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: The liver plays a key role in blood coagulation being involved in both primary and secondary haemostasis (1, 2). It is the site of synthesis of all coagulation factors and their inhibitors except for von Willebrand factor (vWf) (3). Liver damage is commonly associated with impairment of coagulation, when liver function reserve is poor.
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ABSTRACT: In the latest decades an important change was registered in liver surgery, however the management of liver cirrhosis or small size hepatic remnant still remains a challenge. Currently post-hepatectomy liver failure (PLF) is the major cause of death after liver resection often associated with sepsis and ischemia-reperfusion injury (IRI). ''Small-for-size'' syndrome (SFSS) and PFL have similar mechanism presenting reduction of liver mass and portal hyper flow beyond a certain threshold. Few methods are described to prevent both syndromes, in the preoperative, perioperative and postoperative stages. Additionally to portal vein embolization (PVE), radiological examinations (mainly CT and/or MRI), and more recently 3D computed tomography are fundamental to quantify the liver volume (LV) at a preoperative stage. During surgery, in order to limit parenchymal damage and optimize regenerative capacity, some hepatoprotective measures may be employed, among them: intermittent portal clamping and hypothermic liver preservation. Regarding the treatment, since PLF is a quite complex disease, it is required a multi-disciplinary approach, where it management must be undertaken in conjunction with critical care, hepatology, microbiology and radiology services. The size of the liver cannot be considered the main variable in the development of liver dysfunction after extended hepatectomies. Additional characteristics should be taken into account, such as: the future liver remnant; the portal blood flow and pressure and the exploration of the potential effects of regeneration preconditioning are all promising strategies that could help to expand the indications and increase the safety of liver surgery.