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.     

Blood transfusion in orthotopic liver transplantation: six-year experience

Patients undergoing orthotopic liver transplantation (OLT) are susceptible to massive blood loss and require transfusion. Possible reasons for increased transfusion demands include platelet abnormalities, thrombocytopenia secondary to hypersplenism, clotting factor deficiencies, fibrinolysis, increased surgical blood loss associated with portal hypertension and previous surgical procedures, and hypothermia. The purpose of this study was to review trends in blood product usage during our first 6 years of experience performing OLT.     

Leukocyte reduction during orthotopic liver transplantation and postoperative outcome: a pilot study

STUDY OBJECTIVE: To investigate the effect of intraoperative leukocyte reduction of administered blood products on the incidence of acute cellular rejection and postoperative patient outcome. DESIGN: Prospective, nonrandomized, historical control study. SETTING: Academic tertiary medical center. PATIENTS: The study group (Group 1) consisted of 30 consecutive adult patients with end-stage liver disease scheduled to undergo orthotopic liver transplantation (OLT) between 1998 and 2000. The historical control group (Group 2) consisted of 30 adult patients with end-stage liver disease matched to study group patients as closely as possible for age, gender, and etiology of liver disease who underwent OLT between 1995 and 1999. INTERVENTIONS: Group 1 patients had all intraoperative allogeneic and cell salvaged blood products leukocyte reduced before administration. Group 2 patients underwent OLT without leukocyte filtration of any administered blood products. MEASUREMENTS: Demographic data were collected for both patient groups and included age, gender, etiology of liver disease, and both intraoperative and postoperative immunosuppression. Demographic allograft donor data for both patient groups were collected and included age, gender, use of vasopressors during procurement, and cold and warm donor organ ischemic times. Outcome variables measured included incidence of acute cellular rejection, length of intensive care unit (ICU) and length of hospital stay, incidence of both graft loss and retransplantation, and mortality. MAIN RESULTS: The incidence of acute cellular rejection was 40% in Group 1 and 66.7% in Group 2 (p = 0.037). Length of ICU stay was 3.0 (2.0, 5.0) days in Group 1 and 4.0 (3.0, 6.0) days in Group 2 (p = 0.16). Length of hospital stay was 14.0 (11.0, 18.0) days in Group 1 and 18.0 (14.0, 27.0) days in Group 2 (p = 0.035). One allograft was lost in Group 2 because of primary nonfunction requiring retransplantation (p = 0.31), and three postoperative deaths occurred in Group 1 as a result of multisystem organ failure (p = 0.08). CONCLUSIONS: Coincident with leukocyte reduction of all administered blood products during OLT, an improved outcome was observed in Group 1 patients as demonstrated by both a decreased incidence of acute cellular rejection and length of hospital stay.     

Autologous transfusion by peroperative salvage in orthotopic transplantation of the liver

As large quantities of blood are required during orthotopic liver transplantation, intraoperative autotransfusion is therefore often carried out in adult patients. This study aimed to assess the ease of use of this technique, its efficiency and possible side-effects. Intraoperative blood salvage was carried out using a Cell Saver 4R (Haemonetics) in 14 patients. The chest blood was collected, anticoagulated with heparin and sodium citrate, centrifuged and washed with Ringer lactate. During surgery, and the subsequent 5 days, the following data were recorded: red cell and platelet count, haemoglobin concentration, parameters of renal function, potassium, citrate and fibrinogen levels, parameters of renal function, blood cultures and the extubation delay. Autotransfusion was simple to use, with no side-effects during the procedure. An average of 20.5 red cell packs were required, of which 59.2 +/- 2.3% were supplied by autotransfusion. The volume of transfused blood was similar, or inferior, to other studies. The different haematological parameters, blood gases and serum potassium levels remained stable. Only 4 +/- 2.8 red cell packs were required postoperatively to maintain a stable haematocrit value. There was no increase in thrombin time, and therefore no effect due to the used heparin. Citrate levels were correlated with the amount of autotransfused blood. They were lower than in other studies because autotransfusion limited the citrate load. There was no haemolysis. Postoperative renal function remained normal. There was no change in the blood coagulation profile, except when large volumes were transfused, resulting in a dilutional coagulopathy. Extubation was always carried out during the first two postoperative days. Bacteriological studies remained negative, no bacteraemia being noted. During orthotopic liver transplantation autotransfusion is a simple, reliable technique, with few side-effects.     

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.     

Thromboelastography does not reduce transfusion requirements in liver transplantation: A propensity score-matched study

Study objectiveTo compare total blood product requirements in liver transplantation (LT) assisted by thromboelastography (TEG) or conventional coagulation tests (CCTs).DesignRetrospective observational study.SettingA tertiary care referral center for LT.PatientsAdult patients undergoing LT from deceased donor.InterventionHemostasis was monitored by TEG or CCTs and corresponding transfusion algorithms were adopted.MeasurementsNumber and types of blood products (red blood cells, RBC; fresh-frozen plasma, FFP; platelets, PLT) transfused from the beginning of surgery until the admission to the intensive care unit.MethodsWe compared data retrospectively collected in 226 LTs, grouped according to the type of hemostasis monitoring (90 with TEG and 136 with CCTs, respectively). Confounding variables affecting transfusion needs (recipient age, sex, previous hepatocellular carcinoma surgery, Model for End Stage Liver Disease - MELD, baseline hemoglobin, fibrinogen, creatinine, veno-venous by pass, and trans-jugular intrahepatic portosystemic shunt) were managed by propensity score match (PSM).Main resultsThe preliminary analysis showed that patients in the TEG group received fewer total blood products (RBC + FFP + PLT; p = 0.001, FFP (p = 0.001), and RBC (p = 0.001). After PSM, 89 CCT patients were selected and matched to the 90 TEG patients. CCT and TEG matched patients received similar amount of total blood products. In a subgroup of 39 patients in the top MELD quartile (MELD ≥25), the TEG use resulted in lower consumption of FFP units and total blood products. Nevertheless, due to the low number of patients, any meaningful conclusion could be achieved in this subgroup.ConclusionsIn our experience, TEG-guided transfusion in LT does not reduce the intraoperative blood product consumption. Further studies are warranted to assess an advantage for TEG in either the entire LT population or the high-MELD subgroup of patients.     

重组活化凝血因子Ⅶ和抑肽酶在肝移植术中的应用

目的 前瞻性地观察使用重组活化凝血因子Ⅶ（rFⅦa）和抑肽酶对减少肝移植术中出血的有效性和安全性。方法 将中山大学附属第三医院2003—2004年欲行肝移植60例病人术前随机分为3组，第1组为rFⅦa组，第2组为抑肽酶组，第3组为对照组。对3组病人各个时间点的凝血指标、凝血弹性图（TEG）指标进行观察，比较3组术中出血量、输血量、住院时间、住院费用和血管并发症。结果 使用rFⅦa后凝血酶原时间（PT）、TEG中的反应时间（R）和最大幅度（MA）与对照组差异有显著性（P〈0.05）。而部分凝血酶原时间（APTT）、纤维蛋白原水平（FIB）、血小板计数（PLT）和TEG中的血凝块减少速率（LY30）与对照组的差异无显著性（P〉0.05）。抑肽酶组与对照组MA和LY30的差异有显著性（P〈0.05），其他指标无明显改善。rFⅦa组和抑肽酶组术中出血量、输血量均较对照组明显减少（P〈0．05）。结论 rFⅦa能迅速改善外源性凝血系统功能，抑肽酶能改善新肝期的纤溶亢进，未见增加术后血管并发症。     

Measurement of liver tissue oxygenation after orthotopic liver transplantation using a multiparameter sensor. A pilot study

The currently used methods of monitoring liver perfusion and oxygenation after liver transplantation have major limitations in clinical use. We describe the use of a multiparameter sensor to enable continuous monitoring of liver tissue oxygen tension, carbon dioxide tension and hydrogen ion concentration in the early postoperative period in 12 patients after liver transplantation. The sensor was inserted under direct vision via the falciform ligament into the liver before skin closure. Tissue oxygen tension values decreased in the first 24 h and subsequently increased to a mean (SD) = 7.3 (2.8) kPa at 48 h after surgery. This was associated with a decrease in the degree of acidosis. There were no complications attributable to the sensor. This study demonstrates that continuous measurement of liver oxygen tension, carbon dioxide tension and pH is possible. This technique may be useful as a continuous monitor to help identify grafts at risk of ischaemia.     

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.     

Early versus late recombinant factor VIIa in combat trauma patients requiring massive transfusion

BACKGROUND: Coagulopathy is a consequence of severe trauma, especially in massively transfused patients (>or=10 units of red blood cells in 24 hours), and is associated with increased mortality. We hypothesized that recombinant factor VIIa (rFVIIa) administered to massive transfusion patients before transfusion of 8 units of blood (early) would reduce transfusion requirements compared with rFVIIa after 8 units (late). METHODS: We retrospectively reviewed records for trauma admissions to combat support hospitals in Iraq between January 2004 and October 2005. Patients requiring a massive transfusion and receiving rFVIIa were identified. Groups were divided into those who received rFVIIa early or late. RESULTS: Of 5,334 trauma patients (civilian and military), 365 (6.8%) required massive transfusion. Of these, 117 (32%) received rFVIIa. Complete records for blood transfusions were available for 61 patients: 90% had penetrating trauma, 17 received rFVIIa early, and 44 received it late. At admission, temperature, heart rate, blood pressure, Glasgow Coma Scale score, base deficit, hemoglobin, platelets, prothrombin time/International Normalized Ratio, and Injury Severity Score were similar in both groups as were administered units of fresh frozen plasma, fresh whole blood, cryoprecipitate (cryo), and crystalloid. The early rFVIIa group required fewer units of blood during the first 24-hour period (mean 20.6 vs. 25.7, p=0.048) and fewer units of stored red blood cells (mean 16.7 vs. 21.7, p=0.049). Early and late mortality (33.3% vs. 34.2%, p=NS), acute respiratory distress syndrome (5.9 vs. 6.8%, p=NS), infection (5.9% vs. 9.1%, p=NS), and thrombotic events (0% vs. 2.3%, p=NS) were similar. CONCLUSIONS: Early administration of rFVIIa decreased red blood cell use by 20% in trauma patients requiring massive transfusion.     

Risk factors for bleeding and transfusion during orthotopic liver transplantation

Objective

While orthotopic liver transplantation (OLT) can be associated with haemorrhage, the risk factors for bleeding and transfusion remain difficult to predict. Perioperative transfusion has potentially deleterious side effects and impairs graft and patient survival. Preoperative identification of patients at high risk of bleeding is of clinical interest to manage perioperative transfusion and blood product storage.

Study design

Retrospective study.

Patients and methods

All OLT conducted between 2004 and 2008 in the University Hospital of Bordeaux were studied. Risk factors for bleeding greater than one blood volume and for massive red blood cell (RBC) transfusion were determined using univariate and multivariate analysis. Thresholds were determined with ROC curve analysis.

Results

One hundred and forty-eight transplantations were studied. Preoperative haemoglobin and Child class A were independent protective risk factors for bleeding greater than one blood volume (OR 0.81 [0.67-0.98] and 0.27 [0.10-0.72], respectively). Preoperative Hb was a protective risk factor (OR 0.71 [0.58-0.88]) whereas history of oesophageal varicose bleeding was a risk factor (OR 4.67 [1.45-15.05]) for transfusion of more than eight RBC.

Conclusion

Risk factors for bleeding and transfusion during OLT identified in this study were of little clinical usefulness so blood products should always be available during the procedure.     

Recombinant factor VIIa in major abdominal surgery and liver transplantation

The author reviewed the literature regarding recombinant activated Factor VII (rFVIIa) in major abdominal surgery and liver transplantation and concluded that, on the basis of evidence-based medicine, there is no evidence to support an extensive use of rFVIIa. Nevertheless, various case reports suggest the usefulness of rFVIIa to treat life-threatening bleeding after failure of conventional therapies. It appears that there is a consensus that rFVIIa can be used with good results as a rescue therapy in extremely severe situations. Economic cost and potential thrombosis risk remain arguments against more widespread use of rFVIIa. Doses from 5 to 120 kg/kg in each administration have been reported without clear evidence to support a specific protocol. Efficacy of 15 to 20 kg/kg in surgical settings has been reported, but higher doses are more frequently used. The majority of the reviewed investigators accepted the use of rFVIIa after or simultaneously with the use of aprotinin; no data refute the safety of this association.