Abstract
BackgroundIncreased platelet reactivity has been implicated in cardiovascular disease – the major cause of death in patients with end stage renal disease (ESRD). FcGammaRIIA is a component of glycoprotein VI and Ib-IX-V that mediate activation of platelets by collagen and von Willebrand factor. To determine whether expression of FcGammaRIIA impacts platelet reactivity we quantified its expression and platelet reactivity in 33 patients with ESRD who were undergoing hemodialysis.MethodsBlood samples were obtained from patients immediately before hemodialysis and before administration of heparin. Platelet expression of FcGammaRIIA and the activation of platelets in response to low concentrations of convulxin (1 ng/ml, selected to mimic effects of collagen), thrombin (1 nM), adenosine diphosphate (ADP, 0.2 uM), or platelet activating factor (PAF, 1 nM) were determined with the use of flow cytometry in samples of whole blood anticoagulated with corn trypsin inhibitor (a specific inhibitor of Factor XIIa).ResultsPatients were stratified with respect to the median expression of FcGammaRIIA. Patients with high platelet expression of FcGammaRIIA exhibited 3-fold greater platelet reactivity compared with that in those with low expression in response to convulxin (p < 0.01) and 2-fold greater activation in response to thrombin, ADP, and PAF (p < 0.05 for each). For each agonist, expression of FcGammaRIIA correlated modestly but positively with platelet reactivity. The strongest correlation was with thrombin-induced activation (r = 0.6, p < 0.001).ConclusionIncreased platelet reactivity in response to low concentrations of diverse agonists is associated with high expression of FcGammaRIIA and may contribute to an increased risk of thrombosis in patients with ESRD.
Highlights
Increased platelet reactivity has been implicated in cardiovascular disease – the major cause of death in patients with end stage renal disease (ESRD)
Our results demonstrating an association between greater platelet expression of FcγRIIa and increased platelet reactivity are consistent with a previous report demonstrating that increased expression of FcγRIIa is associated with a greater risk of arterial thrombotic events in patients with ESRD [13]
We found that patients with ESRD treated with hemodialysis who exhibit high platelet expression of FcγRIIa exhibit increased platelet reactivity
Summary
Increased platelet reactivity has been implicated in cardiovascular disease – the major cause of death in patients with end stage renal disease (ESRD). FcGammaRIIA is a component of glycoprotein VI and Ib-IX-V that mediate activation of platelets by collagen and von Willebrand factor. One factor contributing to a greater risk of cardiovascular disease and death in patients with ESRD may be increased platelet reactivity. Increased platelet expression of FcγRIIa has been seen in patients with diabetes [12] and ESRD [13], conditions known to be at an increased risk for cardiovascular disease. Increased expression has been observed in patients who have experienced coronary or cerebral thrombosis [14] and was associated with a greater incidence of arterial thrombotic events in patients with ESRD [13]. FcγRIIa appears to participate in thrombotic complications associated with the severe form of heparin-induced thrombocytopenia/thrombosis (HITT) [15]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
