Background: Continuous renal replacement therapy (CRRT) is an important modality in critical care that utilizes a closed blood circuit with a hollow fiber membrane hemofilter (Figure 2A). CRRT circuit failure is a costly complication with an unclear mechanism, prominently observed during the coronavirus disease 2019 (COVID-19) pandemic.

Aims: In this retrospective case series, we study the basis of circuit failure, particularly in the setting of COVID-19, via histopathologic examination of hemofilters after use in CRRT circuits.

Methods: Study patients were identified from critically ill patients, admitted to Weill Cornell Medical Center between April and June 2020, who had acute kidney injury requiring CRRT. Circuit failure was defined as the inability of the circuit to provide the prescribed continuous blood flow rate to the patient, necessitating a hemofilter change in advance of its 72-hour lifespan. Hemofilters from failed and functional circuits were formalin-fixed, sectioned and evaluated with histopathologic stains and immunohistochemistry (IHC). Chart review was completed in accordance with IRB-approved protocols.

Results: Circuit failure occurred in 4 out of 6 study patients. Two patients with severe COVID-19 experienced circuit failure despite anticoagulation with argatroban or regional citrate (Table 1). All hemofilters displayed the accumulation of dense, platelet-rich aggregates at the arterial ends (Figure 2B-2C), with a greater volume found in failed hemofilters. The hollow fiber membranes in hemofilters used for patients with severe COVID-19 displayed fibrinogen localized along the blood-facing lumens by IHC (Figure 2D). While hemofilters used for patients with COVID-19 exhibited such luminal fibrinogen staining regardless of circuit function, for patients without COVID-19 this was seen only in failed hemofilters.

Demographic and laboratory data for study patients. Laboratory values are peak values measured in the 72 hours prior to hemofilter collection. Abbreviations: SARS-CoV-2: severe acute respiratory syndrome coronavirus 2 (testing via nasopharyngeal swab), ESRD: end stage renal disease, DM2: type 2 diabetes mellitus, HTN: hypertension, CAD: coronary artery disease, CKD: chronic kidney disease, CABG: coronary artery bypass grafting.

(A) Schematic representation of a hemofilter, with proximal end prepared for histopathologic analysis boxed in red. (B) Representative gross appearance of the proximal end of a failed hemofilter. Hemofilter fibers (1) and arterial side (2) were examined. (C) Representative hematoxylin and eosin staining of hemofilter cross sections (1) and cellular material collected from the arterial sides (2) of functional and failed hemofilters. (D) IHC for fibrinogen is positive along blood-facing fiber surfaces of hemofilters used for SARS-CoV-2 positive patients and in failed hemofilters, but not in a functional hemofilter used for a SARS-CoV-2 negative patient. Insets show detail under high power.

Conclusions: Fibrinogen adsorption on biocompatible hemofilter surfaces exposed to patient blood appears to be an initial event preceding CRRT circuit failure. With COVID-19, this adsorption occurs despite intensified anticoagulation. Further mechanistic study of hemofilter failure may facilitate direct therapeutic strategies to prevent this complication.

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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/fibrinogen-adsorption-on-hemofilter-membranes-associates-with-severe-covid-19-and-renal-replacement-therapy-circuit-failure/