Acquired Inhibitor of Factor VIII Associated with Prostate Cancer: Case Report
Authors: Urbaniak-Kujda Donata M. , Kapelko-Slowik Katarzyna L. , Dawidziak Maria Podolak- , Kuliczkowski Kazimierz , Frydecka Irena , Dybko Jaroslaw , Wolowiec Dariusz 
Published: April 2020

Acquired haemophilia (AH) is rare disease that occurs at a rate of approximately 1.0 per per million each year, although it is likely that not all affected patients are reported. It is a severe bleeding diathesis that affects both males and females, caused by sudden appearing autoantibodies that interfere with coagulation factor VIII (FVIII) activity. In the approximately half of patients with inhibitors, no concomitant disease can be found, and in the conditions most commonly associated with factor VIII inhibitors include connective tissue disease, inflammatory bowel disease, some dermatologic disorders and malignancy (lymphoproliterative disorders and solid tumours, e.g. neoplasms of the colon, pancreas, kidney, prostate, testes, brain, and lung). Bleeding manifestations are often severe and may occur spontaneously or after minor trauma. In contrast to patients with congenital factor VIII deficiency those with acquired haemophilia principally experience soft tissue bleeding. Overall mortality associated with AH has been reported at between 8% to 42%. A 71 –year- old man presented with sacrospinal, left forearm and brachial muscles non traumatic haematoma and spontaneous hematuria, but otherwise felt well. A coagulation screen was as follows: platelet count 140 G/L (range 150–400 G/l), prothrombin time was normal, Fibrinogen concentration was increased up 0.8 g/L ( normal range 0.2–0.4 g/L). There was a prolongation of the activated partial thromboplastin time (aPTT) up to 99secs (normal range 20–34secs), which did not correct following the in vitro addition of normal plasma. Acute disseminated intravascular coagulation (DIC) was excluded. The Factor VIII level was reduced to 0.6% (normal range 50% –150%). The Bethesda assay demonstrates an inhibitor 5.4 Bethesda Units (BU). He was screened for inflammatory and malignant disorder. Prostate specific antigen (PSA) rate was 400 ng/L (normal range 0–4 ng/L). Prostate cancer has been confirmed with multiple bone metastases. Treatment was aimed at stopping the acute bleeding, eliminating the inhibitor and curing the underlying disease. The patient was treated symptomaticly with rFVIIa (Novo-Seven) 270μg/kg administrated every 3–5 days due to diathesis intensity. Efficacy was judged by decreasing bleeding episodes. Anticancer therapy was ordered by urologist (flutamide and defereline). For eradication of FVIII inhibitor after 10 days to that therapy cyclophosphamide 2mg/kg and prednisone 1mg/kg given every day orally was added. The acute bleeding stopped, but despite these therapyf two weeks of immunosupressive therapy the FVIII level remained very low (0.1%) and the FVIII inhibitor level increased up to 14.7BU. Haematomas and acute mucose bleeding reappeared. Bypass therapy with FEIBA 50U/kg administered every 12 h for 10 days had a small clinical effect, but after next three weeks bleeding symptoms diminished, and there was a notable increase in FVIII level up to 1.74% and significant decrease in FVIII inhibitor to 1.8 BU. Conclusion: In presented patient severe bleeding caused by factor VIII inhibitor associated with prostate cancer was controlled by a complex therapy.