Presented by Dr
Azza Serry

Learning
Objectives
 Definition .
 Clotting mechanism .
 What keeps blood in fluid status
 Control of blood clotting and fibrinolytic systems
 Haemostasis disorders

Components
 Haemostasis is the arrest of bleeding.
 This requires the combined activity of vascular
,platelet ,and plasma factors .
 Vascular : vasoconstriction of injured blood vessel .
 Platelet : platelet plug formation .
 Plasma factors : clotting cascade activation .

 What keeps the body fluidity
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 Endothelial cells secrets nitric oxide and prostacyclin which promote blood fluidity by : prevent platelet stasis dilate intact blood vessels .
 Endothelial cells expresses TPA and antithrombin III .
 These mediators are no longer produced when vascular endothelium is disrupted .

Coagulation cascade
 Clotting cascade
 Coagulation is activated by two mechanisms :
 Extrinsic :initiated by activation of factor VII upon ad mixture of plasma and tissue factor (damaged tissue )
 Intrinsic : initiated by activation of factor XII upon contact with non endothelial surface . ( glass )

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 Regulatory feedback mechanisms counterbalance the tendency of clots to form :
① inactivation of coagulation factors , antithrombin III : inactivate thrombin , VIIa ,IXa , Xa ,XIa. protein C ,and S, inactivate factors Va and VIIIa .
Regulatory feedback mechanisms
 cells
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② fibrinolysis , (tissue plasminogen activator TPA ) by endothelial
↓ plasminogen → plasmin
↓ fibrin → fibrin degradation products
③ Hepatic clearance of activated clotting factors
 Regulation of fibrinolysis : vascular endothelium and activated platelet release plasmin inhibito r .
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 Haemostatic diorders
 Hypercoagulable state
: inherited due to deficiency of natural anticoagulant ( protein C and S)
 Acquired tendency to thrombosis in malignancy or contraception
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: congenital or acquired
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 Congenital :
 Acquired:
Haemophilia A and B
Von Willibrand disease

Bleeding diathesis
Congenital disorders
Haemophilia
 Sex – linked disorder ,present by bleeding into soft tissues ,and weight bearing joints .
 Haemophilia A : defect factor VIII
 Haemophilia B : defect factor IX
 Treated by replacement .

Von Willibrand disease

 Von Willibrand factor : adhere platelet to subendothelium ,carrier of factor
VIII .
 Von Willibrand disease : Presents by menorrhagia ,epistaxis .
 Treated by factor VIII concentrate

Acquired disorders
 Thromocytopenia

 Causes : decreased production ,bone marrow aplasia .
increased consumption : splenomegaly .
 Non steroidal anti-inflammatory ,Aspirin ,interfere with platelet adhesion
.

Vitamen K deficiency
 Cofactor for production of factors II , VII ,IX ,X .
 Causes : hepatocellular disease ,malabsorption ,
 Treated by parenteral Vitamen K ,FFP ( fresh frozen plasma) .

HEPATIC
FAILURE
 Hepatic failure : decrease synthesis of coagulation factors except factor VIII,synthesis of inhibitors ( protein C ,S ) , decreased clearance of activated factors .
Renal failure : decrease aggregation of platelet .