Sallah S, Wan J Y
Department of Medicine, Division of Hematology/Oncology, University of Tennessee, Memphis, Tennessee 38103, USA.
Cancer. 2001 Mar 15;91(6):1067-74. doi: 10.1002/1097-0142(20010315)91:6<1067::aid-cncr1101>3.0.co;2-4.
The spontaneous formation of neutralizing antibodies (inhibitors) to factor VIII (FVIII) in patients with cancer is a well known phenomenon. However, to the authors' knowledge there is lack of information in the literature with respect to the clinical course of these patients and the nature of the association between malignant tumors and acquired hemophilia.
A retrospective study of 41 patients with cancer and acquired hemophilia was conducted. The patients were identified through a MEDLINE search between 1974-2000. All patients had detailed clinical and laboratory information available and descriptions of the course of the inhibitor in relation to cancer treatment. The patients were divided into two groups: responders and nonresponders. The stage of the tumor, inhibitor titer, FVIII level, and survival data were examined and compared between the two groups.
A total of 63 hemorrhagic episodes were reported in 25 patients with solid tumors and 16 patients with hematologic malignancies. The median inhibitor titer at the time of the diagnosis of acquired hemophilia was 14 Bethesda units (BU) (range, 1-435 BU). The complete response (CR) rate to treatment of the inhibitor was 70% and patients who achieved a CR were more likely to have early stage tumors (P = 0.0007) and a lower median inhibitor titer at the time of presentation compared with nonresponders (12 BU vs. 78 BU; P = 0.007). The overall survival was significantly higher in patients who achieved a CR compared with patients with a persistent inhibitor (75% vs. 17%; P = 0.0006).
Although it remains an uncommon occurrence, the development of inhibitors to FVIII should be considered as a cause of bleeding in some patients with malignant diseases. Because of the high response rate and the impact of this type of hemorrhage on cancer patients, efforts should be directed toward immunosuppression of the inhibitor in a fashion similar to that used in other patients with acquired hemophilia. To our knowledge the link between malignancy and the formation of antibodies to FVIII is unclear; however, it appears that treatment of cancer with chemotherapy or surgery may accelerate the eradication of the inhibitor in some patients. Long term prospective studies are needed to better assess the association between cancer and acquired hemophilia.
癌症患者体内自发形成针对凝血因子 VIII（FVIII）的中和抗体（抑制物）是一种众所周知的现象。然而，据作者所知，文献中缺乏关于这些患者临床病程以及恶性肿瘤与获得性血友病之间关联性质的信息。
对 41 例患有癌症和获得性血友病的患者进行了一项回顾性研究。通过 1974 年至 2000 年间的 MEDLINE 检索确定了这些患者。所有患者均有详细的临床和实验室信息，以及关于抑制物与癌症治疗相关病程的描述。将患者分为两组：反应者和无反应者。对两组患者的肿瘤分期、抑制物滴度、FVIII 水平和生存数据进行了检查和比较。
25 例实体瘤患者和 16 例血液系统恶性肿瘤患者共报告了 63 次出血事件。获得性血友病诊断时抑制物的中位滴度为 14 贝塞斯达单位（BU）（范围为 1 - 435 BU）。抑制物治疗的完全缓解（CR）率为 70%，与无反应者相比，达到 CR 的患者更可能患有早期肿瘤（P = 0.0007），且就诊时抑制物的中位滴度较低（12 BU 对 78 BU；P = 0.007）。与抑制物持续存在的患者相比，达到 CR 的患者总体生存率显著更高（75%对 17%；P = 0.0006）。
尽管 FVIII 抑制物的出现仍然不常见，但在一些恶性疾病患者中，应将其视为出血的一个原因。由于这种出血类型对癌症患者的高反应率和影响，应采取类似于其他获得性血友病患者的方式对抑制物进行免疫抑制。据我们所知，恶性肿瘤与 FVIII 抗体形成之间的联系尚不清楚；然而，化疗或手术治疗癌症似乎可能在一些患者中加速抑制物的清除。需要进行长期前瞻性研究以更好地评估癌症与获得性血友病之间的关联。
