Inhibitors against factor VIII in patients with cancer: Analysis of 41 patients

Abstract

BACKGROUND. 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. METHODS. 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. RESULTS. 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). CONCLUSIONS. 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. © 2001 American Cancer Society.