General Principles of. Hemostasis. Kristine Krafts, M.D.

Transcription

1 General Principles of Hemostasis Kristine Krafts, M.D.

2 Hemostasis is a balancing act! pro-ting plugs up holes in blood vessels anti-ting keeps ting under control

3 Pro-Clotting

4 Pro-Clotting vessels platelets cascade

5 Pro-Clotting Blood vessel constricts. Blood loss decreases Platelets and factors meet

6 Pro-Clotting Platelets form a plug. Proteins are exposed Platelets adhese Granules release contents Platelets aggregate Phospholipids are exposed

7 Pro-Clotting Fibrin seals up plug. Tissue factor is exposed Cascade begins Cascade makes fibrin Fibrin solidifies plug

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9 Coagulation Cascade XII XI XIIa thrombin VIII IX XIa VIIIa Intrinsic IXa Final common pathway X Extrinsic exposed TF TF VIIa VII V Va Xa prothrombin thrombin fibrinogen fibrin

10 thrombin Intrinsic Extrinsic exposed TF XI VIII IX XIa VIIIa IXa TF VIIa VII X V Va Xa prothrombin thrombin fibrinogen fibrin

11 thrombin Intrinsic Extrinsic exposed TF XI VIII IX XIa VIIIa IXa TF VIIa VII X V Va Xa prothrombin thrombin fibrinogen fibrin

12 thrombin Intrinsic Extrinsic exposed TF XI VIII IX XIa VIIIa IXa TF VIIa VII X V Va Xa prothrombin thrombin fibrinogen fibrin

13 thrombin Intrinsic Extrinsic exposed TF XI VIII IX XIa VIIIa IXa TF VIIa VII X V Va Xa prothrombin thrombin fibrinogen fibrin

14 thrombin Intrinsic Extrinsic exposed TF XI VIII IX XIa VIIIa IXa TF VIIa VII X V Va Xa prothrombin thrombin fibrinogen fibrin

15 Where does tissue factor come from? Hidden cells exposed during injury Microparticles floating in blood Endothelial cells and monocytes (during inflammation)

16 thrombin Intrinsic Extrinsic exposed TF XI VIII IX XIa VIIIa IXa TF VIIa VII X V Va Xa prothrombin thrombin fibrinogen fibrin

17 thrombin Intrinsic Extrinsic exposed TF XI VIII IX XIa VIIIa IXa TF VIIa VII X V Va Xa prothrombin thrombin fibrinogen fibrin

18 thrombin Intrinsic Extrinsic exposed TF XI VIII IX XIa VIIIa IXa TF VIIa VII X V Va Xa prothrombin thrombin fibrinogen fibrin

19 thrombin Intrinsic Extrinsic exposed TF XI VIII IX XIa VIIIa IXa TF VIIa VII X V Va Xa prothrombin thrombin fibrinogen fibrin

20 Intrinsic Extrinsic VIII IX TF VII V X thrombin fibrin

21 tissue factor fibrin

22 busy distracting sinful simple riveting sexy

23 thrombin Intrinsic Extrinsic exposed TF XI VIII IX XIa VIIIa IXa TF VIIa VII X V Va Xa prothrombin thrombin fibrinogen fibrin

24 thrombin SINtrinsic Intrinsic Extrinsic exposed TF XI VIII IX XIa VIIIa IXa TF VIIa VII X V Va Xa busy distracting sinful prothrombin thrombin fibrinogen fibrin

25 thrombin Intrinsic SEXtrinsic Extrinsic exposed TF XI VIII IX XIa VIIIa IXa TF VIIa VII X V Va Xa prothrombin thrombin fibrinogen fibrin simple riveting sexy

26 SINtrinsic SEXtrinsic VIII IX TF VII V X thrombin fibrin

27 Anti-Clotting 1 cascade inhibition

28 thrombin Intrinsic Extrinsic exposed TF TFPI XI VIII IX XIa VIIIa IXa TF VIIa VII X ATIII protein C V Va Xa prothrombin thrombin fibrinogen fibrin

29 Anti-Clotting 1 cascade inhibition TFPI ATIII Proteins C, S 2 lysis

30 Anti-Clotting plasminogen plasmin t-pa

31 Hemostasis Outline The big picture Laboratory tests

32 Platelet Lab Tests Count Done by particle counter x 10 9 /L Morphology Size Granulation

33 Platelets

34 Normal Platelets

35 Bleeding Time Why? Evaluate platelet response to vascular injury Some platelet disorders have a long bleeding time How? Inflate blood pressure cuff Make incision Time how long it takes to stop bleeding Careful! Lots of things affect the test! Some consider the test unreliable.

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37 Coagulation Lab Tests Draw blood into citrate tube Spin tube, decant plasma Add reagents to plasma Watch for formation of fibrin

38 Prothrombin Time Plasma + thromboplastin Measures extrinsic pathway

39 Intrinsic SEXtrinsic VIII IX TF VII V X thrombin fibrin

40 Intrinsic Extrinsic VIII IX TF VII V X thrombin fibrin The PT is increased in: VII, X, V, II, I Coumadin Heparin DIC

41 When should you order a PT? Never! Order an INR instead.

42 What is an INR? Just a corrected PT.

43 When should you order an INR? To assess liver function To monitor Coumadin therapy To diagnose DIC* To assess pre-op status * Disseminated intravascular coagulation

44 Partial Thromboplastin Time Plasma + phospholipid Measures intrinsic pathway APTT = same thing

45 SINtrinsic Extrinsic VIII IX TF VII V X thrombin fibrin

46 Intrinsic Extrinsic VIII IX TF VII V X The PTT is increased in: hemophilia A hemophilia B DIC heparin thrombin fibrin

47 When should you order a PTT? To investigate a history of abnormal bleeding To monitor heparin therapy To diagnose DIC To assess pre-op status

48 Fibrin Degradation Product Assay Measures FDPs (including D-dimers) VERY sensitive!

49 Anti-Clotting

50 Thrombin XIII fibrinogen fibrin cross-linked fibrin

51 fibrinogen fibrin plasmin cross-linked fibrin FDPs D-dimers

52 Anti-Clotting FDPs are increased when there is: A nasty thrombus Minor ting

53 When should you order an FDP assay? Not to rule in a... but to rule out a.