Coagulation dysfunction in children with secondary hemophagocytic lymphohistiocytosis: a comprehensive analysis.

Abstract

Objective: Coagulation dysfunction plays a critical role in the pathogenesis and prognosis of secondary haemophagocytic lymphohistiocytosis (sHLH) in children. This study aims to systematically analyze the coagulation profiles in paediatric sHLH patients, evaluate their prognostic value and provide an effective basis for reducing mortality in children with HLH.

Methods: A total of 209 paediatric patients with sHLH were enrolled in this study. Coagulation parameters at admission were collected and compared across groups stratified by aetiology, prognosis and presence of disseminated intravascular coagulation (DIC). The dynamic evolution of coagulation parameters was analyzed using LOWESS curve fitting. LASSO regression was applied to screen for potential risk factors for DIC in sHLH patients, followed by univariate and multivariate logistic regression to identify independent risk factors. Similarly, Kaplan-Meier survival analysis along with univariate and multivariate logistic regression models were used to determine independent risk factors associated with prognosis in sHLH patients.

Results: Paediatric patients with secondary haemophagocytic lymphohistiocytosis (sHLH) presented with significant coagulation abnormalities upon hospital admission, as evidenced by markedly elevated prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (APTT), thrombin time (TT) and D-dimer (DD) levels (all p < 0.01). Those with infection-associated HLH demonstrated significantly prolonged PT (p = 0.009), APTT (p < 0.001) and TT (p = 0.0028), along with significantly lower fibrinogen (FIB) levels (p < 0.001), compared to patients with autoimmune-associated HLH. Compared to survivors, deceased HLH patients had significantly higher PT and INR (p < 0.01), as well as significantly elevated DD (p = 0.014). Significant differences were observed in coagulation parameters - PT, INR, APTT, TT, DD, FIB, thrombin-antithrombin complex (TAT) and tissue-type plasminogen activator-inhibitor complex (t-PAIC) - between HLH patients with and without disseminated intravascular coagulation (DIC) (all p < 0.05), and the dynamic changes in these parameters (particularly PT, FIB and DD) also differed notably between the two groups. Neurological involvement, hyper-ferritinaemia and elevated INR were identified as independent risk factors for DIC, while neurological involvement and the presence of DIC itself were independent predictors of mortality in paediatric patients.

Conclusion: Coagulation dysfunction serves as a core pathological driver in paediatric sHLH, being especially severe in infection-associated cases. Dynamic monitoring of key coagulation parameters and ferritin levels is crucial for early risk warning and timely intervention. Targeted management of coagulation abnormalities, together with proactive prevention and control of neurological complications, may improve outcomes in paediatric patients.