Incidence and Risk Factors of Transplantation-Associated Thrombotic Microangiopathy: A Systematic Review and Meta-Analysis

Transplantation-associated thrombotic microangiopathy (TA-TMA) is an increasingly recognized post-transplantation complication, yet the overall incidence of the disease remains under debate. To determine the pooled incidence of TA-TMA in a systematic review of literature and to identify consistent risk factors. We performed a systematic review using the MEDLINE, Embase, and CENTRAL databases to identify cohort studies that reported incidence of and risk factors for TA-TMA from 2004 to 2020. We conducted a meta-analysis of proportion to estimate the pooled incidence of TA-TMA using a random-effects model. We assessed moderators of heterogeneity through subgroup analysis, risk of bias through ROBINS-I, and publication bias through funnel plot. Among 21 cohort studies with a total of 36,163 adult and pediatric patients who underwent allogeneic transplantation, the pooled incidence of TA-TMA was 12% (95% confidence interval, 9% to 16%). The diagnostic criteria used to define the disease was the most significant contributor identified to the high interstudy heterogeneity (I = 98%). Studies using provider/clinician diagnosis instead of laboratory diagnosis reported the lowest incidence, at 3%. The most salient risk factor for TA-TMA reported in 14 studies was preceding acute graft-versus-host disease (GVHD). Other risk predictors described in 5 or more studies included preceding infection, prior transplantation, mismatched donor, and myeloablative conditioning. With a pooled incidence at 12% among a significantly heterogeneous population, TA-TMA is an important but relatively uncommon post-transplantation complication. Given the divergence between reported laboratory-based and provider-based incidence, as well as the multitude of risk factors beyond acute GVHD, future studies should focus on risk-stratifying the subset of TA-TMA patients who would benefit from therapeutic intervention.