Clinical characteristics of thrombotic microangiopathy following ABO incompatible living donor liver transplantation

Abstract

Thrombotic microangiopathy (TMA) may develop after living donor liver transplantation (LDLT), but the mechanism is not fully understood. We retrospectively analyzed all patients undergoing LDLT at our center, including TMA patients, to elucidate the clinical characteristics and presentation and to determine which patients have a higher risk of occurrence of TMA. In all, 57 adult patients were reviewed after LDLT at our institution. TMA was diagnosed by sudden and severe thrombocytopenia, followed by hemolytic anemia with fractionated erythrocytes in the blood smear. Clinical features were compared between the TMA group and the non-TMA group. Of the 57 patients, 4 were diagnosed with posttransplantation TMA. ABO blood group (ABO)-incompatibility, cyclophosphamide (CPA), and recipient blood group (type O) were closely correlated with the occurrence of TMA. Thrombocytopenia appeared 1 to 5 days before hemolytic anemia. Coagulative function markers stayed at the same level after TMA, while marked elevation was shown in fibrinolytic function markers such as plasminogen activator inhibitor type 1 (PAI-1). TMA occurred at a higher prevalence in ABO-incompatible graft recipients. Additional factors associated with ABO-incompatible transplantation, such as an overdose of immunosuppressants, may affect the likelihood of TMA. Sudden and severe thrombocytopenia presented before hemolytic anemia and the serum levels of PAI-1 correlated well with the clinical course of TMA. In conclusion, early recognition of thrombocytopenia and elevation of PAI-1 is crucial to diagnose TMA especially in ABO-incompatible LDLT.

De novo thrombotic microangiopathy after non-renal solid organ transplantation

“…There was a trend towards increased risk for female gender, mean portal vein flow b60 cm/s, anhepatic phase N 180 min and Model for End-stage Liver Disease score N14. The use of tacrolimus versus cyclosporin A, age, blood loss, elevated liver enzymes, CMV infection, acute rejection and small for size syndrome did not increase the risk [12,13,18,23]. Ten out of 18 cases of TMA described in case reports occurred during a concurrent acute event like infection or acute rejection.…”

“…The presence of thrombocytopenia is mandatory but is frequent after transplantation for various reasons. A sharp drop in the platelet count however is rather typical of TMA and is often the first sign [12,13]. The presence of Coombs negative anemia is also mandatory and is recognized by the presence of schistocytes on the peripheral blood smear, elevated lactate dehydrogenase (LDH), reticulocytes and bilirubin, and low haptoglobin levels.…”

“…Transplantation for fulminant hepatic failure and ABO-incompatibility were strong risk factors, not tested by multivariate analysis. Perioperative infusion of a protease inhibitor via the portal vein was suggested to prevent TMA in ABO-mismatched transplants, but not tested in a controlled trial [13]. Receptor blood group O was a risk factor as well, which might be explained by the higher risk to receive an ABO-incompatible graft.…”

Thrombotic thrombocytopenic purpura secondary to ABO group incompatible blood transfusion

“…The previous reports on TTP after ABO mismatched liver and renal transplantations are good example. [23] Hence, the cases of ABO blood transfusion should be no doubt for the pathogenesis of TTP.…”

Accurate and Reasonable Method for Estimation of Graft Volume in Living Donor Liver Transplantation

“…Transplantation-related thrombotic microangiopathy (TA-TMA) is a serious complication of organ transplantation that is associated with a variety of transplantation-related factors, including the use of immunosuppressive agents, conditioning regimens, ABO incompatibility, and opportunistic infections (2)(3)(4). Immunosuppressants such as cyclosporine A and tacrolimus (FK506) are often linked with the occurrence of TA-TMA (2, 3).…”