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, χ 2 = 34.812), and FDP (p < 0.002, χ 2 = 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.
Highlights
Coagulation is a dynamic process that is driven by the regulated proteolytic activation of zymogens in injured vessels
Fibrinolysis is an essential step in homeostasis that is finely controlled by a set of cofactors and Abbreviations: COVID-19, coronavirus disease 2019; PT, prothrombin time; Activated partial thromboplastin time (aPTT), activated partial thromboplastin time; ATIII, antithrombin III; LAC, lupus anticoagulant; ISI, international sensitivity index; INR, international normalized ratio; ICU, Intensive care unit; CRL group, control group; SVR group, severe group; CTL group, critical group
Our results showed that while the average PT result in the CRL group was 13.38 ± 0.73 [the international sensitivity index (ISI) of the kit was 1.05; international normalized ratio (INR) = 1.03 ± 0.06], it was significantly elevated in both patient groups, in which the mean PT in the SVR group was 13.85 ± 1.12s (INR = 1.07 ± 0.09) and that in the CTL group was 15.01 ± 1.68s (INR = 1.17 ± 0.14, p < 0.001)
Summary
Coagulation is a dynamic process that is driven by the regulated proteolytic activation of zymogens (commonly known as coagulation factors) in injured vessels. LACs can prolong the PTT test; a LAC test is used to evaluate prolonged PTT [7] Coagulation regulatory proteins such as antithrombin III (ATIII), protein C, and Ddimer are involved in the normal function and homeostasis of the coagulation system. The mechanistic pathways through which protein C exerts its effects on the coagulation cascades include degrading factors V/ Va and VIII/VIIIa, releasing a tissue-type plasminogen activator, and stimulating fibrinolysis by interacting with the plasminogen activator inhibitor [10]. Fibrinolysis is an essential step in homeostasis that is finely controlled by a set of cofactors and Abbreviations: COVID-19, coronavirus disease 2019; PT, prothrombin time; aPTT, activated partial thromboplastin time; ATIII, antithrombin III; LAC, lupus anticoagulant; ISI, international sensitivity index; INR, international normalized ratio; ICU, Intensive care unit; CRL group, control group; SVR group, severe group; CTL group, critical group
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