HAEMOSTASIS & FIBRINOLYSIS DR B L Mtinangi DEPARTMENT OF PHYSIOLOGY Hubert Kairuki Memorial University December 3, 2015 HEAMOSTASIS & FIBRINOLYSIS

A SUMMARY OF PLATELETS FORMATION HEAMOSTASIS & FIBRINOLYSIS

SUMMARY OF BLOOD COAGULATION BV Injury Platelet Aggregation Activation Blood Vessel Constriction Coagulation Cascade Stable Hemostatic Plug Fibrin formation Reduced Blood flow Contact/ Tissue Factor Primary hemostatic plug Neural

HEAMOSTASIS & FIBRINOLYSIS

HEAMOSTASIS & FIBRINOLYSIS HAEMOSTATIS Haemostasis is prevention of blood loss after rupture or injury/trauma of blood vessels It is achieved through: Vascular spasms Formation of platelet plug formation Blood coagulation i.e. Development of insoluble fibrin clot Clot retraction Clot dissolution HEAMOSTASIS & FIBRINOLYSIS

Vascular spasms (vasoconstriction) Vascular spasms is due to: Nervious reflex due to pain Effects of local and humoral mechanism Thromboxane A2 (prostaglandin) cause vasoconstrition All generate an Action Potential and cause Myogenic spasm (constriction) and REDUCE blood flow The spasm last less than 1 min HEAMOSTASIS & FIBRINOLYSIS

FORMATION OF PLATELET PLUG Initiated when the platelet come into contact with damaged vascular surface or collagen fibers Platelets adhere and aggregate to the damaged site Platelets secrete large quantity of ADP and Thromboxane A2 (prostaglandin) Endothetal cells secrete a Von Willebrands factor (a small protein molecule) Usually attached to factor VIII Bridges the platelets to exposed collagen HEAMOSTASIS & FIBRINOLYSIS

HEAMOSTASIS & FIBRINOLYSIS CONT. Aggregated platelets activate coagulation factors Finally convert FIBRINOGEN to FIBRIN Stabilizing the PLATELET PLUG Platelets normal count 150,000-400,000/µl Platelets maintain normal vascular integrity HEAMOSTASIS & FIBRINOLYSIS

MECHANISMS OF BLOOD COAGULATION Two mechanisms Procoagulant-promote coagulation Predominate during injury Anti coagulant – inhibit coagulation In normal condition it is predominat HEAMOSTASIS & FIBRINOLYSIS

CLOTTING FACTORS AND THEIR ROMANS SYNONYMS Fibrinogen: factor I Prothrombin: factor II Tissue thromboplastin: factor III Calcium: factor IV Proaccelerin: (labile factor V) Prothrombin: factor VII Antihaemophilic: factor (AHF VIII) Plasma thromboplastin component PTC: factor IX HEAMOSTASIS & FIBRINOLYSIS

HEAMOSTASIS & FIBRINOLYSIS CONT. Stuart: factor X Plasma thromboplastin antecedent PTA: factor XI Hegman factor XII (contact factor) Fibrin stabilizing: factor XIII NB: Factor II, VII, IX & X requires vit K for their synthesis IN THE LIVER, therefore Vit K deficiency & liver diseases leads to bleeding tendencies HEAMOSTASIS & FIBRINOLYSIS

HEAMOSTASIS & FIBRINOLYSIS Factor Trivial Name(s) Pathway Characteristic Prekallikrein Fletcher factor Intrinsic   High molecular weight kininogen (HMWK) contact activation cofactor; Fitzgerald, Flaujeac Williams factor I Fibrinogen Both - II Prothrombin Contains N-term. gla segment III Tissue Factor Extrinsic IV Calcium V Proaccelerin, labile factor, accelerator (Ac-) globulin Protein cofactor VI (Va) Accelerin This is Va, redundant to Factor V VII Proconvertin, serum prothrombin conversion accelerator (SPCA), cothromboplastin Endopeptidase with gla residues VIII Antihemophiliac factor A, antihemophilic globulin (AHG) IX Christmas Factor, antihemophilic factor B,plasma thromboplastin component (PTC) X Stuart-Prower Factor XI Plasma thromboplastin antecedent (PTA) Endopeptidase XII Hageman Factor XIII Protransglutaminase, fibrin stabilizing factor (FSF), fibrinoligase Transpeptidase HEAMOSTASIS & FIBRINOLYSIS

INITIATION OF COAGULATION Initiation of coagulation by either: Trauma/injury to the tissue – extrinsic pathway Trauma/injury to the blood – intrinsic pathway Contact of blood with damaged endothelial and collagen HEAMOSTASIS & FIBRINOLYSIS

A SUMMARY OF COAGULATION PATHWAY HEAMOSTASIS & FIBRINOLYSIS

HEAMOSTASIS & FIBRINOLYSIS COAGULATION is also regulated by several natural anticoagulants Antithrombin III inactivate coagulation factors& it neutralizes thrombin Antithrombin III activity is enhanced by heparin Protein C receptor combine thrombomodulin – inhibits thrombin and several coagulation factors Protein S accelerate the action of protein C Deficiency of the above factors leads to HYPERCOAGULOPATHY states leading to increased THROMBOEMBOLISM HEAMOSTASIS & FIBRINOLYSIS

HEAMOSTASIS & FIBRINOLYSIS CLOT RETRACTION Clot retraction requires large numbers of platelets ie consolidate the clot This contributes to haemostasis by joining the edges of the broken vessels HEAMOSTASIS & FIBRINOLYSIS

HEAMOSTASIS & FIBRINOLYSIS

SUMMARY OF FIBRINOLYSIS

FIBRINOLYSIS (CLOT DISSOLUTION) Dissolution of a blood clot begins shortly after its formation Plasma – contains a globulin PLASMINOGEN incooperated in a large amount in the CLOT PLASMINOGEN is activated by Thrombin, factor XIII, and some lysosomal enzymes to PLASMIN with A PROTEOLYTIC like action HEAMOSTASIS & FIBRINOLYSIS

HEAMOSTASIS & FIBRINOLYSIS PLASMIN Plasmin digest formed fibrin thread/clot (FIBRINOLYSIS) Plasmin also digest a number of clotting factors like Factor I, II, V & VII alpha2 antiplasmin is always present in blood which Binds with plasmin and inhibit its action Fibrinolysis system is therefore important for removing small clot from tiny peripheral vessels-preventing occlusion or blockage and thromboembolism HEAMOSTASIS & FIBRINOLYSIS

HEAMOSTASIS & FIBRINOLYSIS Thank you HEAMOSTASIS & FIBRINOLYSIS