Therapeutic plasma exchange for fibrinogen-associated hyperviscosity: results of the COVID-19 PLasma EXchange (COPLEX) randomized controlled trial.

Abstract

Background: Therapeutic plasma exchange (TPE) is the primary intervention for treating symptomatic hyperviscosity from hypergammaglobulinemia, yet its efficacy for treating hyperviscosity related to hyperfibrinogenemia is unclear.

Objectives: Define the safety and efficacy of TPE for critically ill COVID-19 patients with elevated blood viscosity from hyperfibrinogenemia.

Methods: We performed a prospective randomized controlled trial in critically ill COVID-19 patients in a single US healthcare system. Patients with hyperfibrinogenemia (>800 mg/dL) or elevated plasma viscosity (2.3-3.5 centipoise [cP]) were randomized to receive TPE on 2 consecutive days or continued standard of care (SOC).

Results: Twenty participants were enrolled, with 10 receiving TPE and 10 receiving SOC alone. Mean (±SEM) plasma viscosity decreased significantly from 2.35 cP (±0.12) to 1.61 cP (±0.03) in the TPE group and was unchanged in the SOC group (2.47 cP [±0.11] to 2.47 cP [±0.15]). Mean fibrinogen decreased from 934.0 mg/dL (±25.1) to 359.1 mg/dL (±22.5) after TPE vs from 859.6 mg/dL (±57.6) to 807.3 mg/dL (±63.1) in SOC. There was no significant difference in 28-day all-cause mortality between groups, with 2 deaths in the TPE cohort and 5 deaths in the SOC cohort (P = .13). No serious safety events related to TPE were reported. TPE significantly decreased biomarkers of inflammation (erythrocyte sedimentation rate and C-reactive protein) and endothelial activation (von Willebrand factor and factor VIII) but not hemostatic activation (prothrombin fragment 1.2, thrombin-antithrombin complex, and fibrin monomer) or immunoglobulin (IgG and IgM) levels.

Conclusion: TPE is safe and effective for normalizing elevated blood viscosity from hyperfibrinogenemia in COVID-19 patients. Additional studies are needed to determine the impact of TPE on overall patient outcomes, including in those with non-COVID-19 conditions associated with hyperfibrinogenemia.