Coagulation an Overview Dr.Abdolreza Abdolr Afrasiabi Thal assem a & Heamophili hilia G ene i tic R esearc C en er Shiraz Medical Medic University

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1 In The Name God

2 Coagulation an Overview Dr.Abdolreza Afrasiabi Thalassemia & Heamophilia Genetic Research hcenter Shiraz Medical University

3 Bleeding Clotting Hemostasis

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5 Review of platelet function Platelets adhere to the site of endothelial injury Activate Aggregate Secrete & promote further platelet recruitment & aggregation vwf binds to the exposed collagen and binds GP Ib IX V complex on the surface of platelet, adhering platelets to the site of injury Fibrinogen and vwf bind to the GP IIb IIIa complex on the activated platelet s surface, allowing cross linking and formation of clot

6 Platelet Function Review Adherence Only Aggregation & Release Direction of Blood Flow

7 Platelet Adherence vwf Gp Ib von Willebrand Disease Gp Ib vwf Bernard-Soulier Syndrome vwf vwf

8 Platelet Release Function Hermansky-Pudlak syndrome DenseGranule ADP Wiskott-Aldrich syndrome ß-thromboglobulin Platelet factor 4 Alpha-granule Gray platelet syndrome Lysosome Chédiak- Higashi anomaly Hydrolase Platelet-derived Growth Factor Fibrinogen Factor V

9 Platelet Aggregation vwf Gp Ib Dense Granule Thrombasthenia Release Defects ADP IIb IIIa D IIb IIIa ADP IIb III IIb IIIa D E Fibrinogen Afibrinogenemia

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11 False Thrombocytosis

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17 Lab Tests: Prothrombin time (PT) and activated Partial Thromboplastin Time (aptt) Intrinsic Pathway XII Prekallikrein HMWK XI IX VIII VII Extrinsic Pathway tissue factor Common Pathway Activated Partial Thromboplastin Time (aptt) X V Prothrombin Time (PT) Prothrombin aptt is initiated i i with Fibrinogen PT is initiated by adding phospholipid (PL), thromboplastin (PL + TF) calcium and silica. and calcium to plasma. nl time to clot = sec. nl time to clot = sec. Fibrin

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22 Yes Stop PTT ( Normal PT ) Heparin therapy or contamination? NO Perform mixing study Correction of PTT No Correction of PTT Factor deficiency Presence of inhibitor

23 Yes Stop Factor VIII : C Factor VIII : Ag Von Willebrand s disease PTT ( Normal PT ) Heparin therapy or contamination? NO Perform mixing study Correction of PTT No Correction of PTT Factor deficiency Presence of inhibitor Normal Factor VIII : C Normal Factor VIII : Ag Factor IX See next page Factor VIII : C Normal Factor VIII : Ag Factor VIII deficiency

24 Yes Stop Factor VIII : C Factor VIII : Ag Von Willebrand s disease Normal Factor IX Factor XI Factor IX Deficiency PTT ( Normal PT ) Heparin therapy or contamination? NO Perform mixing study Correction of PTT No Correction of PTT Factor deficiency Presence of inhibitor Factor XI Normal Factor VIII : C Normal Factor VIII : Factor IX Ag Factor IX deficiency Normal Factor XI HMWK deficiency Prekallikrein deficiency Factor XII deficiency See next page Factor VIII : C Normal Factor VIII : Ag Factor VIII deficiency Factor IX Confirm with appropriate Factor assays

25 Yes Stop PTT ( Normal PT ) Heparin therapy or contamination? NO Perform mixing study Correction of PTT No Correction of PTT Factor deficiency Presence of inhibitor Factor VIII : C Factor VIII : Ag Von Willebrand s disease Normal Factor IX Factor XI Factor IX Deficiency Factor XI Normal Factor VIII : C Normal Factor VIII : Ag Factor IX Factor IX deficiency Normal Factor XI HMWK deficiency Prekallikrein deficiency Factor XII deficiency See next page Factor VIII : C Normal Factor VIII : Ag Factor IX Factor VIII deficiency Confirm with appropriate Factor assays

26 PTT ( Normal PT ) Presence of inhibitor Time dependent Prolongation of PTT with mixing study Perform platelet ltlt neutralization procedure Correction of PTT Lupus anticoagulant Presence of factor inhibitor Factor VIII inhibitor assay ( + ) Factor VIII inhibitor ( + ) Factor IX inhibitor ( - ) Factor IX inhibitor assay ( - ) Consider : Factor I inhibitor Factor II inhibitor Factor V inhibitor Factor X inhibitor Confirm with appropriate factor inhibitor assay

27 Stop Yes PT / PTT Heparin or Varfarin therapy? NO Consider : DIC Liver disease Vitamin K deficiency Known history of liver disease Hypoalbuminemia Increased AST / ALT Stigmata of liver disease Known precipitant p of or condition associated with DIC Fibrinogen Schistocytes on peripheral blood smear D demer Clinical i l presentation tti and laboratory date not consistent with liver disease or DIC Liver disease DIC Consider vitamin K deficiency

28 Stop Yes PT / PTT Heparin or Cournadin therapy? NO Consider : DIC Liver disease Vitamin K deficiency Known history of liver disease Hypoalbuminemia Increased AST / ALT Stigmata of liver disease Known precipitant p of or condition associated with DIC Fibrinogen Schistocytes on peripheral blood smear D demer Clinical i l presentation tti and laboratory date not consistent with liver disease or DIC Liver disease DIC Consider vitamin K deficiency Administer vitamin K Correction of PT / PTT No correction of PT / PTT vitamin K deficiency correction of PT / PTT Factor deficiency Perform mixing study No correction of PT / PTT Presence of inhibitor..

29 Factor deficiency Presence of inhibitor Consider : Factor I deficiency Factor II deficiency Factor V deficiency Factor X deficiency Confirm with appropriate factor assays Consider : Factor I inhibitor Factor II inhibitor Factor V inhibitor Factor X inhibitor Immediate protongation of PTT / PT with mixing study Correction of PTT / PT Perform platelet neutralization procedure Lupus anticoagulant Time dependent prolongation of PTT / PT with mixing study Presence of factor inhabitor Consider : Factor I inhibitor Factor II inhibitor Factor V inhibitor Factor X inhibitor Confirm with appropriate factor assays Confirm with appropriate factor inhibitor assays

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