Diffuse alveolar hemorrhage (DAH) is a serious complication that occurs in < 20% of patients after hematopoietic stem cell transplantation (HSCT), with a mortality rate of 64%-100%.1 Recombinant activated factor VIIa (rFVIIa) is an approved agent for the treatment of bleeding episodes in patients with hemophilia when inhibitors to factor VIII or IX are present.2 We report a case of DAH after allogeneic HSCT that was treated with rFVIIa in addition to standard therapy.
A 48-year-old male with non-Hodgkin’s lymphoma (NHL) who received an allogeneic HSCT 14 months earlier was admitted to the ICU after developing massive hemoptysis associated with respiratory failure requiring mechanical ventilation. He had presented to the hospital 10 days earlier with mild hemoptysis. His platelet count was 23,000/mm3 and a chest x-ray (CXR) showed clear lung fields. Chest CT revealed bilateral patchy alveolar opacities and small pleural effusions. Fiberoptic bronchoscopy demonstrated old blood in the airways but no active bleeding. Cultures and cytologic exam of bronchial washings were negative for bacteria, AFB, fungi, and malignant cells. Despite treatment with corticosteroids, antibiotics, and transfusions to keep the platelet count >50,000/mm3, his hemoptysis persisted. In the ICU, he was mechanically ventilated but was afebrile and hemodynamically stable. The physical examination was remarkable for bilateral basal rales. Laboratory data were significant only for a hemoglobin level of 8.7 g/dL, and a platelet count of 153,000/mm3. The CXR after intubation revealed bilateral patchy alveolar opacities. Six hours into the ICU admission, rFVIIa was administered using a dose of 90 μg/kg IV every two hours for persistent massive hemoptysis. The hemoptysis subsided rapidly after only two doses of rFVIIa. No adverse effects of rFVIIa were observed. Fiberoptic bronchoscopy 24 hours later showed old blood clots overlying the main carina and both major bronchi with no active bleeding. After 1 week, the patient was extubated with resolution of the alveolar infiltrates on CXR. He was transferred to the ward and discharged home three weeks later. Following treatment with rFVIIa, the patient exhibited no further hemoptysis.DISCUSSION: The high morbidity and mortality rates of DAH after HSCT1 demand that novel therapeutic approaches be considered for this serious condition. Recent advances in our understanding of hemostasis and development of novel hemostatic agents have resulted in the safe and successful application of these agents in clinical practice.2 rFVIIa has been shown to be safe and effective for life-threatening bleeds in patients with hemophilia, congenital, and acquired thrombocytopathies. rFVIIa promotes hemostasis primarily by enhancing thrombin generation on activated platelets independently of tissue factor.2 rFVIIa should be used with caution in patients with an increased risk for thrombotic events. The administration of rFVIIa in our patient highlights the difficulties that clinicians face when choosing to administer a new and expensive agent (>$6,000 per dose) outside of the recommended indication. The dosage regimen used in our patient was developed from hemophilia patients with inhibitors, and not from experience in transplant patients. Therefore, further study is required to determine whether rFVIIa is indeed beneficial in this population, and if so, what the adequate dosage and frequency of administration would be.
This case illustrates the successful use of rFVIIa in an allogeneic HSCT patient with DAH. We propose that rFVIIa be considered in any patient who develops DAH after HSCT, in addition to standard therapy, particularly when hemoptysis is massive and/or recurrent.
L.P. Voigt, None.