to prevent spontaneous bleeding to keep the fluidity of blood Vascular reaction primary hemostatic barrier Cellular reaction Biochemical reaction / secondary hemostatic barrier vaso constriction Stimulates coagulation factors and platelets Substances synthesized by endothelial cells: von Willebrand factor tissue plasminogen activator (t-PA) plasminogen activator inhibitor -1 (PAI-1) prostacyclin (PGI 2 ) Thrombomodulin (PC activation) Glycosaminoglycan (heparan sulphate, dermatan sulphate) Originated from cytoplasm of megakariocyte (fragmentation) Morphology : discoid, biconvex, 2 4 m Cytoplasm contains: a-granule (PF 4 , b-thromboglobulin, platelet derived growth factor, vWF, fibrinogen, F V) Dense granule (Ca, ADP, ATP) Membrane: phospholipid bilayer, glycoprotein (receptor)
Megakaryoblast Megakaryocytes Platelets 1/3 of platelets: stored in spleen
2/3 of plateletes: blood circulation half-lime 3-4 days 15% use daily for haemostasis normal platelet count 140-360 x 10 9 /l The Platelets Platelet plug formation: Platelet adherent (need von Willebrand Factor) Platelet aggregation stimulated by ADP, thrombin, thromboxan A 2 , epinephrine, collagen Platelet release reaction (from a granule and dense granule) Stabilization of the plug : platelet factor 3 (flip flop of membrane phospholipid) phospholipid Arachidonic acid PGG2, PGH2 Thromboxan A2 Phospholipase A2, C cyclooxygenase Thromboxan synthetase Aspirin Prostacyclin PGI2 synthetase Factor I Fibrinogen precursor of fibrin Factor II Prothrombin serine protease Factor III Tissue thrombo initiate extrinsic path. plastin Factor IV Calsium ion bridge between Gla - phospholipid Factor V Proaccelerin Cofactor of Xa Factor VII Proconvertin serine protease Factor VIII Anti hemophilic f. Cofactor of IXa Factor IX Christmas factor serine protease Factor X Stuart Prower factor serine protease Factor XI Antihemophilic C serine protease Factor XII Hageman factor serine protease Factor XIII Fibrin stabilizing f. transglutaminase Prekallikrein Fletcher factor serine protease HMW kininogen Fitzgerald factor cofactor of Kall.
Vit. K is required for carboxylation of glutamic acid g carboxy glutamate Vitamin K dependent protein : prothrombin, VII, IX, X, protein C, protein S, protein Z Deficiency of vit. K PIVKA (protein induced by vitamin K absence or antagonist) Residue Glutamic acid (GLU) Precursor of II, VII, IX, X Prothrombin VII, IX, X Residue g Carboxy glutamat (GLA) carboxylase Vitamin KH2 Vitamin K epoxide Oral Anticoagulant
Ca ++ FPA FPB + F1.2 +
Mechanism of coagulation factor activation Local: fibrin, blood flow Humoral: - Antithrombin - Protein C - Protein S - Heparin cofactor II - TFPI Cellular : liver cell, RES Synthesized in the liver Function : neutralize thrombin and other serine protease (XIIa, XIa, Xa, IXa, VIIa, Kallikrein,plasmin) Heparin cofactor Activities enhanced by heparin Both are vitamin K dependent protein Thrombin with thrombomodulin as cofactor activates Protein C activated Protein C (APC) APC with Protein S as cofactor inactivates F Va and F VIIIa.
Function : inhibit F Xa and F VIIa Mechanism of action: First F Xa + TFPI F Xa-TFPI complex F Xa-TFPI complex + F VIIa-TF complex quartener complexed Mechanism of action of TFPI Fibrinolysis is a physiologic response to the deposition of intra or extra vascular fibrin Function : to destroy fibrin by enzymatic process Consist of : Plasminogen Plasminogen Activator Inhibitor Plasmin : proteolytic enzyme, substrates : fibrin, fibrinogen, V, VIII, hormon, complement PLasminogen : proenzyme of plasmin, found in plasma and other body fluid Plasminogen activator Inhibitor Physiologic plasminogen activators: Tissue-type plasminogen activator (t-PA) Urinary- type plasminogen activator (u-PA) Contact-phase dependent activators: F XIIa, Kallikrein Exogen: Streptokinase (SK) Staphylokinase (SAK) Vampire bat plasminogen activator
Antiplasmin: a 2 plasmin inhibitor a 2 macroglobulin antithrombin a 1 antitrypsin TAFI Transamin Plasminogen activator inhibitor PAI-1 PAI-2 PAI-3 (?)