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Decreased Protein C Pathway Activity in COVID-19 Compared to Non-COVID Sepsis: An Observational and Comparative

Heiko Rühl1, Christian Bode2, Tobias Becher3

  • 1Institute of Experimental Hematology and Transfusion Medicine, University Hospital Bonn, 53127 Bonn, Germany.

Biomedicines
|September 28, 2024
PubMed

Insights

COVID-19 sepsis patients exhibit a reduced anticoagulant response compared to non-COVID sepsis patients, indicated by lower activated protein C (APC) levels relative to thrombin markers. This impaired protein C pathway function may contribute to the increased clotting risk in COVID-19 patients.

Area of Science:

  • Hematology
  • Critical Care Medicine
  • Infectious Diseases

Background:

  • Sepsis-associated coagulopathy is a significant predictor of mortality.
  • The protein C (PC) pathway plays a crucial role in anticoagulation.
  • Dysfunction of the PC pathway may underlie the prothrombotic state observed in coronavirus disease 2019 (COVID-19) sepsis.

Purpose of the Study:

  • To evaluate the functionality of the protein C pathway in COVID-19 and non-COVID sepsis.
  • To compare the levels of key enzymes, thrombin and activated protein C (APC), between patient groups and healthy controls.
  • To investigate the relationship between coagulation activation and anticoagulant response in sepsis.

Main Methods:

  • Plasma levels of thrombin, activated protein C (APC), prothrombin-fragment 1+2 (F1+2), and thrombin-antithrombin complex (TAT) were measured in 30 COVID-19 patients, 47 non-COVID sepsis patients, and 40 healthy controls.
  • Coagulation activation and APC formation were induced in healthy controls using recombinant activated factor VII.
  • Oligonucleotide-based enzyme capture assays were employed for measuring thrombin and APC.

Main Results:

  • Patients with COVID-19 and non-COVID sepsis showed significantly higher levels of thrombin markers (thrombin, F1+2, TAT) compared to stimulated healthy controls.
  • APC levels were elevated in both COVID-19 and non-COVID sepsis groups relative to controls, but the APC response relative to thrombin markers was lower in COVID-19 patients.
  • Adjusted ratios of APC/thrombin, APC/F1+2, and APC/TAT were significantly lower in the COVID-19 group compared to the non-COVID sepsis group and stimulated healthy controls.

Conclusions:

  • COVID-19 sepsis is characterized by a comparatively diminished anticoagulant response, specifically a lower activated protein C (APC) generation relative to thrombin activity.
  • This impaired APC response in COVID-19 sepsis, potentially due to endothelial dysfunction, contributes to its distinct prothrombotic phenotype.
  • Understanding these pathway differences is critical for managing coagulopathy in sepsis and COVID-19.

Keywords:
COVID-19protein Csepsisthrombinthrombophilia

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