Tacrolimus‐induced thrombotic microangiopathy in orthotopic liver transplant patients: case series of four patients

Abstract

Thrombotic microangiopathy (TMA) is a potentially fatal complication in solid organ and bone marrow transplant patients, with reported incidence of 0.5-3% and mortality of about 75%. To emphasise the importance of early diagnosis and prompt commencement of therapy results in improved clinical outcomes. A retrospective study of all patients who underwent orthotopic liver transplantation (OLTX) at the Western Australian Liver Transplantation Service from May 1994 to December 2010 was conducted to identify patients who developed tacrolimus-induced TMA. We identified four patients with tacrolimus-induced TMA post-OLTX, derived from a cohort of 104 patients treated with tacrolimus in our institution. The mean age at diagnosis was 40 years, and the mean time of onset was 63 Ϯ 7.5 weeks after OLTX. The indications for OLTX in the four patients were fulminant hepatic failure in three (Wilson disease, paracetamol overdose and post-partum thrombotic thrombocytopenic purpura) and hepatitis C virus-related cirrhosis. All patients had tacrolimus post-OLTX. At diagnosis, tacrolimus was discontinued in all patients, and three of the four patients underwent plasma exchange and all patients improved clinically. Mean duration of follow up was 15 Ϯ 7.5 months. There was no mortality 6 months post-TMA. Early diagnosis with immediate discontinuation or conversion of calcineurin inhibitors and plasma exchange should be offered to OLTX patients with TMA as it results in good outcomes.

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.…”

“…It was normal in 8, temporarily reduced without correlation to the clinic in 1 and b5% with the presence of an inhibitor in 2 [14,23,25,51,63]. One of these two patients was treated with PEX but did not respond and succumbed, whereas the other responded to PEX and discontinuation of tacrolimus, but relapsed when cyclosporin A was introduced, this time with normal activity of ADAMTS13 without inhibitor.…”

Microangiopatía trombótica asociada a tacrolimus en trasplante pulmonar

“…Las recomendaciones en la literatura se basaban clásicamente en el cambio de la medicación causante por sirolimus, everolimus o ciclosporina. Si el diagnós-tico es precoz, actualmente hay disponibles tratamientos eficaces, como el anticuerpo eculizumab o la plasmaféresis 3,4 . No existen casos publicados en la literatura española de MAT asociada a tacrolimus en trasplante pulmonar, y son contados en la literatura internacional 5 .…”

Immunosuppressive Therapeutic Complications in a Lung Transplant Patient

“…Tacrolimus-associated TMA is a rare, but potentially fatal, complication in solid organ transplantation, with an estimated incidence of 1-4% [5,10]. In lung transplant, the estimated incidence is 2.3%, but only four case series and 11 cases have been reported [3,4,8].…”

“…The calcineurin inhibitors (CI) are the mainstay of immunosuppression in lung transplant. Thrombotic microangiopathy (TMA) is a complication that has been increasingly reported in the recent years [3,4] and CI have been implicated in most cases [5]. We report a case of TMA in a lung transplant recipient receiving tacrolimus, with concomitant infection.…”