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Retired NBME 16 Answers

nbme16/Block 4/Question#5 (reveal difficulty score)
A 60-year-old man with no history of bleeding ...
Kallikrein formation ๐Ÿ” / ๐Ÿ“บ / ๐ŸŒณ / ๐Ÿ“–
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submitted by โˆ—cassdawg(1781)
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The key here is this man has no history of bleeding problems yet he has an extremely prolonged PTT (associated with the intrinsic coagulation cascade pathway). This is suggestive that he is deficient in the "unnecessary" factor of the intrinsic pathway, factor XII. (FA2020 p412)

Factor XIIa (Hageman's factor) of the intrinsic pathway activates prekallikrein to kallikrein.

Histamine release, phagocytosis, and C5a generation are not associated with the intrinsic coagulation cascade. Platelet aggregation impairment could be associated with increased PTT (i.e. vWF deficiency, p428), but not that extreme of prolongation without symptoms of bleeding issues.

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the_enigma28  Adding to this, XII activates prekallikrein โ†’ kallikrein. And, kallikrein converts plasminogen โ†’ plasmin. Plasmin causes fibrin degradation. https://upload.wikimedia.org/wikipedia/commons/thumb/2/28/Kinin-Kallikrein_System_Simplified_.jpg/200px-Kinin-Kallikrein_System_Simplified_.jpg +5
victorlt14  So I'm guessing the patient's deficient in HMWK? Is that correct? +
victorlt14  Sorry, now I get it "Factor XII (FXII) is a coagulation protein that is essential for surface-activated blood coagulation tests but whose deficiency is not associated with bleeding. For over forty years, investigators in hemostasis have not considered FXII important because its deficiency is not associated with bleeding. It is because there is a dichotomy between abnormal laboratory assay findings due to FXII deficiency and clinical hemostasis that investigators sought explanations for physiologic hemostasis independent of FXII" https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2851158/ +



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