Use of recombinant factor VIIa for major haemorrhage.

EDITOR: Haemorrhage associated with trauma and surgery remains a significant cause of death. The development of coagulopathic bleeding is often difficult to manage. Recombinant-activated factor VII (rFVIIa, NovoSeven®; Novo Nordisk, Bagsvaerd, Denmark), which is structurally similar to the naturally occurring activated coagulation factor VII, is licensed for use in patients with haemophilia A or B and inhibitors to coagulation factors VIII or IX and acquired haemophilia. There is considerable interest in the ‘off label’ adjunctive use of rFVIIa in major haemorrhage. A single randomized study has indicated that rFVIIa reduces blood transfusion following blunt trauma [1]. Other evidence for use of rFVIIa as rescue therapy in major haemorrhage remains largely anecdotal. We present our experience from a UK teaching hospital of the use of rFVIIa as rescue therapy in four cases of major haemorrhage, following surgery and blunt trauma. The response to rFVIIa was not consistent and we discuss possible factors limiting its effectiveness. Case 1: A 39-yr-old male with a variant of Marfan’s syndrome had been anti-coagulated with warfarin following aortic valve and root replacement. He had also undergone repair of infra-renal and thoraco– abdominal aneurysms and developed a rupture of an aortic patch graft aneurysm. He underwent emergency aneurysm repair, requiring a massive blood transfusion, and shortly afterwards returned to theatre for a laparotomy for abdominal compartment syndrome. rFVIIa 90 μg kg 1 was administered for continued bleeding unresponsive to conventional therapy in the intensive care unit (ICU, see Table 1). There was no immediate response, and considerable volumes of fresh frozen plasma (FFP), cryoprecipitate and platelets and three further doses of rFVIIa were administered over the next 11 h (see Table 1). Bleeding ceased approximately 2 h after his final dose of rFVIIa. Anti-coagulation was recommenced on the fourth ICU day, by which time the prothrombin time (PT) and activated partial thromboplastin time (APTT) had normalized. He was discharged home 3 months after admission. Case 2: A 53-yr-old male sustained multiple injuries as a result of a 10 m fall onto concrete, including a compound occipital fracture, temporal contusion, subarachnoid and subdural haemorrhage, multiple rib fractures and pulmonary contusions, and a femoral fracture. He received cardiopulmonary resuscitation during 15 min of pulseless electrical activity, which responded to decompression of a tension pneumothorax. He bled considerably from his head wound and chest drain despite FFP and platelet transfusion (see Table 1), and 120 μg kg 1 of rFVIIa was administered prior to laparotomy. Two litres of blood was found in the abdomen and splenectomy was performed. Generalized oozing continued but a bleeding point was not identified. Correction of coagulopathy was advised prior to consideration of cardiothoracic intervention, and a further 120 μg kg 1 rFVIIa was administered following additional transfusion therapy. Bleeding rapidly declined and he stabilized. Unfortunately, the head injuries subsequently found on CT scanning were not amenable to neurosurgical intervention. He developed evidence of brain stem death, and organ harvest was performed approximately 24 h later. Case 3: A 53-yr-old motorcyclist was involved in a collision with a van, sustaining major pelvic and soft tissue injuries, including disruption of the rectum. Over the first 10 days of treatment, he underwent two laparotomies and application of a pelvic external fixator. He had developed septic shock and acute renal failure by the time of his third visit to theatre for a re-exploration and repacking of his wound. He bled considerably intraand postoperatively, despite transfusion therapy (see Table 1). A dose of 90 μg kg 1 rFVIIa was administered, but with no immediate response. After further FFP, cryoprecipitate and platelets, a dose of 120 μg kg 1 rFVIIa was given. The bleeding ceased abruptly. He remained in ICU for 51 days, and was discharged home 6 months after his original injuries. Case 4: A 63-yr-old female underwent elective repair of a supra-renal inflammatory aortic aneurysm, Correspondence to: Richard Pugh, Department of Anaesthesia, Countess of Chester Hospital NHS Foundation Trust, Countess of Chester Health Park, Liverpool Road, Chester, Cheshire CH2 1UL, UK. E-mail: pughr@hotmail.com; Tel: 44 124 436 5000; Fax: 44 124 436 5292