1. BLOODCOUAGULATION 1. Very, very short definition of hemostasis 2. Not so short, but still short description of the general mechanism 3. The cascade - initation, proceeding, control 5. Diseases,deficiencies – and (shortly) about treatments

2. HEMOSTASIS = PREVENTION OF BLOODLOSS Achieved by four phases/mechanisms Vascular phase – damaged vessel contracts Platelet phase – formation of the platelet Coagulation phase – formation of the blood clot Tissue repair

3. GENERAL MECHANISM OF BLOODCOAGULATION Balance between anticouagulants/procoagulants Damage on vessel – cascacade – prothrombinactivator Prothrombin – thrombin Fibrinogen – fibrin

4. Platelets : -adheres to broken vesselwall - prothrombin attach to prothtrombinreceptors on platalets -release fibrin stabilizing factor (FXIII)- covalent crosslinks between the fibrin molecules - activate own contractile elemen = broken wall of vessel is pulled together

5. THE CASCADE formation of prothrombin activator extrinsic pathway intrinsic pathway common pathway = epw and ipw ending the same way...

6. EXTRINSIC PW 1. Initiated by traumatized tissue – releases complex of tissue factors 2. TFs = phospholipids from membranes of tissue + lipoproteincomplex 3. TF + FVII = complex 4. Complex + Ca 2+ act on FX = FXa (activated) 5. FXa + phospholipids + FV – act on prothrombrin in presense of Ca 2+ - prothrombin split – thrombin Thrombin convert fibrinogen to fibrin

7. INTRINSIC PW 1 Damaged vessels wall expose collagenfibers – FXII – FXIIa. Platelets - attach to collagen – release platelet factor 3 (lipoprotein) 2 FXIIa – FXI – FXIa. * HMWkininogen * Prekallikrein (Fletcher factor) 3 FXIa – FIX – FIXa 4 FIXa + FVIII + phospholipids (from platelets) + platelet factor 3 (from platelets) – FX – FXa 5 FXa + FV + phopspholipids (from platelets or tissue) = prothrombin activator – prothrombin – thrombin – fibrinogen – fibrin

8. COMMON PW=5 EXTRINSIC PW explosive initiated by tissue factors clotting within 15 sec if severe trauma INTRINSIC PW slower initiated when FXII + platelets contact with collagen 1 – 6 minutes to cause clotting CA 2+ promotes/ accelerates the bloodclotting reactions

9. WHEN CLOT IS FORMED – it contracts contractile elements of platelets serum (fluid without fibrinogen and clotting factors) is expressed from clot – within 20 – 60 minutes

10. CONTROL OF CASCADE To prevent excessive clotting (which might lead to thromobosis – more about that later): Fibrinolysis Plasminogen is activated = converted into plasmin by: plasma kallikrein t-PA = tissue plasminogen activator urikinase Plasmin: re-dissolves the soluble fibrins – fibrinopeptides inhibits thrombinformation = polymerization of fibrin is halted

11. DISEASES, DEFICIENSIES Vitamin K: needed for synthesis of prothrombin FVII FIX FX protein c HEMOPHILIA HA = FVIII (85%) HB = FIX (15 %) von Willebrand´s THROMBOEMBOLIC CONDITIONS THROMBOEMBOLIC CONDITIONS Thrombus – an abnormal clot in vessel Emboli – thrombus sailing with blood stream - NOT GOOD.