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MLAB 1227: Coagulation Keri Brophy-Martinez

MLAB 1227: Coagulation Keri Brophy-Martinez. Secondary Hemostasis Part Two. Coagulation Cascade. Consists of four interacting sets of reactions Complex formation on phospholipid membranes Intrinsic pathway activation Activated by trauma within vascular system where endothelium is exposed

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MLAB 1227: Coagulation Keri Brophy-Martinez

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  1. MLAB 1227: CoagulationKeri Brophy-Martinez Secondary Hemostasis Part Two

  2. Coagulation Cascade • Consists of four interacting sets of reactions • Complex formation on phospholipid membranes • Intrinsic pathway activation • Activated by trauma within vascular system where endothelium is exposed • Slow • Utilizes enzymes and proteins present in the plasma • Extrinsic pathway activation • Activation occurs when TF enters the vascular system • Fast • Utilizes enzymes and proteins present in the plasma and TF • Common pathway

  3. Complex formation • Cascade occurs on cell surface membranes • Subendothelial tissue and activated platelet surfaces provide the phospholipid • Clotting factors bind to phospholipid membrane surface, which forms a complex of enzyme, substrate and cofactor

  4. Intrinsic Pathway Activation • Contact factors: • Factors XII, XI, PK and HK • Interaction of contact factors activate Factor X • Activated in vitro, when exposed to and bound to negatively-charged surfaces, such as glass, kaolin, celite and ellagic acid • Does not require Ca++ • Purpose • Generation of Thromboplastic Activity

  5. Intrinsic System: Next steps • XII is activated • XIIa activates PK which loops back and activates more XII • XIIa and HK convert XI to XIa • XIa and Ca++ ions covert IX to IXa • IXa forms a complex with PF3 (from platelet membrane), Ca++ and VIII to activate X

  6. Intrinsic Pathway: Coagulation Factors • Factor XII – Hageman Factor, Contact Factor • Produced in liver • Activated by negatively charged substances such as exposed collagen. In vitro it is also activated by glass • XIIa has several functions (which are aided by cofactor HMWK) • activates XI • converts prekallikrein (PK) to kallikrein to make more XII • activates plasminogen in the fibrinolytic system • Deficiencies of this factor causes no coagulation problems

  7. Intrinsic Pathway: Coagulation Factors • Prekallikrein (PK), Fletcher Factor • Produced in liver • Circulates in plasma bound to HK • PK is converted to kallikrein and has several functions: • when converted to kallikrein by Factor XII it then loops back and accelerates the activation of larger amounts of Factor XII • converts HK to kinins • activates plasminogen • activates the complement system • acts as a chemoattractant factor to attract macrophages

  8. Intrinsic Pathway: Coagulation Factors • High molecular weight kininogen (HMWK/HK), Fitzgerald Factor • Produced in liver • HMWK has several functions • Acts as a cofactor with Factor XII to • activate Factor XI • convert Prekallikrein (PK) to kallikrein • activating plasminogen • Is converted to kinins by kallikrein which cause • inflammatory reactions • Pain

  9. Intrinsic Pathway: Coagulation Factors • Factor XI – Plasma Thromboplastin Antecedent (PTA), Rosenthal's antihemophilic C factor • Produced in liver • HK is needed as a cofactor with XII for its activation • Can also be activated by thrombin • Needed for formation of plasma thromboplastin

  10. Intrinsic Pathway: Coagulation Factors • Factor IX – Antihemophilic B Factor, Plasma Thromboplastin Component (PTC), Christmas Factor • Produced in liver • Vitamin K dependent • Necessary to form plasma thromboplastin

  11. Intrinsic Pathway: Coagulation Factors • Factor VIII – Antihemophilic A Factor • MW = >1,000,000 (composed of several parts) • Has two functional subunits: VIII:C and VIII:vWF (VIII:Ag and VIII:R) • VIII:vWF Produced in endothelial cells and platelets; VIII:C production site unknown • Necessary for formation of plasma thromboplastin • Abnormalities of Factor VIII are the most common hereditary coagulation disorders (hemophilia A and vonWillebrands) • Increased in pregnancy & inflammation • Consumed during coagulation, not found in serum • Heat labile: Deteriorates rapidly in stored plasma

  12. Intrinsic Pathway • Monitored by the Activated Partial Thromboplastin Time (APTT) • Detects abnormalities to factor VIII, IX, XI, XII • Monitors heparin therapy

  13. McKenzie, Shirlyn B., and J. Lynne. Williams. "Chapter 30." Clinical Laboratory Hematology. Boston: Pearson, 2010. Print. References

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