XTF/VI

5. (Prothrombinase complex) 8 (Tenase

complex
,
Initiation

complex)
S & Protein Sith Co-factor

.
3 Anti-thrombin : X Factor 92 102 12
, , ,
2a (Thrombin) art
! Givin Proteins/c/Antithrombin >
- Thrombosis (Hereditary)
Hemostatic & Fibrinolytic sys .

Clinical-Bleeding nicos Bleeding Endothelial

1. Petechia (1-3 mm) : ca, unino Thrombocytopenia Bes Platelet o -
Bleeding m dososinis
.
2
Purpura (3-10mm)

.
3
Ecchymosis (10 mm)

4.
Bleeding per gum (noonmat) , Epistaxis (anniantual
.
5 Hemarthroses : on rioto Hemophilia

Approach bleeding
= > so Grea 3 maining
1. Size < No . of bleeding= > Localized or
Systemic ? ① 1 or 20?&
Hypermenorrhea
? / o Bienoonandroi ?X
.
2
Easy of
bleeding= >
Bleeding -

Injury a na11 -

bbb
Acquired ? *
Coagulation
Onset of
Factor
bleeding Hereditary
>
-

3
. >
-
or

4. Fam
. .
x Ex. Hemophilia (d), Hypermenorrhea (wir) Vit.
Antagonist
NSAIDS s Cox 1/2 *0a
&
#
10a , 2 a FA2 7 , 9 , 10
,

.
5
Underlying dx. Ex . Liver/Kidney disease =>
Bleedingsig
(Bleed & 2008)
6 .

Medication Ex . Antiplatelet Anticoagulant, ,

two

·
Lab investigation :
Coagulogram
: Hemoculture Sodium citrate (Coagulogram) Serum * Heparin EDA 0 NaF
our : on Anticoagulant - wate

Normal range 1 .

Screening test

I
1. CBC -
Platelet : 150 000 -
450 000 ① Complete blood count (CBC) => Platelet counting
, ,

i Hemostasis
2 . PT : 10-13 sec
. & Peripheral blood smear (PBS) => ,Owice ,
Mentions vos Platelet bleeding

I
3 . APTT : 30 - 40 sec
. ③ Bleeding time

3
↳ TT : 8-18 Sec ,
# Prothrombin time (PT) : 1800 Extrinsic a Common
pathway (Factor 7
,
10 5
, ,
,
2 1) Prolong PT +
Prolong APTT
·
Join PT reagent (TF , phospholipid ,
(a) incivilia Clot
Prolong PT =
Abnormal Factor = ↓
No bleeding
⑤ Activated Prothrombin time (APTT) : M Intrinsic & Common pathway (Factor 12
,
PK, MW
,
11
,
9
,
8 ,
10 5 2
, , ,
1) Abnormal Common
pathway
- -

Abnormal Factor &W Intrinsic Bleeding

·
dri PTT
reagent (phospholipid ,
&
charge activator) Prolong APTT =

⑥ Thrombin time (T) : M

Fibrinogen
i Thrombin
Prolong ypofibrinogenemia / Hyperfibrinolysis
·
=

·
ri Heparin contaminate :
Heparin - Thrombin >
- No Fibrin (TT prolong
! n screening test - Normal con Bleeding
Ex Hemophilia /, F13 def. Com Fibrin monomer) Platelet dysfunction (Ex Uremia Anti-platelet drug VWD Bernard Glanzmann) Vascular disease, Dysfibrinogenemia (81352a)
·

,
.
, , , , ,

2 Hemostasis bleeding
(Coagulopathy) 2 .

Specific test Fibrin =

Gistsitsis Clot >
-
Prolong T &
Reptilase time
↑
① Reptilase time : non : Dysfibrinogenemia -
(Fibrin l o Heparin effect

Reptilase (Atroxin) =
Thrombin-like enzyme mus >
- in a P A adisia (Thrombin in &FP A & B)

Heparin Year Reptilage ->

> essna Thrombin - in Fibrin =
Reptilage time Normal and Fibrinogen un/inserted
② Mixing study : Check
Coagulation Factor o Tamilaenant + avera (a factor vosandrian

·
correctable= nic Factor =antia Factor
·
Uncorrectable not Factor and dentals Isia Factor o Inhibitor/Antibody minis Factor

③ Factor inhibitor (Bethesda assay) =

Momen Factor inhibitor Lawn dea FA8 a Neutralized 6 50 % Yea 2 Hrs. =
1 Bethesda unit

④ Englobulin lysis time : momoe

Hyperfibrinolysis
Hemostatic & Fibrinolytic sys .

1 hemostatic disorders 1.
Thrombocytopenia (CBC : 150 000
,
& Bleeding o < 100
,
000) (Pseudothrombocytopenia : No bleeding

Superficial cutaneous/mucous membrane bleeding

·
attested (Dilutional/Spleen inside -
Splenomegaly Diag Y Hx
. .
/Phy .
ex
.

wind's sam
·

① Production PBS : No platelet & 000 Downy cell (Atypical lymphocyte)

↳
1.
Megakaryocyte : BM disease (plastic anemia/Radiation / Infection (Ex. Dengue ,
TB) / Toxin (EX Alcohol) .
/Drug/BM infiltration (EX
. Malignancy
.
c Ineffective thrombopoiesis : MDS
, Megaloblastic anemia (Infective hematopoiesis on 12/B9 Def) .

& Destruction ↑

1. Non-Immune :

DIC with Acute promyelocytic leukemia (APL) 1. Disseminated intravascular coagulation (DIC) MBC hainin shear stress- Schistocyte
↑ platelet
>

> Tissue factor PPP

APLcell-
Hypercoagulation Tissue injury Tissue factori Thrombin
generation/Clot ↓
Jansenntetdiro
· >
- ·
- > -> >
-

malignancies)
↳ Coagulation factor/Serum Fibrinogen -PT
:

L
>
- Plasmin

Cytokine
-

>
-
Hyperfibrinolysis
Endothelial
-

damage
Fibrinogen ↓
>
- Clot ↑ Solid
Sepsis-

Hematologic
,
>
Prolong

Immune
Drug induced Autoimmune (Sascositws)
.
2 Alloimmune
:
, (rnsin -
Antibody) ,

1. Immune thrombocytopenia (ITP) < 100 000

,

ITP Ging 1
Pathologic antiplatelet antibody or platelet Macrophage jiz Present antigen In T-cell-nonn B-ce-> Antibody PPP

-
. >
- >
-

~ Megakaryocyte-s Platelet ob
.
2 T-cell n Cytokine >
- Since Platelet

TP u - Autoimmune EX .
SLE
,
Rhumatoid
, HIV, Lymphoma
2. Thrombotic thrombocytopenia purpura (TTP) ! Life-threatening disease
Thrombotic angiopathy (TMA) Use no 3 Autoimmune-ADAMTS 13 A Clot PPP
de
:
·
: VNF 180 :
·

se >
- >
-

⑧ Anemia wil Thrombocytopenia Schistocyte RBC mod

& PBS :
Schistocyte (Fragmented RBC ( Low : Nan Polychromasia
-
& Organ failure : Neuro , Kidney a Thrombosis * ADAMST13 = Protein VWF multimer A2 domain >
- Yaa Clot and intent: in

.
2 Platelet dysfunction wis mangosten
& Hereditary
Ex 1. Bernard-Soulier syndrome : ia Platelet adhesion Ex3 .
Storage pool disease : wa Platelet secretion (Granules may
·
AR, GP 195 (Un VWF) a -granules
⑦ : Grey platelet syndrome
Mucocutaneous bleeding Epistaxis ② dense-granules Pudlak syndrome Albinism
ams (common
Hermansky
·
: -

we · -

PBS : Giant platelet (= RBC)

Chediak-Higashi syndrome Large granule Tw Neutrophil Partial albinism
·
·
:
,

Ex2 .
Glanzmann's thrombasthenia : now a Platelet aggregation x4 .
Von Willebrand disease (WD) : & Platelet adhesion

iG (inwir Fibrinogen)

A type : partiadlefa
·
Ar ba ·

·
ams :
Menorrhagia (600go:Proces UNF (Dysfunctions
PBS Normal type Complete def. ana Hemophilia (UFAS)
·

: 3 : >
-

* UWF Jun Factors In

i
bleeding Coagulant test 000
prolong APTT + Correctable
mixing
& Acquired ·
Treatment : VNF Replacement -·

Exogenous : Cryoprecipitate F8 Concentrate

↳. Endogenous
,

1. Acquired platelet dysfunction with eosinophilia (APDE) : DAVP -nomatens t Plan: Types

ans Ecchymosis Epistaxis

·
: &
·
. Hematotoxin
Ex snakes
·
En Parasite infection >
-
Eosinophil PP >
-
IgE &P - Platelet degranulation (secretion do) =
Storage pool disease
.
2
Drug induced thrombocytopenia or platelet dysfunction :
Antiplatelet
Ex
.
·

Aspirin xThromboxane A2
-

es Platelet activation
·
APR antagonist-ADP ju 70%2

Inhibitor- Platelet
I bla
aggregation
·

2 hemostatic disorders =

Coagulopathy visito nas Pain

Soft tissue hematomal Deep internal hemorrhage / 1 . PT
prolong .
2 APTT prolong 3
. PT & APTT
prolong
Hemarthrosis
miss

(PT) (PT)

A
(000 Contaminate)
⑳

TT Prolong

·
-

common pathway
sinbid Clot
-

Oma 1 °, mis L ↳ awant Hemophilia ra factor arraman - sin Inhibitor

n
↳ Fibrin Lik & Common pathway
↳ S Inhibitor roa, Antoimmune (Acquired hemophilia * Heparin E x 10 a

Ex Hemophilia :
Coagulation factor def.
·

XR 3
type : A n 8 (Common) ,
B 81219
(Factor 5 & 10)

·
ams : Hemarthrosis & Hinge joint Severe
·
: 1 IU/d) Bleed 00]

[
>
-

·
diristian
adashia andato Facia-- Moderate : 1-5 [U/dL Bleedon Minor trauma
aextent
-

Mild 5-40U/L Bleedoir Fibrinolysis prolong TT

Major trauma
· >
- >
-
: -

factor replacement A concentrate/cryoprecipitate

3
·

Clotting : F8
FFP (20 Ange B)
B : F9 Concentrate/Prothrombin complex
/GP Iba

>
- Bernard's