Recombinant Activated Factor VII for Diffuse Alveolar Hemorrhage

Abstract

INTRODUCTION: Diffuse alveolar hemorrhage (DAH) is a life-threatening syndrome characterized by disruption of the alveolar-capillary basement membrane. Treatment with immunosuppressive therapy often fails in patients presenting with an acute onset of massive hemoptysis and respiratory failure. DAH carries a high mortality of over 50% in patients requiring mechanical ventilation. CASE PRESENTATION: A 76-year-old male presented with 4 day history of hemoptysis. The patient has a history of ANCA-associated vasculitis, ESRD on hemodialysis and cerebral venous thrombosis for which he was on warfarin. He was intubated for airway protection and coagulopathy revered. An emergent bronchoscopy with BAL revealed diffuse alveolar hemorrhage. He developed progressively worsening hemoptysis with increasing bilateral infiltrates and increasing oxygen requirements and ventilator support. Conservative measures with aggressive immunosuppressive therapy failed to control the bleeding. Intravenous activated factor VII was used as a possible treatment for the worsening hemoptysis. The bleeding improved over the next 24 hours. DISCUSSION: Recombinant activated factor VII(rFVIIa) was originally developed for the promotion of hemostasis in patients with hemophilia who have an antibody to coagulation factors VIII or IX. However, it has been used increasingly as an off-label general hemostatic agent in a variety of clinical settings such as intracranial hemorrhage, trauma, surgery, and GI and obstetric bleeding. FVIIa treatment can be used as a temporizing measure in refractory cases of DAH to allow more time for standard treatment regimens to control the underlying inflammation and capillary wall injury. Recent case reports have described success with both intravenous and intrapulmonary use of rFVIIa. The systemic use of rFVIIa does have a potential risk of thromboembolic complications based on recent meta-analysis. This risk may be hypothetically lower with the intrapulmonary route. It has been used in various other clinical scenarios including hemoptysis related to cystic fibrosis, trauma, thrombocytopenia and transplantation. The drug carries an orphan drug status as per the FDA for this indication. CONCLUSIONS: FVIIa may be an effective agent in life-threatening pulmonary hemorrhage.