Primary lung cancer with acquired hemophilia A is rare. We report a case of large cell neuroendocrine carcinoma (LCNEC) with acquired hemophilia A diagnosed by endobronchial biopsy. A 75-year-old male was admitted to our hospital due to severe anemia and multiple organ failure. Hematomas, prolonged activated partial thromboplastin time, decreased activity of factor VIII, and the presence of serum factor VIII inhibitors led to the diagnosis of acquired hemophilia A. Administration of recombinant activated factor VIII and steroid treatment resolved the coagulation abnormalities. Simultaneously, a CT scan showed a lung mass and an endobronchial biopsy confirmed the diagnosis of LCNEC. Although acquired hemophilia A can cause severe bleeding symptoms, a lung cancer diagnosis by bronchoscopy was possible under appropriate treatment of acquired hemophilia A.

Autoantibodies against plasma coagulation factors could be developed by some individuals inducing severe and sometimes fatal bleedings. This clinical entity is called acquired haemophilia. It should be suspected in subjects with acute abnormal bleedings, without personal or familiar history of congenital bleeding disorders with an unexplained prolonged aPTT. It is rare disease, although its incidence may be underestimated due to the low knowledge about it by many specialists, the frequent use of anticoagulant or antiplatelet therapies in the affected population that can mask the diagnosis and, sometimes, a so withering effect that avoid its confirmation. Mortality ranges between 9% and 33% depending on the series in the first 2 months after diagnosis. This mortality is attributed in up to 40% of the cases to infections in the context of immunosuppressive treatments used to eliminate the inhibitor. Factor VIII levels below 1% and high inhibitor titers are conditions of worse response rates. Advanced age, patient's ECOG, and underlying conditions are key prognostic factors for response to treatment and patient survival. To reduce morbidity and mortality in these patients, it is important to have clinical knowledge and access to guidelines to achieve an early diagnosis and to optimize the haemostatic and immunosuppressive treatment. This review aims to contribute to the dissemination of basic concepts on the epidemiology etiopathogenesis, diagnosis, treatment and management of these patients, as well as risk factors to get remission and the longest overall survival to allow individualized care. Especial awareness will be proposed in patients with some underlying conditions like cancer, autoimmune diseases, children, pregnancy or drugs.

Acquired hemophilia A (AHA) is a rare, hemorrhagic autoimmune disease, whose pathogenesis involves reduced coagulation factor VIII (FVIII) activity related to the appearance of inhibitors against FVIII. Common etiological factors include autoimmune diseases, malignancy, and pregnancy. We report two cases of AHA in solid cancer. The first case is a 63-year-old man who developed peritoneal and intestinal bleeding after gastrectomy for gastric cancer. He was diagnosed with AHA, and was treated with prednisone, followed by cyclophosphamide. In the second case, a 68-year-old man developed a subcutaneous hemorrhage. He was diagnosed with AHA in hepatocellular carcinoma on CT imaging, and treated with rituximab alone. Hemostasis was achieved for both patients without bypassing agents as the amount of inhibitors was reduced and eradicated. However, both patients died within 1 year due to cancer progression. Successful treatment for AHA in solid cancer can be difficult because treatment of the underlying malignancy is also required.

OBJECTIVES: In acquired hemophilia (AH), autoantibodies (inhibitors) impede blood coagulation factors leading to severe bleedings. Cornerstones of a successful treatment are the control of bleeding and an eradication of autoantibodies. The present study is an update of our previous documentation of the treatment of high-titer AH patients with severe life-threatening bleeding undergoing the modified Bonn-Malmö-Protocol (MBMP). METHODS: 64 AH patients were treated by a standard combination protocol (MBMP) consisting of antibody depletion through immunoadsorption, i.v. immunoglobulin, immunosuppression, and high-dose FVIII substitution. They underwent a long-term follow-up. RESULTS: Primary study endpoints loss of detection of the activity of the inhibitor and FVIII recovery ? 5% were reached in a median time of 3 days (95% CI: 2.6-3.4 days), the median time of FVIII substitution was 13 days (95% CI 10.6-15.3 days), and the median time of immunoadsorption was 16 days (95% CI 13-18.9 days). In 5 patients the AH occurred as paraneoplastic syndrome, and partial remission was achieved. Relapses without bleeding event occurred only in second-line MBMP. Those responded excellently to short time treatment. Overall patients remained in remission over a median follow-up time of 8 years. Conclusion: Except for paraneoplastic AH, MBMP-treated patients have a remarkable prognosis which is confirmed by long-term follow-up with a complete response rate of 93% (53/57) in the first year post MBMP and 100% during long-term follow-up. These outcome in life-threatening AH is unique and until now not achievable via other treatment schedules. In life-threatening bleedings physicians should take into account MBMP as a first line treatment.

Acquired hemophilia A (AH) is an autoimmune disease that leads to potentially severe bleeding. Management relies on rapid and accurate diagnosis, control of bleeding episodes and eradication of the inhibitor by immunosuppression. There is extensive literature about the disease but only few controlled data are available. This paper reviews the current literature on treatment strategies for hemostatic therapy and inhibitor eradication. Potential future developments are discussed.

Acquired haemophilia A (AH) is a rare bleeding disorder with significant risk of mortality. We conducted a study on the treatment and outcomes of patients with AH diagnosed between 1998 and 2004 in our institution. Fourteen patients (age range 17-89, median 64) were followed-up from between 10-64 months (average 32 months). Inhibitor levels ranged from 5 to 450 BU. Ten patients required either recombinant activated factor VIIa or prothrombin complexes for control of bleeding. All patients received a standard immunosuppressive regimen of prednisolone 1 mg kg day(-1) and oral cyclophosphamide 50-100 mg day(-1). In addition, nine patients received intravenous immunoglobulin. Complete remission (CR) was achieved in 88% (eight of nine evaluable patients) over durations ranging from 5-78 days (average 35 days). There were three mortality; from bleeding, sepsis and cerebral infarct. Two patients were lost to follow-up. There were no relapses among patients achieving CR. Conditions associated with AH were not identified at diagnosis or subsequent follow-up in all patients. This series represent one of the largest aetiologically and treatment-wise, uniformed cohort of AH patients. Despite toxicity concerns, the combination of prednisolone and cyclophosphamide remain an effective regimen and should be among the first line of treatment choices, with careful patient selection.