Scott C Kogan MD
@FactorKogan
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Activator of Koagulation Education
San Francisco
Joined April 2014
Also important but less discussed substrates of thrombin include Factor 11 (eleven) and TAFI (Thrombin activatable fibrinolysis inhbitor)
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Thrombin Substrates: So far I mentioned F5 and F8. Other key substrates include Fibrinogen, Platelets, Factor 13 & Protein C.
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Tissue Factor-F7 activates a bit of F9 and F10. F8a-F9a powerfully activates more F10. F5a-F10a powerfully activates thrombin.
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Full activation of thrombin depends on thrombin activating two of its substrates: Factor 8 and Factor 5.
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When a vessel is damaged, Tissue Factor-Factor 7 (F7) complex activates F10 which activates Prothrombin to Thrombin...just a bit at first
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Thrombin (Factor 2) = center of the coagulation universe! How does thrombin get activated? How many substrates of thrombin can you name?
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I would like to welcome all the new residents to UCSF's Anatomic and Clinical Pathology Program. Do you recognize this cell?
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What's wrong with high molecular weight vWF multimers in 2A/2B/2M (simplified)? A=absent, B=bound (to plts), M=messed up (don't bind plts)
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vWD Dx point: If vWF Ristocetin cofactor activity: vWF antigen ratio is low, this can reflect type 2A, 2B, or 2M.
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Thrombin time= underutilized test. Terrific for picking up presence of thrombin inhibitors: heparin, DTIs, paraneoplastic heparinoid.
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A surprising aspect of vWD is that the null alleles associated with type 3 do not cause type 1 when they are heterozygous: 50% VWF is enough
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Factor inhibitors can be quantified in Bethesda Units. Patient & Normal plasma are mixed. 1 BU = Amount that inhibits half of Factor present
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Welcoming new Trainees at UCSF for another year! Coag tweets to follow!!
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Thrombin Sbstrt A4=F11.Thrombin activation of F11 maintains thrombin generation following major injury and in tissues with high fibrinolysis
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Back to Thrombin Substrates. A2/A3: Factors 5 & 8 (the critical cofactors of Factors 10 & 9). Primary amplification for thrombin generation
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Fondaparinux. In the unlikely event that a level will be checked, 3 hours post dose is suggested (as compared to 4 hours post dose for LMWH)
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This anticoagulant medication is a pentasaccharide that will interact with antithrombin and inhibit Factor10a and F9a. Name it.
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Thrombin Substrates? A1-part 2: Fibrinogen. Fibrinogen is also substrate for platelet binding through gpIIbIIIa receptor.
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Thrombin Substrates? A1: Fibrinogen. Converted to Fibrin. Fibrin monomers polymerize to fibrin clot.
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