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 outcomes

PatientDiagnosisPre-interventionrFVIIa used (microgms)PRBC/Platelet transfused (units)Clinical outcome
OW ALL-MUD, BMT, day +75 8.8/12,000 24000/d X 4days 3/10 100 Non-rebreather to 6L nasal cannula O2 
OW ALL-MUD, BMT, day +80 8/8,000 28000/d X 4 days 6/14 Ventilatory support to successful weaning 
CS Relapsed AML, S/P induction 8.8/19,000 8400/d X 2 days 2/4 O2 requirement decreased 
LW CML blast crisis, S/P induction 8.6/101,000 10800/d X 2 days 4/1 Clinically no bleeding, decreased O2 requirement 
RB Relapsed ALL 8.7/7,000 7200/d X 1 day 2/4 Ventilatory support to successful weaning 
PatientDiagnosisPre-interventionrFVIIa used (microgms)PRBC/Platelet transfused (units)Clinical outcome
OW ALL-MUD, BMT, day +75 8.8/12,000 24000/d X 4days 3/10 100 Non-rebreather to 6L nasal cannula O2 
OW ALL-MUD, BMT, day +80 8/8,000 28000/d X 4 days 6/14 Ventilatory support to successful weaning 
CS Relapsed AML, S/P induction 8.8/19,000 8400/d X 2 days 2/4 O2 requirement decreased 
LW CML blast crisis, S/P induction 8.6/101,000 10800/d X 2 days 4/1 Clinically no bleeding, decreased O2 requirement 
RB Relapsed ALL 8.7/7,000 7200/d X 1 day 2/4 Ventilatory support to successful weaning 

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