Recombinant coagulation factor VIIa in major liver resection: a randomized, placebo-controlled, double-blind clinical trial.
ABSTRACT Prevention of bleeding episodes in noncirrhotic patients undergoing partial hepatectomy remains unsatisfactory in spite of improved surgical techniques. The authors conducted a randomized, placebo-controlled, double-blind trial to evaluate the hemostatic effect and safety of recombinant factor VIIa (rFVIIa) in major partial hepatectomy.
Two hundred four noncirrhotic patients were equally randomized to receive either 20 or 80 microg/kg rFVIIa or placebo. Partial hepatectomy was performed according to local practice at the participating centers. Patients were monitored for 7 days after surgery. Key efficacy parameters were perioperative erythrocyte requirements (using hematocrit as the transfusion trigger) and blood loss. Safety assessments included monitoring of coagulation-related parameters and Doppler examination of hepatic vessels and lower extremities.
The proportion of patients who required perioperative red blood cell transfusion (the primary endpoint) was 37% (23 of 63) in the placebo group, 41% (26 of 63) in the 20-microg/kg group, and 25% (15 of 59) in the 80-microg/kg dose group (logistic regression model; P = 0.09). Mean erythrocyte requirements for patients receiving erythrocytes were 1,024 ml with placebo, 1,354 ml with 20 microg/kg rFVIIa, and 1,036 ml with 80 microg/kg rFVIIa (P = 0.78). Mean intraoperative blood loss was 1,422 ml with placebo, 1,372 ml with 20 microg/kg rFVIIa, and 1,073 ml with 80 microg/kg rFVIIa (P = 0.07). The reduction in hematocrit during surgery was smallest in the 80-microg/kg group, with a significant overall effect of treatment (P = 0.04).
Recombinant factor VIIa dosing did not result in a statistically significant reduction in either the number of patients transfused or the volume of blood products administered. No safety issues were identified.
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ABSTRACT: Pulmonary embolism occurs more frequently after hepatectomy than previously thought but is infrequently associated with peripheral deep vein thrombosis. In this paper, we report 2 cases of postoperative hepatic vein thrombosis after liver resection. Both patients had undergone major hepatectomy of a non-cirrhotic liver largely exposing the middle hepatic vein. Clots were incidentally found in the middle hepatic vein 4 and 17 d after surgery despite routine systemic thrombo-prophylaxis with low molecular weight heparin. Coagulation of the transition plan in a context of mutation of the prothrombin gene and inflammation induced biloma were the likely predisposing conditions. Clots disappeared following curative anticoagulation. We conclude that thrombosis of hepatic veins may occur after liver resection and is a potential source of pulmonary embolism.World Journal of Gastroenterology 01/2011; 17(3):403-6. · 2.55 Impact Factor
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ABSTRACT: The benefits and risks of off-label use of recombinant factor VIIa in patients without hemophilia are contested. We performed a systematic review to assess the effectiveness and safety of such use. We searched electronic databases including MEDLINE, EMBASE and CENTRAL for randomized controlled trials comparing recombinant factor VIIa with placebo in any patient population except those with hemophilia up to January 2010. Eligible articles were assessed for inclusion, data were extracted, and study quality was evaluated. Outcomes included mortality, blood loss, requirements for red blood cell transfusion, number of patients transfused and thromboembolic events. We identified 26 trials: 14 on off-label prophylactic use of recombinant factor VIIa (n = 1137) and 12 on off-label therapeutic use (n = 2538). In the studies on prophylactic use, we found no significant difference in mortality or thromboembolic events between the treatment and placebo groups. We found modest benefits favouring recombinant factor VIIa in blood loss (weighted mean difference -276 mL, 95% confidence interval [CI] -411 to -141 mL), red blood cell transfusion (weighted mean difference -281 mL, 95% CI -433 to -129 mL) and number of patients transfused (relative risk 0.71, 95% CI 0.50 to 0.99). In the therapeutic trials, we found a nonsignificant decrease in mortality and a nonsignificant increase in thromboembolic events but no difference in control of bleeding or red blood cell transfusion. Clinically significant benefits of recombinant factor VIIa as a general hemostatic agent in patients without hemophilia remain unproven. Given its potential risks, such use cannot be recommended, and in most cases, it should be restricted to clinical trials.Canadian Medical Association Journal 11/2010; 183(1):E9-19. · 6.47 Impact Factor
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ABSTRACT: Massive postpartum hemorrhage is one of the major complications in the peripartum period. In some critical cases, hemostasis is hard to achieve even after a hysterectomy has been performed. Recombinant activated factor VII has been reported as a promising adjuvant therapy for obstetric hemorrhage, although it remains unlicensed for this indication. Eight cases receiving recombinant activated factor VII in postpartum hemorrhage refractory to the conventional therapy in a Taiwanese hospital were analyzed retrospectively. A good response, defined as bleeding control in 15 min, was achieved in six patients (75%) with a single dose ranging from 55 to 105 µg/kg. The two patients with a poor response were later discovered to have had unsolved birth canal injuries. No drug-related adverse effects were noted. We recommend that any surgical bleeding should first be controlled, as well as the correction of metabolic and hematological abnormalities; however, in the situation of intractable postpartum hemorrhage, recombinant activated factor VII offers a salvage therapy and should be considered early, even before hysterectomy.Journal of Obstetrics and Gynaecology Research 07/2011; 37(7):901-7. · 0.84 Impact Factor