Determinants of plasma fibrin clot lysis measured using three different assays in healthy subjects

• Published in: Thrombosis research Vol. 197; pp. 1 - 7
• Main Authors: Siudut, Jakub, Iwaniec, Teresa, Plens, Krzysztof, Pieters, Marlien, Undas, Anetta
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 01.01.2021
• Subjects: Clot lysis time; CRP; Fibrinolytic capacity; Hematology, Oncology, and Palliative Medicine; HRG; γ′-Fibrinogen; CRP; tPA; Fibrinolytic capacity; Lys50; rtPA; CLT; Clot lysis time; SD; TF; γ′-Fibrinogen; TAFI; CLT2018; hsCRP; PAI-1; HRG; ISTH; C-reactive protein; histidine-rich glycoprotein; tissue factor; tissue plasminogen activator; fibrinolysis measure using the assay by Carter et al; high-sensitivity C-reactive protein; fibrinolysis measure using the assay by Lisman et al; plasminogen activator inhibitor 1; fibrinolysis measure using the assay by Pieters et al; International Society on Thrombosis and Hemostasis; recombinant tPA; thrombin-activatable fibrinolysis inhibitor; standard deviation
• ISSN: 0049-3848; 1879-2472; 1879-2472
• DOI: 10.1016/j.thromres.2020.10.014

Several methods for measuring fibrinolytic capacity in plasma have been developed yielding frequently inconsistent results. We investigated which factors determine fibrinolytic capacity in three plasma-based assays. In 80 apparently healthy controls (aged 43 ± 10 years, 50 women [62.5%]) we evaluated fibrinolysis using three assays: (1) by Pieters et al. (CLT2018), (2) by Lisman et al. (CLT), and (3) by Carter et al. (Lys50). Coagulation factors and fibrinolytic proteins, including histidine-rich glycoprotein (HRG) and γ′-fibrinogen, were determined. Regression models were performed to identify determinants of lysis times. Positive correlations were observed between CLT2018 and both CLT (r = 0.73) and Lys50 (r = 0.61), as well as between CLT and Lys50 (r = 0.46, all p < 0.001). The main determinants of both CLT2018 and CLT were plasminogen activator inhibitor-1 (PAI-1), followed by thrombin-activatable fibrinolysis inhibitor (TAFI) and α2-antiplasmin. Histidine-rich glycoprotein was a predictor of the longest-normal CLT2018 alone (OR 1.04, 95% CI 1.02–1.06). α2-Antiplasmin and fibrinogen levels, followed by PAI-1 and TAFI determined Lys50. After adjustment for age, sex, and body mass index, C-reactive protein (CRP) was an independent predictor of the top quartiles of the three lysis times. We showed that apart from PAI-1, TAFI, and α2-antiplasmin, several other factors, in particular CRP, can affect the results of global fibrinolysis tests used in research. Our findings may help understand why the choice of a specific fibrinolysis assay can affect the presence and/or magnitude of intergroup differences in fibrinolytic capacity in a given disease state. •Associations between commonly used fibrinolysis capacity assays in healthy subjects are moderate-to-strong.•CRP affects results of global plasma fibrinolysis assays.•The assay by Carter et al. is the only test affected by γ′-fibrinogen and fibrinogen.•The assay by Pieters et al. is the only test affected by histidine-rich glycoprotein.•Choice of a fibrinolysis assay may impact assessment of fibrinolytic capacity in a specific patient group.