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

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.