Lecture 7: Hemostasis and Fibrinolysis PDF

21-Feb-23 LECTURE 7 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 the unstable platelet plug. • Secondary he...

21-Feb-23 LECTURE 7 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 the 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. 21-Feb-23 LECTURE 7 COAGULATION MECHANISM: •The reaction involved in coagulation in which the circulating inactive coagulation factor precursor or zymogens are activated to their enzyme form. •It involves intrinsic pathways, extrinsic pathways, and common pathways. •The coagulation factors assigned roman numerals I to XIII The coagulation proteins are divided into three groups: 1. Prothrombin group 2. Fibrinogen group COAGULATION PROTEIN : Vitamin K Dependant 3. Contact group. 21-Feb-23 LECTURE 7 1-PROTHROMBIN GROUP: •it include II, VII, IX,X. ( 2 , 7 , 9 , 10 ) -It is produced in the liver, and all contain γ-carboxy glutamic region for calcium-binding properties of these proteins. -The prothrombin group is referred to as vitamin K dependent because it requires it to be functional. 2-FIBRINOGEN GROUP: •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 includes XI, XII, PK, and HK. •The contact group is involved in the initial activation of the intrinsic pathway and requires contact with a negatively charged surface for activation. •-It also has a role in the fibrinolysis, kinin, and complement system and in the inflammatory response. 21-Feb-23 LECTURE 7 COAGULATION CASECADE: •Most of the coagulation reactions occur on the surface membrane on the activated platelet surface providing the critical phospholipid for coagulation as a result of subendothelial tissue exposed when the blood vessel injury occurs. •it involves an intrinsic pathway, that requires enzymes and protein cofactors that are all present in plasma. •Extrensic pathway, which requires enzymes and protein cofactors present in plasma and tissue factors. •common pathway to generate fibrin clot. 1-INTERENSIC PATHWAY: •it is also called the contact system pathway. •-it's initiated when the four contact factors, XII, XI, PK, and HK, are activated when exposed to a negatively charged surface such as glass, or kaolin. •Activation of these factors does not require Ca+. •Activation of these contact groups results 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. 21-Feb-23 LECTURE 7 2.EXTRINSIC PAHWAY: when the injured vessel occurs, TF on its surface is exposed to blood. TF binds VII in the presence of Ca+, forming the VIIa/TF complex, once formed converting X to Xa. 3-COMMON PATHWAY: •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 cleaves fibrinogen to form fibrin. -The fibrin formed is initially unstable. -The final reaction in fibrin formation is the stabilization by XIIIa. 21-Feb-23 LECTURE 7 F VII AND CA2+ IN BLOOD INTERACT WITH (TISSUE THROMBOPLASTIN FIII) FROM INJURED TISSUE TO ACTIVATE Exposed collagen activates (F XII) that finally result in factor (F X) activation. 21-Feb-23 LECTURE 7 Activated F X in the presence of Ca 2+ forms complexes with FV to form prothrombin activator 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 the site of fibrin formation without causing systemic effects. 21-Feb-23 LECTURE 7 FIBRINOLYTIC SYSTEM: •Fibrin formation initiates fibrinolysis. •when clotting begins. Plasminogen binds to fibrin. •tissue-plasminogenactivator(tPA) also binds to fibrin ,converting plasminogen(PLG) to plasmin(PLN). •-plasminogen digests fibrin to soluble degradation products producing fibrin fragments. 21-Feb-23 LECTURE 7 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 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 21-Feb-23 LECTURE 7 ERYTHROCYTE INDICES: •2-Mean Corpuscular Hemoglobin(MCH): •Its average weight of hemoglobin in individual erythrocytes. MCH=Hb×10\ RBC The normal value=28-34pg ERYTHROCYTE INDICES: •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