High-Shear Stress Sensitizes Platelets to Subsequent Low-Shear Conditions
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Individuals with mechanical heart valve implants are plagued by flow-induced thromboembolic complications, which are undoubtedly caused by platelet activation. Flow fields in or around the affected regions involve brief exposure to pathologically high-shear stresses on the order of 100 to 1000 dyne/cm2. Although high shear is known to activate platelets directly, their subsequent behavior is not known. We hypothesize that the post-high-shear activation behavior of platelets is particularly relevant in understanding the increased thrombotic risk associated with blood-recirculating prosthetic cardiovascular devices. Purified platelets were exposed to brief (5–40 s) periods of high-shear stress, and then exposed to longer periods (15–60 min) of low shear. Their activation state was measured using a prothrombinase-based assay. Platelets briefly exposed to an initial high-shear stress (e.g., 60 dyne/cm2 for 40 s) activate a little, but this study shows that they are now sensitized, and when exposed to subsequent low shear stress, they activate at least 20-fold faster than platelets not initially exposed to high shear. The results show that platelets in vitro exposed beyond a threshold of high-shear stress are primed for subsequent activation under normal cardiovascular circulation conditions, and they do not recover from the initial high-shear insult.
KeywordsThrombosis Hemodynamics Shear-induced platelet activation
The authors would like to thank Philip Chiu, Mohammed Hoque, and Thomas Claiborne for their contributions to the experiments in this study. This study was supported by the American Heart Association (Award no. 0340143N, DB) and the National Institutes of Health (Award no. 1R01EB008004-01, DB).
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