Use of Therapeutic Plasma Exchange in Children With Thrombocytopenia-Associated Multiple Organ Failure in the Turkish Thrombocytopenia-Associated Multiple Organ Failure Network

Abstract

Objective Thrombocytopenia-associated multiple organ failure can lead to high mortality in critically ill children, possibly related to consequences of thrombotic microangiopathy. Plasma exchange therapy may improve thrombotic microangiopathy. The purpose of this observational cohort study is to describe whether there is an association between use of plasma exchange therapy and outcome in the Turkish thrombocytopenia-associated multiple organ failure network. Setting-Interventions We performed a retrospective cohort analysis in patients with thrombocytopenia-associated multiple organ failure at three different PICUs comparing those who received plasma exchange (+) plus standard therapies with those who did not receive plasma exchange (−) and only received standard therapies. Results Among 42 of the enrolled patients with thrombocytopenia- associated multiple organ failure, all had a primary or secondary sepsis diagnosis. Fifteen received plasma exchange therapy (PE [+] group) and 27 received standard medical treatment without plasma exchange (PE [−] group). The mean age was 17.69 months (8.24–54.22) in the PE (+) group and 13.46 months (6.47–20.55) in the PE (−) group. Age (p = 0.232), gender (p = 0.206), thrombocyte count (p = 0.09), Organ Failure Index score (p = 0.111), and pediatric logistic organ dysfunction score (p = 0.177) at admission were not statistically different between groups. The overall 28-day mortality was higher in the PE (−) group (70.37%) compared with the PE (+) group (26.67%) (univariate p = 0.006; multivariate controlling for pediatric logistic organ dysfunction, Organ Failure Index, Pediatric Risk of Mortality scores, and neurological failure p = 0.048). Length of stay was increased in the PE (+) group (p = 0.004). Conclusions The positive association found between use of plasma exchange therapy and improved survival supports the potential of this therapy in Turkish children with thrombocytopeniaassociated multiple organ failure. The positive, although less so, associated treatment effect observed after controlling for illness severity provides further rationale for performing a randomized controlled trial in the pediatric Turkish thrombocytopenia-associated multiple organ failure network. Sample size calculations call for a 100-patient trial with a pre hoc interim analysis after enrollment of 50 patients with thrombocytopenia-associated multiple organ failure.

Three Hypothetical Inflammation Pathobiology Phenotypes and Pediatric Sepsis-Induced Multiple Organ Failure Outcome*

“…9–13 Therapeutic plasma exchange restores ADAMTS13 levels, removes ultra large vWF multimers, reverses thrombotic microangiopathy, and improves outcomes in adult patients with DIC, aHUS/ TMA, and TTP. 28,34,35 . Multiple mutations in the inhibitory component of complement, particularly complement H, have been found to contribute to over activation of complement and coagulation in aHUS/TMA leading to use of the C5A monoclonal antibody (eculizumab) as well as plasma exchange therapy in clinical practice in adults and children.…”

“…9,13,28 Hyper-inflammation in these children has been associated with complement over-activation in thrombotic thrombocytopenic purpura/atypical hemolytic uremic syndrome (TTP/aHUS) as well as necrosis related to microvascular thrombosis in disseminated intravascular coagulation (DIC). Eculizumab (C5a antibody) is an FDA approved drug for aHUS that reverses hyper-complementemia driven inflammation.…”

Thrombocytopenia-Associated Multiple Organ Failure and Acute Kidney Injury

“…Similar to the incidence of TTP-induced AKI, a large US multicenter pediatric TAMOF registry and a pediatric Turkish TAMOF network reported that 56.8% and 47.6% of patients with TAMOF, respectively, have AKI requiring renal replacement therapy. 86,87 These studies suggest that platelet/VWF-mediated thrombosis might be the underlying pathophysiologic process.…”

Therapeutic Plasma Exchange May Improve Hemodynamics and Organ Failure Among Children With Sepsis-Induced Multiple Organ Dysfunction Syndrome Receiving Extracorporeal Life Support*

“…This low rate of survival has led to the aggressive use of extracorporeal therapies in patients with MODS, such as venoarterial (VA) extracorporeal life support (ECLS) for refractory shock (3). Another extracorporeal therapy that has shown promise in pediatric patients with MODS is therapeutic plasma exchange (TPE) (10–12). …”