To the Editor:—

Recombinant factor VIIa has recently been developed to reduce bleeding complications in hemophilic patients. 1After injury to the vessel wall, tissue factor (TF) is exposed to the circulating blood and forms complexes with already activated FVII (FVIIa). The complex TF-FVIIa initiates hemostasis at the site of injury by activating FX into FXa, thereby providing the first amount of thrombin. 2 

It has been argued that FVIIa, in combination with extensive tissue damage, sepsis, and disseminated intravascular coagulation would be contraindicated. 3So far, there are few reports concerning rFVIIa treatment in situations of life-threatening bleeding caused by trauma, 4bowel surgery in patients with Crohn disease, and bowel lymphoma and profuse gastrointestinal bleeding. 5This report describes a patient successfully treated with rFVIIa in an attempt to control bleeding from necrotizing pancreatitis.

A 50-yr-old woman was admitted to our hospital with severe gallstone-induced pancreatitis. After initial treatment at the intensive care unit she developed necrosis and a pseudocyst of the pancreas. An attempt to drain this endoscopically resulted in massive hemorrhaging from the splenic artery. Immediate laparotomy was performed with repeated packing. She continued, however, to bleed. During reoperation the aorta was clamped and the diseased part of the pancreas resected. Furthermore, a subtotal gastrectomy, splenectomy, and ligation of the gastric and splenic arteries close to the aortic wall was performed. After declamping there was residual oozing from the region of the resected pancreatic necrotic tissue that was covered with an omental patch. At the end of this second laparotomy she had received 19 l of packed red cells; 4.5 l fresh frozen plasma; 300 g of platelets; prothrombin complex concentrate 1,200, i.e. , desmopressin 30 μg (Octostim®, Ferring Läkemedel AB, Limhamn, Sweden); antithrombin III 2,000; fibrinogen 1,000 mg; antifibrinolytic therapy with tranexamic acid 1 g; aprotinin 500,000/24 h infusion. Coagulation–fibrinolytic determination showed antithrombin III 47% (normal range > 50%), prothrombintime 32 s (normal range 10–12 s), APTT 35 s (normal range 26–36 s), fibrinogen 1.4 g/L (normal range 2–4 g/l), D-dimer 0.3 mg/ml (normal range < 0.3 mg/ml). She continued, however, to bleed and received another 8 l packed red cells during the next 11 h. She was in a state of circulatory shock.

In response to this uncontrollable hemorrhage a 120 μg/kg dose of recombinant factor VIIa (rFVIIa, NovoSeven®, Novo Nordisk, Bagsvaerd, Denmark) was given and repeated 5 h later. Bleeding decreased after the first dose and ceased after the second, without thromboembolic adverse effects. Coagulation and fibrinolytic parameters normalized. The patient and her hemoglobulin stabilized with no recurrence of bleeding. She was reoperated 3 days later with evacuation of residual necrosis and hematoma and the Roux-en-Y gastric jejunostomy was reconstructed without any problems of coagulopathy.

The successful use of rFVIIa in this patient suggests that its use should be considered and studied in patients with massive bleeding from septicaemia when other standard therapy has failed.


Hedner U: Recombinant activated factor VII as a universal haemostatic agent. Blood Coagul Fibrinolysis 1998; 9(suppl.1): S147–52
Rapaport SI, Rao LV: The tissue factor pathway: How it has become a “prima ballerina”. Thromb Heamost 1995; 74(1): 7–17
Essex D, Bluth N, Gloster E, Dimaio TH, O'Neill P, Waly D, Kurtz R, Strauss R: Successful use of recombinant factor VIIa (rFVIIa) for trauma associated massive haemorrhage. Am Soc Hematol 2000; 1150
Kenet G, Walden R, Eldad A, Martinowitz U: Treatment of traumatic bleeding with recombinant factor VIIa. Lancet 1999; 354: 1879
White B McHale Ravi N Reynholds J Stephens R Moriarty J Smith OP: Successful use of recombinant FVIIa (NovoSeven®) in the management of intractable post-surgical intra-abdominal haemorrhage. Br J Haematol 1999; 107: 677–8