Efficacy and safety of repeated perioperative doses of recombinant factor VIIa in liver transplantation.

Patients undergoing orthotopic liver transplantation (OLT) have excessive blood loss during surgery that requires blood transfusions, leading to increased postoperative morbidity and mortality. We studied the efficacy and safety of activated recombinant factor VII (rFVIIa) in reducing transfusion requirements in OLT. This multicenter, randomized, double-blind, placebo-controlled trial enrolled patients undergoing OLT because of cirrhosis (Child-Turcotte-Pugh class B or C). Patients received a repeated intravenous bolus regimen of rFVIIa 60 or 120 microg/kg or placebo. The primary efficacy endpoint was the total number of red blood cell (RBC) units transfused during the perioperative period. A total of 182 patients were analyzed for efficacy and 183 for safety. No significant effect of rFVIIa was observed on the number of RBC units transfused or intraoperative blood loss compared with the placebo group. A significantly higher number of patients in the rFVIIa study groups avoided RBC transfusion. Administration of rFVIIa but not placebo restored the preoperative prolonged prothrombin time to normal value during surgery. Patients receiving rFVIIa and placebo did not experience a significant difference in rate of thromboembolic events. Additionally, there was no statistically significant effect of rFVIIa treatment on hospitalization rate, total surgery time, and the proportion of patients undergoing retransplantation. In conclusion, use of rFVIIa during OLT significantly reduced the number of patients requiring RBC transfusion. There was no increase in thromboembolic events with rFVIIa administration compared with placebo.     

Recombinant coagulation factor VIIa in major liver resection: a randomized, placebo-controlled, double-blind clinical trial

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.     

Recombinant Coagulation Factor VIIa in Major Liver Resection: A Randomized, Placebo-controlled, Double-blind Clinical Trial

Background: 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.

Methods: Two hundred four noncirrhotic patients were equally randomized to receive either 20 or 80 [mu]g/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.

Results: The proportion of patients who required perioperative red blood cell transfusion (the primary endpoint) was 37% (23 of 63) in the placebo group, 41% (26of 63) in the 20-[mu]g/kg group, and 25% (15 of 59) in the 80-[mu]g/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 [mu]g/kg rFVIIa, and 1,036 ml with 80 [mu]g/kg rFVIIa (P = 0.78). Mean intraoperative blood loss was 1,422 ml with placebo, 1,372 ml with 20 [mu]g/kg rFVIIa, and 1,073 ml with 80 [mu]g/kg rFVIIa (P = 0.07). The reduction in hematocrit during surgery was smallest in the 80-[mu]g/kg group, with a significant overall effect of treatment (P = 0.04).     

Recombinant FVIIa decreases perioperative blood transfusion requirement in burn patients undergoing excision and skin grafting--results of a single centre pilot study

BACKGROUND: Excision of burn wounds is frequently associated with a large volume of blood loss requiring allogeneic blood transfusion. We conducted a pilot study to investigate the effect of activated recombinant coagulation factor VII (rFVIIa) on the reduction of blood transfusion requirements in burn patients undergoing excision and skin grafting. METHODS: Eighteen consecutive patients scheduled for the surgery were randomised to receive either placebo or 40 microg/kg rFVIIa administered at first skin incision, and a second dose (40 microg/kg) at 90 min later. Blood transfusion requirements during, and up to 24h post-surgery per patient and percentage full thickness wound excised were compared. In addition, postoperative complications commonly seen in patients with burns as well as adverse events related to rFVIIa were monitored. RESULTS: rFVIIa significantly decreased the total number of units of blood components transfused per patient and percentage full thickness burn wound excised compared with placebo (0.9 versus 2.2, p=0.0013) including significant fewer red blood cell units (0.5 versus 1.1, p=0.004). We further observed a trend towards improved graft survival (p=0.1) and a reduction in multiple organ failures (p=0.08) in the rFVIIa-treated group. There were no adverse events, in particular thromboembolic events. CONCLUSION: rFVIIa might be useful in decreasing blood transfusion requirements in burn patients undergoing excision and skin grafting.     

Recombinant factor VIIa as adjunctive therapy for bleeding control in severely injured trauma patients: two parallel randomized, placebo-controlled, double-blind clinical trials

BACKGROUND: Uncontrolled bleeding is a leading cause of death in trauma. Two randomized, placebo-controlled, double-blind trials (one in blunt trauma and one in penetrating trauma) were conducted simultaneously to evaluate the efficacy and safety of recombinant factor VIIa (rFVIIa) as adjunctive therapy for control of bleeding in patients with severe blunt or penetrating trauma. METHODS: Severely bleeding trauma patients were randomized to rFVIIa (200, 100, and 100 microg/kg) or placebo in addition to standard treatment. The first dose followed transfusion of the eighth red blood cell (RBC) unit, with additional doses 1 and 3 hours later. The primary endpoint for bleeding control in patients alive at 48 hours was units of RBCs transfused within 48 hours of the first dose. RESULTS: Among 301 patients randomized, 143 blunt trauma patients and 134 penetrating trauma patients were eligible for analysis. In blunt trauma, RBC transfusion was significantly reduced with rFVIIa relative to placebo (estimated reduction of 2.6 RBC units, p = 0.02), and the need for massive transfusion (>20 units of RBCs) was reduced (14% vs. 33% of patients; p = 0.03). In penetrating trauma, similar analyses showed trends toward rFVIIa reducing RBC transfusion (estimated reduction of 1.0 RBC units, p = 0.10) and massive transfusion (7% vs. 19%; p = 0.08). Trends toward a reduction in mortality and critical complications were observed. Adverse events including thromboembolic events were evenly distributed between treatment groups. CONCLUSION: Recombinant FVIIa resulted in a significant reduction in RBC transfusion in severe blunt trauma. Similar trends were observed in penetrating trauma. The safety of rFVIIa was established in these trauma populations within the investigated dose range.     

Use of activated recombinant coagulation factor VII in patients undergoing reconstruction surgery for traumatic fracture of pelvis or pelvis and acetabulum: a double-blind, randomized, placebo-controlled trial

Background. Activated recombinant coagulation factor VII (rFVIIa)effectively prevents and controls bleeding in patients withcoagulopathy. Data show that rFVIIa may reduce blood loss andeliminate the need for transfusion in patients with normal haemostasisundergoing major surgery. We assessed the efficacy of rFVIIain patients with normal haemostasis undergoing repair surgeryof major traumatic fracture of the pelvis or the pelvis andacetabulum, who were expected to have a large volume of bloodloss. Methods. We performed a double-blind, randomized, placebo-controlledtrial involving 48 patients undergoing major pelvic–acetabularsurgery. Patients were randomized to receive an i.v. bolus injectionof rFVIIa 90 µg kg^–1 or placebo as add-on therapyat the time of the first skin incision. All patients also receivedintraoperative salvaged red blood cells (RBC). Results. There was no significant difference in the total volumeof perioperative blood loss, the primary outcome variable, betweenthe rFVIIa and placebo groups. In addition, there were no differencesbetween the two groups in the total volume of blood components,including salvaged RBC transfused, number of patients requiringallogeneic blood components, total volume of fluids infused,total operating time, time taken after entry to the intensivecare unit to reach normal body temperature and acid–basestatus, and time spent in hospital. No adverse events, in particularthromboembolic events, were reported in either group. Conclusions. In patients with normal haemostasis undergoingrepair surgery of traumatic pelvic–acetabular fracture,the prophylactic use of rFVIIa does not decrease the volumeof perioperative blood loss.      

rFVIIa in the treatment of persistent hemorrhage in pediatric patients on ECMO following surgery for congenital heart disease

BACKGROUND: Patients who require extracorporeal membrane oxygenation (ECMO) postsurgery for congenital heart disease (CHD) frequently experience severe bleeding episodes. Whereas recombinant-activated factor VII (rFVIIa) has proven efficacy in counteracting intractable hemorrhage in various scenarios, its use in patients on ECMO is limited by the increased risk for thrombotic events. METHODS: Between December 2004 and January 2006, ECMO was used in 10 pediatric patients following cardiac surgery, of whom seven were treated with rFVIIa because of intractable hemorrhage. Their medical records were reviewed with respect to variations in chest tube output and transfusion requirements, occlusion of or thrombus formation in the ECMO circuit and the occurrence of thromboembolic events. Outcome and rate of ECMO circuit occlusion were compared with historic controls. RESULTS: Three patients died, and four survived (none of the deaths was attributable to thrombus formation or bleeding). All patients were treated with aprotinin prior to and during rFVIIa therapy. Two patients developed an occlusion of the oxygenator, one after receiving co-medication with a FXIII concentrate, another after RBC transfusion in the ECMO system. In two patients, thrombus formation was observed in the ECMO system on inspection after discontinuation. Thromboembolic events were not observed. CONCLUSIONS: Recombinant-activated factor VII in a median dosage of 90 microg.kg(-1) was used in seven pediatric patients on ECMO. Rates of ECMO system occlusions and mortality did not differ from historic controls. Neither the reduction of chest tube output nor the blood product transfusion requirements did reach statistical significance.     

Activated recombinant factor VII in orthotopic liver transplantation

Orthotopic liver transplantation (OLT) is affected by important alterations of hemostasis. The aim of this study was to evaluate the efficacy of recombinant factor VII activated (rFVIIa) to reduce intraoperative bleeding during OLT. METHODS: Twenty OLT patients were assigned in double-blind way to a rFVIIa group or a control group. Inclusion criteria were hemoglobin > 8 g/dL: INR > 1,5 and fibrinogen > 100 mg/dL. We administered a single bouls of rFVIIa (40 microg/kg) or placebo. We determined INR, partial thromboplastin time, fibrinogen, ATIII, and blood cell counts. Blood products were administered as follows: 4 units of fresh frozen plasma when INR > 1.5, and 1 unit of RBC for Hb < 10 g/dL. The study ended 6 hours after the bolus. RESULTS: No thromboembolic events occurred. The INR was different between rFVIIa group and the controls at T0 (1.9 vs 1.6 P < .021) and during T1 (1.2 vs 1.6 P < .004). The total transfused red blood cells was 300 mL +/- 133 in rFVIIa group and 570 mL +/- 111 in control group (P < .017). The total fresh frozen plasma was 600 mL +/- 154 in rFVIIa group and 1400 mL +/- 187 in control group (P < .001). Total blood loss was greater in the control group than the rFVIIa group: 1140 mL +/- 112 vs 740 mL +/- 131 (P < .049). DISCUSSION: The use of rFVIIa during OLT can reduce the risk of bleeding during surgery. The literature has described cases who did not benefit from the treatment. An adequate cut-off of INR, allowed us to treat only patients at greater bleeding risk.     

Safety and efficacy of a single bolus administration of recombinant factor VIIa in liver transplantation due to chronic liver disease.

Orthotopic liver transplantation (OLT) can be associated with excessive blood loss. As a result, there may be increased risk of adverse outcomes. Activated recombinant factor VII (rFVIIa) has demonstrated the ability to improve hemostasis in a variety of disorders; however, there has been a limited amount of research into its use in OLT. The purpose of this dose-finding study was to examine the efficacy and safety of rFVIIa in the reduction of bleeding in patients undergoing OLT. In this double-blind trial, patients with end-stage liver disease scheduled for OLT were randomized to 1 of 4 parallel study groups. They received a single intravenous bolus of rFVIIa (20, 40, or 80 microg/kg) or placebo prior to surgery. The primary assessment endpoint was the total number of red blood cell (RBC) units transfused perioperatively. Safety was evaluated by adverse events reported. Eighty-three comparable patients were randomized to receive study product, with 82 ultimately undergoing OLT. There were no significant differences in required RBC units between the placebo and rFVIIa study groups. The number of adverse events was comparable between study groups. In conclusion, rFVIIa has a good safety profile in patients undergoing OLT. However, the doses studied did not have any effect on the number of RBC transfusions required.     

Efficacy and safety of tranexamic acid in hip fracture surgery. How does dosage affect outcomes: A meta-analysis of randomized controlled trials

AimThe objective of this study was to assess the efficacy and safety of intravenous TXA administration in elderly patients undergoing hip fracture surgery focusing on the effect of various dosages.MethodsA systematic search of PubMed, Embase and Cochrane Library was conducted until February 2021. Our primary outcome was peri?operative total blood loss, while secondary outcomes included transfusion rate, mean count of transfused RBC units and thromboembolic events’ incidence. A subgroup analysis was performed with respect to TXA dosage.ResultsOut of 146 records identified, 10 randomized controlled studies met the selection criteria. Data synthesis revealed that TXA resulted in a significant reduction in total blood loss by 229.45 ml in favor of TXA; 95% CI: [189.5, 269.4] and transfusion rate by 40%, RR = 0.60; 95% CI: [0.47, 0.78]. No increase in thromboembolic events rate was observed (RR = 1.08, 95% CI: [0.68, 1.69]) Furthermore, sub-analysis with respect to TXA dosage showed no significant difference in total blood loss reduction between “single” and “multiple doses” studies (223 vs 233.5 ml, p = 0.85.), while a trend for lower complications rate was observed in patients receiving a single dose of ≤ 15 mg/kg.ConclusionsThis meta-analysis provides strong evidence that TXA is a safe and effective agent to reduce perioperative blood loss in hip fracture surgery. When compared with higher dosages, a single dose of 15 mg/kg is associated with a non-significant reduction in adverse events, while achieving comparable outcomes.     

Recombinant Factor VIIa for Life-Threatening Hemorrhage in Trauma Patients: Review of the Literature

Abstract The control of hemorrhage and coagulopathy is a vital component of trauma care, and failure to achieve hemostasis can contribute to mortality. Recombinant factor VIIa (rFVIIa) is a well-established therapy for bleeding episodes and surgical prophylaxis in hemophilia patients with inhibitors. However, there has been increasing utilization of rFVIIa in the treatment of trauma-related blood loss in patients without pre-existing coagulopathy. This paper reviews published experience in this area. Database searches identified 126 rFVIIa-treated trauma patients reported in 15 publications between November 1999 and November 2004. Ages ranged from 20 months to 88 years, and the majority of patients (68.7%) had suffered blunt injury. In most cases, rFVIIa was used as a salvage therapy when bleeding continued despite the appropriate application of available conventional hemostatic methods. Doses of rFVIIa varied widely (36–178 μg/kg), with patients receiving a single dose or multiple doses separated by an interval of 2–12 h. Efficacy of treatment (reduction in blood loss, transfusion requirements and mortality) was reported for 79.4% of subjects. Most publications also described shortening or normalization of coagulation parameters following rFVIIa administration. No non-thrombotic adverse events were noted in any patient, but five cases (4.0%) of thromboembolic events were recorded. Recently reported clinical trial data offer support to these anecdotal observations. In conclusion, data appear to support the utility of rFVIIa as an adjunctive therapy for the reduction of hemorrhage and transfusion requirements in trauma patients. However, further information relating to the use of rFVIIa in the trauma setting is required.     

Is recombinant activated factor VII effective in the treatment of excessive bleeding after paediatric cardiac surgery?

A best evidence topic in paediatric cardiac surgery was written according to a structured protocol. The question addressed was whether recombinant activated factor VII was effective for the treatment of excessive bleeding after paediatric cardiac surgery. Altogether 150 papers were found using the reported search; 13 papers were identified that provided the best evidence to answer the question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these studies were tabulated. A total of 311 children experienced excessive bleeding following cardiac surgery that was refractory to the conventional methods of achieving haemostasis. One hundred and ninety-two patients received the rFVIIa while 116 were in control arm from five studies. The primary end-point was on chest tube drainage, the plasma prothrombin time, the activated partial thromboplastin time after the administration of rFVIIa and the secondary end-point was reduction of blood products transfusion. Thrombosis was a complication in 8 patients (4.2%); three deaths (1.6%) but not attributable to thromboembolic events following the use of rFVIIa. Most of the studies failed to clearly state the doses but the extracted doses ranged between 30 and 180?μg/kg/dose, the interval between doses ranged between 15 and 120?min with a maximum of four doses. However, most of the patients had 180?μg/kg/dose with interval between dose of 2?h and maximum of two doses with dosage moderated with respect to weight, prior coagulopathy and responsiveness. There were two randomized studies with good sample size. One showed no significant differences in the secondary end points between the two arms and noted no adverse complications. However, the rFVIIa was used prophylactically. The other observed that there were no increase in thromboembolic events rather rFVIIa was effective in decreasing excessive bleeding that may complicate cardiac surgery in children. In conclusion, the studies were in support of the notion that the use of rFVIIa was effective in decreasing excessive bleeding which may complicate paediatric cardiac surgery, and care should be exercised when using it in the children on ECMO circuit.     

Reduced transfusion requirements by recombinant factor VIIa in orthotopic liver transplantation: a pilot study

BACKGROUND: Large transfusion requirements, i.e., excessive blood loss, during orthotopic liver transplantation (OLT) are correlated with increased morbidity and mortality. Recombinant factor VIIa (rF-VIIa) has been shown to improve hemostasis in a variety of conditions, but has never been studied in liver transplantation. METHODS: We performed a single-center, open-label, pilot study in adult patients undergoing OLT for cirrhosis Child-Pugh B or C, to assess efficacy and safety of rFVIIa. rFVIIa (80 microg/kg) was administered at the start of the operation, to be repeated according to predefined criteria. Packed red blood cells (RBC), fresh-frozen plasma, and platelet concentrates were administered according to predefined criteria. Perioperative transfusion requirements in study patients were compared with matched controls. RESULTS: Six patients were enrolled in the study. All received a single dose of rFVIIa. Transfusion requirements (given as median, with range in parentheses) were lower in the study group than in matched controls: 1.5 (0-5) vs. 7 (2-18) units of allogeneic RBC (P=0.006), 0 (0-2) vs. 3.5 (0-23) units of autologous RBC (P=0.043), total amount of RBC 3 (0-5) vs. 9 (4-40) units (P=0.002). Transfused fresh-frozen plasma was 1 (0-7) vs. 8 (2-35) units (P=0.011). Blood loss was 3.5 L (1.4-5.3) vs. 9.8 L (3.7-35.0) (P=0.004). One study patient developed a hepatic artery thrombosis at day 1 postoperatively. CONCLUSIONS: A single dose of 80 microg/kg rFVIIa significantly reduced transfusion requirements during OLT. Further study is needed to establish the optimally effective and safe dose of rFVIIa in orthotopic liver transplantation.     

Aprotinin and nafamostat mesilate in liver surgery: effect on blood loss

The origin of blood loss during liver surgery is multifactorial. Surgical skill, technique, anesthesiological care, but also hyperfibrinolysis have been shown to play a role in the origin of bleeding during partial hepatectomy and liver transplantation. The latter has provided the scientific basis for the prophylactic use of antifibrinolytic drugs, such as aprotinin and nafamostat mesilate in liver surgery. Recently however, concern has been voiced about potential risks associated with aprotinin, including renal failure and thromboembolic events. In this review we discuss the efficacy and safety issues of aprotinin and nafamostat mesilate in liver surgery. We identified a total of 19 studies on the use of either aprotinin or nafamostat mesilate in liver surgery reported in the time period between 1966 and July 2006. The use of aprotinin or nafamostat mesilate in partial hepatectomies was studied in three studies. In 16 studies the use of aprotinin in liver transplantation was investigated. With respect to partial hepatectomy, improvements in surgical technique and anesthesiological care seem to be more important in reducing blood loss than the use of the antifibrinolytic drugs. Aprotinin may be indicated in a selected group of patients with cirrhosis undergoing liver resection, but further studies in this specific group of patients will be needed. In liver transplantation, the use of aprotinin is associated with a significant reduction in blood loss and transfusion requirements of around 30-40%. Results of prospective studies do not provide support for safety concerns as no increased risk for thromboembolic events or renal dysfunction has been observed in liver transplant patients treated with aprotinin. In conclusion, there is currently no scientific support for the routine use of aprotinin or nafamostat mesilate in patients undergoing partial hepatectomy, whereas the efficacy of aprotinin in liver transplantation is well established. More studies will be needed to address the safety aspects of aprotinin in patients undergoing liver surgery in more detail.     

The use of recombinant activated factor VII in trauma patients: Experience from the Australian and New Zealand haemostasis registry

BACKGROUND: There is increasing use of rFVIIa (eptagog alpha, Novoseven) in injured patients with critical bleeding. The role of rFVIIa is not defined in this group of patients. Registries provide an opportunity to review the patients, reported response and adverse events for rFVIIa. AIM: To determine the pattern of use, reported response and adverse events in patients receiving rFVIIa following injury using the Australian and New Zealand Haemostasis Registry (ANZHR). METHODS: The ANZHR (commenced May 2005) collects data from 53 hospitals on all patients receiving rFVIIa in those hospitals. RESULTS: Of 695 cases in the registry, 108 patients from 19 hospitals were submitted with a primary trauma diagnosis. Most (88) patients received one 90microg/kg dose of rFVIIa. There was a significant reduction in the use of all blood products following rFVIIa (p<0.001) and rFVIIa was thought to have decreased or stopped bleeding in 59% of cases. There was wide variation in the timing of rFVIIa use. There were two adverse events that were considered possibly linked and a total of three thromboembolic events. Following multivariate analysis, pH provided the best model of response to rFVIIa. Patients with a pH<7.05 were significantly less likely to respond (OR=0.3, 95% CI=0.0-0.3). Only two patients would fit the criteria for the present prospective study of rFVIIA in trauma patients. CONCLUSION: The best approach to managing critical bleeding in trauma patients is not agreed. The role of rFVIIa will only be clarified if there is a standardised approach to fluid management and transfusion of blood products. The registry allows tracking of current practice, outcomes and adverse events and will complement present phase 2 and 3 trials.     

Recombinant coagulation factor VIIa—a novel haemostatic agent in scoliosis surgery?

Astract Spinal fusion surgery in children and adolescents with idiopathic scoliosis is often associated with severe haemorrhage. Recombinant coagulation factor VIIa (rFVIIa) has previously been shown to be an effective haemostatic treatment for severe bleeding associated with a variety of coagulopathic and non-coagulopathic indications. The aim of this retrospective study was to assess the safety and haemostatic efficacy of rFVIIa in a series of 26 consecutive adolescent patients with scoliosis (22 females; mean age 16.6 years) undergoing correctional surgery. A second series of 26 consecutive patients (20 females; mean age 16.2 years) who received standard therapy during surgery, represented historical controls. Blood loss, transfusion requirements, duration of surgery, and peri-operative measurements of coagulation parameters were compared between the two groups. Intra-operative and combined intra-operative and post-operative blood losses were significantly smaller in the rFVIIa-treatment group than in the historical controls (P=0.003 and 0.032, respectively); rFVIIa-treated patients also demonstrated significantly reduced blood loss per vertebral segment fused (P=0.032) and per hour of surgery (P<0.001). Intra-operative requirements for packed red blood cells were also significantly lower in the treatment group (P=0.042). Patients in the treatment group demonstrated rapid and maintained reduction of prothrombin time and international normalised ratio; values among rFVIIa-treated patients remained significantly lower than those in the control group at all time points evaluated (P<0.001). There were no deaths and no adverse events. These results suggest that rFVIIa is a safe and effective haemostatic agent for use during spinal fusion surgery in adolescent patients with idiopathic scoliosis; however, further research and randomised, placebo-controlled trials are needed to confirm these findings.     

Rescue treatment with recombinant factor VIIa is effective in patients with life-threatening bleedings secondary to major wound excision: a report of four cases

Major burn wound excision is associated with excessive perioperative blood loss. Treatment of massive microvascular bleeding represents a special problem in the burn setting, characterized by extensive damage at the capillary level, and resulting in a profound blood loss; which together with the consumptive states makes adequate replacement therapy with coagulation factors and platelets difficult. We described our experience with rescue treatment with rFVIIa in four patients undergoing major wound excision, developing life-threatening perioperative bleeding, and not responding to conventional therapy. Hemostasis was achieved within 15 minutes of intravenous rFVIIa administration, at a dose of 100 microg/kg, in all patients. No treatment-related adverse events, in particular, no thromboembolic events were observed. We conclude that rFVIIa may be an effective hemostatic treatment for patients undergoing major wound excision developing life-threatening bleedings.     

Acute coagulopathy after reperfusion of the liver graft in children correction with recombinant activated factor VII

BACKGROUND: Several studies have proven that massive blood loss increases postoperative morbidity and mortality in liver graft recipients. Since we have successfully corrected coagulopathy preoperatively using an intravenous (IV) bolus of recombinant activated factor VII (rFVIIa) in 2 patients with fulminant liver failure, we observed that there was rapid reversal of preexisting advanced coagulopathy in another 40 patients with high risk for intraoperative bleeding by this treatment immediately before transplantation. Recently to control hemostasis we have administered rFVIIa also to patients presenting with acute coagulopathy and nonsurgical bleeding after graft reperfusion as described herein. MATERIALS AND METHODS: We have used rFVIIa in 7 children presenting with severe coagulopathy and nonsurgical bleeding after liver graft reperfusion. The dosage of rFVIIa ranged between 37 and 148 mcg/kg. An antifibrinolytic agent (aprotinin, tranexamic acid) was administered simultaneously. RESULTS: APTT before rFVIIa was 86.10 to 183 seconds, (mean, 132.1 +/- 39.88), after the bolus of rFVIIa 49.4 to 206.1 (mean, 112.7 +/- 58.53), and at the end of surgery 71.70 to 180 (mean, 110.3 +/- 40.98). INR after reperfusion was 1.82 to 3.91 (mean, 2.56 +/- 0.67), 1.03 to 1.92 (mean, 1.54 +/- 0.35) after rFVIIa, and 1.74 to 5.58 (mean, 2.64 +/- 1.35) at the end of surgery. Before rFVIIa administration intraoperative blood transfusions after graft reperfusion were 900 to 4200 mL of red blood cells (RBC) (0.82-5.4 total blood volume) and after reperfusion 0 to 1800 mL of RBC (0-2.5 TBV). No postoperative vascular complications were observed. CONCLUSIONS: A single dose of rFVIIa effectively reverses the severe coagulopathy developing after graft reperfusion, establishing effective hemostasis in liver transplant recipients without an increased risk of thrombotic complications.     

The role of recombinant factor VIIa in the treatment of life-threatening haemorrhage in blunt trauma

BACKGROUND: Recombinant factor VIIa (rFVIIa) is a novel haemostatic agent originally developed to treat bleeding in haemophiliacs. Several case reports suggest effectiveness of rFVIIa in the treatment of patients without pre-existing bleeding disorders. The aim of this study is to evaluate treatment with recombinant (rFVIIa) in blunt trauma patients with uncontrolled bleeding. PATIENTS AND METHODS: This study was designed as a retrospective case review. Consecutive patients with life-threatening uncontrolled bleeding due to blunt trauma who were treated with rFVIIa were selected. Data were obtained from medical records. RESULTS: A total of eight blunt trauma patients were treated with rFVIIa for uncontrolled bleeding. After treatment the need for transfusion of red blood cells (RBC) decreased significantly from 31.3 +/- 15.8 to 6.1 +/- 6.8 units (P = 0.003), fresh frozen plasma (FFP) from 13.3 +/- 6.6 to 5 +/- 6.3 units (P = 0.02), and platelets from 3.6 +/- 1.8 to 1.5 +/- 2.3 units (P = 0.01). Three patients died of non-bleeding complications. The other five fully recovered. CONCLUSION: Treatment with rFVIIa reduced or stopped bleeding in all patients. No adverse events were registered. Prospective studies are mandatory to elucidate the role of rFVIIa in blunt trauma.     

Small-dose recombinant activated factor VII (NovoSeven) in cardiac surgery

Recombinant activated factor VII (rFVIIa) has been used at different doses in cardiac surgery patients. We tested the efficacy of small-dose rFVIIa in patients with intractable bleeding after cardiac surgery. The study group comprised 15 cardiac surgery patients with intractable bleeding treated with small-dose (1.2 mg) rFVIIa as a slow IV bolus at the end of complete step-by step transfusion protocol. Fifteen matched patients undergoing the same transfusion protocol in the pre-rFVIIa era represented the control group. Blood loss at the end of the transfusion protocol was a primary outcome. Median, 25th-75th 24-h blood loss percentiles were 1685 (1590-1770) mL versus 3170 (2700-3850) mL in study group and controls, respectively (P = 0.0004). Transfused red blood cells, fresh-frozen plasma, and platelets in the study group and controls were as follows: 7 (4-8) U versus 18 (12-21) U (P = 0.001); 7.5 (6-11) U versus 11 (9-15) U (P = 0.003); 0 (0-4) U versus 9 (6-13) U (P = 0.001). In addition, significant improvements of prothrombin time (P = 0.015), international normalized ratio (P = 0.006), activated partial prothrombin time (P = 0.01), and platelet count (P = 0.003) were detected in the study group versus controls. Finally, patients receiving rFVIIa showed a reduced intensive care unit length of stay (chi2 = 15.9, P = 0.0001) and had infrequent surgical re-exploration (chi2 = 16.2,P < 0.0001). Small-dose rFVIIa showed satisfactory results in cardiac patients with intractable bleeding. Further randomized studies are necessary to confirm our findings.