Coagulation MLS1004 (Student).pdf

HONG KONG METROPOLITAN UNIVERSITY MLS 1004SEF H.LEE Hemostasis 8-2-2024 8/2/2024 LEE YC MLS 1004 SEF 1 Hemostasis 8/2/2024 Heme= blood stasis= to halt Process of retaining blood within the vascular system Repairs injury to blood vessels Stops or prevents blood loss LEE YC MLS 1004 SEF 2 Balance of H...

HONG KONG METROPOLITAN UNIVERSITY MLS 1004SEF H.LEE Hemostasis 8-2-2024 8/2/2024 LEE YC MLS 1004 SEF 1 Hemostasis 8/2/2024 Heme= blood stasis= to halt Process of retaining blood within the vascular system Repairs injury to blood vessels Stops or prevents blood loss LEE YC MLS 1004 SEF 2 Balance of Hemostasis - Balance of bleeding (hemorrhaging) and clotting (thrombosis) - Imbalance in one direction can lead to: bleeding : hypocoagulable state OR thrombosis: hypercoagulable state 8/2/2024 LEE YC MLS 1004 SEF 3 Hemostasis Components 1. Vascular System Controls rate of blood flow 2. Platelet System Interaction of vasculature and platelets form a temporary plug 3. Coagulation System Forms a stable insoluble plug (i.e) fibrin forming 4. Fibrinolytic System Fibrin lysing 5. Coagulation Inhibition System Natural inhibitors Control fibrin formation and fibrin lysis 8/2/2024 LEE YC MLS 1004 SEF 4 Hemostasis Failure or deficiencies in any of the five systems involved with hemostasis can lead to varying degrees of uncontrolled hemorrhaging or clotting 8/2/2024 LEE YC MLS 1004 SEF 5 Hemostasis Three stages of Hemostasis 1. Primary Hemostasis 2. Secondary Hemostasis 3. Fibrinolysis 8/2/2024 LEE YC MLS 1004 SEF 6 Stages of Hemostasis 8/2/2024 LEE YC MLS 1004 SEF 7 Stages of Hemostasis Primary Hemostasis Process of blood clotting in response to vascular injury Blood vessels (vasculature) and platelets are the main “players.” Primary Hemostatic plug is formed Platelet plug temporarily arrests bleeding. Insoluble fibrin strands deposit on the initial plug to reinforce and stabilize. The fibrin originates from soluble plasma proteins. 8/2/2024 LEE YC MLS 1004 SEF 8 Stages of Hemostasis Secondary Hemostasis Actions of the protein coagulation factors form fibrin in response to injury Fibrin is stabilized by Factor XIII At this time, blood has changed into a solid state 8/2/2024 LEE YC MLS 1004 SEF 9 Stages of Hemostasis Fibrinolysis Clot is removed following healing of wound 8/2/2024 LEE YC MLS 1004 SEF 10 Vascular System Following Injury Initiate hemostasis: FIRST RESPONSE Vasoconstriction of the arterioles Minimizes blood flow to injured area Prevents blood loss Delivers platelets and plasma proteins to the vessel wall Immediate Short-lived 8/2/2024 LEE YC MLS 1004 SEF 11 FORMATION OF PRIMARY HEMOSTATIC PLUG Once the platelets “normal” environment is changed, they become activated or adhesive Stages of plug formation Adhesion Secretion Aggregation Stabilization 8/2/2024 LEE YC MLS 1004 SEF 12 8/2/2024 LEE YC MLS 1004 SEF 13 COAGULATION SYSTEM Composed of 3 pathways : 1. Intrinsic Pathways - activate Factor X to Xa 2. Extrinsic Pathways - activate Factor X to Xa 3. Common Pathways - formation of fibrin clot 8/2/2024 LEE YC MLS 1004 SEF 14 COAGULATION SYSTEM Composed of 14 coagulation factors (serine proteases) which are interdependent (Factors I through XIII – there is no Factor VI – and PK and HMWK) ◦ Inactive form of each is an enzyme precursor which is usually designated by a Roman numeral but also given a name – e.g. Factor I fibrinogen. Numbers correspond to order of discovery NOT order in cascade. ◦ Active forms are usually designated by the letter “a” after the Roman numeral and may also have a different name – e.g. Ia Fibrin ◦ Cofactors are needed for many reactions in the cascade – e.g. Calcium, platelet factor 3 (PF3) ◦ Each molecule must be present in sufficient quantity as well as functioning normally Final product is fibrin mesh or clot which completely stops bleeding ◦ Secondary hemostasis Slow contraction or retraction and lysis of the clot occurs 8/2/2024 LEE YC MLS 1004 SEF 15 8/2/2024 LEE YC MLS 1004 SEF 16 FIBRINOLYTIC SYSTEM Fibrin is a product formed during hemostasis, tissue repair or inflammation Once injury heals, the fibrin clot is lysed Plasmin enzymatically attacks the fibrin molecule producing fibrin degradation products (FDPs, sometimes called FSPs) that are cleared from the circulation by macrophages 8/2/2024 LEE YC MLS 1004 SEF 17 COAGULATION INHIBITION SYSTEM Function : To provides balance and control of clotting mechanisms 1. Natural inhibitors and 2. Anticoagulants Which circulate in the plasma to: Prevent clotting when it’s not needed Limit or localize the clotting that is needed Examples: Protein C and S, antithrombin III 8/2/2024 LEE YC MLS 1004 SEF 18 Laboratory Testings 1. Bleeding Time (BT) The bleeding time test is a useful tool to test for platelet plug formation and capillary integrity. 2. Prothrombin time (PT) The Prothrombin time (PT) measures functional activity of the extrinsic and common pathways. 3. Partial thromboplastin time (APTT) The Prothrombin time (PT) measures functional activity of the intrinsic and common pathways. 8/2/2024 LEE YC MLS 1004 SEF 19