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Control of life-threatening pulmonary bleeding with activated recombinant factor VII

      To the Editor:
      Massive pulmonary hemorrhage is a serious and life-threatening complication that is associated with high (10% to 40%) mortality (
      • Lee T.W.
      • Wan S.
      • Choy D.K.L.
      • Chan M.
      • et al.
      Management of massive hemoptysis a single institution experience.
      ). Current treatment involves the infusion of fresh frozen plasma, packed cells, and, when bleeding persists, embolization of the bleeding vessel or surgical treatment (
      • Fernando H.C.
      • Stein M.
      • Benfield J.R.
      • et al.
      Role of bronchial artery embolization in the management of hemoptysis.
      ). Despite this therapy, bleeding may continue. We report the successful use of activated recombinant factor VII (rFVIIa) (Novoseven, Novo Nordisk, Copenhagen, Denmark) in life-threatening pulmonary bleeding that was uncontrollable with standard treatment.
      A 44-year-old man was hit by a train while attempting suicide. At the site of the accident, his right leg was amputated, and the profound bleeding at the stump was stopped with bandages and compression. The patient underwent tracheal intubation, and a chest drain was inserted in the right side because of a suspected pneumothorax. On admission, the patient was hemodynamically unstable. Hemoglobin level was 3.0 mmol/L (normal, >8.4 mmol/L), platelet count was 104 x 109/L (normal, >150 x 109/L), activated partial thromboplastin time was 89.8 seconds (normal, <40 seconds), and prothrombin time was 22.2 seconds (normal, <14 seconds). A chest radiograph revealed contusion of both lungs, without fractures of the rib, and there were fractures of the pelvis (stabilized with an external fixator), and acetabulum. Profuse bleeding in a ruptured right iliac artery was successfully embolized, and the patient was transferred to the intensive care unit.
      Two hours later, heavy bleeding from the thoracic drain began at a rate of 200 mL/h. The patient became hemodynamically unstable, with signs of multiorgan failure. The hemoglobin level decreased from 5.7 mmol/L to 3.1 mmol/L, and treatment with rapid infusion of fluids (packed cells, 32 units; fresh frozen plasma, 24 units; platelets; tranexamic acid; and desmopressin) was started over 12 hours. Chest radiograph revealed a right-sided hemothorax. Despite improved coagulation parameters (platelet count, 105 x 109/L; prothrombin time, 14.9 seconds; activated partial thromboplastin time, 51.8 seconds), drain production increased to 250 mL/h. During thoracotomy, several adherent clots were found in the right lung, without localized bleeding, which were controlled surgically. After insertion of a second drain, the chest was closed. The patient continued to bleed heavily and seemed likely to have a fatal outcome. He was treated with 60 μmg/kg of intravenous rFVIIa, which led to a decrease in the drain production to 30 mL/h, as well as in transfusion of packed cells to 4 units in the following 48 hours (Figure). Twelve hours later, drain production increased to 110 mL/h and a second 60-μmg/kg dose of intravenous rFVIIa was given, after which no further bleeding occurred. Two days later, chest radiograph showed resolution of the hemothorax. The patient recovered fully.
      Figure thumbnail gr1
      FigureDrain production and transfusion requirements. Administration of activated recombinant factor VII is indicated by vertical arrows. rFVIIa = activated recombinant factor VII ; T = 0: start of the thoracic drain production.
      Life-threatening bleeding due to lung or airway injury can be treated with supportive care, bronchial artery embolization, or surgical resection (
      • Fernando H.C.
      • Stein M.
      • Benfield J.R.
      • et al.
      Role of bronchial artery embolization in the management of hemoptysis.
      ), which may not always be successful. In such instances, treatment with rFVIIa may be an option. Activated recombinant factor VII is a new hemostatic agent that forms tissue factor:factor VIIa complexes at the site of vessel injury, where the endothelium is damaged and tissue factor expression is increased. This leads to thrombin generation and stable local clot formation (
      • Ten Cate H.
      • Bauer K.A.
      • Levi M.
      • et al.
      The activation of factor X and prothrombin by recombinant factor VIIa in vivo is mediated by tissue factor.
      ). Activated recombinant factor VII may be effective in bleeding associated with use of inhibitors in patients with hemophilia (
      • Hedner U.
      • Glazer S.
      • Pingel K.
      • et al.
      Successful use of recombinant factor VIIa in a patient with severe hemophilia A during synovectomy.
      ), thrombocytopenia (
      • Meijer K.
      • Sieders E.
      • Slooff M.J.H.
      • et al.
      Effective treatment of severe bleeding due to acquired thrombocytopenia by single dose administration of activated recombinant factor VII.
      ), severe abdominal bleeding (
      • Vlot A.J.
      • Ton E.
      • Mackaay A.J.C.
      • et al.
      Treatment of a severely bleeding patient without preexisting coagulopathy with activated recombinant factor VII.
      ), and hemoptysis due to invasive aspergillosis (
      • Meijer K.
      • de Graaff W.E.
      • Daenen S.M.G.J.
      • et al.
      Successful treatment of massive hemoptysis in acute leukemia with recombinant activated factor VII.
      ). We believe that this new treatment has a potential role in severe pulmonary bleeding that does not respond to conventional therapy.

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