A hypercoagulable state follows orthotopic liver transplantation

Abstract

Orthotopic liver transplantation may be associated during the postoperative period with hepatic artery thrombosis, a catastrophic occurrence generally necessitating emergency retransplantation. To assess the contribution of the coagulation mechanism to this complication, the levels of procoagulant and anticoagulant proteins were followed in 41 liver transplant patients during the first 10 postoperative days. The mean activities of all procoagulant factors reach normal values on day 1 except for factors V and VII, which achieve normal activity by day 3. Supernormal levels of factor VIII activity and antigen are noted (peak values on day 5 of 334% +/- 113% and 481% +/- 260%, respectively). The anticoagulant proteins show delayed recovery, with deficient antithrombin III levels seen in 81% of patients on day 3 and 57% on day 5. Similarly, proteins C and S are subnormal in 24% and 21%, respectively on day 3, and 20% and 10%, respectively, on day 5. During this period, elevated levels of thrombin/antithrombin complexes are encountered, reflecting in vivo activation of the coagulation mechanism. Activated thrombin is, therefore, being generated at a time when a decrease in the major regulatory anticoagulant proteins exists. These data suggest an imbalance between the hemostatic and thrombotic mechanisms and indicate a sustained prothrombotic state that may contribute to the risk for hepatic artery thrombosis. Using a regimen of low-dose heparin and fresh frozen plasma infusion, no thromboses have been seen in 65 consecutive liver transplants.

Cigarette smoking is associated with an increased incidence of vascular complications after liver transplantation

“…Although technical factors may play a major role, the exact etiology of vascular complications is still unknown. Many suspected potential risk factors have been implicated in the incidence of arterial complications, such as CMV serologic incompatibility between recipients and donors, 32 hypercoagulable state, [30][31] and cold ischemic duration between explantation and transplantation. [27][28][29] Modern technology and newer diagnostic modalities available for prompt and accurate diagnosis have decreased mortality after LT.…”

“…24,25 Technical factors such as intimal dissection, clamp injury, kinking or stenosis of the anas-tomosis, and size of the recipient hepatic artery have been associated with severe acute rejection in the pathogenesis of early onset HAT. 26 Furthermore, other factors, e.g., cold ischemic time, [27][28][29] hypercoagulable states (deficiency of protein C, protein S, and antithrombin III), 30,31 increased hematocrit, 24 and cytomegalovirus (CMV) serologic incompatibility (CMVseronegative recipients receiving a CMV-seropositive allograft), 32 have also been associated with an increased incidence of HAT in the early postoperative period. In contrast, late onset HAT has been associated with chronic allograft rejection 25 and ABO-incompatible grafts.…”

Detection and treatment of coronary artery disease in liver transplant candidates

“…25 Another possible, although probably less likely, explanation for increased cardiac morbidity and mortality after OLT is the hypercoagulable state that occurs early after OLT. 26 Levels of protein C, protein S, and antithrombin III are depressed for 5 to 10 days after OLT and contribute to the hypercoagulable state. Rubin et al 27 retrospectively evaluated the electrocardiograms (ECGs) of 45 patients before and after OLT and compared findings with a similar cohort of patients undergoing major intra-abdominal surgery.…”

Repeated graft loss caused by recurrent hepatic artery thrombosis after liver transplantation

“…Immunologic or infectious events, as well as the complex process of recovery of the hemostatic function after transplantation, which can result in a transient hypercoagulable state, can contribute to the development of HAT in the early postoperative period. 5,9,10 However, when HAT develops in the late postoperative period, it is even more difficult to identify specific risk factors. 11 Our experience seems to indicate that in the presence of underlying coagulative conditions, such as the presence of APA/LAC or, even worse, paroxysmal nocturnal hemoglobinuria, HAT can recur after retransplantation.…”