GPF is higher in patients with severe COVID-19
COVID-19 disease progression can be accompanied by a "cytokine storm" that leads to secondary sequelae such as thrombosis and acute respiratory distress syndrome.
Several inflammatory cytokines have been associated with COVID-19 disease progression, but have far too variability to be useful as a biomarker.
We measured Gamma Prime Fibrinogen) GPF in serial blood samples from COVID-19 patients at a tertiary care medical center in order to investigate its association with clinical measures of disease progression.
We discovered that GPF has a 6-fold lower coefficient of variability compared to other inflammatory markers.
Hypothesis
Our hypothesis was that GPF levels would be elevated in COVID-19 patients compared to historical controls, and that the degree of elevation would be associated with disease severity.
Method
COVID-19 patients at a tertiary care medical center were retrospectively enrolled between 3/16/2020 and 8/1/2020. GPF was measured using the GammaCoeur ELISA (Gamma Diagnostics, Patent Pending).
Results
Our results showed that ten out of the eighteen patients with COVID-19 had the highest levels of GPF ever recorded. The previous highest GPF level of 80.3 mg/dL was found in a study of 10,601 participants in the ARIC study. GPF levels were significantly associated with the need for ECMO and mortality.
Conclusions
We found that COVID-19 patients can develop extraordinarily high levels of GPF. This has several important clinical implications. GPF contains a high affinity binding site for thrombin that binds to anion-binding exosite II on thrombin and protects it from inactivation by heparin. High levels of GPF therefore provide a reservoir of heparin-resistant clot-bound thrombin when the GPF is clotted. These findings have potential clinical implications regarding prophylactic anticoagulation of COVID-19 patients and suggest that heparin prophylaxis may be less effective than using other anticoagulants, particularly direct thrombin inhibitors.