In idiopathic thrombotic thrombocytopenic purpura, which enzyme deficiency is most characteristic?

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Multiple Choice

In idiopathic thrombotic thrombocytopenic purpura, which enzyme deficiency is most characteristic?

ADAMTS13 is the enzyme that normally cleaves ultra-large von Willebrand factor multimers, limiting their capacity to promote platelet adhesion. In idiopathic thrombotic thrombocytopenic purpura, autoantibodies inhibit ADAMTS13, causing a severe deficiency of its activity. Without this cleavage, ultra-large VWF multimers persist and drive widespread platelet aggregation in small vessels, forming microthrombi. This leads to platelets being consumed (thrombocytopenia) and red cells being sheared as they pass through narrowed vessels (microangiopathic hemolytic anemia). That’s why deficiency of ADAMTS13 is characteristic of the condition. The other enzymes listed don’t fit the mechanism: Factor VIII deficiency causes bleeding disorders (hemophilia A) rather than microangiopathic thrombosis; plasminogen deficiency impairs fibrinolysis but doesn’t explain the VWF-mediated microthrombi; Protein C deficiency predisposes to venous thrombosis, not the distinct microvascular thrombosis seen in TTP.

ADAMTS13 is the enzyme that normally cleaves ultra-large von Willebrand factor multimers, limiting their capacity to promote platelet adhesion. In idiopathic thrombotic thrombocytopenic purpura, autoantibodies inhibit ADAMTS13, causing a severe deficiency of its activity. Without this cleavage, ultra-large VWF multimers persist and drive widespread platelet aggregation in small vessels, forming microthrombi. This leads to platelets being consumed (thrombocytopenia) and red cells being sheared as they pass through narrowed vessels (microangiopathic hemolytic anemia). That’s why deficiency of ADAMTS13 is characteristic of the condition. The other enzymes listed don’t fit the mechanism: Factor VIII deficiency causes bleeding disorders (hemophilia A) rather than microangiopathic thrombosis; plasminogen deficiency impairs fibrinolysis but doesn’t explain the VWF-mediated microthrombi; Protein C deficiency predisposes to venous thrombosis, not the distinct microvascular thrombosis seen in TTP.

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