Therapeutic Plasma Exchange for Fibrinogen-Associated Hyperviscosity: Results of the 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.

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

Method: A prospective, randomized controlled trial in critically ill COVID-19 patients at a single US healthcare system. Patients with hyperfibrinogenemia (>800 mg/dL) or elevated plasma viscosity (2.3-3.5 cP) were randomized to receive TPE on two 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 2.35cP (±0.12) to 1.61cP (±0.03) in the TPE group and was unchanged in the SOC group (2.47cP (±0.11) to 2.47cP (±0.15). Mean fibrinogen decreased from 934.0mg/dL (±25.1) to 359.1mg/dL (±22.5) after TPE, versus from 859.6mg/dL (±57.6) to 807.3mg/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=0.13). No serious safety events related to TPE were reported. TPE significantly decreased biomarkers of inflammation (ESR, CRP) and endothelial activation (vWF, FVIII), but not hemostatic activation (PF1.2, TAT, FM) or immunoglobulin (IgG, 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 conditions associated with hyperfibrinogenemia.