Search Results (23)

Recurrent spontaneous miscarriages represent a significant reproductive challenge, often associated with inherited thrombophilia. Among the genetic factors involved, methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms have been increasingly studied. The two main variants, MTHFR C677T and MTHFR A1298C, have been suggested to contribute to thrombotic events and adverse pregnancy outcomes. This study aims to evaluate the higher prevalence and potential role of MTHFR gene polymorphisms (C677T and A1298C) in the etiology of recurrent spontaneous miscarriages in pregnant women with inherited thrombophilia, in comparison with the classical thrombophilia-associated SNPs—F5 Leiden and the F2 G20210A gene mutation. In this single-center retrospective observational study, 64 women with recurrent pregnancy loss and confirmed inherited thrombophilia were evaluated. Genomic DNA extracted from peripheral blood samples was analyzed for thrombophilia-associated polymorphisms, including F5 Leiden (G1691A), F2 G20210A, MTHFR C677T, MTHFR A1298C, SERPINE1 4G/5G, and F13A1 V34L, using a real-time PCR-based Bosphore^® Thrombophilia Panel. The presence of MTHFR C677T and A1298C polymorphisms was investigated and compared to the incidence of F5 Leiden and F2 G20210A gene SNPs. Associations between genotypes and clinical characteristics, including the number of pregnancy losses, were assessed using chi-square tests, Kruskal–Wallis analysis, and logistic regression models. The most frequently detected polymorphisms were heterozygous variants of the MTHFR gene, with prevalences of 57.8% for C677T and 53.1% for A1298C. Homozygous MTHFR C677T was significantly associated with a higher number of pregnancy losses (Kruskal–Wallis test, p = 0.001). Similarly, the homozygous MTHFR A1298C genotype showed a significant association with increased miscarriage frequency (p = 0.012). Classical thrombophilic mutations were less frequent, with F2 G20210A identified in only two patients, although its presence was associated with a higher number of pregnancy losses (p = 0.030). These findings suggest that combined thrombophilic polymorphisms may contribute to recurrent pregnancy loss, although larger studies are required to confirm these observations. Full article

COVID-19 not only affects the respiratory system but also increases the risk of cerebrovascular complications, including ischemic stroke. Experimental and clinical data suggest that cytokine dysregulation and polymorphisms of thrombophilia-related genes (MTHFR, MTR, and MTRR) may jointly promote hypercoagulation, endothelial dysfunction, and thromboinflammation, thereby contributing to post-COVID ischemic stroke. This study included 160 patients treated at Zangiota Infectious Diseases Hospitals (2021–2023): 60 patients with ischemic stroke in the acute or post-COVID period (experiment group), 50 COVID-19 patients without ischemic stroke (comparison group), and 50 ischemic stroke patients without COVID-19 (control group). Clinical–neurological and immunological parameters were assessed, and polymorphisms in thrombophilia/folate cycle genes (MTHFR C677T, MTR, and MTRR) were genotyped by PCR/real-time PCR. Statistical analysis included χ² tests, t-tests, logistic regression with odds ratios (OR) and 95% confidence intervals (CI); Hardy–Weinberg equilibrium was verified. A strong association was identified between the MTHFR C677T polymorphism and ischemic stroke on the background of COVID-19 (OR = 5.4; 95% CI: 2.1–13.8; p < 0.001). The TNF-α rs1800629 polymorphism was also significantly associated with COVID-19-related cerebrovascular events (OR = 3.27; 95% CI: 1.4–7.6; p = 0.006). Carriage of two or more minor alleles produced a synergistic effect, markedly increasing the risk of post-COVID ischemic stroke (OR = 5.59; 95% CI: 2.3–13.6; p < 0.001). These polymorphisms were linked to hyperhomocysteinemia, endothelial dysfunction, and mechanisms contributing to multifactorial arterial ischemic events. The combined assessment of thrombophilia and folate cycle-related genotypes and clinical indicators may provide a potential framework for improved risk stratification. Polymorphisms in MTHFR may appear to represent important genetic determinants of ischemic stroke following COVID-19, particularly in the context of arterial ischemic mechanisms. Full article

Legg–Calvé–Perthes disease (LCPD) is a rare disease caused by avascular necrosis of the femoral head. Although its etiology is still not fully understood, evidence suggests that heritable prothrombotic and inflammatory factors, as well as environmental factors, may be implicated in its onset and progress. The objective of this study is to describe the genetic, biochemical, and environmental factors that may be associated with the etiology of LCPD. This study was conducted in three families and included seven related patients with an LCPD diagnosis. We evaluated the following gene alterations using real-time PCR: MTHFR, CBS, COL1A1, COL2A1, PT, FVL, FVIII, FIX, PAI-1, eNOS, IL-23R, TNF-α, RANNK, RANNK-L, OPG and IL-6. Additionally, we assessed fourteen thrombophilia-associated biochemical markers, as well as environmental factors that may be associated with the etiology of LCPD in family cases. The results show different hemostatic alterations in every individual analyzed, presenting out-of-range values in one or more parameters. Concentrations of hemoglobin and fibrinogen and the FIX activity percentage showed statistically significant differences (p < 0.001) when compared with healthy controls. All patients presented at least one mutated allele for the MTFHR (rs1801133), IL-23R (rs1569922) and OPG (rs2073618) polymorphisms, as well as isolated cases with other genetic variants. Our results show environmental elements from every family, and hemostatic and inflammatory disorders, may be involved in the development of LCPD. Furthermore, genetic variants could contribute to the onset of the disease. This study highlights the multifactorial nature of this pathology, involving various environmental, genetic, inflammatory, and prothrombotic factors in three families that included seven patients diagnosed with LCPD. Full article

Thrombophilia is considered one of the key mechanisms underlying reproductive disorders. Clinical heterogeneity of reproductive disorders and a lack of stratification by phenotype often limit interpretation. Therefore, evaluating thrombophilia-associated genetic markers separately in fetal loss syndrome, postpartum hemorrhage (PPH), and hypertensive disorders of pregnancy is essential. Background/Objectives: To assess the frequency of thrombophilia-related genetic polymorphisms in women with various reproductive disorders and evaluate their association with clinical–anamnestic characteristics and obstetric antiphospholipid syndrome. Methods: A total of 132 women with reproductive disorders (fetal loss syndrome, postpartum hemorrhage, preeclampsia). Results: Statistically significant differences were found when comparing between the groups. Thus, heterozygous F13 genetic polymorphisms were statistically more common in the group with a history of preeclampsia compared to the group with PPH (the G/A genotype was detected in 22.2% versus 10.7%, p = 0.045), and heterozygous ITGA2 gene genetic polymorphisms were also more common (the C/T genotype was detected in 66.7% versus 42.9%, p = 0.023). In women with a history of PPH, homozygous ITGA2 genetic polymorphisms were statistically more common (the T/T genotype was detected 2.6 times more often—21.4% versus 8.8% compared to the group with fetal loss syndrome, p = 0.022; and 3.8 times more often—21.4% versus 5.6% compared to the group with PE, p = 0.022). Conclusions: A study of thrombophilia gene polymorphisms in women with reproductive disorders showed that the G/A genotype of F13, the C/T genotype of ITGA2, and the A/G genotype of MTR:2756 were significantly more common in women with preeclampsia than in the group with postpartum hemorrhage; the T/T genotype of the ITGA2 gene was detected in postpartum hemorrhage. The MTHFR 1286A > C (A/C) polymorphism was associated with a reduced risk of postpartum hemorrhage. In contrast, the MTR 2756A > G (A/G) genotype was associated with an increased risk of preeclampsia. Full article

Background/Objectives: Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder driven by mutations in the NF1 gene, whose pathogenesis centers on the loss of neurofibromin function and subsequent hyperactivation of the RAS/MAPK pathway. Notably, to the best of our knowledge and following a systematic literature search conducted by our research team, no cases of NF1 complicated by severe cardiac structural abnormalities that ultimately lead to cerebral infarction have been reported to date. Thus, it is of paramount importance to avoid missed diagnosis by performing comprehensive cardiac-related examinations in patients with NF1. Case Presentation: A 20-year-old male patient diagnosed with NF1 presented with right-sided limb weakness and was initially identified with cerebral infarction. To clarify the underlying etiology, a comprehensive clinical evaluation was performed, including cardiac imaging assessments (to characterize cardiac structural changes) and whole-exome sequencing (to identify the presence of procoagulant gene mutations). Comprehensive evaluation revealed a spectrum of cardiac structural abnormalities in the patient: aortic valve prolapse with severe regurgitation, non-infective vegetations on the aortic valve leaflets, mild-to-moderate mitral regurgitation, left ventricular hypertrophy and dilation, and left atrial dilation. Whole-exome sequencing detected exclusively a pathogenic variant in the NF1 gene, with no other pathogenic/likely pathogenic variants or thrombophilia-associated polymorphisms being found. Laboratory investigations ruled out infectious etiologies, supporting the notion that NF1-mediated cardiac structural and developmental anomalies are the primary driver of cardiac vegetation formation, given the absence of other identified contributing factors; embolization of one such vegetation ultimately led to both splenic and cerebral infarction. Conclusions: This case emphasizes the necessity of implementing early and proactive cardiac evaluations in patients with NF1. Additionally, for NF1 individuals—particularly those presenting with suggestive vascular or cardiac symptoms—a comprehensive multifactorial assessment of thrombotic risk is critical. Collectively, maintaining clinical vigilance for cardiac abnormalities in NF1 patients and avoiding diagnostic oversight is essential to reduce life-threatening risks. Full article

Background and Objectives: Thrombophilia is a prothrombotic disorder that increases the risk of blood clotting and can pose serious health problems. It is considered a condition of gene–gene or gene–environment interactions. Variation in the prevalence of thrombophilia mutations and their interaction among populations necessitates localized genetic assessments. However, population-based genetic data remains limited for developing effective preventive strategies. Materials and Methods: This cross-sectional observational study was conducted over five years (2020–2024) at a tertiary university hospital in Northern Greece. A total of 2961 individuals aged 18–85 years (mean: 50.5) were registered based on family or medical history of venous thromboembolism (VTE) or clinical symptoms of VTE. The final analysis included 2078 participants comprising 1143 males (55%) and 935 females (45%), who met all the inclusion criteria. Inclusion criteria were absence of acute illness or malignancy, informed consent, and an adequate DNA quantity for genotyping, whereas excluded criteria included incomplete laboratory data, active inflammatory or malignant disease, and cognitive or psychiatric conditions. Peripheral blood samples were collected in 2 mL K₃-EDTA tubes, and genomic DNA was analyzed using real-time polymerase chain reaction (PCR) with melting curve analysis and hybridization probes (LightMix^® in vitro diagnostics, TIB MolBiol, Berlin, Germany). Five thrombophilia-related polymorphisms, Factor V Leiden (F5 G1691A), prothrombin (F2 G20210A), methylenetetrahydrofolate reductase (MTHFR C677T and MTHFR A1298C), and Plasminogen Activator Inhibitor-1 (PAI-1) 4G/5G, were examined for allele and genotype frequencies, Hardy–Weinberg equilibrium testing, pairwise linkage disequilibrium (D′ and r²), and power analysis. For subjects tested for Factor V Leiden (n = 1476), the activated protein C resistance (APC) ratio was additionally evaluated using the ACL TOP 750 analyzer. Results: Allele frequencies were 7.3% for FV Leiden and 3.7% for FII. The PAI-1 allele was distributed at 44%, while the MTHFR (C677T and A1298C) alleles were each present at 33%. Significant linkage disequilibrium was identified between MTHFR (C677T and A1298C) and between MTHFR A1298C and PAI-1. No evolutionary pressure or demographic bias was found in the Hardy–Weinberg equilibrium. The APC ratio demonstrated a high sensitivity (99.2%) and specificity (96.6%), indicating that it may serve as a reliable screening method. Conclusions: Our findings highlight informative patterns in the genetic predisposition to thrombophilia, which may help develop rule-based strategies for implementing thromboprophylaxis guidelines and personalized medical interventions. Full article

Background and Clinical Significance: Arterial and venous thromboses are typically distinct clinical entities, each governed by unique pathophysiological mechanisms. The concurrent manifestation of both, particularly in the setting of massive pulmonary embolism (PE), is exceptionally rare and poses significant diagnostic and therapeutic challenges. Case Presentation: This report describes a 61-year-old male with well-controlled hypertension and type 2 diabetes who developed extensive thromboses involving deep vein thrombosis (DVT) of the right popliteal vein, arterial thrombosis of the left iliac artery, and massive PE. The patient was initially managed conservatively, in accordance with the European Society of Cardiology (ESC) 2019 Guidelines for Acute PE, using unfractionated heparin (UFH), low-molecular-weight heparin, a direct oral anticoagulant (DOAC), and adjunctive therapy. This approach was chosen due to the absence of hemodynamic instability. However, given failed percutaneous revascularization and persistent arterial occlusion, surgical thromboendarterectomy (TEA) was ultimately required. Post hoc genetic testing was prompted by the complex presentation in the absence of classical provoking factors—such as trauma, surgery, malignancy, or antiphospholipid syndrome—consistent with recommendations for selective thrombophilia testing in atypical or severe cases. The analysis revealed four thrombophilia-associated polymorphisms: heterozygous Factor V Leiden (FVL; R506Q genotype), Plasminogen Activator Inhibitor-1 (PAI-1; 4G/5G genotype), Methylenetetrahydrofolate reductase (MTHFR; c.677C > T genotype), and homozygous Angiotensin-Converting Enzyme Insertion/Deletion (ACE I/D; DD genotype). Conclusions: While each variant has been individually associated with thrombotic risk, their co-occurrence in a single patient with simultaneous arterial and venous thromboses has not, to our knowledge, been previously documented. This case underscores the potential for gene–gene interactions to amplify thrombotic risk, even in the presence of variants traditionally considered to confer only modest to moderate risk. It highlights the need for a multidisciplinary approach and raises questions regarding pharmacogenetics, anticoagulation, and future research into cumulative genetic risk in complex thrombotic phenotypes. Full article

Recurrent pregnancy loss (RPL) is defined as the occurrence of two or more pregnancy losses before 20 weeks of gestation. RPL is a common medical condition among reproductive-age women, with approximately 23 million cases reported annually worldwide. Up to 5% of pregnant women may experience two or more consecutive pregnancy losses. Previous studies have investigated risk factors for RPL, including maternal age, uterine pathology, genetic anomalies, infectious agents, endocrine disorders, thrombophilia, and immune dysfunction. However, RPL is a disease caused by a complex interaction of genetic factors, environmental factors (e.g., diet, lifestyle, and stress), epigenetic factors, and the immune system. In addition, due to the lack of research on genetics research related to RPL, the etiology remains unclear in up to 50% of cases. Platelets play a critical role in pregnancy maintenance. This study examined the associations of platelet receptor and ligand gene variants, including integrin subunit beta 3 (ITGB3) rs2317676 A > G, rs3809865 A > T; fibrinogen gamma chain (FGG) rs1049636 T > C, rs2066865 T > C; glycoprotein 1b subunit alpha (GP1BA) rs2243093 T > C, rs6065 C > T; platelet endothelial cell adhesion molecule 1 (PECAM1) rs2812 C > T; and platelet endothelial aggregation receptor 1 (PEAR1) rs822442 C > A, rs12137505 G > A, with RPL prevalence. In total, 389 RPL patients and 375 healthy controls (all Korean women) were enrolled. Genotyping of each single nucleotide polymorphism was performed using polymerase chain reaction–restriction fragment length polymorphism and the TaqMan genotyping assay. All samples were collected with approval from the Institutional Review Board at Bundang CHA Medical Center. The ITGB3 rs3809865 A > T genotype was strongly associated with RPL prevalence (pregnancy loss [PL] ≥ 2: adjusted odds ratio [AOR] = 2.505, 95% confidence interval [CI] = 1.262–4.969, p = 0.009; PL ≥ 3: AOR = 3.255, 95% CI = 1.551–6.830, p = 0.002; PL ≥ 4: AOR = 3.613, 95% CI = 1.403–9.307, p = 0.008). The FGG rs1049636 T > C polymorphism was associated with a decreased risk in women who had three or more pregnancy losses (PL ≥ 3: AOR = 0.673, 95% CI = 0.460–0.987, p = 0.043; PL ≥ 4: AOR = 0.556, 95% CI = 0.310–0.997, p = 0.049). These findings indicate significant associations of the ITGB3 rs3809865 A > T and FGG rs1049636 T > C polymorphisms with RPL, suggesting that platelet function influences RPL in Korean women. Full article

Background/Objectives: The objective of the study was to explore the combined effect of polymorphisms in the platelet glycoproteins Ia (GpIa) and IIIa (GpIIIa), along with the platelet-endothelial cell adhesion molecule-1 (PECAM-1) and P-Selectin genes, on the risk of recurrent pregnancy loss. Methods: This study involved 162 women with primary unexplained recurrent miscarriages and 60 fertile controls who had at least one uncomplicated full-term pregnancy without experiencing fetal loss. All participants were of Greek origin and were genotyped for four single nucleotide polymorphisms (SNPs), GpIa-C807T, GpIIIa-PlA1/PlA2, PECAM-1-C373G, and P-Selectin-A37674C, using pyrosequencing. A genetic risk score (GRS) was calculated in two forms: one based on the number of SNPs (dominant model) and the other based on the number of polymorphic alleles (additive model), utilizing logistic regression and receiver operator characteristic (ROC) analyses. Results: A statistically significant increase in the risk of miscarriage was observed with the number of polymorphic genes, with an odds ratio (OR) of 2.2 (95% confidence interval [CI]: 1.5 to 3.2, p < 0.001) for each additional SNP. The ROC analysis revealed an area under the curve (AUC) of 0.689 (95% CI: 0.614 to 0.763, p < 0.001). The presence of two or more polymorphic genes demonstrated a sensitivity of 69.8% and specificity of 65%, with an OR = 4.3 (95% CI: 2.3 to 8.0, p < 0.001). The performance of the GRS improved in younger patients and those experiencing late miscarriages. An AUC = 0.839 (95% CI: 0.749 to 0.930, p < 0.001) and an OR = 7.0 (95% CI: 2.8 to 17.8, p < 0.001) per SNP were achieved for the age group < 30 years. For subjects with second trimester fetal loss, the GRS yielded an AUC = 0.742 (95% CI: 0.610 to 0.874, p = 0.002) and an OR = 3.6 (95%OR = 7.0, 95% CI: 2.8 to 17.8) per SNP. The allelic GRS produced similar or slightly diminished results. Conclusions: This study highlights the promising potential of a genetic risk score based on four SNPs in predicting unexplained recurrent miscarriages, particularly in younger individuals and in cases of late miscarriage. These findings contribute to a deeper understanding of the epidemiology of unexplained recurrent miscarriage, emphasizing the role of platelet thrombophilia. Full article

Numerous studies have tried to evaluate the potential role of thrombophilia-related genes in retinal vein occlusion (RVO); however, there is limited research on genes related to different pathophysiological mechanisms involved in RVO. In view of the strong contribution of oxidative stress and inflammation to the pathogenesis of RVO, the purpose of the present study was to investigate the association of inflammation- and oxidative-stress-related polymorphisms from three different genes [apolipoprotein E (APOE), paraoxonase 1 (PON1) and stromal cell-derived factor 1 (SDF-1)] and the risk of RVO in a Greek population. Participants in this case-control study were 50 RVO patients (RVO group) and 50 healthy volunteers (control group). Blood samples were collected on EDTA tubes and genomic DNA was extracted. Genotyping of rs854560 (L55M) and rs662 (Q192R) for the PON1 gene, rs429358 and rs7412 for the APOE gene and rs1801157 [SDF1-3′G(801)A] for SDF-1 gene was performed using the polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) method. Multiple genetic models (codominant, dominant, recessive, overdominant and log-additive) and haplotype analyses were performed using the SNPStats web tool to assess the correlation between the genetic polymorphisms and the risk of RVO. Binary logistic regression analysis was used for the association analysis between APOE gene variants and RVO. Given the multifactorial nature of the disease, our statistical analysis was adjusted for the most important systemic risk factors (age, hypertension and diabetes mellitus). The dominant genetic model for the PON1 Q192R single nucleotide polymorphism (SNP) of the association analysis revealed that there was a statistically significant difference between the RVO group and the control group. Specifically, after adjusting for age and hypertension, the PON1 192 R allele (QR + RR) was found to be associated with a statistically significantly higher risk of RVO compared to the QQ genotype (OR = 2.51; 95% CI = 1.02–6.14, p = 0.04). The statistically significant results were maintained after including diabetes in the multivariate model in addition to age and hypertension (OR = 2.83; 95% CI = 1.01–7.97, p = 0.042). No statistically significant association was revealed between the other studied polymorphisms and the risk of RVO. Haplotype analysis for PON1 SNPs, L55M and Q192R, revealed no statistically significant correlation. In conclusion, PON1 192 R allele carriers (QR + RR) were associated with a statistically significantly increased risk of RVO compared to the QQ homozygotes. These findings suggest that the R allele of the PON1 Q192R is likely to play a role as a risk factor for retinal vein occlusion. Full article

Background: Despite pregnancy’s hypercoagulable state, the correlation between inherited thrombophilia and thrombotic adverse pregnancy outcomes remains uncertain. The objective of this study was to determine the prevalence of inherited thrombophilic polymorphisms among asymptomatic pregnant individuals and to examine their potential correlation with adverse perinatal outcomes. Methods: in this single-center prospective study, 105 healthy pregnant women were included. Genotyping was conducted for factor V Leiden (FVL), prothrombin gene mutation, methylenetetrahydrofolate reductase enzyme (MTHFR) C677T, MTHFR A1298C, and plasminogen activator inhibitor-1 (PAI-1), alongside the assessment of protein C (PC), protein S (PS), and antithrombin (AT) levels. The study analyzed the association between inherited thrombophilic polymorphisms and pregnancy complications linked to placental insufficiency, such as gestational hypertension (GH), preeclampsia (PE), intrauterine death (IUD), fetal growth restriction (FGR), and placental abruption. Results: The prevalence of identifiable thrombophilic polymorphism mutations was 61.9% (95% confidence interval—CI 52.4–70.8%), with the most common single mutation being PAI-1 4G/5G (12/105, 11.4%, 95% CI 6.4–18.5). The most frequent combined mutation was heterozygosity for MTHFR C677T and PAI-1 (12/105, 11.4%, 95% CI 6.4–18.5). Notably, no FVL homozygous carriers or single homozygous and heterozygous carriers for prothrombin polymorphisms were found. Additionally, no deficiencies in PC and AT were detected among participants. Except for homozygosity for PAI-1, none of the studied polymorphisms demonstrated a significant association with pregnancy complications linked to placental insufficiency. Conclusions: The asymptomatic carriers of inherited thrombophilic polymorphisms do not have an increased risk of adverse perinatal outcomes. Full article

Background: Congenital factor VII (FVII) deficiency, a rare bleeding disorder resulting from mutations in the F7 gene with autosomal recessive inheritance, exhibits clinical heterogeneity that lacks a strong correlation with FVII:C levels. The objective of this study was to discern genetic defects and assess their associations with the clinical phenotype in a substantial cohort comprising 785 white women exhibiting FVII:C levels below the age-dependent cut-off percentage. Patients and Methods: Individuals with verified inherited factor VII deficiency underwent i) genotyping using the Sanger method and multiplex ligation-dependent probe amplification (MLPA) to identify F7 mutations, including common polymorphic variants. Additionally, they were ii) categorized based on clinical bleeding scores (BS). Thrombophilic variants and blood groups were also determined in the study participants. Results: The probands in this study encompassed both asymptomatic individuals (referred for a laboratory investigation due to recurrent prolonged prothrombin time; n = 221) and patients who manifested mild, moderate, or severe bleeding episodes (n = 564). The spectrum of bleeding symptoms included epistaxis, gum bleeding, gastrointestinal bleeding, hematuria, postoperative bleeding, and gynecologic hemorrhage. The median ISTH bleeding score (BS) recorded within a two-year period prior to the work-up was 2 (0–17). Notably, this score was significantly higher in symptomatic women compared to their asymptomatic counterparts (3 versus 0; p < 0.001). The corresponding PBAC score before hormonal treatment stood at 225 (5–1200), exhibiting a positive correlation with the ISTH BS (rho = 0.38; p = 0.001). Blood group O was more prevalent in symptomatic women compared to asymptomatic individuals (58 versus 42%; p = 0.01). Among the 329 women (42%), known and novel mutations in the F7 gene, encompassing coding regions, exon/intron boundaries, and the promoter region, were identified, while common polymorphisms were detected in 647 subjects (95%). Logistic regression analysis, adjusted for clinical and laboratory data (including blood group, FVII activity, the presence of F7 gene mutations and/or polymorphisms, thrombophilia status, and additional factor deficiencies) revealed that older age at referral (increase per year) (odds/95% CI: 1.02/1.007–1.03), the presence of blood group O (odds/95% CI: 1.9/1.2–3.3), and the coexistence of further bleeding defects (odds/95% CI: 1.8/1.03–3.1) partially account for the differences in the clinical bleeding phenotype associated with FVII deficiency. Conclusion: The clinical phenotype in individuals with FVII deficiency is impacted by factors such as age, blood group, and the concurrent presence of other bleeding defects. Full article

Background and objectives: Thrombophilia in pregnant women is a condition whose incidence is constantly increasing worldwide, and, under these conditions, the development of preventive procedures is becoming essential. In this study, we aimed to evaluate thrombophilia in pregnant women in the western part of Romania and to establish anthropometric characteristics, socioeconomic features, and genetic and risk factors. Material and Methods: 178 pregnant women were divided into three study groups, according to the type of thrombophilia, aiming to carry out the genetic profile and the acquired one. Anthropometric measures and biological tests were performed. Results: The mixed type of thrombophilia predominates. The particularities of pregnant women diagnosed with thrombophilia are higher age, living in an urban environment, with normal BMI, approximately 36 weeks of gestational period, and having at least one miscarriage. Regarding the most frequent thrombophilic genetic markers, we obtained the MTFHR gene mutation C677T and A1298C, followed by the PAI-1 4G/5G gene mutation. Smoking represents an aggravating factor in the evolution of this pathology, manifested through the increase of D-dimers and the decrease in antithrombin values, simultaneously with the increase in therapeutic need. Conclusions: The predominance of MTHFR and PAI-1 4G/5G gene polymorphism is a particularity of pregnant women with thrombophilia from the western part of Romania. Smoking is confirmed as an important risk factor in spontaneous abortion. Full article

(1) Background. One of the causes of myocardial infarction (MI) with nonobstructive coronary arteries (MINOCA) is thrombus formation in situ followed by lysis, resulting in a morphologically normal angiogram but with an underlying prothrombotic state that is potentially predisposed to recurrence. Recent studies have shown that a subset of MINOCA patients may have thrombophilic conditions at screening. Objective: To compare the prothrombotic trend in MINOCA patients with that of subjects with MI and obstructive coronary arteries (MIOCA) by testing for known congenital thrombophilias and markers of coagulation activation. (2) Materials and methods. Screening included congenital thrombophilias (factor V Leiden; assessment of protein C, protein S, and antithrombin III) and eight genes. Of these, four genes represented the folate pathway enzymes: MTHFR 677 C>T (rs1801133), MTHFR 1298 A>C (rs1801131), MTR 2756 A>G (rs1805087), and MTRR 66 A>G (rs1801394). The other four genes represented the blood coagulation system: F13 (163 G>T) rs5985, F1 (−455 G>A) rs1800790, GP IIb–IIIa (1565 T>C) rs5918, and PAI-I (−675 5G>4G) rs1799889. Additionally, we examined the levels of homocysteine and lipoprotein (LP) (a). (3) Results. Our study included 269 patients: 114 MINOCA patients and 155 MIOCA patients with lesions of one coronary artery. The frequencies of polymorphisms in the genes of the blood coagulation system and the folate pathway did not differ between the groups. The following genes were associated with in-hospital mortality in the MINOCA group: MTHFR 1298 A>C rs1801131 (OR 8.5; 95% CI 1.67–43.1) and F1 (−455 G>A) rs1800790 (OR 5.8; 95% CI 1.1–27.8). In the MIOCA group, the following genes were associated with in-hospital mortality: MTHFR 1298 A>C rs1801131 (OR 9.1; 95% CI 2.8–28.9), F1 (−455 G>A) rs1800790 (OR 11.4; 95% CI 3.6–35.9), GP IIb–IIIa (1565 T>C) rs5918 (OR 10.5; 95% CI 3.5–30.8), and PAI-I (−675 5G>4G) rs1799889 (OR 12.9; 95% CI 4.2–39.7). We evaluated long-term outcomes (case fatality rate, recurrent MI, and stroke) over a period of 12 months in both groups. The variables associated with these outcomes were laboratory parameters, such as protein C deficiency, hyperhomocysteinemia, and a content of LP (a) > 30 mg/dL. However, we did not reveal the prognostic value of polymorphisms of the studied genes representing the blood coagulation system and the folate pathway. (4) Conclusion. We established no statistically significant differences between the MINOCA and MIOCA groups in the prevalence of congenital thrombophilias and the prevalence of folate pathway enzyme genes and blood coagulation system genes. The MTHFR 1298 A>C (rs1801131) and F1 (−455 G>A) rs1800790 genes were associated with in-hospital mortality in both groups. More significant prognostic factors in both groups during the one-year period were protein C deficiency, hyperhomocysteinemia, and LP (a) > 30 mg/dL. Full article

Aiming to evaluate the role of ten functional polymorphisms in long COVID, involved in major inflammatory, immune response and thrombophilia pathways, a cross-sectional sample composed of 199 long COVID (LC) patients and a cohort composed of 79 COVID-19 patients whose follow-up by over six months did not reveal any evidence of long COVID (NLC) were investigated to detect genetic susceptibility to long COVID. Ten functional polymorphisms located in thrombophilia-related and immune response genes were genotyped by real time PCR. In terms of clinical outcomes, LC patients presented higher prevalence of heart disease as preexistent comorbidity. In general, the proportions of symptoms in acute phase of the disease were higher among LC patients. The genotype AA of the interferon gamma (IFNG) gene was observed in higher frequency among LC patients (60%; p = 0.033). Moreover, the genotype CC of the methylenetetrahydrofolate reductase (MTHFR) gene was also more frequent among LC patients (49%; p = 0.045). Additionally, the frequencies of LC symptoms were higher among carriers of IFNG genotypes AA than among non-AA genotypes (Z = 5.08; p < 0.0001). Two polymorphisms were associated with LC in both inflammatory and thrombophilia pathways, thus reinforcing their role in LC. The higher frequencies of acute phase symptoms among LC and higher frequency of underlying comorbidities might suggest that acute disease severity and the triggering of preexisting condition may play a role in LC development. Full article