Case Report: A Patient with Haemorrhagic Bleeding, an Acquired Factor VIII Inhibitor and Massive Pulmonary Embolism.

A female, 48-year old patient was referred to an emergency ward with dyspnoea, haemoptysis and suspected respiratory infection that had been refractory to prior antimicrobial therapy. The onset of dyspnoea dated back to a febrile episode three months prior to presentation. The patient continued to work in spite of severe shortness of breath. Her history revealed a cervical cancer which had been treated by neoadjuvant radiochemotherapy and extended hysterectomy in 2005. Upon admission, extensive spontaneous haematomas were noted on the upper extremities. Following a diagnostic puncture of the radial artery, severe haemorrhage and compartmentalization developed, and the patient was transferred to our hospital for a surgical emergency intervention and haemostaseological counselling. A decreased factor VIII activity was noted, with a prolonged partial thromboplastin time, a normal von Willebrand Factor activity and concentration, a prolonged bleeding time and a low-titer inhibitor to factor VIII. Additionally, a profound hyponatremia (117 mmol/l) awaited explanation. Haemorrhage was treated with recombinant Factor VIIa, allowing for a successful surgical de-compartmentalization. With regard to the consistent feature of dyspnoea and partial respiratory insufficiency, bronchoscopic examination revealed only minor hemorrhagic suffusion of the bronchial epithelium, but no sign of infection or major pulmonary bleeding. Chest X-ray and laboratory findings showed right ventricular enlargement, bilateral infiltrates and an excessively high NT-pro-BNP concentration in plasma (13027 ng/l). Chest X-ray radiographs performed two months previously for suspected respiratory infection showed pulmonary infiltrates of comparable size, albeit no right ventricular enlargement. Computerized tomography of the chest showed a complete obstruction of the right pulmonary artery and of the lower branch of the left pulmonary artery. Pulmonary arterial pressure was measured at 70 mm Hg. Immunosuppressive therapy was initiated, with concomitant aPTT-adjusted anticoagulation. Upon clinical deterioration with right-ventricular failure, a catheter-based disruption of the emboli was attempted, albeit with no success. A cardio-surgical intervention with thrombendectomy was performed successfully; however, the patient succumbed to sepsis and multiorgan failure ten days later. The autopsy revealed multiple thrombi, a bilateral pulmonary haemorrhagic infarction and a disseminated lymphangiosis and hemangiosis carcinomatosa of the lungs. We conclude that the acquired inhibitor to factor VIII was of paraneoplastic origin and, although detected at a low titre, clinically relevant. Based on previous radiographic findings, a massive pulmonary embolism must be assumed to have occurred months prior to presentation. The anticoagulatory effect of the acquired inhibitor to Factor VIII may have averted the timely detection of the pulmonary embolism.