PB2432 POSSIBLE GENETIC RISK FACTORS OF PULMONARY EMBOLISM IN YOUNG PATIENTS FROM THE NORTH‐WESTERN REGION OF RUSSIA
Authors: A. Chechulova, S. Kapustin, S. Svitina, V. Soldatenkov, L. Papayan, V. Soroka, P. Chechulov
Journal: HemaSphere (2019)

Background: Pulmonary embolism (PE) and deep‐vein thrombosis (DVT) are the most common clinical manifestations of venous thromboembolism (VTE) which associated with high rates of morbidity and mortality in population. To date, little is known about the factors which could predict PE development in VTE patients. Several studies have shown that fibrin clot structure as well as the rate of clot lysis could influence the risk of PE development. Moreover, nucleotide variations in genes coding for components involved in processes of thrombus formation or its lysis are well‐described. Nevertheless, association between patient's genotype and features of clinical VTE manifestation, in particular, risk of PE development, remains debatable. Aims: To reveal possible association between the alpha‐fibrinogen (FI‐A), factor XIII A‐subunit (FXIII‐A), tissue plasminogen activator (TPA) and plasminogen activator inhibitor type I (PAI‐1) gene polymorphisms and the features of clinical VTE manifestation in patients with early‐onset disease from the North‐Western region of Russia. Methods: We analyzed 243 young patients under 45 years old (119 men and 124 women, mean age – 37.4 years) with at least one confirmed episode of acute VTE. Isolated DVT (“DVT only”) was diagnosed in 154 (63.4%), DVT complicated by PE (“DVT + PE”) – in 53 (21.8%), and isolated PE (“PE only”) – in 36 (14.8%) patients. Genotyping for the FI‐A Thr312Ala, FXIII‐A Val34Leu, PAI‐1 ‐675 4G/5G and TPA 311 bp Ins/Del variations was performed by PCR‐RFLP. To assess intergroup differences in genotype frequencies, the odds ratios (OR), their 95% confidence intervals (CI) and p‐values were calculated by Fisher's exact method. Results: Distributions of the FI‐A, FXIII‐A, PAI‐1 and TPA genotypes in patients with different clinical manifestations of VTE have shown several differences. Frequency of the TPA Del/Del genotype was significantly increased in VTE patients with the signs of PE when compared to those with isolated DVT (31.5% vs. 18.8%, respectively, OR = 2.0; 95% CI: 1.1‐3.6; p = 0.029). Homozygosity for the TPA Del allele was most prevalent in patients with isolated PE (38.9% vs. 18.8% in the group “DVT only”, OR = 2.7; 95% CI: 1.3‐6.0; p = 0.014). In this group, the frequency of the FI‐A 312 Ala/Ala variant was 2‐fold increased when compared to patients with isolated DVT (22.2% vs. 11.0%, respectively, OR = 2.3; 95% CI: 0.9‐5.9; p = 0.098). In patients with the signs of PE, homozygosity for the FXIII‐A 34Leu variant was observed more frequently than in the “DVT only” group (11.2% vs. 6.5%, respectively, OR = 1.8; 95% CI: 0.7‐4.6; p = 0.23). At the same time, the frequency of heterozygous FXIII‐A genotype was significantly increased in patients with isolated DVT when compared to “DVT + PE” group (48.7% vs. 30.2%, respectively, OR = 2.2; 95% CI: 1.1‐4.3; p = 0.024). Summary/Conclusion: TPA Del/Del genotype is associated with the risk of PE development in young VTE patients from the North‐Western region of Russia, whereas heterozygous FXIII‐A variant (34 Val/Leu) could protect from PE in patients with DVT. Role of the FI‐A 312 Ala/Ala and FXIII‐A 34 Leu/Leu variants as possible determinants of different clinical course of VTE needs further clarification.