EVIDENCE THAT FIBRIN ALPHA-CHAIN RGDX SEQUENCES ARE NOT REQUIRED FOR PLATELET-ADHESION IN FLOWING WHOLE-BLOOD

The role of the RGDX putative receptor-recognition sites, which are pr esent on the alpha chains of fibrin, in promoting platelet adhesion ha s been examined in flowing whole blood using the rectangular perfusion chamber at wall shear rates of 340 and 1,600/s, Platelets adhered to a comparable extent to surfaces coated with native fibrin and surfaces coated with fragment X-fibrin, a product of limited fibrinolysis that lacks the RGDS sites normally present at positions 572 to 575 of the alpha chains, The strengths of these adhesive interactions were compar able based on the concentrations of the antiadhesive peptide D-RGDW re quired to block platelet deposition to native and fragment X-fibrin at both low and high wall shear rate, Blocking either or both RGDX seque nces with peptide-specific monoclonal antibodies did not inhibit plate let deposition in perfusion experiments performed with normal blood at 340/s, indicating that neither RGD motif is required for adhesion. Ho wever, adhesion was partly inhibited by anti-RGDX antibodies when perf usions were performed with blood from an afibrinogenemic patient, sugg esting the RGDX sequences may play a limited role in platelet depositi on. Exposure of fibrin surfaces to plasminogen/tissue-type plasminogen activator did cause a time-dependent loss of adhesiveness, but this e ffect was only weakly correlated with proteolysis of the fibrin alpha chains, These observations provide evidence that neither RGDX sequence is required for platelets to adhere avidly to fibrin in flowing blood . These results further suggest that incomplete fibrinolysis yields a highly thrombogenic surface.(C) 1995 by The American Society of Hemato logy.