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General Principles of Hemostasis Kristine Krafts, M.D.
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Hemostasis is a balancing act!
pro-clotting anti-clotting plugs up holes in blood vessels keeps clotting under control
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Pro-Clotting clot
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Pro-Clotting vessels platelets cascade
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Pro-Clotting Blood vessel constricts. Blood loss decreases
Platelets and factors meet
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Pro-Clotting Platelets form a plug. Proteins are exposed
Platelets adhese Granules release contents Platelets aggregate Phospholipids are exposed
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Pro-Clotting Fibrin seals up plug. Tissue factor is exposed
Cascade begins Cascade makes fibrin Fibrin solidifies plug
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Platelets Tissue factor Fibrin
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Anti-Clotting clot
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Anti-Clotting clot 1 cascade inhibition TFPI ATIII Proteins C, S
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clot Anti-Clotting 1 cascade inhibition TFPI ATIII Proteins C, S 2
clot lysis t-PA plasmin
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Platelets
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Platelet activation
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clot Coagulation Cascade Intrinsic Extrinsic Xa prothrombin thrombin
exposed TF XII XIIa XI XIa TF VIIa IX IXa VII VIII VIIIa Final common pathway X V Va Xa prothrombin thrombin clot fibrinogen fibrin
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clot Intrinsic Extrinsic Xa prothrombin thrombin fibrinogen fibrin
exposed TF XI XIa TF VIIa IX IXa VII VIII VIIIa X V Va Xa prothrombin thrombin clot fibrinogen fibrin
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clot Intrinsic Extrinsic Xa prothrombin thrombin fibrinogen fibrin
exposed TF XI XIa TF VIIa IX IXa VII VIII VIIIa X V Va Xa prothrombin thrombin clot fibrinogen fibrin
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clot Intrinsic Extrinsic Xa prothrombin thrombin fibrinogen fibrin
exposed TF XI XIa TF VIIa IX IXa VII VIII VIIIa X V Va Xa prothrombin thrombin clot fibrinogen fibrin
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clot Intrinsic Extrinsic Xa prothrombin thrombin fibrinogen fibrin
exposed TF XI XIa TF VIIa IX IXa VII VIII VIIIa X V Va Xa prothrombin thrombin clot fibrinogen fibrin
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clot Intrinsic Extrinsic Xa prothrombin thrombin fibrinogen fibrin
exposed TF XI XIa TF VIIa IX IXa VII VIII VIIIa X V Va Xa prothrombin thrombin clot fibrinogen fibrin
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Where does tissue factor come from?
“Hidden” cells exposed during injury Microparticles floating in blood Endothelial cells and monocytes (during inflammation)
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clot Intrinsic Extrinsic Xa prothrombin thrombin fibrinogen fibrin
exposed TF XI XIa TF VIIa IX IXa VII VIII VIIIa X V Va Xa prothrombin thrombin clot fibrinogen fibrin
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clot Intrinsic Extrinsic Xa prothrombin thrombin fibrinogen fibrin
exposed TF XI XIa TF VIIa IX IXa VII VIII VIIIa X V Va Xa prothrombin thrombin clot fibrinogen fibrin
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clot Intrinsic Extrinsic Xa prothrombin thrombin fibrinogen fibrin
exposed TF XI XIa TF VIIa IX IXa VII VIII VIIIa X V Va Xa prothrombin thrombin clot fibrinogen fibrin
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clot Intrinsic Extrinsic Xa prothrombin thrombin fibrinogen fibrin
exposed TF XI XIa TF VIIa IX IXa VII VIII VIIIa X V Va Xa prothrombin thrombin clot fibrinogen fibrin
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Intrinsic Extrinsic TF VII IX VIII X V thrombin fibrin clot
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tissue factor fibrin clot
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busy simple distracting riveting sinful sexy
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clot Intrinsic Extrinsic Xa prothrombin thrombin fibrinogen fibrin
exposed TF XI XIa TF VIIa IX IXa VII VIII VIIIa X V Va Xa prothrombin thrombin clot fibrinogen fibrin
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SINtrinsic clot Intrinsic Extrinsic Xa prothrombin thrombin busy
exposed TF XI XIa TF VIIa IX IXa VII VIII VIIIa X V Va Xa prothrombin thrombin busy clot fibrinogen fibrin distracting sinful
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SEXtrinsic clot Intrinsic Extrinsic Xa prothrombin thrombin simple
exposed TF XI XIa TF VIIa IX IXa VII VIII VIIIa X V Va Xa prothrombin thrombin simple fibrinogen fibrin riveting sexy clot
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SINtrinsic SEXtrinsic TF VII IX VIII X V thrombin fibrin clot
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Anti-Clotting fibrinogen fibrin clot FDPs
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Anti-Clotting fibrinogen fibrin clot FDPs plasminogen plasmin t-PA
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clot Intrinsic Extrinsic Xa prothrombin thrombin fibrinogen fibrin
TFPI thrombin exposed TF XI XIa ATIII TF VIIa IX IXa VII VIII VIIIa protein C X V Va Xa prothrombin thrombin clot fibrinogen fibrin
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Hemostasis Outline The big picture Laboratory tests
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Platelet Lab Tests Count Morphology Done by particle counter
150 – 450 x 109/L Morphology Size Granulation
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Platelets
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Normal Platelets
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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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Coagulation Lab Tests Draw blood into citrate tube
Spin tube, decant plasma Add reagents to plasma Watch for formation of fibrin
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Prothrombin Time Plasma + thromboplastin Measures extrinsic pathway
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Intrinsic Extrinsic TF VII IX VIII X V thrombin fibrin clot
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Intrinsic Extrinsic TF VII IX VIII X V thrombin fibrin clot
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SINtrinsic SEXtrinsic TF VII IX VIII X V thrombin fibrin clot
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clot Intrinsic Extrinsic X thrombin PT increased VII, X, V, II, I
TF VII IX VIII X V thrombin PT increased VII, X, V, II, I Coumadin Heparin DIC fibrin clot
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When should you order a PT?
Never! Order an INR instead.
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What is an INR? Just a corrected PT.
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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
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Partial Thromboplastin Time
Plasma + phospholipid Measures intrinsic pathway APTT = same thing
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Intrinsic Extrinsic TF VII IX VIII X V thrombin fibrin clot
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Intrinsic Extrinsic TF VII IX VIII X V thrombin fibrin clot
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SINtrinsic SEXtrinsic TF VII IX VIII X V thrombin fibrin clot
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clot Intrinsic Extrinsic X PTT increased: hemophilia A thrombin
TF VII IX VIII X V PTT increased: hemophilia A hemophilia B DIC heparin thrombin fibrin clot
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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
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Fibrin Degradation Product Assay
Measures FDPs (including D-dimers) VERY sensitive!
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Anti-Clotting clot
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Thrombin XIII cross-linked fibrin fibrinogen fibrin
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cross-linked fibrin fibrinogen fibrin plasmin FDPs D-dimers
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Anti-Clotting clot FDPs increased: Thrombi Minor clotting
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When should you order an FDP assay?
Not to rule in a clot... but to rule out a clot.
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