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Deep vein thrombosis is a major cause of morbidity and mortality worldwide. However, because of the absence of overt blood vessel damage, how venous thrombosis is actually initiated remains unclear. Using endothelialized fluidic devices, we show that aberrant flow patterns that may occur in venous valve pockets of individuals with common stasis-related risk factors can cause the formation of von Willebrand factor–platelet tangles that are resistant to ADAMTS13 removal. These von Willebrand factor–bound platelets specifically recruit neutrophils in a manner that is dependent on platelet-activated α IIb β 3 , neutrophil SLC44A2, and endothelial P-selectin. The interaction of SLC44A2 with activated α IIb β 3 promotes formation of prothrombotic neutrophil extracellular traps. These data provide molecular and cellular insights into the proclivity for venous thrombosis to develop in venous valve pockets and suggest an alternative strategy to protect against the initiation of venous thrombosis.
Mereweather et al. (Wed,) studied this question.