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...

A venous bypass technique (BP) that does not require the use of systemic anticoagulation is used routinely at our institution in all adult patients during the anhepatic phase of liver transplantation (L T). Complete cardiopulmonary profiles were obtained in a subset of 28 consecutive cases. During the anhepatic phase while on bypass, mean arterial pressure, central venous pressure, and pulmonary arterial wedge pressure were maintained at prehepatectomy levels. Oxygen consumption fell secondary to a decrease in temperature and the removal of the liver. Consequently, cardiac index fell without an increase in arterial-venous O2 content difference, reflecting adequate tissue oxygenation. Compared with 63 patients in a previous series given L T without bypass (NBP), the 57 total BP patients experienced better postoperative renal function (p < 0.001), required less blood use during surgery (p < 0.01), and had better survival 30 days after LT. The equivalency of 90-day survival in these groups results from the lack of effect of BP on the long-term survival of patients considered at high risk for metabolic reasons. BP patients at high risk for technical considerations, however, survived LT whereas NBP patients did not. BP offers other advantages important in establishing L T as a service-oriented procedure.T HE DRAMA TIC IMPACT of cyclosporine on survival following liver transplantation has been widely reported. I -4 Yet despite extensive experience with the operation during the preceding 17 years, only a few important technical improvements were reported to have significantly enhanced survival. 3 • 5 -s In fact, during the first 3 years in which cyclosporine was used, mortality related to a difficult intraoperative course remained a disturbing problem. For the most part, these difficulties centered around the anhepatic phase and repeatedly underscored the need for an effective method of venous bypass. The need for the development of new methodology was clearly demonstrated by the severe penalty imposed by the requirement for systemic heparinization during a trial of venous bypass using conventional

The anhepatic phase of an orthotopic liver transplantation procedure occurs when the surgeon has removed the native liver (along with the intrahepatic portion of the vena cava) and is involved in sewing in the donor organ. During this interval, the inferior vena cava is cross-clamped at the diaphragm and at a point just above the entry of the renal veins. The result is a complete interruption of venous return from the inferior vena cava, as is evident from a sudden decrease in both central venous and pulmonary arterial wedge pressures, resulting in a profound reduction of cardiac output. 1 The portal vein is also clamped, of necessity, during this phase. A sudden and marked increase in hydrostatic pressure in both the portal and systemic venous beds thus occurs. This not only causes damage to the kidneys, bowel, and pancreas, but also can profoundly exacerbate hemorrhage from the tissues that were cut during the recipient hepatectomy. Early Approaches to the ProblemEarly attempts at transplantation of the liver in dogs required the use of some means of relieving pressure in the obstructed portal vein because dogs usually died 20 to 30 minutes after clamping the portal vein. To avoid this problem, Starzl routinely constructed an end-toside anastomosis between the divided portal vein and the vena cava just below the liver, then bypassed flow from the lower vena cava to the superior vena cava (via the jugular vein) using passive shunts. 2 Similar shunts were used during the first human trials of orthotopic transplantation of the liver. However, pulmonary embolism played a major role in the deaths of three of the first four patients in the Denver experience. 3 The passive shunts were thought to be the major cause.In previous studies, Starzl's group had also shown that dogs that were made cirrhotic (by chronic bile duct ligation) did not require shunting. 1 Apparently, adequate portal decompression was provided by the formation of spontaneous shunts through collaterals resulting from chronic portal hypertension. This finding led Starzl to attempt the next few clinical transplants without the use of shunts. Starzl's group subsequently found that, in general, all humans, not just those with portal hypertension, tolerated the anhepatic phase much better than did dogs. , 1963, , to March 1980, the group in Denver was involved in the transplantation of the liver in 170 patients using azathioprine and prednisone for immunosuppression. Other modalities, such as antilymphocyte serum or its globulin derivative and thoracic duct drainage, were also used as adjuvant immunosuppression during the latter part of this period. Although these drug regimens were able to provide more than 50% 1-year kidney graft survival, they proved unsatisfactory for liver transplantation. 4 Rejection remained the major source of morbidity and mortality. Technical improvements continued to be important during this period, but ultimately, their capacity to improve patient survival was severely handicapped because of rejection.Beginning in March, 198...

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