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Jaime Pereira M.D. Department of Hematology-Oncology School of Medicine

BLEEDING AND THROMBOTIC DISORDERS: EVALUATION BY HAEMOSTASIS LABORATORIES Overview of H aemostasis. Jaime Pereira M.D. Department of Hematology-Oncology School of Medicine Pontificia Universidad Católica de Chile.

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Jaime Pereira M.D. Department of Hematology-Oncology School of Medicine

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  1. BLEEDING AND THROMBOTIC DISORDERS: EVALUATION BY HAEMOSTASIS LABORATORIESOverview of Haemostasis Jaime Pereira M.D. Department of Hematology-Oncology School of Medicine Pontificia Universidad Católica de Chile Latin America Confederation of Clinical Biochemistry (COLABIOCLI) Symposium Istanbul 24 June, 2014

  2. Definition Hemostasis is the physiological process that helps to maintain blood in the fluid state and prevent the escape of blood from damaged blood vessels through clot formation

  3. Thehaemostaticsystem Primaryhaemostasis Secondaryhaemostasis Fibrinolysis Haemostasisregulation

  4. Cell-basedmodel of haemostasis

  5. INITIATION X II Va Xa IIa VIIa Xa FT TF-bearingcell IX IXa

  6. TFPI PRIMING Xa VIIa FvW IIa TF-bearingcell FT VIII/FvW XI V Platelet XIa VIIIa Va VIIIa IX Va IXa XIa Activatedplatelet

  7. PROPAGATION X II IXa IX IIa IXa Xa VIIIa XIa Va Activatedplatelet

  8. Intrinsicpathway Extrinsicpathway Contactactivation Tissueinjury Tissue factor (TF) Prothrombin Thrombin Fibrinogen Fibrin

  9. Regulatorymechanisms of haemostasis

  10. - PGI2, NO, CD39 - Extrinsic pathway inhibitor (TFPI) -Antithrombin -Protein C/S system FIBRINOLYSIS INHIBITORS

  11. PGI2 NO Ecto-ADPase (CD39) EC EC VWF Platelets Coagulation PC Thrombin Thrombin TM XaX PS Va, VIIIa FVIIa PCA Antithrombin Heparan TF IXaIX IIa, Xa, XIa, IXa TFPI FVIIa/TF/FXa Prothrombin Fibrinolysis PAI-1 t-PA

  12. Inhibition of plateletfunctionbyendothelialcells cGMP NO cAMP IP A2A NO PGI2 Adenosin ATP/ADP AMP ADPase CD39 CD73 COX

  13. - Thefibrinolyticsystem - PAI t-PA Trombolysis Plasminogen Plasmin FDP 2-antiplasmin Inactive complex

  14. Bloodcoagulationinhibitors

  15. TFPI TFPI

  16. Laboratoryevaluation of haemostasis

  17. Basic study • Primaryhaemostasis • Plateletcount • Bleeding time • “In vitro bleeding time“ • PFA-100® • Secondaryhaemostasis • ActivatedPartialThromboplastin Time (aPTT) • Prothrombin Time (PT) • Thrombin Time

  18. Bleeding time

  19. Low sensitivity of bleeding time for screening mild bleeding disorders 7% 27% 19% 41% 39% 56% 18% (n=299) (n=280) *Normal valuesfor BT: <11min, subjects >6 years; <7min, children <6 años Quiroga T et al, 2007

  20. Low sensitivity of PFA-100® for screening mild bleeding disorders 2% 24% 10% 50% 18% 89% 2% 21% 6% 54% 15% 78% Quiroga T et al, 2004

  21. Fibrinogen Fibrin Thrombin Prothrombin FXII FXIIa FXI FXIa FIX FVIIa TF PL Ca++ FX FIXa PL Ca++ FVIIIa Contact Activ. PL Ca++ Fxa PL Ca++ FVa aPTT

  22. Fibrinogen Fibrin Thrombin Prothrombin FXII FXIIa FXI FXIa FIX FVIIa TF PL Ca++ FX FIXa PL Ca++ FVIIIa PT TF PL Ca++ Fxa PL Ca++ FVa

  23. Fibrinogen Fibrin Thrombin Prothrombin FXII FXIIa FXI FXIa FIX FVIIa FT PL Ca++ FX FIXa PL Ca++ FVIIIa PT TF PL Ca++ Fxa PL Ca++ FVa

  24. Thankyou

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