Continuous renal replacement therapy in COVID-19—associated AKI: adding heparin to citrate to extend filter life—a retrospective cohort study

Abstract

Background Coronavirus disease 2019 (COVID-19) may predispose patients to thrombotic events. The best anticoagulation strategy for continuous renal replacement therapy (CRRT) in such patients is still under debate. The purpose of this study was to evaluate the impact that different anticoagulation protocols have on filter clotting risk. Methods This was a retrospective observational study comparing two different anticoagulation strategies (citrate only and citrate plus intravenous infusion of unfractionated heparin) in patients with acute kidney injury (AKI), associated or not with COVID-19 (COV + AKI and COV − AKI, respectively), who were submitted to CRRT. Filter clotting risks were compared among groups. Results Between January 2019 and July 2020, 238 patients were evaluated: 188 in the COV + AKI group and 50 in the COV − AKI group. Filter clotting during the first filter use occurred in 111 patients (46.6%). Heparin use conferred protection against filter clotting (HR = 0.37, 95% CI 0.25–0.55), resulting in longer filter survival. Bleeding events and the need for blood transfusion were similar between the citrate only and citrate plus unfractionated heparin strategies. In-hospital mortality was higher among the COV + AKI patients than among the COV − AKI patients, although it was similar between the COV + AKI patients who received heparin and those who did not. Filter clotting was more common in patients with D-dimer levels above the median (5990 ng/ml). In the multivariate analysis, heparin was associated with a lower risk of filter clotting (HR = 0.28, 95% CI 0.18–0.43), whereas an elevated D-dimer level and high hemoglobin were found to be risk factors for circuit clotting. A diagnosis of COVID-19 was marginally associated with an increased risk of circuit clotting (HR = 2.15, 95% CI 0.99–4.68). Conclusions In COV + AKI patients, adding systemic heparin to standard regional citrate anticoagulation may prolong CRRT filter patency by reducing clotting risk with a low risk of complications.

An Innovative Approach to Minimizing Downtime in Continuous Kidney Replacement Therapy

“…29 The association between COVID-19 infection and decreased filter life span has been replicated in other analyses. 29,30 Other patient populations for whom shortened filter life span secondary to clotting or clogging might present a clinical challenge include those with sepsis, burns, or liver failure. 21,27,31,32 Existing Technology to Reduce Clotting and Clogging Optimizing filter life and performance efficiency are key to reducing downtime, improving outcomes, and reducing the cost of CKRT.…”

Good practice statements for antithrombotic therapy in the management of COVID‐19: Guidance from the SSC of the ISTH

“… 41 Adding systemic UFH to regional citrate anticoagulation is associated with less frequent filter thrombosis without increased rates of bleeding and with similar rates of mortality compared to citrate alone. 42 , 43 , 44 , 45 If filter thrombosis occurs despite systemic UFH, an option is to consider an intravenous direct thrombin inhibitor such as argatroban monitored with a standardized APTT nomogram. Patients with COVID‐19 pneumonia requiring CRRT have generally been excluded from trials of escalated‐dose thromboprophylaxis, though in the INSPIRATION trial there was a non‐significant increase in need for CRRT among patients receiving intermediate‐dose enoxaparin.…”

“…In these cases, not only does the hyperinflammatory state predispose patients to thrombosis, but it may also lead to thrombosis of the extracorporeal CRRT circuit 41 . Adding systemic UFH to regional citrate anticoagulation is associated with less frequent filter thrombosis without increased rates of bleeding and with similar rates of mortality compared to citrate alone 42–45 . If filter thrombosis occurs despite systemic UFH, an option is to consider an intravenous direct thrombin inhibitor such as argatroban monitored with a standardized APTT nomogram.…”

Continuous KRT

“…5,6,35 The use of anticoagulation appears especially important in patients with COVID-19-associated AKI receiving CKRT, who appear to be at very high risk of filter clotting, with some requiring dual anticoagulation with regional citrate and systemic heparin to maintain filter patency. 52 In regional citrate anticoagulation, citrate is infused prefilter (generating a blood citrate concentration of 3-6 mmol/L) to produce a low intrafilter ionized calcium (iCa) level (typically targeted to ,0.4 mmol/L), which prevents clotting in the filter. Intravenous calcium is infused either in the postfilter limb of the CKRT circuit before return of blood to the patient, or via a separate systemic infusion to prevent hypocalcemia in the patient.…”

“…5,6,35 The use of anticoagulation appears especially important in patients with COVID-19–associated AKI receiving CKRT, who appear to be at very high risk of filter clotting, with some requiring dual anticoagulation with regional citrate and systemic heparin to maintain filter patency. 52…”