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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
