Postoperative paraneoplastic factor VIII auto‐antibodies in patients with solid tumours

Abstract

Paraneoplastic FVIII antibodies may occur concurrent with the diagnosis or at various times after diagnosis and treatment of cancer. Between 2002 and 2009, we observed two patients with acquired haemophilia A due to an FVIII auto-antibody, which appeared 4 and 5 months after uncomplicated cancer surgery. We aimed to evaluate if such an association of cancer surgery and FVIII antibody formation has been observed previously. We retrieved all published case reports of cancer-associated FVIII auto-antibodies from PubMed for the period 1950-2010. The search in the literature revealed 13 patients in whom a FVIII inhibitor developed after uncomplicated surgery for cancer and a bleeding-free time interval of up to 6 months; 11/15 patients had abdominal cancers (five colon cancer, four pancreatic cancer, gastric cancer and choledochus carcinoma one each). The median time period between surgery and antibody detection was 3 months (1 week-6 months). In most cases, the antibody titre was low (median: 14 BU mL⁻¹, range: 1.7-64 BU mL⁻¹). Immunosuppressive treatment was successful in most of the cases - nine of the treated patients reached a sustained CR of the antibody after a median time of 3 months. Postoperative paraneoplastic FVIII inhibitors may be regarded as a special, not yet recognized subgroup of acquired FVIII antibodies. They share some characteristics with postpartum FVIII inhibitors with regard to the latency period between the triggering event and the appearance of the antibody, and between the usually low antibody titres and their good response to immunosuppressive treatment.

Myelofibrosis and acquired hemophilia A: a case report

“…Immune dysfunction in patients with a tumor may result in the development of AAFVIIIs. Alternatively, it is possible that FVIII autoantibodies are triggered by cancer cells or cancer cell products, which possibly contain antigen material similar to FVIII [ 14 ].…”

“The Immune Conundrum”: Acquired Hemophilia A, Immune Thrombocytopenia, and Neutropenia in a Patient with Pancreatic Cancer

“…Most patients had low antibody titers (median 14 BU; range 1.7–64 BU). 14 Our case is unique in the rapid occurrence of high-titer autoantibody to factor VIII following surgery. It is also possible that underlying pancreatic cancer, 15 infection (cholangitis), or medications such as antibiotics and anesthetics during surgery triggered the abnormal antibody production.…”

Unforeseen encounter of acquired hemophilia A in a preoperative case of periampullary carcinoma: A case report

“…Case report of solid organ malignancy with acquired hemophilia had been reported previously in gastrointestinal stromal tumor, duodenal and pancreatic cancer [ 8 ]. Prevalence of paraneoplastic FVIII inhibitors is 11.8% according to European Acquired Haemophilia Registry (EACH2) out of which 67.8% associated with solid tumors and 32.2% in hematological malignancies [ 4 ]. Sometimes it disappears after surgery with removal of cause as happened in our case [ 9 ].…”

“…Acquired hemophilia A (AHA) is rare but potentially life threatening bleeding disorder characterized by development of auto antibodies against factor VIII in cases of malignancy, autoimmune disorders, pregnancy and due to medications [ 3 ]. AHA presenting as paraneoplastic syndrome in lung, prostate, bladder, gastrointestinal and hematological malignancy had been described before in postoperative cases [ 4 ]. Only few cases of AHA associated with periampullary carcinoma had been reported in literature and mostly in postoperative period.…”