1. Haemostasis Presented by Dr Azza Serry

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

3. 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.

4.  What keeps the body fluidity  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.

5. 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 )

6. Regulatory feedback mechanisms  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.  ② fibrinolysis, (tissue plasminogen activator TPA ) by endothelial cells  ↓  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. 

7.  Haemostatic diorders  Hypercoagulable state : inherited due to deficiency of natural anticoagulant ( protein C and S)  Acquired tendency to thrombosis in malignancy or contraception  Bleeding diathesis : congenital or acquired  Congenital :Haemophilia A and B  Von Willibrand disease  Acquired:

8. 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.

9. 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

10. 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).

11. 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.