White P W, Sadd J R, Nensel R E
Ann Surg. 1979 Nov;190(5):595-608. doi: 10.1097/00000658-197911000-00007.
Thrombotic complications of heparin administration were observed in eight patients during a two year period. At sites of subcutaneous heparin injection, six patients developed areas of the skin and subcutaneous necrosis. Systemic thrombotic events and thrombocytopenia were observed in two of these patients when they received intravenous heparin and in two other patients who did not have primary skin necrosis. The complications included peripheral ischemia in three patients (two requiring amputation), myocardial infarction in two, and a cerebral infarction in one. All patients were receiving heparin for at least six days before complications occurred. Seven patients received heparin of bovine origin. Heparin-induced in vitro platelet aggregation was present in all six of the eight patients tested. (It was marked in four of these patients). It is theorized that skin necrosis and the other thrombotic complications observed are the result of heparin-induced in vivo platelet aggregation followed by intravascular thrombosis. Heparin-induced skin necrosis is a rare but serious hazard encountered with prophylactic heparin regimens. If heparin-induced thrombosis is present, the further use of heparin is contraindicated in most instances.
在两年期间,观察到8例患者在使用肝素时出现血栓形成并发症。在皮下注射肝素的部位,6例患者出现皮肤和皮下组织坏死区域。其中2例患者在接受静脉注射肝素时出现全身血栓形成事件和血小板减少症,另外2例没有原发性皮肤坏死的患者也出现了这种情况。并发症包括3例患者出现外周缺血(2例需要截肢)、2例心肌梗死和1例脑梗死。所有患者在并发症发生前至少接受肝素治疗6天。7例患者接受的是牛源性肝素。在接受检测的8例患者中的6例(其中4例表现明显)体内均出现肝素诱导的血小板聚集。据推测,观察到的皮肤坏死和其他血栓形成并发症是肝素诱导的体内血小板聚集继而导致血管内血栓形成的结果。肝素诱导的皮肤坏死是预防性肝素治疗方案中罕见但严重的风险。如果存在肝素诱导的血栓形成,在大多数情况下应禁忌进一步使用肝素。