Investigation of the Molecular Mechanism of Coagulopathy in Severe and Critical Patients With COVID-19

Front Immunol. 2021 Dec 16:12:762782. doi: 10.3389/fimmu.2021.762782. eCollection 2021.

Abstract

Coagulopathy is a frequently reported finding in the pathology of coronavirus disease 2019 (COVID-19); however, the molecular mechanism, the involved coagulation factors, and the role of regulatory proteins in homeostasis are not fully investigated. We explored the dynamic changes of nine coagulation tests in patients and controls to propose a molecular mechanism for COVID-19-associated coagulopathy. Coagulation tests including prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen (FIB), lupus anticoagulant (LAC), proteins C and S, antithrombin III (ATIII), D-dimer, and fibrin degradation products (FDPs) were performed on plasma collected from 105 individuals (35 critical patients, 35 severe patients, and 35 healthy controls). There was a statically significant difference when the results of the critical (CRT) and/or severe (SVR) group for the following tests were compared to the control (CRL) group: PTCRT (15.014) and PTSVR (13.846) (PTCRL = 13.383, p < 0.001), PTTCRT (42.923) and PTTSVR (37.8) (PTTCRL = 36.494, p < 0.001), LACCRT (49.414) and LACSVR (47.046) (LACCRL = 40.763, p < 0.001), FIBCRT (537.66) and FIBSVR (480.29) (FIBCRL = 283.57, p < 0.001), ProCCRT (85.57%) and ProCSVR (99.34%) (ProCCRL = 94.31%, p = 0.04), ProSCRT (62.91%) and ProSSVR (65.06%) (ProSCRL = 75.03%, p < 0.001), D-dimer (p < 0.0001, χ2 = 34.812), and FDP (p < 0.002, χ2 = 15.205). No significant association was found in the ATIII results in groups (ATIIICRT = 95.71% and ATIIISVR = 99.63%; ATIIICRL = 98.74%, p = 0.321). D-dimer, FIB, PT, PTT, LAC, protein S, FDP, and protein C (ordered according to p-values) have significance in the prognosis of patients. Disruptions in homeostasis in protein C (and S), VIII/VIIIa and V/Va axes, probably play a role in COVID-19-associated coagulopathy.

Keywords: COVID-19; D-dimer (DD); antithrombin III (ATIII); coagulopathy; fibrinogen; protein C (PC); protein S.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Blood Coagulation Disorders / blood*
  • Blood Coagulation Disorders / complications
  • Blood Coagulation Disorders / diagnosis
  • Blood Coagulation Factors / metabolism
  • Blood Coagulation Tests / methods*
  • Blood Coagulation*
  • COVID-19 / complications*
  • COVID-19 / virology
  • Female
  • Fibrin / metabolism
  • Fibrin Fibrinogen Degradation Products / metabolism
  • Homeostasis
  • Humans
  • Male
  • Middle Aged
  • Partial Thromboplastin Time
  • Prognosis
  • Protein C / metabolism
  • Prothrombin Time
  • SARS-CoV-2 / genetics
  • SARS-CoV-2 / physiology

Substances

  • Blood Coagulation Factors
  • Fibrin Fibrinogen Degradation Products
  • Protein C
  • fibrin fragment D
  • Fibrin