Recombinant Human Factor VIIa for Alveolar Hemorrhage Following Allogeneic Stem Cell Transplantation

Abstract

The mortality rate of alveolar hemorrhage following allogeneic hematopoietic stem cell transplantation is greater than 60% with supportive care and high dose steroids. We performed a retrospective cohort analysis to assess the benefits and risks of rFVIIa as a therapeutic adjunct for alveolar hemorrhage. From 2005 to 2012, 57 episodes of alveolar hemorrhage occurred in 37 patients. Fourteen episodes (in 14 patients) were treated with steroids alone and 43 episodes (in 23 patients) were treated with steroids and rFVIIa. The median (interquartile range) steroid dose was 1.9 mg/kg/d (0.8 – 3.5; methylprednisolone equivalents) and did not differ statistically between the two groups. The median rFVIIa dose was 41 μg/kg (39-62) and a median of 3 doses (2-17) was administered per episode. Concurrent infection was diagnosed in 65% of the episodes. Patients had moderately severe hypoxia (median PaO2/FiO2, 193 [141-262]); 72% required mechanical ventilation and 42% survived to extubation. The addition of rFVIIa did not alter time to resolution of alveolar hemorrhage (p = 0.50), duration of mechanical ventilation (p = 0.89), duration of oxygen supplementation (p = 0.55), or hospital mortality (p = 0.27). Four possible thrombotic events (9% of 43 episodes) occurred with rFVIIa. rFVIIa when used in combination with corticosteroids did not confer clear clinical advantages compared to corticosteroids alone. In patients with AH following hematopoietic stem cell transplant, clinical factors (i.e. worsening infection, multiple organ failure or recrudescence of primary disease) may be more important than the benefit of enhanced hemostasis from rFVIIa.

Low-, medium- and high-dose steroids with or without aminocaproic acid in adult hematopoietic SCT patients with diffuse alveolar hemorrhage

“…24 Other agents such as recombinant factor VIIa have also been studied retrospectively, with a recent study suggesting no benefit. 7 ACA is an antifibrinolytic agent classically used intravenously to control perioperative bleeding, mainly in cardiac surgery. [28][29][30][31] To our knowledge, the only previous study of i.v.…”

“…5 It has been reported to affect~5-12% of HSCT patients yearly; however, more recent studies indicate the incidence to be closer to 5%. [6][7][8] BAL fluid, however, lacks sensitivity and specificity when compared with autopsy findings, which hinders early and accurate diagnoses. 9 Despite prompt therapy and supportive care, the mortality rate for DAH remains high at 60-100%.…”

Non-Infectious Early Complications of Allogeneic Stem Cell Transplantations

“…DAH is generally seen in the first 30 days after allo-HSCT with the incidence of 2-14% and the mortality rates of over 60%. 62,63 DAH etiology is not elucidated in the context of transplantation. While infections, cardiac causes including heart failure, toxicity from pre-transplant thoracic radiation, chemotherapy and early marrow engraftment are the factors leading to DAH, no definite cause could be detected in 20% of patients.…”

“…Predictably, supportive therapy includes oxygen and ventilation support, transfusion of blood products and antimicrobial therapy. 62 Rathi NK et al classified the cases of post transplant DAH in three groups according to methylprednisolone doses in the treatment 66 : (1) low dose: < 250 mg/day, (2) medium dose: 250-1000 mg/day and (3) high dose: ≥ 1000 mg/day. Authors concluded that intensive care unit and hospital mortality significantly low only in low-dose steroid group and stated that treatment strategies may need to be reanalyzed in order to avoid potential unnecessary therapies.…”

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“…6 In addition, aminocaproic acid and recombinant factor VIIa have been tried in some studies with variable results. 11 However, a recent report showed no difference in outcome with methylprednisolone at low doses (≤ 250 mg/d), medium doses (250-1000 mg/d), or high doses (≥ 1000 mg/d) with or without the addition of aminocaproic acid. 12 Mortality rates in patients with DAH range from 74% to 100%.…”