Reininger C B, Greinacher A, Eibl-Eibesfeldt B, Lasser R, Steckmeier B, Schweiberer L
Chirurgische Klinik und Poliklinik Innenstadt, Ludwig-Maximilians-Universität München, Germany.
Int Angiol. 1996 Sep;15(3):207-14.
We sought to verify earlier reports of increased platelet reactivity in patients with peripheral arterial disease (PAD) during perioperative heparin administration, and to test the hypothesis of platelet hypersensitivity to heparin in these patients. Before and after incubation of platelet rich plasma with unfractionated (UH), low molecular weight heparin (LMWH), and a low molecular weight heparinoid, real-time quantitative assessment of platelet function was performed by stagnation point flow adhesio-aggregometry (SPAA) in 21 patients with PAD and 14 healthy volunteers. With SPAA the occurrence of spontaneous aggregation is pathological. In the 15 patients requiring operation, platelet function and count were measured at regular intervals. To detect heparin dependent antibodies, the heparin induced platelet activation assay (HIPA) 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%) patients and no controls (p < 0.001). In controls heparinoid reduced, whereas UH and LMWH slightly increased adhesion. Spontaneous aggregation was 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 pronounced and nonsignificant. In patients requiring operation, postoperative increases in platelet function and reductions in count were significant (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 postoperative 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-associated thrombocytopenia. Our findings suggest that a thrombin antagonist which does not interact with platelets may give the best perioperative protection in these patients.
我们试图验证早期关于外周动脉疾病（PAD）患者围手术期使用肝素期间血小板反应性增加的报道，并检验这些患者对肝素血小板超敏反应的假说。将富含血小板血浆与普通肝素（UH）、低分子量肝素（LMWH）和一种低分子量类肝素孵育前后，通过驻点流黏附聚集测定法（SPAA）对21例PAD患者和14名健康志愿者的血小板功能进行实时定量评估。采用SPAA时，自发聚集的出现是病理性的。在15例需要手术的患者中，定期测量血小板功能和计数。为检测肝素依赖性抗体，术前及肝素治疗10天后进行肝素诱导的血小板活化试验（HIPA）。患者的平均基线血小板黏附率是对照组的两倍（p<0.001）。9例（43%）患者出现自发聚集，而对照组未出现（p<0.001）。在对照组中，类肝素降低了黏附率，而UH和LMWH则使黏附率略有增加。使用UH时观察到1次自发聚集。与对照组相比，患者的血小板与UH和LMWH一起时显示出显著增强的黏附性和聚集性（p<0.05）。类肝素的作用不太明显且无统计学意义。在需要手术的患者中，术后血小板功能增加和计数减少具有显著性（p<0.001）。10例（67%）患者血小板计数下降>50%。术前HIPA试验未显示抗体证据，而肝素给药后4例（32%）患者证实有抗体，6例（40%）不能排除有抗体。3例发生术后血栓形成，1例死亡。已证实PAD患者体外和体内对肝素存在超敏血小板反应，并且大量患者发生免疫型肝素相关性血小板减少症。我们的研究结果表明，一种不与血小板相互作用的凝血酶拮抗剂可能为这些患者提供最佳的围手术期保护。
