Departments of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada.
J Thromb Haemost. 2011 Dec;9(12):2389-96. doi: 10.1111/j.1538-7836.2011.04487.x.
Fondaparinux is theoretically an attractive agent for the treatment of immune heparin-induced thrombocytopenia (HIT), a prothrombotic disorder caused by platelet-activating anti-platelet factor 4/heparin antibodies. Although reports of the use of fondaparinux for this indication have thus far been favorable, the diagnosis of HIT in most cases was not based on definitive laboratory confirmation of heparin-dependent, platelet-activating antibodies.
To report thrombotic and major bleeding outcomes with fondaparinux in patients with a high likelihood of having acute HIT based on clinical features and a positive result in the confirmatory platelet serotonin-release assay (SRA), a sensitive and specific test for platelet-activating HIT antibodies.
METHODS/PATIENTS: We reviewed consecutive eligible patients with SRA-positive HIT (mean peak serotonin release, 91% [normal, < 20%]; mean IgG-specific PF4/heparin enzyme immunoassay result, 2.53 optical density units [normal, < 0.45 units]) in one medical center over a 30-month period who received fondaparinux for anticoagulation during acute HIT (platelet count, < 150 × 10(9) L(-1)). Where available, plasma samples were used to measure thrombin-antithrombin (TAT) complex levels.
Sixteen patients with SRA-positive HIT received fondaparinux: 14 surgical (11 after cardiac surgery; three after vascular surgery) and two medical (acute stroke). Fifty-six per cent of patients had HIT-associated thrombosis at the time of diagnosis. No patient developed new, recurrent or progressive thrombosis; one patient developed a major bleed (calf hematoma). One patient judged to have irreversible tissue necrosis before receiving fondaparinux therapy ultimately required limb amputation. TAT complex levels were reduced within 24 h of starting fondaparinux, and 13 of 13 patients were successfully switched to warfarin.
Fondaparinux shows promise for the treatment of patients with SRA-positive acute HIT.
法安明®在理论上是一种有吸引力的药物，可用于治疗免疫性肝素诱导的血小板减少症（HIT），这是一种由血小板激活的抗血小板因子 4/肝素抗体引起的血栓前疾病。尽管迄今为止，已有报道用法安明®治疗这种疾病，但大多数情况下 HIT 的诊断并非基于对肝素依赖性、血小板激活抗体的明确实验室确认。
报告在基于临床特征和血小板 5-羟色胺释放试验（SRA）阳性的情况下，使用法安明®治疗急性 HIT 患者的血栓形成和大出血结局，该试验是一种用于检测血小板激活性 HIT 抗体的敏感和特异的检测方法。
方法/患者：我们回顾了在一个医疗中心的 30 个月期间，连续入选的 SRA 阳性 HIT 患者（平均最大 5-羟色胺释放率为 91%[正常，<20%]；平均 IgG 特异性 PF4/肝素酶免疫测定结果为 2.53 光密度单位[正常，<0.45 单位]），他们在急性 HIT 期间（血小板计数，<150×10(9) L(-1)）接受了法安明®抗凝治疗。如有可能，使用血浆样本测量凝血酶-抗凝血酶（TAT）复合物水平。
16 例 SRA 阳性 HIT 患者接受了法安明®治疗：14 例为手术患者（11 例为心脏手术后，3 例为血管手术后），2 例为内科患者（急性脑卒中）。56%的患者在诊断时存在 HIT 相关血栓形成。没有患者发生新的、复发的或进行性血栓形成；1 例患者发生了大出血（小腿血肿）。1 例在开始法安明®治疗前被判断为存在不可逆转组织坏死的患者最终需要截肢。在开始使用法安明®后 24 小时内 TAT 复合物水平降低，13 例患者成功转换为华法林。
法安明®在治疗 SRA 阳性急性 HIT 患者方面显示出良好的效果。
