Coagulation and Platelet PDF

Coagulation and Mary Anne Bernas, MD, DPSP Platelet  Outline 1. Overview of Hemostasis 2. Evaluation of hemostasis Bleeding Time Clotting Time APTT, PT, TT  Normal hemostasis Physiologic coagulation of blood with the purpose of prevent...

Coagulation and Mary Anne Bernas, MD, DPSP Platelet  Outline 1. Overview of Hemostasis 2. Evaluation of hemostasis Bleeding Time Clotting Time APTT, PT, TT  Normal hemostasis Physiologic coagulation of blood with the purpose of preventing bleeding  Normal hemostasis COMPONENTS: Vascular Wall (Endothelium) Platelets Coagulation Cascade Fibrinolytic System PRIMARY HEMOSTASIS  ENDOTHELIUM The balance between the anticoagulant and procoagulant activities of endothelium often determines whether clot formation, propagation, or dissolution occurs Endothelial cells are activated by trauma, infectious agents, hemodynamic forces, plasma mediators and cytokines  ENDOTHELIUM PROTHROMBOTIC PROPERTIES Platelet effects Interaction with ECM (vWF) after injury Procoagulant effects Tissue Factor Anti-fibrinolytic effect secrete PAI (plasminogen activator inhibitor)  ENDOTHELIUM ANTI-THROMBOTIC PROPERTIES Antiplatelet effects Intact Endotheium, Prostacyclin, NO Anti-coagulant effects Thrombomodulin, Tissue Factor Pathway Inhibitor Fibrinolytic effects tPA(tissue plasminogen activator)  ENDOTHELIUM ENDOGENOUS ANTICOAGULANTS: - inhibit the activity of 1. Antithrombin III thrombin and other serine proteases (IXa, Xa, 2. Protein C and protein S XIa, and XIIa) 3. Tissue Factor Pathway Inhibitor - activated by binding to heparin-like molecules on endothelial cells  ENDOTHELIUM ENDOGENOUS ANTICOAGULANTS: 1. Antithrombin III - vitamin K–dependent 2. Protein C and protein S proteins that act in a complex to inactivate 3. Tissue Factor Pathway Inhibitor factors Va and VIIIa  ENDOTHELIUM ENDOGENOUS ANTICOAGULANTS: 1. Antithrombin III 2. Protein C and protein S - produced by 3. Tissue Factor Pathway Inhibitor endothelium that inactivates tissue factor–factor VIIa complexes  COAGULATION CASCADE third arm in homeostatic process series of enzymatic conversions, each step proteolytically cleaves an inactive proenzyme into an active enzyme, culminating in thrombin formation  “contact system” FXII auto-activates when associated with a negatively charged surface such as a glass tube and several physiologic substances  Phospholipid bound Allows binding of these proteins to phospholipids and cell membranes (activated)  Act as receptors for coagulation proteins. Accelerate the reactions in which they participate Functions as a substrate of one or more enzymes that participate in their formation and inactivation SECONDARY HEMOSTASIS  SUMMARY Primary Hemostasis (Platelet Plug Formation): 1. Adhesion: platelet to non platelet interaction 2. Platelet shape change and secretion 3. Aggregation: platelet to platelet interaction Secondary Hemostasis (Fibrin Clot Formation): 1. Formation of Thrombin 2. Formation of Stable Fibrin Clot INTRINSIC SYSTEM COMMON PATHWAY  FIBRINOLYTIC SYSTEM Fibrinolysis - process by which cross-linked fibrin is broken down in order to avoid excessive thrombosis Proteins involve in fibrinolysis: ❖ Plasmin - directly degrades fibrin ❖ Plasminogen is an inactive protein (zymogen) made in endothelial cells and found in tissues, urine, plasma, lysosomal granules & vascular endothelium ❖ Tissue plasminogen activator from endothelial cells converts plasminogen to its active form, plasmin FIBRINOLYTIC SYSTEM  FIBRINOLYTIC SYSTEM INHIBITORS OF FIBRINOLYSIS: ❖ Plasminogen activator inhibitor 1 (PAI-1) - rapidly inhibits tPA ❖ a-2-Antiplasmin (a-2-AP) - inactivates plasmin by forming inhibitory complex with circulating plasmin ❖ Thrombin-activatable fibrinolysis inhibitor (TAFI) - cleaves the C-terminal lysine residues of fibrin, preventing the co- activation of plasminogen by fibrin  FIBRINOLYTIC SYSTEM ❖ cascade Evaluation of Hemostasis  Evaluation of Hemostasis Test of the Vascular Platelet Phase: ❖ Bleeding Time Tests of the Coagulation Cascade: ❖ Clotting Time ❖ Activated Partial Thromboplastin Time ❖ Prothrombin Time ❖ Thrombin Time  Bleeding Time O measures the time taken for blood vessel constriction and platelet plug formation O detects defective platelet function O screening tests for acquired and congenital platelet defects  Bleeding Time O DUKE METHOD - earlobe O IVY METHOD - forearm; preferred method pressure & incision can be fairly well standardized allows multiple testing easier control of bleeding if it becomes excessive O do not perform if platelet count is