Evaluation of the prothrombin fragment 1.2 in patients with coronavirus disease 2019 (COVID-19)

Am J Hematol. 2020 Dec;95(12):1479-1485. doi: 10.1002/ajh.25962. Epub 2020 Sep 2.

Abstract

Coronavirus disease 2019 (COVID-19) may cause a hypercoagulable state. The D-dimer is frequently elevated in COVID-19, but other markers of coagulation activation, including the prothrombin fragment 1.2 (PF1.2) are poorly described. We studied hospitalized adults with COVID-19 and PF1.2 measurements performed at any time during hospitalization. We evaluated the relationship between PF1.2 and synchronously measured D-dimer. We utilized receiver operating characteristic (ROC) analysis to evaluate optimal thresholds for diagnosing thrombosis and multivariable logistic regression to evaluate association with thrombosis. A total of 115 patients were included [110 (95.7%) critically ill]. Both PF1.2 and D-dimer were moderately positively correlated (r = 0.542, P < .001) but significant discordance was observed in elevation of each marker above the laboratory reference range (59.0% elevated PF1.2 vs 98.5% elevated D-dimer). Median PF1.2 levels were higher in patients with thrombosis than those without (611 vs 374 pmol/L, P = .006). In ROC analysis, PF1.2 had superior specificity and conferred a higher positive likelihood ratio in identifying patients with thrombosis than D-dimer (PF1.2 threshold of >523 pmol/L: 69.2% sensitivity, 67.7% specificity; >924 pmol/L: 37.9% sensitivity, 87.8% specificity). In multivariable analysis, a PF1.2 >500 pmol/L was significantly associated with VTE [adjusted odds ratio (OR) 4.26, 95% CI, 1.12-16.21, P = .034] and any thrombotic manifestation (adjusted OR 3.85, 95% CI, 1.39-10.65, P = .010); conversely, synchronously measured D-dimer was not significantly associated with thrombosis. 90.6% of patients with a non-elevated PF1.2 result did not develop VTE. So, PF1.2 may be a useful assay, and potentially more discriminant than D-dimer, in identifying thrombotic manifestations in hospitalized patients with COVID-19.

MeSH terms

  • Aged
  • Biomarkers / blood
  • COVID-19 / blood*
  • Critical Illness
  • Female
  • Fibrin Fibrinogen Degradation Products / analysis
  • Hospitalization
  • Humans
  • Male
  • Middle Aged
  • Peptide Fragments / blood*
  • Prothrombin
  • ROC Curve
  • SARS-CoV-2*
  • Sensitivity and Specificity
  • Thrombosis / blood*
  • Venous Thromboembolism / blood

Substances

  • Biomarkers
  • Fibrin Fibrinogen Degradation Products
  • Peptide Fragments
  • fibrin fragment D
  • prothrombin fragment 1.2
  • Prothrombin