Liver Transplantation in Man--IV, Haemorrhage and Thrombosis

Flute, P.T.; Rake, M. O.; Williams, Roger; Seaman, M. J.; Calne, R Y

doi:10.1136/bmj.3.5661.20

Cited by 34 publications

(16 citation statements)

References 13 publications

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“…25 Flute et al reported a possible beneficial role of EACA in liver transplantation patients. 7 Pharmacologic antifibrinolytic therapy was instituted by von Kaulla et al, who reported giving EACA (1 g/h) to three patients during liver transplantation and several days postoperatively. 6 EACA appeared to stop fibrinolysis in all three patients, but one died intraoperatively with uncontrollable bleeding.…”

Section: Discussionmentioning

confidence: 99%

“…Von Kaulla et al, on the basis of postoperative thrombotic complications in patients with hepatic neoplasms, suggested that administration of ε-aminocaproic acid (EACA) might be harmful in transient fibrinolysis, 6 whereas Flute et al suggested a possible beneficial role of EACA in patients receiving liver transplants. 7 Thus far, antifibrinolytic therapy has been empirical; its indications have been ill defined, monitoring of fibrinolysis has been inadequate, and, usually, a large dose of EACA has been used in cases of uncontrolled bleeding. We designed the present study to investigate the significance of fibrinolysis, to evaluate the clinical effectiveness of EACA, and to identify a clinically effective dose of EACA in patients receiving liver transplants.…”

mentioning

confidence: 99%

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Epsilon-aminocaproic Acid for Treatment of Fibrinolysis during Liver Transplantation

Kang¹,

Lewis²,

Navalgund³

et al. 1987

Anesthesiology

209

103

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In 97 adult patients receiving liver transplants, the coagulation system was monitored by thrombelastography and by coagulation profile including PT; aPTT; platelet count; level of factors I, II, V, VII, VIII, IX, X, XI, and XII; fibrin degradation products; ethanol gel test; protamine gel test; and euglobulin lysis time. Preoperatively, fibrinolysis defined as a whole blood clot lysis index of less than 80% was present in 29 patients (29.9%), and a euglobulin lysis time of less than 1 h was present in 13 patients. Fibrinolysis increased progressively during surgery in 80 patients (82.5%) and was most severe on reperfusion of the graft liver in 33 patients (34%). When whole blood clot lysis (F < 180 min) was observed during reperfusion of the graft liver, blood coagulability was tested by thrombelastography using both a blood sample treated in vitro with ε-aminocaproic acid (0.09%) and an untreated sample. Blood treated with ε-aminocaproic acid showed improved coagulation without fibrinolytic activity in all 74 tests. When whole blood clot lysis time was less than 120 min, generalized oozing occurred, and the effectiveness of ε-aminocaproic acid was demonstrated in vitro during the pre-anhepatic and post-anhepatic stages, ε-aminocaproic acid (1 g, single intravenous dose) was administered. In all 20 patients treated with ε-aminocaproic acid, fibrinolytic activity disappeared; whole blood clot lysis was not seen on thrombelastography during a 5-h observation period, and whole blood clot lysis index improved from 28.5 ± 29.5% to 94.8 ± 7.4% (mean ± SD, P < 0.001). None of the treated patients had hemorrhagic or thrombotic complications. In patients undergoing liver transplantation, the judicious use of a small dose of ε-aminocaproic acid, when its efficacy was confirmed in vitro, effectively treated the severe fibrinolysis without clinical thrombotic complications. KeywordsBlood; coagulation; fibrinolysis; Liver; transplantation; Measurement techniques; thrombelastography; Pharmacology; ε-aminocaproic acid Orthotopic liver transplantation is frequently associated with surgical bleeding that requires massive blood transfusion. 1 The surgical bleeding is compounded by preexisting coagulopathy, dilutional coagulopathy, fibrinolysis, and, possibly, disseminated intravascular In a recent series of patients undergoing liver transplantation, the degree of coagulopathy and volume of transfusion decreased with the introduction of replacement therapy guided by the frequent thrombelastographic monitoring of the coagulation system and the use of heparin-coated veno-venous bypass. 3,4 However, active fibrinolysis, manifest as generalized oozing from a previously dry surgical field and unresponsive to replacement therapy, has been a major difficulty in the intraoperative management of liver transplantation.Since the early experience in hepatic transplantation, activation of the fibrinolytic system has been recognized, 5,6 and, although antifibrinolytic treatment appears beneficial, it has been used only sporadically. Vo...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Epsilon-aminocaproic Acid for Treatment of Fibrinolysis during Liver Transplantation

Kang¹,

Lewis²,

Navalgund³

et al. 1987

Anesthesiology

209

103

View full text Add to dashboard Cite

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“…Previous studies on the blood coagulation system in humans and in animals undergoing liver transplantation have demonstrated dilutional coagulopathy associated with massive blood transfusion, decreased fibrinogen levels, and thrombocytopenia (4,5). Fibrinolysis, beginning during the anhepatic stage of surgery and becoming "explosive" on reperfusion of the homograft, has been reported (6).…”

Section: Blood-coagulation; Liver-transplantationmentioning

confidence: 99%

“…Frequently we have seen thrombocytopenia, which may result from gastrointestinal bleeding, splenomegaly, or malnutrition (3). At the same time, numerous collateral channels and portal hypertension, together with increased capillary fragility, make maintenance of surgical hemostasis very difficult.Previous studies on the blood coagulation system in humans and in animals undergoing liver transplantation have demonstrated dilutional coagulopathy associated with massive blood transfusion, decreased fibrinogen levels, and thrombocytopenia (4,5). Fibrinolysis, beginning during the anhepatic stage of surgery and becoming "explosive" on reperfusion of the homograft, has been reported (6).…”

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confidence: 99%

Intraoperative Changes in Blood Coagulation and Thrombelastographic Monitoring in Liver Transplantation

Kang

Martin

Marquez

et al. 1985

Anesthesia & Analgesia

623

432

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The blood coagulation system of 66 consecutive patients undergoing consecutive liver transplantations was monitored by thrombelastograph and analytic coagulation profile. A poor preoperative coagulation state, decrease in levels of coagulation factors, progressive fibrinolysis, and whole blood clot lysis were observed during the preanhepatic and anhepatic stages of surgery. A further general decrease in coagulation factors and platelets, activation of fibrinolysis, and abrupt decrease in levels of factors V and VIII occurred before and with reperfusion of the homograft. Recovery of blood coagulability began 30-60 min after reperfusion of the graft liver, and coagulability had returned toward baseline values 2 hr after reperfusion. A positive correlation was shown between the variables of thrombelastography and those of the coagulation profile. Thrombelastography was shown to be a reliable and rapid monitoring system. Its use was associated with a 33% reduction of blood and fluid infusion volume, whereas blood coagulability was maintained without an increase in the number of blood product donors. Keywords BLOOD-coagulation; LIVER-transplantationLiver transplantation, which began as highly experimental surgery 20 yr ago, is now recognized as a major means of therapy for patients with end-stage liver disease (1). However, massive blood loss during liver transplantation is still a major concern. The liver produces most of the blood coagulation factors, so it is not surprising that we see very low levels of these factors and prolonged prothrombin time (PT) and activated partial thromboplastin time (aPTT) in many patients receiving liver transplants (2). Frequently we have seen thrombocytopenia, which may result from gastrointestinal bleeding, splenomegaly, or malnutrition (3). At the same time, numerous collateral channels and portal hypertension, together with increased capillary fragility, make maintenance of surgical hemostasis very difficult.Previous studies on the blood coagulation system in humans and in animals undergoing liver transplantation have demonstrated dilutional coagulopathy associated with massive blood transfusion, decreased fibrinogen levels, and thrombocytopenia (4,5). Fibrinolysis, beginning during the anhepatic stage of surgery and becoming "explosive" on reperfusion of the homograft, has been reported (6). A consumption coagulopathy accompanied by an increased level of fibrin degradation products appeared to play a major role (7). However, these observations were limited to a few patients in the early era of liver transplantation, and comprehensive information is still lacking.Another difficulty in the intraoperative management of liver transplantation has been actively monitoring the coagulation system and determining the appropriate treatment during dynamic blood volume changes. The use of the thrombelastograph (TEG) was suggested by von Kaulla et al. (4) and Howland et al. (8). However, the efficacy of thrombelastographic monitoring of blood coagulation during liver transplantatio...

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“…Transplantation has, however, been successfully performed after attempting to correct the deficiencies: by intravenous fibrinogen and fresh frozen plasma and the coagulation defect rapidly reversed after insertion of the new liver ( Fig. 1) (Flute et al, 1969}. A wide spectrum of neuropsychiatric changes occurs in liver disease (Williams and ToghiII, 1968) and the EEG often shows characteristic changes. One patient was deeply comatose before transplantation but two days later he was alert and talking rationally.…”

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confidence: 97%

The Selection of Patients for Hepatic Transplantation and the Place of Chemical Pathology in the Postoperative Management

Murray‐Lyon

1970

Ann Clin Biochem

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Liver Transplantation in Man--IV, Haemorrhage and Thrombosis

Cited by 34 publications

References 13 publications

Epsilon-aminocaproic Acid for Treatment of Fibrinolysis during Liver Transplantation

Epsilon-aminocaproic Acid for Treatment of Fibrinolysis during Liver Transplantation

Intraoperative Changes in Blood Coagulation and Thrombelastographic Monitoring in Liver Transplantation

The Selection of Patients for Hepatic Transplantation and the Place of Chemical Pathology in the Postoperative Management

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