重组活化人凝血因子VII在肝脏移植术中应用

重组活化人凝血因子VII(recombinant factorVIIa,rFVIIa),是一种新型止血药,最初用于治疗存在有因子VIII(FVIII)和因子IX(FIX)抗体(抑制物)的先天性血友病和继发性血友病患者的自发性或手术性出血。目前,已证实该药对控制多种临床出血情况是有益的[1]。1分子结构活化人凝血因子     

Recombinant activated factor VII in critical bleeding after orthotopic liver transplantation

Critical bleeding throughout the intraoperative phase of orthotopic liver transplantation (OLT) strongly increases patient mortality and intensive care unit (ICU) stay. The aim of this study was to report our experience on the use of recombinant activated factor VII (rFVIIa) in postoperative critical bleeding after OLT. In 7 patients with persistent severe bleeding after application of a standard transfusion protocol, we administered a 90 microg/kg bolus of rFVIIa and if necessary eventually repeated it after 3 hours. We recorded the blood loss and the need for transfusions before and after the rFVIIa therapy. Blood losses and need for platelets significantly decreased after rFVIIa administration; a nonsignificant decrease in red blood cells and fresh frozen plasma transfusions also occurred. In 6 patients treatment with rFVIIa was effective; only 1 patient died because of hemorrhagic shock and no thromboses were detected among the treated patients. Awaiting stronger evidence from randomized controlled trials, we suggest that in some challenging cases of massive bleeding rFVIIa should be considered a useful option to control bleeding.     

Benefits of recombinant activated factor VII in complicated liver transplantation

INTRODUCTION: Recombinant activated factor VII (rFVIIa, NovoSeven, NovoNordiskA/S, Bagsvaerd, Denmark) has shown benefits in hemophilic patients and recently in transplant recipients. This study presents our experiences with rFVIIa in complicated liver transplant recipients. METHODS: From May 2001 to August 2004, rFVIIa was administered to 7 patients undergoing liver transplantation. All treatments were made on emergency bases, except for 1 case with hemophilia A, who received prophylactic treatment. The drug was delivered when severe bleeding with coagulopathy persisted despite the usual treatment with blood products. The drug doses were 60-90 mug/kg; the results were evaluated clinically and analytically. RESULTS: Seven patients undergoing liver transplantation were treated with FVIIa. Mean prothrombin times before and after treatment were 17.5 and 10.9 seconds, respectively, with a mean reduction of 7.2 seconds (P = .03). Mean thromboplastin times before and after treatment were 38.1 and 29.4 seconds, respectively, with a mean reduction of 8.7 seconds (P = .034). The average dose was 83.6 mug/kg, leading to decreased consumption of blood products (P < .01). In all cases, rFVIIa allowed sufficient hemostasis to carry on definitive treatment. There was no mortality in this series. CONCLUSIONS: These results provide new evidence on the potential benefits of rFVIIa in liver transplantation, especially for rescue therapy in cases of severe bleeding.     

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.     

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。     

Rapid correction of prothrombin time after low-dose recombinant factor VIIA in patients undergoing orthotopic liver transplantation

Orthotopic liver transplantation (OLTx) is associated with a major risk of blood loss resulting from portal hypertension, collateral circulation, and clotting disturbances. Application of a recombinant factor VIIa (rFVIIa) has been reported to promptly correct clotting abnormalities reducing the risk of intraoperative bleeding. This study included 8 patients who underwent OLTx for end-stage liver cirrhosis, with protrombin times (PT) exceeding the upper limit of normal by more than 4 seconds before surgery. All subjects were administered a small single intravenous dose of rFVIIa [mean 68.37 microg/kg body mass (range, 32.88-71.64)] 10 minutes prior to the skin incision. The PT was then measured 15 minutes later, following graft reperfusion, and 12 hours since drug application. All patients showed rapid correction of PT within 15 minutes after injection (median PT before injection 20.25 seconds vs 11.5 seconds after injection, P <.0001). Following the reperfusion PT was found to be prolonged again. These values are not significantly differ from those before surgery and are comparable to PT values after reperfusion in patients who did not receive rFVIIa. None of the patients developed thromboembolic complications. In conclusion, lower than recommended dose of rFVIIa caused rapid improvement in the PT shortly after injection. After reperfusion PT became prolonged again, which may account for the lack of thromboembolic complications observed in this group of patients.     

Transmission of factor VII deficiency through liver transplantation

The liver is the primary site of synthesis for the majority of coagulation factors. There are published accounts of liver donor-to-recipient transmission of protein C deficiency with dysfibrinogenemia and factor XI deficiency. In this article, we report what we believe to be the first observation, of transmission of factor VII deficiency, a rare, autosomal recessive coagulation disorder, from an affected liver donor to a naive liver recipient. At 300 days after transplantation, the recipient remains with an isolated prolongation of the prothrombin time and a below-normal level of factor VII, and has had no bleeding complications. Received: 6 November 1998 Received after revision: 26 April 1999 Accepted: 4 May 1999     

Human natriuretic factor in cirrhotic patients undergoing orthotopic liver transplantation

We measured the plasma levels of atrial natriuretic factor (ANF) during orthotopic liver transplantation (OLT) in eight adult patients with cirrhosis and ascites. The aim of this study was to determine whether significant differences in ANF concentration may be detected during the individual phases of OLT and to correlate these changes with hemodynamics. In each patient a hemodynamic assessment was achieved using a Swan-Ganz fiber optic catheter for continuous monitoring of cardiac output (CO), systemic vascular resistance index (SVRI), right filling pressure as assessed by central venous pressure (CVP), and left filling pressure by means of pulmonary arterial wedge pressure (PAWP). During reperfusion a clear-cut increase in ANF values was observed (P<0.05). Concurrently, an increase in CVP (P<0.05) and a decrease in SVRI were observed without any significant increase in diuresis. These data suggest that ANF might play a role in the development of the reperfusion syndrome.     

Canine orthotopic liver transplantation

For the purpose of increasing long-term survival in canine orthotopic hepatic allotransplantation, immunosuppression by mizoribine and/or cyclosporin was instituted with the following results: 1) The survival of control dogs without treatment (n = 5) was 10.0 +/- 2.9 days (Mean +/- S.E.), and the survival of dogs treated with mizoribine (n = 15) was 44.6 +/- 31.8 days. There was no statistical difference between the two groups. On the other hand, the mean survival of dogs that were initially treated with cyclosporin and were then switched to mizoribine at one to three months after transplantation reached 145.4 +/- 70.8 days. The survival rate of dogs in the cyclosporin-mizoribine group was significantly greater than that of control group (p less than 0.02); and the survival rate of the former group proved also significantly better than that of the mizoribine group at 20 days after transplantation (X2, p less than 0.05); 2) in cases of acute rejection of the allograft, a gradual increase of the serum bilirubin level with a concomitant rise of S-GPT and alkaline phosphatase was generally observed. For an accurate diagnosis, however, an assessment of the biopsy findings of the allograft is important; 3) in chronic rejection, one animal developed the selective disappearance of interlobular bile ducts, often referred to as the "vanishing bile duct syndrome"; and 4) for differential diagnosis of vascular and/or biliary tract complications, specific morphological diagnostic procedures such as vascular and/or biliary tract angiographies are needed.