Early recurrent hemofilter thrombosis despite regional citrate anticoagulation during continuous renal replacement therapy: a prospective observational study

Abstract Regional citrate anticoagulation (RCA) is the recommended first-line anticoagulation strategy during continuous renal replacement therapy (CRRT). However, early and recurrent hemofilter thrombosis may still occur despite apparently adequate RCA at the measured time points. This complication is poorly described and its mechanisms are unknown. We aimed to describe the clinical and laboratory profile of affected patients and to explore candidate mechanisms of thrombosis. We conducted a prospective observational cohort study in six medical and surgical ICUs in Lyon, France (September 2023–September 2025). Adult patients with early hemofilter thrombosis, defined as filter failure within 24 h of extracorporeal circuit initiation during RCA-CRRT, were included. Clinical, technical, and laboratory parameters were collected at the time of thrombosis. When available, laboratory variables were compared, using a paired within-patient design, with control samples obtained after thrombosis resolution and CRRT discontinuation. Retrieved thrombi were analyzed by fluorescence and electron microscopy with immunolabeling. Given the sample size and observational design, all analyses were exploratory and not adjusted for multiple comparisons. Twenty-five patients were included. All exhibited sepsis, and 17 (68%) had septic shock, defined by vasopressor requirement, with high severity at admission (sequential organ failure assessment (SOFA) 10 [8–14]) and at CRRT initiation (SOFA 13 [9–15]). CRRT was delivered mainly as continuous veno-venous hemodialysis (64%). Post-filter calcium remained within target range in 90.3% of patients, and early thrombosis frequently recurred (median of 2 episodes per patient). At the time of thrombosis, patients showed leukocytosis, neutrophilia, elevated C-reactive protein, and high fibrinogen, whereas conventional coagulation tests, natural anticoagulants, and thrombin generation assay parameters did not show overt systemic hypercoagulability. In exploratory paired analyses (n = 9), inflammatory markers were higher during thrombosis than at the control time point. Thrombus analyses showed abundant fibrin, platelets, neutrophil-rich cellular material, and extracellular citrullinated histone H3 labeling. In this exploratory study, early hemofilter thrombosis during RCA-CRRT occurred in critically ill septic patients with marked inflammatory activation despite apparently adequate regional anticoagulation, and was accompanied by neutrophil-rich, citrullinated histone H3–positive intrafilter thrombi. These findings are hypothesis-generating and suggest a predominantly local thrombo-inflammatory process. They need to be confirmed in larger, controlled studies including comparator groups before informing tailored anticoagulation strategies.