Whose action leads to the increased platelet aggregation seen in acquired TTP?

In acquired Thrombotic Thrombocytopenic Purpura (TTP), the inhibition of the ADAMTS-13 enzyme plays a crucial role in the pathophysiology of the condition. ADAMTS-13 is a von Willebrand factor-cleaving protease that regulates the size of von Willebrand factor (vWF) multimers in circulation. When this enzyme is inhibited, either due to the presence of inhibitory antibodies or other mechanisms, the larger, uncleaved vWF multimers accumulate in the bloodstream.

These larger vWF multimers have a higher propensity to bind platelets, promoting excessive platelet aggregation. This process leads to the formation of microthrombi in small blood vessels, which can cause a range of clinical symptoms, including hemolytic anemia and thrombocytopenia. Therefore, the inhibition of the ADAMTS-13 enzyme directly contributes to the increased platelet aggregation associated with acquired TTP by allowing for the accumulation of these pro-aggregatory vWF multimers in the circulation.

Understanding this mechanism is key to grasping the complexities of TTP and the importance of platelet aggregation in its pathogenesis.