Treatment of Diffuse Alveolar Hemorrhage with Recombinant Factor VIIa in Patients with Hematologic Malignancies.

Abstract

Diffuse alveolar hemorrhage (DAH) is a potentially life-threatening pulmonary complication in patients following hematopoietic stem-cell transplantation (HSCT) or acute leukemia induction therapy. This syndrome is associated with a high mortality rate. Current management strategies include high-dose steroids, platelet transfusions and mechanical ventilatory support to treat acute respiratory failure. Recombinant factor VIIa (rFVIIa) is approved for treatment of bleeding in patients with hemophilia A/B with inhibitors. A greater understanding of the mechanism by which rFVIIa restores hemostasis has become available; with the in-vitro evidence supporting that the thrombin burst achieved by rFVIIa is independent of the presence or binding to tissue factor. This insight has suggested a range of other potential clinical uses for the drug. We report our experience of using rFVIIa for the treatment of DAH in the setting of HSCT and acute leukemia induction therapy. We treated 5 episodes of DAH in 4 adult patients with hematologic malignancies. Two patients had undergone matched unrelated donor HSCT. Clinically, DAH was suspected because of progressive respiratory failure. DAH was confirmed by radiologic and bronchoscopic exams. All patients received high-dose steroids, broad-spectrum antibiotics and respiratory support, as indicated. Packed red cells and platelets were transfused to keep the hemoglobin above 8gm/dL and platelets above 50,000/μL. Patients received boluses of rFVIIa at 90mcg/kg, every 3-12 hrs. The dose of rFVIIa ranged from 7,200–28,000 mcg/day. All five episodes of DAH achieved clinicoradiologic improvement. No toxicity or adverse events were observed with rFVIIa use. Our experience indicates that rFVIIa might be an effective treatment option for patients with DAH, post-HSCT or acute leukemia induction therapy. The optimal dosing schedule in this clinical situation needs to be studied.Patient demographics and outcomesPatientDiagnosisPre-interventionrFVIIa used (microgms)PRBC/Platelet transfused (units)Clinical outcomeOWALL-MUD, BMT, day +758.8/12,00024000/d X 4days3/10100 Non-rebreather to 6L nasal cannula O2OWALL-MUD, BMT, day +808/8,00028000/d X 4 days6/14Ventilatory support to successful weaningCSRelapsed AML, S/P induction8.8/19,0008400/d X 2 days2/4O2 requirement decreasedLWCML blast crisis, S/P induction8.6/101,00010800/d X 2 days4/1Clinically no bleeding, decreased O2 requirementRBRelapsed ALL8.7/7,0007200/d X 1 day2/4Ventilatory support to successful weaning