Abstract Number: PB0400
Meeting: ISTH 2021 Congress
Background: Pulmonary embolism (PE) remains a major cause of mortality. Prothrombotic fibrin clot properties in acute PE are associated with eightfold increased risk of death. To our knowledge, no reports assessed the impact of fibrinogen and factor XIII (FXIII) polymorphisms on plasma fibrin clot features in acute PE.
Aims: We investigated whether a fibrinogen alpha chain (FGA) Thr312Ala, fibrinogen beta chain (FGB) Arg448Lys and FXIII Val34Leu polymorphisms are associated with fibrin clot properties assessed on admission in acute PE patients.
Methods: In 126 normotensive acute PE patients (aged 58±14 years) we assessed 3 genetic polymorphisms FGA rs6050 C___2892877_10, FGB rs1800790 C___7429790_20 and factor XIII rs5958 C___1639938_20 in relation to fibrin clot permeability (Ks), clot lysis time (CLT), and endogenous thrombin potential (ETP).
Results: Patients with the SNP Arg448Lys in the FGB (n=40, 31.7%, 4 homozygous) compared to non-carriers had 15.7% reduced Ks (p=0.0003), 11.1% prolonged CLT (p=0.019), and 10.9% higher ETP (p=0.011). The FXIII 34Leu allele (n=49, 38.9%, 9 homozygous) was associated with 18.3% reduced Ks (p<0.0001), 9.8% prolonged CLT (p=0.004), and 9.2% higher ETP (p=0.018) compared to non-carriers, also after adjustment for fibrinogen (all p<0.01). There was no impact of the FGA Thr312Ala polymorphism on fibrin clot properties or ETP (all p>0.05). The Arg448Lys polymorphism explained 13% of the variance in Ks and17% in CLT, while FXIII 34Leu allele explained 25% of the variance in Ks and 23% in CLT.
Conclusions: Fibrinogen B Arg448Lys and FXIII Val34Leu polymorphisms are associated with formation of more compact fibrin networks in acute PE patients, suggesting that despite heightened thrombin generation and inflammation typical of acute thromboembolism the 2 common generic variants have detectable effect on clot properties, similar to those reported in subjects at risk of venous thrombosis.
This work was supported by the Polish National Science Centre (UMO-2015/B/NZ5/02215).
To cite this abstract in AMA style:Klajmon A, Chmiel J, Ząbczyk M, Natorska J, Undas A. Fibrinogen B Arg448Lys and Factor XIII Val34Leu Polymorphisms Are Associated with Prothrombotic Fibrin Clot Properties in Patients with Acute Pulmonary Embolism [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/fibrinogen-b-arg448lys-and-factor-xiii-val34leu-polymorphisms-are-associated-with-prothrombotic-fibrin-clot-properties-in-patients-with-acute-pulmonary-embolism/. Accessed December 5, 2021.
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