| Autor: |
David H. Farrell, Matthew Hudkins, Heather Hamilton, Samantha J. Underwood, Elizabeth N. Dewey, Diana E. Kazmierczak, Steven C. Kazmierczak, William B. Messer, Akram Khan, Martin A. Schreiber |
| Rok vydání: |
2022 |
| DOI: |
10.1101/2022.01.20.22269321 |
| Popis: |
BackgroundCOVID-19 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 progression, but have far too much daily intra-individual variability to be useful in tracking the course of the disease. In contrast, we have shown that the inflammatory biomarker γ’ fibrinogen (γ’ Fbg) has a 6-fold lower coefficient of variability compared to other inflammatory markers such as hs-CRP. Objectives: The aims of the study were to measure γ’ Fbg 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.MethodsCOVID-19 patients at a tertiary care medical center were retrospectively enrolled between 3/16/2020 and 8/1/2020. γ’ Fbg was measured using a commercial ELISA. Results: Our results showed that nine out of the seventeen patients with COVID-19 had extremely high levels of γ’ Fbg. γ’ Fbg levels were significantly associated with the need for ECMO and with mortality.ConclusionsWe found that COVID-19 patients can develop extraordinarily high levels of γ’ Fbg. The previous highest γ’ Fbg level that we are aware of was 80.3 mg/dL found in a study of 10,601 participants in the ARIC study. These results have several important clinical implications. γ’ Fbg 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 γ’ Fbg therefore provide a reservoir of heparin-resistant clot-bound thrombin when the γ’ Fbg is clotted. These findings have potential 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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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