lecture 17 introduction to haemostatsis (1).pptx

SECONDARY HAEMOSTASIS & FIBRINOLYSIS By Abdulfatah albakkoush :INTRODUCTION Hemostasis consists of two stages: primary and secondary. platelet-platelet interaction( primary hemostatic plug) platelet-coagulation protein interaction( secondary hemosatic plug). Primary hemostasis: formation of unstab...

SECONDARY HAEMOSTASIS & FIBRINOLYSIS By Abdulfatah albakkoush :INTRODUCTION Hemostasis consists of two stages: primary and secondary. platelet-platelet interaction( primary hemostatic plug) platelet-coagulation protein interaction( secondary hemosatic plug). Primary hemostasis: formation of unstable platelet plug. Secondary hemostasis: reinforcement of unstable platelet plug ( transform the soluble fibrinogen to insoluble fibrin). The platelet-fibrin plug seals the injured vessel preventing blood loss, enabling the vessel to begin to repair itself and initiate fibrinolysis. :COAGULATION MECHANISM • The reaction involved in coagulation in which the circulating inactive coagulation factor precursor or zymogens are activated to their enzyme form. • It involve: interensic pathway, extrinsic pathway and common pathway. • The coagulation factors assigned roman numerals I to XIII The coagulation proteins divided into three groups: 1. Prothrombin group 2. Fibrinogen group 3. Contact group. Vitamin K Dependa nt Factor Common Name Function 1 I Fibrinogen Fibrin precursor 2 II Prothrombin Thrombin precursor 3 III Tissue Factor Cofactor 4 IV Ionized calcium Essential Mineral 5 V Labile Factor Cofactor 7 VII Stable Factor Serine Protease 8 VIII Antihemophilic Factor Cofactor vWF Von Willebrand Factor VIII Carrier & PLT Adhesion 9 IX Christmas Factor Serine Protease 10 X Stuart-Prower Factor Serine Protease 11 XI 12 XII 13 XIII Plasma Thromboplastin Antecedent Serine Protease Hageman Factor Serine Protease Fibrin-stabilizing Factor Transglutaminase Prekallikrein Fletcher Factor Serine Protease HMWK Fitzgerald Factor Cofactor PLT Factor 3 Phosphotidyl Serine Assembly Molecule Aisha NASEF :Prothrombin Group-1 • it include II, VII, IX,X. ( 2 , 7 , 9 , 10 ) It produced in the liver, and all contains γ-carboxyglutamic region for calcium.binding properties of these proteins The prothrombin group is referred as vitaminK dependent because require vitamin K to .be functional :Fibrinogen Group-2 • It includes I,V,VIII and XIII ( 1 , 5 ,8 & 13 ) • -They are not found in serum because they are consumed during coagulation. • 3- contact group: • -It include XI, XII, PK, HK. • The contact group is involved in initial activation of interensic pathway and require contact a negative charged surface for activation. • -It also has a role in the fibrinolysis, kinin and complement system and in inflammatory response. :COAGULATION CASECADE • Most of the coagulation reactions occur on the surface membrane on the activated platelet surface provide the critical phospholipid for coagulation as a result of subendothelial tissue exposed when the blood vessel injury occurs. • it involve interensic pathway, that requires enzymes and proteins cofactors that are all present in plasma. • Extrensic pathway, which requires enzymes and proteins cofactors present in plasma and tissue factors. • common pathway to generate fibrin clot. :INTERENSIC PATHWAY-1 • -it also called contact system pathway. • -its initiated when the four contact factor, XII, XI, PK, HK, are activated when exposed to negatively charged surface such as, glass, kaolin. • Activation of these factors does not require Ca+. • Activation of these contact groups result in activation of factor IX. • -When activated factor IXa forms a complex with cofactor VIIIa and ca on the surface of activated platelet to activate X. • :EXTRINSIC PAHWAY.2 • when the injured vessel occurs ,TF on their surface exposed to blood. • TF bind VII in the presence of Ca+, forming the VIIa/TF complex, once formed converting X to Xa. :COMMON PATHWAY-3 • In this pathway FXa forms a complex with cofactor Va, phospholipid and Ca+ which activate prothrombin to thrombin. Xa/Va/ca+\phospholipid ↓ Prothrombin→thrombin. -thrombin generation cleave fibrinogen to form fibrin. -The fibrin formed is initially unstable. -The final reaction in fibrin formation is the stabiliazation by XIIIa. F VII and Ca2+ in blood interact with (tissue thromboplastin FIII) from injured tissue to activate Hageman factor (XII) Stuart factor (F X). X inactive active Stage I: Formation of prothrombin activator ! CLOT Exposed collagen activates (F XII) that finally result in factor (F X) activation. Hageman factor (XII) X inactive active ! CLOT Hageman factor (XII) X inactive active Activated F X in the presence of Ca 2+ forms complexes with FV to form prothrombin activator ! CLOT :FIBRINOLYTIC SYSTEM • Hemostasis requires not only the formation of a fibrin clot to stop bleeding but also the lysis of the clot following repair to the vessel wall. • -The process of removing fibrin is called fibrinolysis. • -Like the coagulation system, the fibrinolytic system normally acts locally at site of fibrin formation without causing systemic effects. • -Fibrin formation initiate fibrinolysis. • -when clotting begins. Plasminogen bind to fibrin. • -tissue-plasminogen activator(tPA) also binds to fibrin ,converting plasminogen(PLG) to plasmin(PLN). • -plasminogen digests fibrin to soluble degradation products producing fibrin fragments. Aisha NASEF :ERYTHROCYTE INDICES • The erythrocyte indices help classify the erythrocyte as to their size and hemoglobin content. • -Hemoglobin, hematocrit and erythrocyte count values are used to calculate the three indices: • 1-mean cell volume(MCV). • 2-mean corpuscular hemoglobin(MCH). • 3-mean corpuscular hemoglobin concentration.(MCHC) • - these indices used to classify the anemia Aisha NASEF :ERYTHROCYTE INDICES • 1-Mean Cell Volume( MCV): • Its average volume of erythrocyte expressed in femtoliters(fl). • MCV= Htc×1000\RBC • The normal value of MCV: 80-100 fl • -Classification Of Erythrocyte Based On MCV: • 1-Normocytic= MCV: 80-100FL • 2-microcytic= MCV<80 fl • 3-macrocytic= MCV >100fl Aisha NASEF • 2-Mean Corpuscular Hemoglobin(MCH): • Its average weight of hemoglobin in idividual erythrocyte. MCH=Hb×10\ RBC The normal value=28-34pg • 3- Mean Corpuscular Hemoglobin concentration( MCHC): • Its average concentration of hemoglobin in in a deciliter of erythrocyte. MCHC=Hb\ Htc The noraml value=32-36gm\dl classification of erythrocyte based on MCHC: • Normochromic= MCHC; 32-36g\dl • Hypochromic=MCHC<32g\dl • Hyperchromic=MCHC>36g\dl Aisha NASEF