Complement mediated thrombotic microangiopathy after liver transplantation in combination with a novel C6 variant of uncertain significance.

Thrombotic microangiopathies (TMAs) encompass a spectrum of severe pathological conditions mostly characterized by hemolytic anemia, microvascular thrombosis with organ failure, and thrombocytopenia. The etiological spectrum of TMA is diverse, with a notable association in transplant recipients, particularly linked to the administration of calcineurin inhibitors (CNI) and due to perioperative stress factors. The clinical case presented concerns the occurrence of complement-mediated TMA (cTMA) in a recipient following liver transplantation (LT) who had previously been diagnosed with autoimmune hepatitis (AIH). The patient received total plasma exchange, followed by treatment with the anti-complement factor C5 antibody ravulizumab shortly after diagnosis. Significant improvement in the patient's clinical condition and a decline in renal impairment was observed. Subsequently, dialysis therapy could be discontinued. In addition, an enhancement in liver functionality was detected. The diagnosis of cTMA was undoubtedly attributable to a multifactorial cause. Genetic testing identified variants involving complement factor H-related protein 5 (CFHR5) and complement component 6 (C6). The identified C6 variant was classified as a variant of uncertain significance (VUS), and its pathogenic relevance in complement-mediated TMA remains unclear. Notably, a sustained clinical response was documented six months after starting ravulizumab treatment, highlighting the complexities of managing complement-mediated disorders and the potential for durable responses using the therapy at the earliest possible time.