PLATELETS OF PATIENTS WITH PERIPHERAL ARTERIAL-DISEASE ARE HYPERSENSITIVE 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 unfractianated (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%) p atients and no controls (p < 0.001). In controls heparinoid reduced, w hereas UH and LMWH slightly increased adhesion. Spontaneous aggregatio n was observed once with UH. Platelets from patients showed significan tly enhanced adhesiveness and aggregability (p < 0.05) with UH and LMW H when compared to controls. Effects with the heparinoid were less pro nounced and non-significant. In patients requiring operation, postoper ative increases in platelet function and reductions in count were sign ificant (p < 0.001). Ten (67%) experienced a fall in platelet count of > 50%. Preoperatively the HIPA assay showed no evidence of antibodies , whereas after heparin administration antibodies were verified in 4 ( 32%) patients and could not be ruled out in 6 (40%). Three developed p ostoperative thrombosis, in one case fatal. A hypersensitive in vitro and in vivo platelet response to heparin was verified in patients with PAD and a large number developed the immunological type of heparin-as sociated thrombocytopenia. Our findings suggest that a thrombin antago nist which does not interact with platelets may give the best perioper ative protection in these patients.