with CLB CD41

against the

intact IIb-IIIa


CLB-CD42b (MB45) against the glycocalicin moiety of GPIb, CLB thromb/4 against the ot subunit of VLA2, SAM 1 against the ot subunit ofVLA5, and GoH3 against the ot subunit of VLA6. This pattern was different from the heterogenous staining we found in patients not treated with streptokinase.2 The increase in circulating megakaryocytes suggests either a defective marrow blood barrier or an abnormal stimulus for megakaryocyte release. Secretion of proteinases by megakaryocytes might provide a normal mechanism for megakaryocytes to enter the sinusoidal lumen. This effect could be augmented by circulating plasmin that degrades basement membrane glycoproteins, which would explain the 100% staining by circulating megakaryocytes for all adhesion antigens because they would not have to lose anchors to leave the bone marrow. A second explanation could be that plasma induces the cytoskeletal changes necessary in megakaryocytes for transendothelial migration. A third possibility, unrelated to plasmin, involves the activation of the immune system or activation of platelets by streptokinase antibodies. End-products of both reactions are capable of affecting endothelial permeability. If changes of the endothelial surface and the underlying matrix are responsible for this megakaryocyte migration, the effects of aspirin may be twofold. Besides acting as an antiplatelet agent, aspirin may also partly prevent the endothelial permeability response to thrombolytic

agents,3 thereby attenuating megakaryocyte migration. Departments of Haematology and Cardiology, Free University Hospital, 1081 HV Amsterdam, Netherlands


1. Slater DN, Trowbridge EA, Martin JF. The megakaryocyte in thrombocytopenia: a microscopic study which supports the theory that platelets are produced in the pulmonary circulation. Thromb Res 1983; 31: 163-76. 2 van Pampus ECM, Denkers IAM, van Geel BJM, et al. Expression of adhesion antigens on human marrow megakaryocytes, circulating megakaryocytes and blood

platelets. Eur J Haematol (in press). Johnstone MT, Rabbani LRE, George D, Ware JA, Loscalzo J. Thrombolytic therapy causes an increase in the vascular permeability that is reversed by 1- deamino-8-D-vasopressin. Circulation 1991; 84: 2568-73.

3. Rudd MA,

Aprotinin and orthotopic liver transplantation SIR,-Dr Groh and colleagues’ report (July 18, p 173) on the effect of aprotinin on transfusion requirements during orthotopic liver transplantation (OLT) seems to refute previous fmdings.1 In this particular study, however, the small sample size and rather high blood loss in both groups make it difficult to reach any definitive conclusion about the efficacy of aprotinin in decreasing perioperative bleeding during OLT. As Groh et al rightly point out, blood loss during OLT is determined by many factors and one would not expect a haemostatic agent to influence all of them. Certainly, the experience of surgical and anaesthetic teams is critical, and most centres have documented a steady fall in mean blood usage over time. However, as expertise is acquired, higher risk cases are increasingly taken on and these will have the effect of skewing mean figures. For adequate interpretation of intraoperative transfusion requirements during OLT the diagnostic category of the patient groups should be clearly identified. Patients with severe hepatocellular disease and portal hypertension generally have a much higher blood loss than do patients with cholestatic disease, and are more likely to develop fibrinolysis intraoperatively.2 It is noteworthy that Groh et al report a 20% incidence of fibrinolysis in their controls and none in the aprotinin group. Various protocols for the management of coagulation in different centres, especially in relation to administration of platelets and treatment of fibrinolysis, also make comparison and interpretation of transfusion figures difficult. Central to the issue of estimating the efficacy of a pharmacological intervention is that surgical bleeding is differentiated from bleeding due to coagulopathy. During OLT, the periods most associated with haemostatic changes and coagulopathy are the late anhepatic phase and that immediately after reperfusion.3 Motschman and


*March, 1991, to May, 1992 total 50 patients, figures are mean values for units of red cells (RBC) transfused with ranges m parentheses tTotal of 50 adult liver transplants 21 cirrhotics, 15 PBC, 6 PSC, 4 Budd Chlarl, 1 amyloid, 2 metabolic



PBC = primary biliary cirrhosis, PSC = primary sclerosing cholangitis

co-workers’ review4 of the first 100 transplants showed that the rapid rate of transfusion of red cells and component therapy during OLT was early after reperfusion and that transfusion requirements were frequently highest in this stage. Intervention that attenuates or inhibits the development of coagulopathy during this phase would therefore be expected to have a fairly important effect on stage 3 (post-reperfusion) transfusion requirements. By contrast, bleeding during the dissection phase is often due to surgery, and the contribution to reduction of blood loss by pharmacological methods correspondingly less. We have used aprotinin in the same regimen as described in our pilot study’ in a further 50 patients. We have continued to find that our transfusion figures for both blood and component therapy remain low, and both the pattern of blood loss and thrombelastographic data demonstrate few difficulties with coagulopathy and bleeding after reperfusion (table). The results of larger prospective studies that are in progress might clarify the use and effects of aprotinin in liver transplantation. Hard data on different dose regimens and identification of patient most

groups most likely to benefit from pharmacological intervention are still needed. Ways to keep bleeding to a minimum during OLT should be a priority since this factor has such substantial influence on the patient’s subsequent morbidity and mortality and early survival after liver transplantation. The balance of evidence so far points to aprotinin having an important role in this respect.

Departments of Anaesthesia and Surgery, Royal Free Hospital, London NW3 2QG, UK


1. Neuhaus P, Bechstein WO, Lefebre B, Blumhardt G, Slama K. Effect of aprotinin on intraoperative bleeding and fibrinolysis m liver transplantation Lancet 1989; ii: 924-25. 2. Bontempo FA, Lewis JH, Ragni MV, Kang Y. The preoperative coagulation pattern In. Winter PM, Kang YG, eds. Hepatic in liver transplant patients. transplantation: anaesthetic and perioperative management Praeger: New York, 1986: 135-41 3. Porte RJ, Knot AR, Bontempo FA. Hemostasis in liver transplantation. Gastroenterology 1989; 97: 488-501. 4. Motschman TL, Taswell Hf, Brecher ME, Rettke SR, Weisner RH, Krom RAF. Blood bank support of a liver transplantation program. Mayo Clin Proc 1989; 64: 103-11. 5. Mallett SV, Cox D, Burroughs AK, Rolles K The intraoperative use of trasylol (aprotinin) in liver transplantation. Transplant Int 1991, 4: 227-30

Magnetic resonance imaging of the hepatic veins in split liver transplantation SIR,-Split liver transplantation is used increasingly to keep up with the growing demand for donor organs. The splitting requires information about the liver vessels to ensure proper circulation in both grafts postoperatively.’ Details of the hepatic-artery system (with the portal-vein branches) can be obtained from workbench arteriography. The anatomy of the hepatic veins can hardly be visualised. From 15 pretransplant studies of livers destined for transplantation we learned that magnetic resonance imaging (MRI) can be used to visualise the architecture of the hepatic veins, especially their confluence. From differences between the

Aprotinin and orthotopic liver transplantation.

493 positive with CLB CD41 against the intact IIb-IIIa complex, CLB-CD42b (MB45) against the glycocalicin moiety of GPIb, CLB thromb/4 against t...
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