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HEMOSTASIS

Steps of hemostasis: As injury occurs following steps come in role

1. Vasoconstriction
2. Formation of platelet plug ( primary hemostatic plug)
3. Coagulation cascade ( clot formation )

HOW PLATELET FUNCTIONS ?

After injury →
1. Platelet adhesion:
 Platelets via gpIb/ IX binds with von Wilibrand factor (Vwf) present on
endothelial cells.

2. Platelet activation :
 Change in shape of platelets
 Release of contents from platelets

Thromboxane A2 [IX A2]

ADP (As a result of this release there is activation of

coagulation cascade )

3. Platelet aggregation:
 Multiple platelets arrive forming a hemostatic plug

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 Binding between two platelets is aided by another receptors
gp2b/3a

Activation of coagulation cascade

Thrombin

↓
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Fibrin

This fibrin makes the clot firm/stable

[Forms the meshwork between platelets ]
 BLEEDING DISORDERS

BLEEDING
DISORDERS

Can be due to Due to platelet Due to

vascular causes causes coagulation defect

 Due to vascular causes:

They are said to be diagnosis of exclusions i.e we think about vascular causes
after ruling out all other causes because in vascular causes
BT , CT ,PT , Aptt are normal.
 Due to platelet causes:

It can be due to defect in number.

Normal platelet count – (1.5-4 lac/mm³).

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Decreased platelet count(thromboctyopenia

MEGAKARYOCYTIC
THROMBOCYTOPENIA AMEGAKARYOCYTIC
↓ THROMBOCYTOPENIA
marrow eill try to compensate ↓
and there will be increase in no rise in megakaryocyte in seen
megakaryocytes.

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 CAUSES OF MEGAKARYOCYTIC THROMBOCYTOPENIA

IMMUNE
 ITP
 SLE
 Dengue
 Drugs

NON IMMUNE

 DIC
 HUS
 TTP
 CAUSES OF AMEGAKARYOCYTIC THROMNOCYTOPENIA
 Aplastic anemia
 Bone marrow fibrosis
 Vitamin B12,folic acid deficiency
 Drugs.

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 IMMUNE THROMBOCYTOPRNIC PURPURA
 TYPE 2 Hypersensitivity reaction (antibody me diated)

Antibodies like IgG [opsonins] will attack platelets

These platelets coated by antibodies while passing through spleen undergo

phagocytosis as they are opsonized

Therefore, decrease seen in platelet count

 CLINCAL FEATURES (seen due to superficial tissue bleeding)

 Petechiae
 Purpura
 Gum bleeding
 Hemorrhagic bulla
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TYPES OF ITP

ACUTE CHRONIC

ACUTE

 Sudden onset
 Resolve within 6 months
 More severe
 History: child with viral infection
 Platelet count<50,000
 Treatment –symptomatic

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CHRONIC

 Delayed onset
 Takes 6 months
 Less severe
 Seen in adults and no viral infection
 Platelet count→ 3,000-5,000
 Treatment – steroids
 DIAGNOSIS OF ITP:
 Diagnosis of exclusion
 Platelet count decreased
 BT increased
 PT and aPTT are normal as there is no change in coagulation pat hway
 COOMB`s test →positive
 Bone marrow examination → increase in megakaryocytes

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 ANGIOPATHIC HAEMOLYTIC ANEMIA
 There in anemia due to hemolysis which in turn is because of blood vessels.
 It can involve large blood vessels or small blood vessels.

ANGIOPATHIC HAEMOLYTIC ANEMIA

MAHA(Macroangiopathi MIHA(Microangiopathic
c haemolytic anemia) haemolytic anemia)

 MACROANGIOPATHIC HAEMOLYTIC ANEMIA

(involves large blood vessels )
EXAMPLE:
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1. Prosthetic heart valve causes MAHA
(Aortic valves>mitral valves )
2. Aortic stenosis
[increased pressure through valves
↓
RBCs will start breaking resulting in MAHA ]
3. Vascular grafting
4. Cavernous hemangioma

 MICROANGIOPATHIC HAMEOLYTIC ANEMIA

(involves small blood vessels)
Causes:
1. DIC
2. HUS
3. TTP
4. Malignant hypertension
5. March haemoglobulinemia

NOTE: Causes of both MAHA and MIHA will result in fragmented RBCs also known as

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SCHISTOCYTES .
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HEMOLYTIC UREMIC SYNDROME

 Non-immune megakaryocytic thrombocytopenia

 It is of 2 types:
o Typical HUS:
 Will give typical history of a child with acute gastro -enteritis
which is caused by E. Cali [O157/H7] and Shigella [toxin], Both will
result in formation of platelet rich Thrombi
o Atypical HUS:
 Defect in complement proteins Factor H/ Factor I / CD46
 Or due to drugs:
 Mitomycin
 Ticlopidine
also result in Platelet rich Thrombi
 Now as there is thrombi in BV, the RBCs on striking with thrombi underg oes
hemolysis that is microangiopathic hemolytic anemia occurs

 4]
 As platelets are consumed in thrombi formation , platelet count decreases 
Thrombocytopenia
 Platelet rich thrombi can go & Block renal vessels & cause renal failure
 Thus in HUS there is Triad of:
o Macroangiopathic hemolytic anemia
o Thrombocytopenia
o Renal Failure
 C/Fs:
o Petechiae / Purpura

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 o Bloody diarrhea
 Diagnosis:
o Decreased Platelet Count
o BT increased
o PT normal
o aPTT normal
 Thrombotic Thrombocytopenia Purpura [TTP]:
o Liver produces a protein, Protease ADAM TS 13 which breaks VWF
polymers into VWF monomers, If there is decrease in ADAM TS 13, due
to congenital deficiency  condition is called UPSHAW SCHULMANN
Syndrome and due to Acquired conditions seen in Autoimmune
conditions
o As ADAM TS 13 decreases  VWF Polymers will not convert into VWF
monomers  Aggregate Platelets:
 Thrombosis
 Decreased Platelet Count
 C/Fs:
o MIHA
o Decreased Platelet Count
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o Renal failure
o Fever
o CNS Involvement
 Treatment [For acquired TTP]: Plasmapheresis

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DISSEMINATED INTRAVASCULAR
COAGULATION [DIC]

 Consumptive Coagulopathy
 Causes:
o Obstetric Causes:
 Retained placenta
 Retained product of conception
 Amniotic fluid embolism
o Infection
o Cancers: All cancers where mucin can be liberated
 AMLM 3
 Gastric
 Colonic
 Pancreatic
o Burns / Trauma
 Note: Obstetric causes, Infection, Cancers  cause Endothelial cell
damage/injury  Activation of Intrinsic Pathway of Coagulation
Burns / Trauma  Release of Tissue Factors  Activation of Extrinsic
Pathway
 By activation of extrinsic, intrinsic pathway thrombi formation occurs; this
process will go on & on leading to consumptive coagulopathy [that is all
coagulation factors get consumed]  Resulting in BLEEDING
 Thrombi will activate fibrinolytic pathway [that is activate plasmin] therefore
clot will break resulting in bleeding

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 Within BV, RBCs will strike with thrombi & form SCHISTOCYTES / Fragmented
RBCs
 Diagnosis:
o ↓ Hb [Anemia]
o ↓ Platelet count
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o Peripheral smear  Schistocytes
o Bleeding time ↑
o PT ↑
o aPTT ↑ [as both intrinsic, extrinsic pathway are affected]
o D-DIMER + [Activation of fibrinolytic pathway; breakage of
fibrin/thrombus forming by product D -DIMER
 C/Fs: affects / blacks BVs of
o CNS [Most commonly]
o Heart
o Lung
o Kidney [Acute Tubular Necrosis (ATN)]
o Adrenal Gland [If there is meningococci infection Hemorrhage occurs;
Waterhouse Freidrichson syndrome]

 Treatment: Treat the underlying cause

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DEFECT IN FUNCTION

 Defect in G p IB/ IX receptor  Bernard Soullier Syndrome  Shows +nce of

big/giant Platelets
 Defects in G p IIB/IIIa receptor  Glanzmann Thrombasthenia
 Defect in VWF  Von Willibrand Disease

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 CLOTTING DISORDERS

 HEMOPHILIA:
o A: Factor VIII deficiency
o B: Factor IX deficiency [Christmas Disease]
o C: Factor Eleven deficiency
o Para hemophilia: Factor V deficiency
 Common C/Fs:
o Deep tissue bleed
o Hemarthrosis
o Organ bleeding
o Intracranial bleeding [most dangerous]
o Bleeding after Trauma
o Example : Tooth Extraction Circumcision

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8.9 HEMOPHILIA A

 Deficiency of Factor VIII

 Synthesis : 2 sources –
o From Liver:
 Kuffer cells
 Sinusoidal endothelial cells
o From Kidney –
 Tubular epithelial cells
 Deficiency:
o 90% cases show Quantitative defect
o 10% cases show Qualitative defect
 Effect:
o Intrinsic Pathway is affected
 Diagnosis:
o Platelet Count – Normal
o BT – Normal
o PT – Normal
o aPTT – Increased [Associated with intrinsic pathway]
o Factor VIII assay  Based on this assay:
 MILD  6-50% of functional activity is +nt
 MODERATE  1-5% of functional activity +nt
 SEVERE  <1%
 Rx:
o Mild Deficiency  Desmopressin; as it will release factor VIII from
liver endothelial cells
o Severe Deficiency  Recombinant factor VIII [HUMATE]
o We can manage the pt. till the use of H UMATE by using Blood
Transfusion process that is CRYOPRECIPITATE [Blood product rich in
F.VIII]
 HEMOPHILIA B

 Deficiency of Factor IX
 Christmas disease
 Involves Intrinsic Pathway
 Diagnosis:
o Platelet Count – Normal
o BT – Normal
o PT – Normal
o aPTT – increases
o Factor IX assay
 Tt:
o Recombinant Factor IX
o Blood Transfusion = Fresh Frozen Plasma [FFP]

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FACTOR INHIBITORS

 There are some inhibitors in the form of antibodies which inhibit clotting
factors; are called factor inhibitors
 Such Abs are formed in, example:
o Pregnancy
o Autoimmune disease
 Such individuals have risen in aPTT
 Note: Isolated ↑↑ aPPT can occur in [when all other timings are normal]:
o Heparin Toxicity
o Factor Deficiency or Factor Inhibitor
1. Therefore treat sample with heparinase; if aPTT becomes normal then
diagnosis is Heparin Toxicity
2. Mixing Studies: Take pt. sample & control sample & mix them in 1:1  Repeat
aPTT:
a. Normal aPTT:
i. Diagnosis = Factor Deficiency [because control sample provided
deficient factor which corrected the aPTT]
b. Rise in aPTT:
i. Diagnosis = Factor inhibitor

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 VON WILILBRAND DISEASE

 Source of VWF:
o Endothelial cells [WIEIBEL PALADE]  which have P selectin VWF
o Megakaryocytes
o Liver
 Functions of VWF:
o Carrier of factor VIII:
 Therefore, if factor VIII is bounded with VWF then it’s t 1 / 2 = 12
hours
 If factor VIII is free, then its t 1 / 2 = 2.4 hours
o Helps in platelet adhesion
 Deficiency of vWF:
 As t 1 / 2 of factor VIII decreases therefore, deficiency of VWF
will affect the intrinsic pathway, PT  Normal, aPTT 
Increases
 As platelet adhesion will decrease therefore, BT  Increases,
Platelet count  Normal
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 VWD is of 3 types:
o Type I:
 AD
 Quantitative defect
 Most common VWD
o Type II:
 AD
 Qualitative defect
 Subtypes are, IIA [most common type II], IIB, IIC, IID
o Type II:
 AR
 Quantitative defect
 Most severe
 C/Fs:
o Mucosal bleeds [Therefore, more towards Platelet disorders than
Coagulation disorders]
 Diagnosis:
o Platelet count – Normal

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o BT increases
o PT normal
o aPTT increases
o RISTOCETIN AGGREGATION TEST
 RISTOCETIN - A chemical that promotes attachment of VWF
with G p Ib/IX
 We take formalin fixed platelets to which RISTOCETIN is added
+ Patient sample
 If VWF is +nt in pt. sample then in +nce of RISTICETIN it will
bind to G p Ib/IX of formalin fixed platelets
 Therefore, Formalin fixed platelets + RISTOCETIN + PATIENT
SAMPLE 
 +ve Aggregation: tested on a machine called
aggregometer  the sample is normal
 -ve Aggregation: Von Willebrand Disease
 t
T :
o Mild deficiency  Desmopressin
o Severe deficiency  Cryoprecipitate