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

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SummaryAmyloid diseases are characterized by the misfolding of a precursor protein that leads to amyloid fibril formation. Despite the fact that there are different precursors, some commonalities in the misfolding mechanism are thought to exist. In light chain amyloidosis (AL), the immunoglobulin light chain (LC) forms amyloid fibrils that deposit in the extracellular space of vital organs. AL proteins are thermodynamically destabilized compared to non-amyloidogenic proteins and some studies have linked this instability to increased fibril formation rates. Here we present the crystal structures of two highly homologous AL proteins, AL-12 and AL-103. This structural study shows that these proteins retain the canonical germline dimer interface. We highlight important structural alterations in two loops flanking the dimer interface and correlate these results with the somatic mutations present in AL-12 and AL-103. We suggest that these alterations are informative structural features that are likely contributing to protein instability that leads to conformational changes involved in the initial events of amyloid formation.