The risk of transplant-associated thrombotic microangiopathy (TA-TMA) was found to be elevated in children with sickle cell disease (SCD), according to the results of a recent study. The study’s findings were reported in the journal Blood Advances.

SCD has some features in common with TA-TMA, including endothelial activation and complement activation. Because of this, the research team had a hypothesis that SCD may be a risk factor for TA-TMA. They also predicted that patients with SCD would display elevated levels of markers of complement activation and endothelial dysfunction prior to hematopoietic cell transplantation (HCT).

“Identifying whether SCD confers an increased risk for TA-TMA post-HCT could better inform patients and caregivers and potentially permit pre-emptive or preventative strategies in those at highest risk,” the researchers explained in their report.

Continue Reading

The researchers conducted a single-center, retrospective analysis of TA-TMA outcomes in patients with SCD who underwent HCT at Children’s Healthcare of Atlanta in Atlanta, Georgia. Patients were children undergoing a first HCT and with a haploidentical or matched sibling donor. The primary study objective was the odds of developing TA-TMA with or without SCD, as well as the determination of any differences in pre-HCT markers of endothelial or complement activation. Other characteristics and outcomes were also analyzed.

There were 115 children included in the study, with 52 having SCD and 63 receiving HCT for non-SCD indications. Patients with SCD had a median age of 8 years, while patients without SCD had a median age of 10 years. TA-TMA was reported in 13% of patients who had SCD and in 2% of patients without SCD overall. In a multivariable analysis, SCD was an independent risk factor for TA-TMA development (odds ratio [OR], 12.22; 95% CI, 1.15-129.6; P =.038).

TA-TMA appeared to occur more often in patients with SCD even while the non-SCD population showed higher frequencies of certain risk factors. The population without SCD had higher rates of the risk factors of cytomegalovirus positivity (P <.0001), preparative regimens involving radiotherapy (P <.0001), and use of peripheral blood stem cell graft sources (P =.0008).

Prior to HCT, patients with SCD showed significantly greater levels of soluble vascular cell adhesion molecule 1 and P-selectin, which are markers of endothelial activation. However, levels of complement biomarkers did not appear to significantly differ by SCD or non-SCD status. After HCT, there also were not significant differences seen in grade 3 or 4 acute graft vs host disease in patients with or without SCD.

The researchers concluded that SCD was independently associated with a greater risk of TA-TMA in this population. They also concluded that endothelial activation may differ for patients with SCD, but that complement biomarkers were similar prior to HCT regardless of whether or not patients had SCD.

Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.


Schoettler M, Stenger E, Spencer K, et al. Sickle cell disease is a risk factor for transplant-associated thrombotic microangiopathy in children. Blood Adv. Published online September 8, 2022. doi:10.1182/bloodadvances.2022008058