Prevalence of Thrombophilia Genes in Patients with Idiopathic Thromboembolic Disease.
Authors: Mandala Eudokia , Lafaras Christos , Dardavesis Theodoros , Speletas Mattheos , Platogiannis Dimitrios , Tsioni Constantina , Douvleti Eudoxia , Ilonidis George 
Published: April 2020

Abstract
Thromboembolic disease (TED) is one of the main reasons of morbitity and mortality. Its manifestations are acute coronary syndromes (ACS), PE, DVT and ischemic cerebrovascular disease (CVD). Inherited thrombophilia’s contribution to arterial thrombosis is still controversial.
Aim: investigation of thrombophilia genes’ prevalence (FV Leiden G1691A-FVL, FII G20210A), and homocystein metabolism (MTHFR polymorphism C677T), in patients with documented idiopathic TED (ITED), comparison between venous, arterial and mixed episodes and correlation with acquired factors (dyslipidemia, smoking and homocysteine). 774 patients, 515 fulfilling the criteria of ITED, 50.8% males, 15–68 years (median age 44), were studied in Northern Greece. Patients were divided into three groups: 258 (50.1%) had venous thrombosis (group A), 239 (46.4%) with arterial (group B) and 18 (3.5%) had mixed episodes (Group C). They filled detailed questionnaire, personal and family history, origin, smoking. Antithrombin, protein C, S, APCR, homocystein and antiphospholipid antibodies were measured. Lipid profile was determined. Molecular assessment of FVL, FII, and MTHFR were performed. Genetic defect was detected in 82.7% in group A, 81.9% in group B and 66.7% in group C. Patients with venous TED were positive for FVL in 39.8% (37.2% heterozygous and 2.6% homozygous), 28.4% positive for FII (26.9% and 1.5% respectively) and 42.2% had MTHFR (34.9% and 7.3% respectively). Combined genetic defects were found in 27.7% of group A (25.3% double, 2.4% triple). Patients with arterial disease were heterozygous for FVL in 37.3%, 6.65% heterozygous for FII and 62.3% had MTHFR (48% heterozygous and 14.3% homozygous). Combined genetic defects were found in 18.6% in group B (17.4% double, 1.2% triple). Patients with mixed TED were heterozygous for FVL in 33.3%, nobody had FII and 83.3% MTHFR (50% heterozygous and 33.3% homozygous), combined defects1.2%. Number of positive and negative for FVL patients did not have any statistically significant difference between groups A and B (x2=0,097; p=0.440). Number of positive and negative for FII patients revealed statistically significant difference among three groups, with significant increase in venous disease (x2=12.009; p=0.001). Number of positive and negative for MTHFR had statistically significant difference between groups A and B, with increase in arterial disease (x2=3.410; p=0.05). Population studied was homogenous, as regards age (one way ANOVA, p=0.943), lipid profile (x2=2.611; p=0.271), smoking (x2=1.490; p=0.506), homocystein levels (x2=3.458; p=0.177) and positive family history (x2=4.490; p=0.099). Significant correlation of FII with venous TED and statistically significant increase in MTHFR prevalence in arterial TED was found. It is known that FVL is associated with increased risk of venous TED. There was no difference in prevalence of FVL between venous and arterial disease, demonstrating that it is associated with arterial disease, too. So, young patients with arterial events (ACS and/or CVD) should undergo thrombophilia testing including FVL. Nowadays, combined (double or triple) genetic defects are frequently detected (22.9% of our cases). Identification of these mutations is important in the overall assessment and management of patients at high risk.