Tranexamic Acid Reduces Blood Loss, Transfusion Requirements, and Coagulation Factor Use in Primary Orthotopic Liver Transplantation

Boylan, John F.; Klinck, John R.; Sandler, Alan N.; Arellano, Ramiro; Greig, Paul D.; Nierenberg, H.; Roger, S.; Glynn, Michael

doi:10.1097/00000542-199611000-00012

Cited by 237 publications

(128 citation statements)

References 22 publications

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“…Hyperfibrinolysis, either assessed by global fibrinolytic assays or by plasma levels of fibrin(ogen) degradation products plus t-PA antigen or activity, has been reported to be a predictor of bleeding in cirrhotic patients, [33][34][35] and there is evidence that antifibrinolytic drugs may be effective for the treatment of bleeding complications. 33,36,37 It is tempting to speculate that TAFI assay may represent an additional tool to estimate the risk of bleeding in cirrhosis and help select patients who might benefit from an antifibrinolytic treatment.…”

Section: Discussionmentioning

confidence: 99%

Deficiency of Thrombin Activatable Fibrinolysis Inhibitor in Cirrhosis Is Associated With Increased Plasma Fibrinolysis

et al. 2003

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Hyperfibrinolysis is thought to contribute to bleeding associated with advanced cirrhosis. Thrombin activatable fibrinolysis inhibitor (TAFI) is a plasma precursor of a carboxypeptidase (TAFIa) with antifibrinolytic activity and was recently shown to be reduced in cirrhosis. In this study, we evaluated the influence of TAFI deficiency on in vitro fibrinolysis in cirrhotic patients. Fifty-three patients with cirrhosis and 43 healthy controls were studied. TAFI antigen was measured by enzyme-linked immunosorbent assay and TAFI activity by chromogenic assay. Fibrinolysis was evaluated as tissue plasminogen activator-induced plasma clot lysis time in the absence and in the presence of a specific inhibitor of TAFIa. TAFI antigen and activity levels were markedly reduced in cirrhotic patients (P < .0001). In these patients, the lysis time of plasma clots was shorter than in controls (median, interquartile range: 25 minutes, 21-36 minutes vs. 48 minutes, 40-60 minutes, respectively; P < .0001) and was poorly influenced by the TAFIa inhibitor. Accordingly, TAFIa and thrombin activity, generated in cirrhotic samples during clot lysis, were significantly lower than in control samples. Addition of purified TAFI to cirrhotic plasma prolonged the lysis time and enhanced the response to TAFIa inhibitor in a dose-dependent manner. In conclusion, our results indicate that in vitro plasma hyperfibrinolysis in cirrhosis is largely due to a defective TAFIa generation resulting from low TAFI levels and probably from impaired thrombin generation. Impairment of the antifibrinolytic TAFI pathway might contribute to bleeding associated with this disease. (HEPATOLOGY 2003;38:230-237.) H yperfibrinolysis is a common finding in cirrhosis and is thought to contribute to the bleeding tendency associated with this disease by causing a premature removal of the hemostatic plug at sites of vascular injury. The abnormalities of the fibrinolytic system encountered in cirrhosis are complex and result from both impaired synthesis and altered clearance of the fibrinolytic factors. 1 Of particular relevance to hyperfibrinolysis are the imbalance between tissue plasminogen activator (t-PA) and its specific inhibitor (PAI-1), which results in an enhancement of free t-PA in the circulation and the reduction of ␣ 2 -plasmin inhibitor (␣ 2 -PI). [2][3][4][5][6] In recent years, a new plasma protein has been identified that may play an important regulatory role in fibrinolysis. It is a procarboxypeptidase synthesized by the liver and named thrombin activatable fibrinolysis inhibitor (TAFI) or procarboxypeptidase B or U. 7-9 Upon activation by thrombin or plasmin, it is converted to an enzyme (TAFIa) with carboxypeptidase B-like activity that inhibits fibrinolysis through the removal of C-terminal lysines from partially degraded fibrin. 10,11 In so doing, TAFIa reduces the cofactor function of fibrin in the plasminogen activation catalyzed by t-PA, thereby decreasing plasmin generation. The most likely physiologic activator of TAFI is thrombin, 12,13 whi...

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Section: Discussionmentioning

confidence: 99%

Deficiency of Thrombin Activatable Fibrinolysis Inhibitor in Cirrhosis Is Associated With Increased Plasma Fibrinolysis

et al. 2003

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“…It has been used successfully to reduce the blood loss in cardiac surgery [22], liver surgery [4], and gynecology [30]. The efficacy of tranexamic acid administered intravenously in preventing blood loss in TKA has been established in numerous studies [2,6,[12][13][14][15]29].…”

Section: Introductionmentioning

confidence: 99%

Most Effective Regimen of Tranexamic Acid in Knee Arthroplasty: A Prospective Randomized Controlled Study in 240 Patients

Maniar

Kumar²,

Singhi

et al. 2012

Clinical Orthopaedics &Amp; Related Research

277

256

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Background The antifibrinolytic tranexamic acid reduces surgical blood loss, but studies have not identified an optimal regimen. Questions/purposes We studied different dosages, timings, and modes of administration to identify the most effective regimen of tranexamic acid in achieving maximum reduction of blood loss in TKA. Methods We prospectively studied five regimens (four intravenous, one local; 40 patients each) with a control group (no tranexamic acid). The four intravenous (10-mg/kg dose) regimens included (1) intraoperative dose (IO) given before tourniquet deflation, (2) additional preoperative dose (POIO), (3) additional postoperative dose (IOPO), and (4) all three doses (POIOPO). The fifth regimen was a single local application (LA). Two independent parameters of drain loss and total blood loss, calculated by the hemoglobin balance method, were evaluated statistically. Results Both parameters were reduced in all five regimens as against the control. A significant reduction in drain loss was seen in the POIO, IOPO, and POIOPO groups whereas total blood loss was significantly reduced in the POIO, POIOPO, and LA groups. The POIOPO group had the least drain loss (303 mL) and least total blood loss (688 mL). The IO group had the greatest drain loss and the IOPO group the greatest total blood loss. Conclusions Single-dose tranexamic acid did not give effective results. The two-dose regimen of POIO was the least amount necessary for effective results. When compared against the control, this regimen produced reduction of drain loss and total blood loss, whereas the IOPO regimen did not. The three-dose regimen of POIOPO produced maximum effective reduction of drain loss and total blood loss.

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“…Protease inhibitors, such as aprotinin, ⑀-aminocaproic acid, and tranexamic acid, reduce hyperfibrinolysis and platelet dysfunction and have been found to reduce blood transfusion requirements in cardiac surgery with cardiopulmonary bypass 11 and liver surgery. [12][13][14][15][16][17] This effect on blood transfusion requirements can be achieved with no side effects in most patients. 18 Other factors such as the experience of the surgeon, improvements in surgical and anesthesiological techniques, venovenous bypass, and donor graft cold ischemia time are more likely to be important factors in intraoperative and/or postoperative blood loss than in intraoperative coagulation monitoring.…”

confidence: 95%

Coagulation Techniques Are Not Important In Directing Blood Product Transfusion During Liver Transplantation

Reyle-Hahn

1997

Liver Transplantation

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Preoperative acquired clotting parameters such as prothrombin time, activated partial thromboplastin time, antithrombin III, platelet concentration, and fibrinogen show coagulopathy caused by insufficiency of the diseased liver. Intraoperative determination of clotting factors or parameters is not helpful to direct intraoperative transfusion of blood, blood components, or platelets because transfusions performed solely for correction of clotting data do not correlate with the real intraoperative requirements and increase the costs of orthotopic liver transplantation. However, the use of antihyperfibrinolytic drugs seems to reduce intraoperative blood loss. Patients with cirrhotic disorders caused by portalvenous hypertension show extensive collaterals and increased intravascular blood volume. Thus it is plausible that especially overcorrection of blood loss during the surgical preparation in the preanhepatic phase of the operation results in extensive blood loss. Therefore, to avoid blood loss we attempt to keep volume substitution to a minimum during the preanhepatic phase of the operation. In contrast, during the anhepatic and postanhepatic phases we attempt to reestablish normovolemia by transfusing red packed blood cells and fresh-frozen plasma. Strictly confined use of blood products in the preanhepatic phase, followed by later correction of intravascular blood volume, may reduce intraoperative blood loss; it also seems to ensure adequate substitution of clotting factors.

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Tranexamic Acid Reduces Blood Loss, Transfusion Requirements, and Coagulation Factor Use in Primary Orthotopic Liver Transplantation

Abstract: High-dose tranexamic acid significantly reduces intraoperative blood loss and perioperative donor exposure in patients with end-stage parenchymal liver disease who are undergoing orthotopic liver transplantation, with marked reductions in platelet and cryoprecipitate requirements.

Cited by 237 publications

References 22 publications

Deficiency of Thrombin Activatable Fibrinolysis Inhibitor in Cirrhosis Is Associated With Increased Plasma Fibrinolysis

Deficiency of Thrombin Activatable Fibrinolysis Inhibitor in Cirrhosis Is Associated With Increased Plasma Fibrinolysis

Most Effective Regimen of Tranexamic Acid in Knee Arthroplasty: A Prospective Randomized Controlled Study in 240 Patients

Coagulation Techniques Are Not Important In Directing Blood Product Transfusion During Liver Transplantation

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