BLOODCOUAGULATION1. 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

 

HEMOSTASIS = PREVENTION OF BLOODLOSS

Achieved by four phases/mechanismsVascular phase – damaged vessel contractsPlatelet phase – formation of the platelet Coagulation phase – formation of the blood clotTissue repair

GENERAL MECHANISM OF BLOODCOAGULATION

• Balance between anticouagulants/procoagulants

• Damage on vessel – cascacade – prothrombinactivator

• Prothrombin – thrombin

• Fibrinogen – fibrin

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

THE CASCADE

• formation of prothrombin activator

• extrinsic pathway• intrinsic pathway• common pathway = epw and ipw ending the same way...

EXTRINSIC PW1. Initiated by traumatized tissue – releases complex of tissue factors

2. TFs = phospholipids from membranes of tissue + lipoproteincomplex

3. TF + FVII = complex

4. Complex + Ca2+ act on FX = FXa (activated)

5. FXa + phospholipids + FV – act on prothrombrin in presense of Ca2+ - prothrombin split – thrombin  

Thrombin convert fibrinogen to fibrin

INTRINSIC PW1 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

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 • CA2+

• promotes/ accelerates the bloodclotting reactions

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

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

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