What is the probable cause for thrombotic thrombocytopenic purpura?
a. Deficiency of a metalloprotease needed to enzymatically degrade unusually large von Willebrand factor (VWF) multimers
b. Abnormal synthesis of unusually large VWF multimers by endothelial cells
c. Abnormal synthesis of unusually large VWF multimers by megakaryocytes
d. Abnormal complexing of normal VWF multimers to create unusually large VWF multimers
ANS: A
Patients with the more common form of thrombotic thrombocytopenic purpura are deficient in a metalloprotease (ADAMTS 13) needed to cleave unusually large VWF into the smaller VWF multimers normally found in plasma. Both endothelial cells and megakaryocytes normally make these unusually large VWF multimers.
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