PLATELETS OF PATIENTS WITH PERIPHERAL ARTERIAL-DISEASE DEMONSTRATE A HYPERSENSITIVE RESPONSE TO HEPARIN

We sought to verify earlier reports of increased platelet reactivity i n patients with peripheral arterial disease (PAD) during perioperative heparin administration, and to test the hypothesis of platelet hypers ensitivity to heparin in these patients. Before and after incubation o f platelet rich plasma with unfractionated (UH), low molecular weight heparin (LMWH), and a low molecular weight heparinoid, real-time quant itative assessment of platelet function was performed by stagnation po int flow adhesio-aggregometry (SPAA) in 21 patients with PAD and 14 he althy volunteers. With SPAA the occurrence of spontaneous aggregation is pathological. In the 15 patients requiring operation, platelet func tion and count were measured at regular intervals. To detect heparin d ependent antibodies, the heparin induced platelet activation assay (HI PA) was performed preoperatively and after 10 days of heparin therapy. Mean baseline platelet adhesion in patients was double that observed in controls (p<0.001). Spontaneous aggregation was seen in 9 (43%) pat ients and no controls (p<0.001). In controls heparinoid reduced, where as UH and LMWH slightly increased adhesion. Spontaneous aggregation wa s observed once with UH. Platelets from patients showed significantly enhanced adhesiveness and aggregability (p<0.05) with UH and LMWH when compared to controls. Effects with the heparinoid were less pronounce d and nonsignificant. In patients requiring operation, postoperative i ncreases in platelet function and reductions in count were significant (p<0.001). Ten (67%) experienced a fall in platelet count of >50%. Pr eoperatively the HIPA assay showed no evidence of antibodies, whereas after heparin administration antibodies were verified in 4 (32%) patie nts and could not be ruled out in 6 (40%). Three developed postoperati ve thrombosis, in one case fatal. A hypersensitive in vitro and in viv o platelet response to heparin was verified in patients with PAD and a large number developed the immunological type of heparin-associated t hrombocytopenia. Our findings suggest that a thrombin antagonist which does not interact with platelets may give the best perioperative prot ection in these patients.