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Objective: Thrombophilia screening has been performed in patients with conditions such as previous fetal death, (fetal growth restriction) FGR, preeclampsia, (hemolysis. elevated liver enzyme, low platelet count) HELLP Syndrome, previous abruptio placentae, previous thrombosis in pregnancy, and abnormal placental histology. The actual role of hereditary thrombophilia in recurrent pregnancy loss (RPL) is still debated. This study was intended to determine the incidence of specific gene defects for hereditary thrombophilia and to ascertain their impact on RPL in central Anatolia in Turkey. Methods: This retrospective cohort study was performed between January 2012 and December 2022. All pregnant women with a complete hereditary screening profile were included. The investigated gene polymorphisms were methylenetetrahydrofolate reductase (MTHFR) C677T, MTHFR A1298C, Factor V Leiden G1691A, and Factor II prothrombin G20210A. Cases of pregnant women at least two or more consecutive pregnancy losses before 22 weeks of gestation were defined as RPL. The rates of genetic screening and their association with RPL were analyzed. Results: RPL was identified in 224 (27.58%) of the 812 pregnant women with complete genetic screening. Although there was no difference in terms of age, body mass index, numbers of ectopic pregnancies, molar pregnancies, or dilatation & curettage (p > 0.05), gravity (2.0 [2.0–3.0] vs. 4.0 [3.0–5.0]), parity (1.0 [1.0–2.0] vs. 1.0 [0–1.0]), live birth (1.0 [1.0–2.0] vs. 1.0 [0–1.0]), anembryonic pregnancy (0 [0–0] vs. 0 [0–0]), miscarriage (0 [0–1.0] vs. 3.0 [2.0–3.0]), and stillbirth (0 [0–0] vs. 0 [0–0]) numbers differed significantly between the groups (p < 0.05). While no significant differences were determined in MTHFR A1298C, Factor V Leiden, factor II prothrombin G20210A, or homocysteine levels (p > 0.05), the homozygous MTHFR C677T positivity rates differed significantly (6.3% in the non-RPL group vs. 11.6% in the RPL group, p = 0.027). Conclusion: The homozygous MTHFR C677T polymorphisms was found to be more frequent in women with RPL. Further studies with larger cohorts are needed to confirm our results. [ABSTRACT FROM AUTHOR]

Although inherited thrombophilias are lifelong risk factors for a first thrombotic episode, progression to thrombosis is multifactorial and not all individuals with inherited thrombophilia develop thrombosis in their lifetimes. Consequently, indiscriminate screening in patients with idiopathic thrombosis is not recommended, since presence of a thrombophilia does not necessarily predict recurrence or influence management, and testing should be selective. It follows that a decision to undertake laboratory detection of thrombophilia should be aligned with a concerted effort to identify any significant abnormalities, because it will inform patient management. Deficiencies of antithrombin and protein C are rare and usually determined using phenotypic assays assessing biological activities, whereas protein S deficiency (also rare) is commonly detected with antigenic assays for the free form of protein S since available activity assays are considered to lack specificity. In each case, no single phenotypic assay is capable of detecting every deficiency, because the various mutations express different molecular characteristics, rendering thrombophilia screening repertoires employing one assay per potential deficiency, of limited effectiveness. Activated protein C resistance (APCR) is more common than discrete deficiencies of antithrombin, protein C, and protein S and also often detected initially with phenotypic assays; however, some centres perform only genetic analysis for factor V Leiden, as this is responsible for most cases of hereditary APCR, accepting that acquired APCR and rare F5 mutations conferring APCR will go undetected if only factor V Leiden is evaluated. All phenotypic assays have interferences and limitations, which must be factored into decisions about if, and when, to test, and be given consideration in the laboratory during assay performance and interpretation. This review looks in detail at performance and limitations of routine phenotypic thrombophilia assays. [ABSTRACT FROM AUTHOR]

The factor V Leiden (FVL) polymorphism is known as the most common inherited risk factor for venous thrombosis. In turn, FVL is the leading cause of an activated protein C resistance (APCR) phenotype, in which the addition of exogenous activated protein C to plasma does not result in the expected anticoagulant effect. In the routine laboratory approach to the formal diagnosis of FVL, an initial positive screening plasma-based method for APCR is often performed, and only if needed, this is followed by a confirmatory DNA-based assay for FVL. Multiple methods with accepted sensitivity and specificity for determining an APCR/FVL phenotype are commonly categorized into two separate groups: (1) screening plasma-based assays, including qualitative functional clot-based assays, for APCR, and (2) confirmatory DNA-based molecular assays, entailing several tests and platforms, including polymerase chain reaction-based and non-PCR-based techniques, for FVL. This review will describe the methodological aspects of each laboratory test and prepare suggestions on the indication of APCR and FVL testing and method selection. [ABSTRACT FROM AUTHOR]

In neonates admitted to the neonatal intensive care unit (NICU), arterial and venous thromboembolism is a major cause of morbidity and death which could be attributed to multiple risk factors exposure. This study aimed to evaluate the clinical characteristics, laboratory and radiological assessments, predisposing risk factors, and outcomes of thrombosis in neonates admitted to NICU. This prospective cohort study was conducted at NICU, Minia, and Alexandria University Children's Hospital. Screening of 886 patients admitted to NICU over one year with different clinical presentations, patients were classified into the thrombotic and non-thrombotic groups based on the presence or absence of thrombosis. Thrombosis was diagnosed based on clinical, laboratory and different radiologic assessments. Genetic testing for factor V Leiden mutations G1691A, prothrombin mutation G20210A, protein C, protein S, and antithrombin III gene mutations were performed for patients with a family history of thrombosis. Out of a total of 886 neonatal admissions, 36 patients were diagnosed with evident thrombosis (40 per 1000 NICU admissions). The sites of venous thrombosis detection were Portal vein thrombosis in 11 patients (30.6%), superior vena cava thrombosis in 7 patients (19.4%), deep venous thrombosis in 5 patients (13.9%), central venous thrombosis in 5 patients (13.9%), intra-cardiac thrombosis in 3 patients (8.3%) and necrotic skin patches in one patient (2.8%). Only 69% of enrolled thrombosis patients showed genetic mutations the most common of which was factor V Leiden mutation (52.3%). Sepsis, central venous line (CVL) insertion, C reactive protein (CRP), and duration of NICU admission were significantly more common in the thrombotic group (p < 0.001) and were associated with a higher risk of thrombosis (ORs: 1.02, 7.7, and 1.11, respectively) (p < 0.001). Higher mortality occurred in thrombosis neonates compared with a non-thrombotic group (52.8% versus 17.4%) (p < 0.001). NICU-admitted neonates are exposed to multiple overlapped risk factors, the detection of which is important for preventing potential thrombosis and improving the patient's outcomes. The complexity of sepsis pathogenesis and management could potentiate multiple acquired risk factors. inherited thrombophilia detection is required for prevention of further morbidities. [ABSTRACT FROM AUTHOR]

Total hip arthroplasty (THA) is a common procedure that requires consideration of preexisting comorbidities. Factor V Leiden (FVL), an inherited thrombophilia, is one such condition that predisposes patients to venous thromboembolism (VTE, deep vein thrombosis, and pulmonary embolism). The present study aimed to characterize the risks associated with FVL patients undergoing THA and evaluate the effect of VTE chemoprophylactic agents on these risks. A total of 544,022 adult patients who underwent primary THA for osteoarthritis indications between 2010 and October 2021 were identified in an administrative claims database. Of these, FVL was identified in 1,138 (0.21%). Patients who had and did not have FVL were matched at a 1:4 ratio (1,131 with FVL and 4,519 without FVL) based on age, sex, and Elixhauser comorbidity index. Univariable and multivariable analyses were assessed for 90-day complications. Implant survival at 5 years was assessed and compared with log-rank tests. The relative use of different chemoprophylactic agents, including aspirin, warfarin, heparin, or direct oral anticoagulant (DOAC), was assessed. Bleeding events and VTE were compared for those prescribed either aspirin or warfarin, heparin, or DOAC. A Bonferroni correction was applied. On multivariable analysis, FVL patients were found to have increased odds of 90-day deep vein thrombosis (odds ratio (OR) = 9.20), pulmonary embolism (OR = 6.89), and aggregated severe and all adverse events (OR = 4.74 and 1.98, respectively), but not elevated risk of other perioperative adverse events or 5-year reoperations. More potent chemoprophylactic agents (warfarin, heparin, DOAC) reduced, but did not completely eliminate, the increased VTE risks (without increasing bleeding events). This study quantified the significantly elevated VTE risk associated with FVL patients undergoing THA. The lack of difference in other specific adverse events and 5-year reoperations is reassuring. Clearly, chemoprophylactic agents are important in this population and may need further attention. [ABSTRACT FROM AUTHOR]

This systematic review and meta-analysis assesses venous thromboembolism (VTE) risk in adults with hereditary thrombophilia, including Factor V Leiden (FVL) mutation, prothrombin G20210A (FII) mutation, compound heterozygosity, protein C (PC), protein S (PS), and antithrombin (AT) deficiency. Eligibility criteria included studies suitable for quantitative synthesis with extractable information on VTE risk in adults (> 15 years). There were no restrictions on VTE type, location, or occurrence. Two authors reviewed all studies and extracted data from 107 publications, encompassing 107,130 individuals (21,560 experiencing VTE). We used a random effects model and calculated odds ratios (ORs) with 95% confidence intervals (CIs). The highest risk was associated with homozygous FVL (OR 5.58, 95% CI 4.61–6.74), homozygous FII (OR 5.16, 95% CI 3.12–8.52), and compound heterozygosity (OR 4.64, 95% CI 2.25–9.58). In contrast, VTE risk was lowest for FVL heterozygosity (OR 2.97, 95% CI 2.41–3.67) and FII heterozygosity (OR 2.21, 95% CI 1.70–2.87), whereas PC (OR 3.23, 95% CI 2.05–5.08), PS (OR 3.01, 95% CI 2.26–4.02), and AT deficiency (OR 4.01, 95% CI 2.50–6.44) demonstrated an intermediate VTE risk. These results highlight an increased risk of venous thromboembolism in adults with hereditary thrombophilia. However, the risk for patients with PC, PS, and AT deficiency appears to be lower than previously stated, likely due to varying thrombogeneity of the underlying genetic mutations. Further research addressing this aspect of VTE risk in hereditary thrombophilia is imperative to improve patient management. Trial registration: PROSPERO registration number CRD42022376757. [ABSTRACT FROM AUTHOR]

Background: Thrombophilias are characterized by excessive venous and arterial thrombosis at regular or unusual sites. It may result from inherited, acquired, or a combination. Hereditary thrombophilia (HT) is detected in 30–40% of patients with thromboembolism. Venous/arterial thrombosis is considered a multifactorial disorder, some patients may have more than one risk factor which may be transient or permanent. Objectives: Assess the clinical characteristics of patients with unprovoked thromboembolic events and the role of inherited thrombophilia as a causative or additive risk factor. Methods: 210 consecutive adult patients with unprovoked thromboembolic events were reviewed in hematology units at three tertiary Egyptian centers between September 2022 and September 2023. The diagnosis of thromboembolic events was confirmed by clinical and radiological findings. Laboratory screening for thrombophilia-associated. Results: Among our patients, 53(25.2%) patients presented with isolated DVT, followed by portal vein thrombosis, 32(15.2%) had a pulmonary embolism, and sagittal sinus thrombosis was developed in 23(10.9%) patients. Conclusion: Younger people who experience spontaneous thromboembolism run the chance of having hereditary thrombophilia; the more mutations discovered, the higher the risk of thrombosis; the lower leg and deep vein thrombosis were the most common sites. Lastly, MTHFR C677T was the most common polymorphism in Egyptians, detected in almost half of the cases. [ABSTRACT FROM AUTHOR]

Background/Aim: Endocrine therapy is the standard treatment for hormone receptor-positive (HR+) breast cancer (BC). Yet, it is accompanied by treatment-related toxicities, leading to poor treatment adherence, high relapse, and low rates of survival. While pharmacogenomic variants have the potential to guide personalized treatment, their predictive value is inconsistent across published studies. Materials and Methods: To systematically assess the literature's current landscape of pharmacogenomics of endocrine therapy-related adverse drug effects, systematic searches in MEDLINE, Embase, Cochrane CENTRAL, Google Scholar and PharmGKB databases were conducted. Results: We identified 87 articles. Substantial heterogeneity and variability in pharmacogenomic effects were evident across studies, with many using data from the same cohorts and predominantly focusing on the Caucasian population and postmenopausal women. Meta-analyses revealed Factor V Leiden mutation as a predictor of thromboembolic events in tamoxifen-treated women (p<0.0001). Meta-analyses also found that rs7984870 and rs2234693 were associated with musculoskeletal toxicities in postmenopausal women receiving aromatase inhibitors (p<0.0001 and p<0.0001, respectively). Conclusion: Overall, the current body of evidence regarding the potential role of pharmacogenomics in endocrine therapy-related toxicity in BC remains largely inconclusive. Key concerns include the heterogeneity in toxicity definitions, lack of consideration for genotype-treatment interactions, and the failure to account for multiple testing. The review underscores the necessity for larger and well-designed studies, particularly with the inclusion of premenopausal women and non-Caucasian populations. [ABSTRACT FROM AUTHOR]

This article examines the risk factors and prevalence of deep vein thrombosis (DVT) in patients undergoing major surgeries. It highlights the importance of understanding factors such as age, obesity, smoking, malignancy, and medical conditions, which contribute to two-thirds of initial DVT episodes. The study conducted at a government hospital found that 24% of patients developed DVT, with males and older age groups being more prone to it. Risk factors for DVT included higher BMI, smoking, previous chemotherapy or radiotherapy, general anesthesia, and longer surgery duration. Preoperative DVT prophylaxis is crucial for high-risk patients to reduce DVT incidence post-surgery. [Extracted from the article]

Aim: To investigate the effect of factor V Leiden mutation on neonatal and maternal morbidity and mortality in hypertensive pregnant groups. Materials and Methods: The study was carried out as a prospective case-controlled study with 108 pregnant women who applied to the Gynecology and Obstetrics Outpatient Clinic of Karadeniz Technical University, Faculty of Medicine within 2 years. Patients were divided into four groups: mild preeclampsia (n=20), severe preeclampsia (n=54), chronic hypertension (n=14), and normal pregnant women as a control group (n=20). Since superimposed preeclampsia (n=6), eclampsia (n=23), and HELLP syndrome (n=27) are variants of severe preeclampsia, these patients were included in the severe preeclampsia group. The clinical study aimed at investigating whether FVL mutation has any significant correlation with neonatal morbidity (IUGR, 1st and 5th minute < 7 Apgar score), intrauterine fetal death, neonatal mortality, maternal morbidity (ablatio placenta, deep vein thrombosis, intracranial hemorrhage, cesarean section rate) and mortality risk in hypertensive pregnant women. Results: Factor V Leiden mutation was most common in the severe preeclampsia group. Maternal and neonatal outcomes of pregnant women with and without FVL mutations were similar in all study groups (p > 0.05). Conclusion: Although FVL mutation was more common than usual in severe preeclamptic pregnant women, it did not affect maternal and neonatal outcomes. Prospective studies with larger patient populations investigating the effects of FVL mutation in preeclampsia are needed. [ABSTRACT FROM AUTHOR]

Background: The clinically significant Factor V Leiden (FVL) point mutation (1691 G/A) causes replacement of Arg with Gln (glutamine), preventing activated protein C from inactivating Factor V leading to a lengthened clotting process. Individuals with the Factor V Leiden mutations have an increased risk for venous thrombosis. The aim of this study is to compare an unlabeled probe high-resolution melting analysis (HRMA) assay for Factor V Leiden mutation to a TaqMan hydrolysis assay (fluorogenic 5' nuclease PCR hydrolysis assay). HRMA is a post-PCR, homogenous, closed-tube system for the detection of sequence variants. Post-PCR, the amplicons are heated gradually until the melting temperature is reached and the fluorescent dye unbinds from the amplicon and exhibits low fluorescence. A melt-curve analysis is generated that is characteristic of a particular sequence variant. Therefore, HRMA allows for comparison of one base changes in genetic sequences based on their differences in melting rate. Methods: Blood samples were collected in EDTA tubes and DNA extracted using the Roche MagNaPure. Reactions of both HRMA and TaqMan were carried out on 3 controls (1691 G/G, 1691 G/A, and 1691 G/G and G/A) and 20 samples. Results: The genotypes for 3 reference controls purchased from Coriell (F5 1691 G/G, FVL 1691 G/A, and Heterozygote 1691 G/G and G/A) were confirmed by both the HRMA and TaqMan FVL assays. All 20 samples were confirmed to be F5 1691 G/G by both HRMA and TaqMan assays. Conclusions: Comparing the results of the unlabeled probe HRMA FVL assay with a real-time TaqMan probe end point genotyping assay resulted in 100% sensitivity and 100% specificity for both assays. [ABSTRACT FROM AUTHOR]

Background/aim: We aimed to determine the genetic risk factors in patients aged 45 years and below with a history of early myocardial infarction (MI), compared to individuals over 60 years of age with no history of MI. Materials and methods: In this study, we selected different age groups to more clearly distinguish genetic differences. Accordingly, we compared individuals who had experienced MI at an early age with those who were older and had not experienced any cardiovascular events. The patient group consisted of 99 volunteers under the age of 45 with a history of MI, while the control group included 99 volunteers aged 60 and over without a history of MI. MTHFR (C677T, A1298C), Factor V Leiden (G1691A), Prothrombin (G20210A), PAI (4G/5G), Factor XIII (V34L), APOA1 (rs670, rs1799837, rs5069), and APOB were studied using blood samples taken from the patients. Results: In the logistic regression analysis of thrombophilia markers and gene polymorphisms in the patient and control groups, no statistically significant increase was observed in markers other than APOA1 rs5069 gene polymorphism. APOA1 rs5069 gene polymorphism was found to be higher in the patient group than those without this polymorphism. The frequencies of homozygous MTHFR (C677T, A1298C) and heterozygous Factor XIII V34L were higher in the patient cohort compared to the controls. Conclusion: In our study, we found that prothrombotic gene variants and APOA1 rs5069 polymorphism were statistically significantly associated with coronary artery disease. Thus, prothrombotic gene variants and APOA1 rs5069 polymorphism may serve as predictors of early myocardial infarctions. Individuals with early family histories of coronary artery disease could be screened for these mutations. [ABSTRACT FROM AUTHOR]

Traditionally considered to be absent in India, prothrombin gene G20210A (NM_000506.5(F2): c.*97G > A) mutation (PGM) has recently been reported in few Indian patients. We aimed to assess the prevalence of PGM in patients with thromboembolic events from north India region. The thrombophilia workup comprising Protein C, Protein S, Antithrombin functional activity, lupus anticoagulant and anti-ACA and anti-ß2GP1 antibodies were performed in coagulation analyzer (ACLTOP-500, Instrumentation Laboratory, USA) and automated chemiluminescent assay analyzer (ACUSTAR, IL) respectively. PCR–RFLP was used to perform PGM and FVL mutation. Out of 509 patients, DVT and CVT/CSVT were identified in 208 and 250 patients respectively. A total of 42 (8.2%) cases showed inherited thrombophilia and 11 (2.1%) acquired thrombophilia. Among the inherited defects, the most common was FVL mutation 31 (6%) The PGM was seen in only 2/509 (0.3%) patients. The prevalence of PGM in North Indian patients with DVT, stroke and CVT is 0.41% (2/509). Although PGM is rare in this population, its presence emphasizes its association with these conditions. However, the role of PGM testing remains debatable due to its scarcity among North Indians. [ABSTRACT FROM AUTHOR]

Objective: To evaluate Antithrombin II and Factor V Leiden mutation in stroke among young patients and its association with various socio-demographic aspects. Study Design: Cross-sectional study. Place and Duration of Study: Pak-Emirates Military Hospital, Rawalpindi Pakistan, from Jan to Dec 2020. Methodology: A total of 103 individuals, aged 18-65 years, with acute ischemic stroke were included. The diagnosis was confirmed using computed tomography/Magnetic Resonance Imaging Brain scan. Plasma AT II activity and Factor V Leiden mutation were analyzed using standard techniques. Various socio demographic features like age, gender, body mass index, smoking, deployment at High altitude (>10,000 feet), family history of stroke and hyperlipidemia were recorded and statisticaly analyzed. Results: Only two (1.9%) patients had AT II deficiency while one (0.9%) patient showed Factor V Leiden mutation. Al patients were male. Working at high altitude, family history of stroke and tobacco smoking were related with the presence of low AT II levels (p-value <0.05). Conclusion: Testing for hypercoagulable states in the seting of stroke in young may be useful if there is family history of stroke, smoking and high-altitude deployment. Investigations to search for the cause should be tailored as per individual patients. [ABSTRACT FROM AUTHOR]

Introduction. Malignant tumor is one of the leading factors of venous and arterial thrombosis. But there is no data on the need for a genetic testing protocol of cancer patients for genetic predisposition thrombotic conditions, despite the fact that a number of polymorphisms of hemostasis genes are considered to be unconditionally proven factors of high cumulative thrombogenic risk, and proteins encoded by these genes are direct links in the cascades of pathological hypercoagulation in neoplastic processes.Aim. To identify groups of high genetic risk of thrombotic complications among patients with malignant thoracoabdominal tumors.Materials and methods. The study included 223 patients with malignant tumors of the lung, stomach, esophagus, operated in the Department of Thoracic Oncology of the N.N. Blokhin National Research Center of Oncology in 2018–2019. The study groups consisted of patients with myocardial infarction (n = 62), ischemic stroke (n = 24), venous thrombosis/ venous thromboembolic complications (n = 40), patients without cardiovascular diseases, but with a family history burdened by cardiovascular diseases (n = 33). The control group included 81 patients.Results. Among patients with malignant tumors of thoracoabdominal localization, a statistically significant difference was determined in the frequency of carriage of the heterozygous genotype FV 1691GA (Arg506Gln) in patients who had a myocardial infarction (χ2 = 4.0; p = 0.046), who had venous thrombosis (χ2 = 4.118; p = 0.043), in the group of patients with burdened with a family history (χ2 = 4.997; p = 0.026) in comparison with the control group. Statistically significant difference in the frequency of carriage of the heterozygous variant of the mutation in the FII G20210A gene relative to the control group, it was determined in the group of patients who had an acute cerebrovascular accident (χ2 = 6.881; p = 0.009) and among patients with a burdened history (χ2 = 7.563; p = 0.006).Conclusion. In order to assess the risk of development and prevention of thrombotic complications in the perioperative period in patients with malignant thoracoabdominal tumors, who have suffered myocardial infarction, ischemic stroke, venous thrombosis/venous thromboembolic complications, as well as patients without cardiovascular pathology, but with thrombotic conditions in relatives of the first degree, it is advisable to perform DNA diagnostics at the prehospital stage to identify of gene polymorphisms FII G20210A and FV G1691A (Arg506Gln).

Background: Various factors, such as genetic causes, anatomic abnormalities of the uterus, infectious diseases, coagulative disorders, and endocrinological and immunological diseases, might influence recurrent pregnancy loss (RLP). This study aimed to evaluate the prevalence and frequency of the FII G20210A, FVL G1691A, and MTHFR C677T polymorphisms in Sudanese women with RPL. Methods and Results: This descriptive cross-sectional study involved 100 women with a history of 3 or more RPLs (the case group) and 94 healthy multiparous women without pregnancy complications (the control group). DNA was extracted from peripheral blood samples. The study of the FII G20210A, FVL G1691A, and MTHFR C677T polymorphisms was performed by PCR and RFLP analysis. For the FII G20210A, the genotype distribution in the case group and control group was as follows: GG=97.0%, GA=3.0%, AA=0% and GG=94.0%, GA=0%, AA=0%, respectively. In the case group, the allelic distribution was as follows: G=98.5%, A=1.5%. In the control group, the A allele was absent, and the frequency of the G allele was 100%. For the MTHFR C677T, the genotypic and allelic frequencies in the case group were 97%, 3%, and 0%, respectively, for the CC, CT, and TT genotypes, and 98.5% and 1.5%, respectively, for the C and T alleles. In the control group, the genotype distribution was as follows: CC-100% CT-0%, TT-0%; the T allele was absent, and the frequency of the C allele was 100%. For the FVL G1691A, the genotype distribution in the case group and control group was as follows: GG=92.0%, GA=8.0%, AA=0% and GG=93.6%, GA=6.4%, AA=0%, respectively. For G and A alleles, the frequencies were 96.0% and 4.0%, respectively, for the case group, and 96.8% and 3.2%, respectively, for the control group. Our analysis did not reveal a significant positive association between the MTHFR C677T, FII G20210A, and FVL G1691A polymorphisms and the risk of RPL across the dominant model, multiplicative model, and a comparison of the frequencies of the heterozygous and homozygous dominant genotypes. Conclusion: The research findings suggest that the MTHFR C677T, FVL G1691A, and FII G20210A variants do not significantly contribute to the increased susceptibility to RPL in this specific population of Sudanese women. Continued scientific inquiry is crucial for developing more nuanced and personalized strategies for the diagnosis and prevention of RPL, ultimately improving women's reproductive health.

Cardiovascular diseases, among which includes coronary artery disease, represent one of the most important causes of mortality and morbidity worldwide. Research aimed at determining the risk factors involved recognizes a group of "traditional" risk factors, but also more recent studies identified over 100 "novel" ones which may have a role in the disease. Among the latter is the thrombophilia profile of a patient, a pathology well-established for its involvement in venous thromboembolism, but with less studied implications in arterial thrombosis. This paper reviews the literature, explaining the pathophysiology of the thrombophilia causes associated most with coronary thrombosis events. Results of several studies on the subject, including a meta-analysis with over 60,000 subjects, determined the significant involvement of factor V Leiden, prothrombin G20210A mutation, plasminogen activator inhibitor–1 and antiphospholipid syndrome in the development of coronary artery disease. The mechanisms involved are currently at different stages of research, with some already established and used as therapeutic targets. [ABSTRACT FROM AUTHOR]

Duodenal varices are a rare consequence of portal hypertension, which constitute 17% of ectopic varices, if these varices bleed, the mortality is around 40%. Medical therapies, including vasopressin, have limited success in controlling active duodenal variceal bleeding. We present a case of a 52 y-o woman who presented with hematochezia and deep anemia requiring multiple transfusions. She has a history of being diagnosed with cirrhosis, FMF, hemochromatosis and factor V Leiden mutation with multiple deep vein thrombosis. The abdomen computer tomography (CT) revealed active bleeding vat the proximal duodenum. She underwent emergent esophagogastroduodenoscopy, which showed actively pulsatile bleeding duodenal varices. Endoscopic hemostasis was achieved successfully with variceal band ligation. Endoscopic band ligation is an effective intervention for actively bleeding duodenal varices, especially for those located in the proximal duodenum, which were more accessible endoscopically than the distal ones [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background and Objectives: This retrospective cohort study investigates the role of genetic thrombophilia in pregnant women experiencing early pregnancy loss compared to those with late pregnancy loss. Materials and Methods: Participants were categorized into early and late pregnancy loss groups based on gestational age. A total of 156 patients were included, out of which 103 had early-trimester pregnancy losses and 96 had multiple miscarriages. Results: The study revealed a synergistic effect of Factor V Leiden (FVL G1691A) and Methylenetetrahydrofolate Reductase (MTHFR C677T) mutations (coefficient 3.42). Prothrombin (PT) G20210A and β-Fibrinogen 455 G>A mutations exhibited a significant interaction (coefficient 1.98). Additionally, MTHFR A1298C and Plasminogen Activator Inhibitor-1 (PAI-1 4G/5G) mutations showed a significant interaction (coefficient 1.65). FVL G1691A and Endothelial Protein C Receptor (EPCR) allele A1/A2 mutations also demonstrated a significant association (coefficient 2.10). Lastly, MTHFR C677T and Glycoprotein IIb/IIIa T1565C mutations interacted significantly (coefficient 1.77). Risk factor analysis identified several mutations associated with early pregnancy loss, including PAI-1 4G/5G homozygous (OR 3.01), FVL G1691A heterozygous (OR 1.85), and MTHFR A1298C heterozygous (OR 1.55). Both homozygous and heterozygous MTHFR C677T mutations were significant risk factors (OR 2.38; OR 2.06), as was PT G20210A homozygous mutation (OR 1.92). The PAI-1 4G/4G homozygous variant posed a risk (OR 1.36). Late pregnancy loss was associated with MTHFR A1298C homozygous mutation (OR 3.79), β-Fibrinogen 455 G>A heterozygous mutation (OR 2.20), and MTHFR A1298C heterozygous mutation (OR 2.65). Factor XIII G1002T heterozygous mutation (OR 1.18) and PAI-1 4G/5G homozygous mutation (OR 2.85) were also significant risk factors. EPCR allele A1/A2 (OR 1.60) and A2/A3 (OR 1.73) mutations were identified as significant risk factors for late pregnancy loss. Furthermore, FVL G1691A homozygous mutation, PT G20210A homozygous mutation, MTHFR C677T heterozygous mutation, MTHFR A1298C heterozygous mutation, and EPCR allele A1/A2 were identified as significant risk factors for multiple miscarriage. Conclusions: This study highlights significant interactions and risk factors related to genetic thrombophilia mutations in different types of pregnancy loss, contributing valuable insights for miscarriage management guidelines. [ABSTRACT FROM AUTHOR]

Objectives: Patients with COVID-19 infection appear to develop virus-induced hypercoagulability resulting in numerous thrombotic events. The aim of the present study was to determine the relationship between the thrombophilia genes mutations (prothrombin G20210A, factor V Leiden, and methyltetrahydrofolate reductase (MTHFR)) and the severity of COVID-19 patients. Design: Prospective cross-sectional study. Method: One hundred and forty patients (80 adults and 60 children) were included in the current study. They were divided into the severe COVID-19 group and the mild COVID-19 group, with each group comprising 40 adults and 30 children. The patients were assessed for FV R506Q, FV R2H1299R, MTHFR A1298C, MTHFR C677T, and prothrombin gene G20210A polymorphisms. CBC, D-dimer, renal and liver function tests, hs-CRP, ferritin, and LDH were also assessed. Thrombotic events were clinically and radiologically documented. Results: Severe COVID-19 cases were significantly more frequent to have a heterozygous mutation for all the studied genes compared to mild COVID-19 cases (p<0.05 for all). Being mutant to gene FV R506Q carried the highest risk of developing a severe disease course (p<0.0001). Patients with abnormally high D-dimer levels were significantly more frequent to be heterozygous for FV R506Q, FV R2H1299R, and prothrombin gene G20210A (p = 0.006, 0.007, and 0.02, respectively). Conclusion: We concluded that there is an evident relationship between severe COVID-19 and inherited thrombophilia. In the current study, FV R506Q gene mutation carried the highest risk of developing a severe COVID-19 disease course. [ABSTRACT FROM AUTHOR]

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Background: Diabetic retinopathy (DR) is expanding to epidemic levels globally due to the progressing prevalence of diabetes mellitus (DM). In this study, the association between factor V Leiden (FVL), MTHFRC677T, and FXIIIVal34Leu polymorphisms and diabetic retinopathy was investigated in Eastern Iran. Methods: This case-control study enlisted the participation of 300 people (diabetic patients=100, diabetic retinopathy patients=100, healthy controls=100), and polymorphisms were examined by Tetra primer ARMS-PCR. Results: The frequency of FVL (p=0.294) and FXIIIVal34Leu (P=0.349) polymorphism showed no significant results between the genotype frequency in the mentioned groups. In contrast, MTHFRC677T SNP was significantly different in diabetic patients and controls (P=0.008). The MTHFRC677T polymorphism was found to be connected with increased systolic blood pressure in patients who had the TT genotype (130.96±11.92mm/Hg; P=0.011). Conclusion: Our study recommended that the MTHFRC677T polymorphism may offer to DR development. Studies with larger sample sizes and a wider spectrum of populations are authorized to verify this finding.

A 53-year-old man with severe psoriasis presented with painful subcutaneous masses on both legs. He had a history of pulmonary embolism and bilateral incompetence of veins. The patient was on medication for psoriasis and had received multiple biologic agents. Radiographic and ultrasound examinations revealed subcutaneous calcification and ossification. The diagnosis was secondary cutaneous ossification in the context of chronic venous insufficiency. Treatment involved managing the underlying venous insufficiency and conservative measures, resulting in a significant reduction in pain. [Extracted from the article]

Background: In this case series, a perioperative anticoagulation protocol for microvascular head and neck surgery in patients with thrombophilia is presented. Microvascular free-flap surgery is a standard procedure in head and neck surgery with high success rates. Nevertheless, flap loss—which is most often caused by thrombosis—can occur and has far-reaching consequences, such as functional impairment, prolonged hospitalization, and increased costs. The risk of flap loss owing to thrombosis is significantly increased in patients with thrombophilia. Therefore, perioperative anticoagulation is mandatory. To date, no perioperative anticoagulation protocol exists for these high-risk patients. Case presentation: We present three exemplary male Caucasian patients aged 53–57 years with free flap loss owing to an underlying, hidden thrombophilia. Conclusion: We present a modified anticoagulation protocol for microvascular surgery in these high-risk patients, enabling successful microsurgical reconstruction. [ABSTRACT FROM AUTHOR]

Background: Inherited thrombophilia (IT) has a complex pathophysiology and is associated with recurrent miscarriage (RM) by causing placental insufficiency and inhibiting fetal development. However, thrombophilia screening in unexplained RM cases is still questionable. This study aimed to investigate the association between the common eight IT mutations and their combinations among Palestinian women with unexplained RM. Methods: This is an unmatched case-control study with 200 women (100 unexplained RM cases, 100 controls). Eight common IT mutations namely Factor V Leiden (FVL), prothrombin gene (FII) G202120A, Methylenetetrahydrofolate Reductase (MTHFR) gene (C677T and A1298C), B-fibrinogen gene − 455G > A, FV HR2 A4070G, Plasminogen activator inhibitor 1 (PAI1) 5G/4G and Factor XIIIA (FXIIIA) V34L; were analyzed. The first five mutations were analyzed by Restriction Fragment Length Polymorphism PCR and the other three mutations were analyzed using Amplification Refractory Mutation System PCR. Results: The prevalence of the eight IT mutations among the control group was in the order PAI1 5G/4G (69%), MTHFR C677T (53%) and A1298C (47%), BFG − 455G > A (35%), FVL and FV HR2 (each 18%), FXIIIA V34L (16%) and FII G20210A (3%). Patients had a higher percentage of MTHFR A1298C (heterozygotes and mutant homozygote) compared to controls (p = 0.016). Frequencies of mutant alleles MTHFR A1298C (p < 0.001) and FXIIIA V34L (p = 0.009) were higher among patients compared to controls. No significant differences were observed for all other mutations or mutant alleles. Most patients (75%) and controls (75%) have 2–4 mutant alleles out of 8 mutant alleles studied, while 1% of patients and 2% of controls have zero mutant alleles. None of the combinations of the most often studied mutations (FVL, FII G20210A, MTHFR C1677T, and MTHFR A1298C) showed a significant difference between patients and controls. Conclusions: There was a significant association between unexplained RM and the mutant alleles of MTHFR A1298C and FXIIIA V34L. No significant association was observed between unexplained RM and the combination of both mutant alleles for the mutations studied. This study is the first Palestinian report that evaluates eight inherited thrombophilia mutations and their alleles' combinations in unexplained RM cases. [ABSTRACT FROM AUTHOR]

Background: Kearns-Sayre syndrome (KSS) is classified as one of the mitochondrial DNA (mtDNA) deletion syndromes withmultisystemic involvement. Additionally, the negative prognosis is associated with inherited thrombophilia, which includes the presence of homozygous Factor V G1691A Leiden mutation, MTHFR gene polymorphisms C677T and A1298C, and PAI-1 675 homozygous genotype 5G/5G. Case presentation: This case report presents a 48-year-old man with chronic progressive external ophthalmoplegia, bilateral ptosis, cerebellar ataxia, cardiovascular signs (syncope, dilated cardiomyopathy, and cardiac arrest) with electrocardiographic abnormalities (first-degree atrioventricular block and major right bundle branch block), endocrine dysfunction (short stature, growth hormone insufficiency, primary gonadal insufficiency, hypothyroidism, and secondary hyperparathyroidism), molecular genetic tests (MT-TL2 gene), and abnormal MRI brain images, thus leading to the diagnosis of KSS. The patient came back 4 weeks after the diagnosis to the emergency department with massive bilateral pulmonary embolism with syncope at onset, acute cardiorespiratory failure, deep left femoral-popliteal vein thrombophlebitis, and altered neurological status. In the intensive care unit, he received mechanical ventilation through intubation. Significant improvement was seen after 2 weeks. The patient tested positive for inherited thrombophilia and was discharged in stable conditions on a new treatment with Rivaroxaban 20 mg/day. At 6 months of follow-up, ECG-Holter monitoring and MRI brain images remained unchanged. However, after 3 months, the patient died suddenly while sleeping at home. Conclusion: The genetic tests performed on KSS patients should also include those for inherited thrombophilia. By detecting these mutations, we can prevent major complications such as cerebral venous sinus thrombosis, coronary accidents, or sudden death. [ABSTRACT FROM AUTHOR]

Background: Diabetic retinopathy (DR) is expanding to epidemic levels globally due to the progressing prevalence of diabetes mellitus (DM). In this study, the association between factor V Leiden (FVL), MTHFRC677T, and FXIIIVal34Leu polymorphisms and diabetic retinopathy was investigated in Eastern Iran. Methods: This case-control study enlisted the participation of 300 people (diabetic patients=100, diabetic retinopathy patients=100, healthy controls=100), and polymorphisms were examined by Tetra primer ARMS-PCR. Results: The frequency of FVL (p=0.294) and FXIIIVal34Leu (P=0.349) polymorphism showed no significant results between the genotype frequency in the mentioned groups. In contrast, MTHFRC677T SNP was significantly different in diabetic patients and controls (P=0.008). The MTHFRC677T polymorphism was found to be connected with increased systolic blood pressure in patients who had the TT genotype (130.96±11.92mm/Hg; P=0.011). Conclusion: Our study recommended that the MTHFRC677T polymorphism may offer to DR development. Studies with larger sample sizes and a wider spectrum of populations are authorized to verify this finding. [ABSTRACT FROM AUTHOR]

Infertility is a major issue at present and is a common disease that exists in both male and female reproductive systems, described as failure to attain pregnancy. The most important physiological phenomenon for establishing clinical pharmacy is defined as female infertility (FI). Obesity enhances the risks for many chronic disorders, especially causing a high risk for women's reproductive health. The relationship between infertile women and thrombophilia is characterized by abnormal blood coagulation. Among the thrombophilic variants, Factor V Leiden (FVL), prothrombin (PT) and methyl tetrahydrofolate reductase (MTHFR) in genes such as G1691A (rs6020), G20210A (rs1799963) and C677T (rs1801133) are commonly studied in the majority of human diseases. In this case–control study, we investigated the role of thrombophilic variants such as G1691A, G20210A and C677T in the FVL, PII and MTHFR genes in Saudi infertile women. Based on sample size calculation, 100 female infertile and 100 control (fertile) women were selected based on inclusion and exclusion criteria. Genotyping was performed with polymerase chain reaction and followed with precise restriction enzymes, which can accurately detect the nucleotide amendment variants in G1691A, G20210A and C677T. The required statistics were applied between the case (infertile) and control (fertile) women to document the role of the G1691A, G20210A and C677T variants in Saudi infertile women. In this study, age, weight and BMI were found to be high in the control women in comparison to the infertile women. None of the genotypes, genetic models or allele frequencies were associated with G1691A, G20210A or C677T SNPs (p > 0.05). Furthermore, the regression model and ANOVA analysis also showed negative statistical associations. The combination of genotypes and allele frequencies among G1691A, G20210A and C677T SNPs showed positive associations in the recessive model (p = 0.0006). Finally, the GMDR model showed moderate associations with the gene–gene interaction, dendrogram and depletion models. Finally, this study confirmed that thrombophilic SNPs have no role and may not be involved in Saudi infertile women. [ABSTRACT FROM AUTHOR]

Objective: Association between a genetic polymorphism and disease, either positively or negatively, within a population may not necessarily predict association in other race-ethnic populations. The aim of this study was to genotype well recognized thrombophilia associated polymorphisms as common risk factors for miscarriage and investigate their benefit to use as risk factors in southwest region of Iran females (Khuzestan) in the Arabs ethnic minority group with spontaneous miscarriage. We developed a Reverse Dot Blot Assay for the genotyping of four polymorphisms. Results: There were significant differences in the genotype distribution and allelic frequencies of the MTHFR 1298 A > C, MTHFR 677 C > T, Factor V Leiden 1691 G > A, PAI-1-844G > A polymorphisms between the case and control groups. The MTHFR 1298 A > C, MTHFR 677 C > T and Factor V Leiden 1691 G > A polymorphisms were significantly associated with spontaneous miscarriage risk. Unlike some other race-ethnic populations, PAI-1-844G > A polymorphism was associated with risk of developing unplanned miscarriage in Iranian Arabs ethnic minority group females. [ABSTRACT FROM AUTHOR]

Thromboembolic disease is a common complication of cancer and is the second most common cause of death in cancer patients. Cancer-associated thrombosis (CAT) can disrupt anticancer treatment and negatively impact patients' quality of life. Research efforts have focused on understanding the mechanisms behind CAT, identifying biomarkers, and developing improved treatments. This issue of Seminars in Thrombosis and Hemostasis addresses the prevalence of thrombosis in different cancer types, risk factors for arterial thrombosis, and various biomarkers for CAT. It also explores the role of the hemostatic system in promoting cancer growth and metastasis. The issue concludes with discussions on the effect of hyperthermic intraperitoneal chemotherapy on hemostasis and the interactions between antineoplastic agents and direct oral anticoagulants. Overall, the issue provides valuable insights for researchers, clinicians, and cancer patients. [Extracted from the article]

The text discusses the history and current challenges of the bleeding time test, which has been used for over 100 years to assess primary hemostasis and platelet function. The test involves making standardized skin incisions on the forearm and measuring the time it takes for bleeding to stop. However, the test has limitations in terms of sensitivity, specificity, reproducibility, and scarring. Newer laboratory tests and point-of-care platelet function devices are now used to assess bleeding risk and the effects of antiplatelet agents. The bleeding time test is no longer used in everyday practice but may still be of interest for research purposes. [Extracted from the article]

Key recommendations: In this guideline, recurrent miscarriage has been defined as three or more first trimester miscarriages. However, clinicians are encouraged to use their clinical discretion to recommend extensive evaluation after two first trimester miscarriages, if there is a suspicion that the miscarriages are of pathological and not of sporadic nature.Women with recurrent miscarriage should be offered testing for acquired thrombophilia, particularly for lupus anticoagulant and anticardiolipin antibodies, prior to pregnancy. [Grade C]Women with second trimester miscarriage may be offered testing for Factor V Leiden, prothrombin gene mutation and protein S deficiency, ideally within a research context. [Grade C]Inherited thrombophilias have a weak association with recurrent miscarriage. Routine testing for protein C, antithrombin deficiency and methylenetetrahydrofolate reductase mutation is not recommended. [Grade C]Cytogenetic analysis should be offered on pregnancy tissue of the third and subsequent miscarriage(s) and in any second trimester miscarriage. [Grade D]Parental peripheral blood karyotyping should be offered for couples in whom testing of pregnancy tissue reports an unbalanced structural chromosomal abnormality [Grade D] or there is unsuccessful or no pregnancy tissue available for testing. [GPP]Women with recurrent miscarriage should be offered assessment for congenital uterine anomalies, ideally with 3D ultrasound. [Grade B]Women with recurrent miscarriage should be offered thyroid function tests and assessment for thyroid peroxidase (TPO) antibodies. [Grade C]Women with recurrent miscarriage should not be routinely offered immunological screening (such as HLA, cytokine and natural killer cell tests), infection screening or sperm DNA testing outside a research context. [Grade C]Women with recurrent miscarriage should be advised to maintain a BMI between 19 and 25 kg/m2, smoking cessation, limit alcohol consumption and limit caffeine to less than 200 mg/day. [Grade D]For women diagnosed with antiphospholipid syndrome, aspirin and heparin should be offered from a positive test until at least 34 weeks of gestation, following discussion of potential benefits versus risks. [Grade B] Aspirin and/or heparin should not be given to women with unexplained recurrent miscarriage. [Grade B]There are currently insufficient data to support the routine use of PGT‐A for couples with unexplained recurrent miscarriage, while the treatment may carry a significant cost and potential risk. [Grade C]Resection of a uterine septum should be considered for women with recurrent first or second trimester miscarriage, ideally within an appropriate audit or research context. [Grade C]Thyroxine supplementation is not routinely recommended for euthyroid women with TPO who have a history of miscarriage. [Grade A]Progestogen supplementation should be considered in women with recurrent miscarriage who present with bleeding in early pregnancy (for example 400 mg micronised vaginal progesterone twice daily at the time of bleeding until 16 weeks of gestation). [Grade B]Women with unexplained recurrent miscarriage should be offered supportive care, ideally in the setting of a dedicated recurrent miscarriage clinic. [Grade C] [ABSTRACT FROM AUTHOR]

Background: Several genetic mutations in female thrombotic defects have recently been shown to affect recurrent pregnancy loss (RPL); however, it is unclear which common parental mutations are involved in thrombosis-associated repeated pregnancy loss RPL. Aims: In this study, the prevalence of some combined parental thrombophilia gene mutation defects was studied in couples with RPL. Settings and Design: The observational study was done in babol infertility research center (Iran) in 2022. Materials and Methods: Sixty-two infertile women with a history of RPL and their male partners (124 individuals) participated in this study. The frequencies of common defects associated with methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, factor V Leiden, protein C, protein S and homocysteine were analysed in these couples. Statistical analysis used: The data were statistically analysed using the Mann-Whitney test. Results: Sixty-two couples (124 individuals) were analysed. 56.2% of couples with a history of RPL had MTHFR C677T and 23.1% had MTHFR A1298C. Forty percent of couples showed homocysteine deficiency and 12.5% protein C deficiency. Other genes tested were only observed in the mother or father but not both. Conclusions: Results obtained with RPL couples demonstrate the importance of further investigating combined parental thrombophilia gene mutation defects (not only maternal). [ABSTRACT FROM AUTHOR]

Thrombosis in the inferior vena cava (IVC) is a rare but serious condition that can lead to significant morbidity and mortality. We present a case report of a 39-year-old male who presented to the emergency department with right flank pain that had progressed to severe back pain, bilateral flank pain, scrotal pain, and leg pain over the course of two days. The pain was severe enough to affect his daily activities. Laboratory investigations revealed a D-dimer level of 17 ng/mL, creatinine level of 110 µmol/L, and a white blood cell count of 10 × 109/L with a CRP level of 5 mg/L. Urine analysis was positive for blood. Doppler ultrasound of both legs showed deep vein thrombosis extending from the external iliac veins to the distal veins of both legs. Further investigation with computed tomography of the abdomen revealed a large thrombus in the distal vena cava extending to the renal artery and both external and internal iliac veins. The patient was diagnosed with Factor V Leiden syndrome based on genetic testing, which revealed a heterozygous mutation in the F5 gene. He was successfully treated with low molecular weight heparin and warfarin, and after five days of hospitalization, he was discharged with warfarin for long-term anticoagulation. This case report emphasizes the importance of considering IVC thrombosis in patients with a constellation of symptoms, including scrotal pain, and the role of genetic testing in identifying underlying hypercoagulable states. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to compare the ovarian reserve tests and abnormal test results in couples with 2 to more than 2 recurrent pregnancy losses in our population. Material and Methods: Seventy-five couples aged 20-44 years, who had two or more consecutive abortions at 20 weeks or less from the last menstrual period, were included in the study. The women were divided into two groups as those who had two miscarriages (Group 1, n=34) and those who had three or more miscarriages (Group 2, n=41). Women in both groups were compared in terms of serum hormone levels, biochemical parameters, karyotype analysis, thrombophilic, and uterine factors. The spermiogram values and karyotype analyzes of the male partners in both groups were compared. Results: The women in Group 2 were older than those in Group 1, and live birth history and Factor V Leiden heterozygosity were found to be statistically significantly higher. The follicle stimulating hormone values in the secondary recurrent pregnancy loss patients were found to be statistically significantly higher than in the primary recurrent pregnancy loss patients. Conclusion: Maternal age and Factor V Leiden heterozygosity may be associated with the number of miscarriages in couples with recurrent pregnancy loss. [ABSTRACT FROM AUTHOR]

Background: FV Leiden is an autosomal dominant disease, representing one of the most prevalent genetic causes for hereditary thrombophilia manifested by venous thromboembolism. Methods: We report a case of a 30-year-old patient who was admitted for enrollment in phase II cardiac rehabilitation. The cardiovascular disease onset was five years ago when the patient was diagnosed with superficial vein thrombosis, for which anticoagulant treatment was recommended. However, he discontinued the prescribed treatment independently, which resulted in the development of deep vein thrombosis. A screening for risk factors associated with venous thromboembolism was conducted, leading to the identification of a heterozygous mutation of factor V Leiden. Later, the patient was hospitalized for acute coronary syndrome necessitating stent implantation. Following this procedure, the patient started a cardiac rehabilitation program, where the patient received multidisciplinary counseling. Conclusions: At the end of the cardiac rehab, significant improvements were observed in clinical and hemodynamic parameters. Consequently, the patient was advised to continue rehabilitation treatment in the outpatient setting. Also, for patients with suboptimal maintenance of the therapeutic range of INR, the use of apixaban might be considered. Furthermore, the utilization of a reduced dosage of apixaban has demonstrated its effectiveness in preventing further venous thromboembolism. [ABSTRACT FROM AUTHOR]

(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.

This article is a themed issue of Seminars in Thrombosis and Hemostasis focused on laboratory diagnostics for thrombosis and hemostasis testing. It includes comprehensive reviews and an original research article on diagnostic algorithms for heparin-induced thrombocytopenia. The issue also features editorials, announcements of award winners and journal metrics, as well as articles on topics such as activated protein C resistance, internal quality control in hemostasis assays, lupus anticoagulant testing, measuring direct oral anticoagulants, and monitoring anticoagulant and hemostatic therapies. The issue concludes with the re-publication of a historical paper on platelet physiology and an accompanying commentary. [Extracted from the article]

The editorial discusses the potential inclusion of activated partial thromboplastin time (APTT) in thrombophilia screening, highlighting the complexity of thrombophilia as a predisposition to thrombosis due to various molecular abnormalities. The cost-effectiveness of comprehensive thrombophilia screening remains controversial, especially in asymptomatic populations with higher thrombosis risk. The study by Radišić Biljak et al. explores the causes of shortened APTT, emphasizing the importance of considering elevated factor VIII levels as a potential risk factor for venous thromboembolism. The editorial underscores the need for further research to determine the clinical utility of APTT in detecting elevated coagulation factors and managing thrombotic risk. [Extracted from the article]

Infection with SARS-CoV-2 has been shown to predispose to thromboembolic events. The risk of such thromboses further increases in those with underlying inherited or acquired prothrombotic states. The authors present a 30-yearold lady who developed acute abdominal pain, three days after recovery from a mild COVID-19 infection. She was also using oral contraceptive pills. Laboratory investigations revealed elevated inflammatory markers, and a contrastenhanced abdominal CT scan demonstrated portal vein thrombosis (PVT). Due to the unusual site of thrombosis, a thrombophilia screen was performed, which detected a heterozygous Factor V Leiden mutation (FVL). Thus, her PVT was attributed three simultaneous risk factors, namely COVID-19 infection, OCP use and FVL mutation. She was initiated on anti-coagulation, with which she improved significantly. In patients presenting with thromboses at uncommon sites, investigation for evidence of recent Covid-19 infection and screening for inherited and acquired thrombophilia should be considered, while discontinuing any offending medications. [ABSTRACT FROM AUTHOR]

Background. Legg–Calvé–Perthes (LCPD) disease is a complex condition affecting the femoral head's epiphysis in children. It occurs with a prevalence ranging from 0.4 to 29.0 cases per 100,000 children under the age of 15. It involves various factors, including genes associated with coagulation and fibrinolysis, pro-inflammatory factors, and vasoactive substances. Methods. We investigated the relationship between genetic mutations associated with coagulation and vascular disorders and the occurrence of LCPD in Polish patients. We performed a study involving 25 patients with LCPD and 100 healthy controls. All subjects were genotyped for eNOS4, Factor V Leiden, prothrombin, tPA25, and MTHFR polymorphism. Results. The analysis revealed that the frequencies of eNOS4 genotypes were significantly different in LCPD patients than in the control group (p = 0.018). The frequencies of 4a allele were significantly higher in patients with LCPD than in the healthy population (26% vs. 9%, p = 0.0012). There were no significant differences in genotype and allele frequencies for Factor V Leiden, prothrombin tPA 25, and MTHFR gene polymorphisms between patients with LCPD and the controls. Conclusions. Genotype and allele frequencies of eNOS4 were significantly higher in patients with LCPD. These findings suggest a potential association between the eNOS gene polymorphism and an increased risk of developing LCPD. [ABSTRACT FROM AUTHOR]

Background: Cerebral venous thrombosis is a rare type of stroke, occurring more among young individuals. The presentation is highly variable, and this can delay diagnosis and management, thereby affecting outcome. The aim is to study the clinical, radiological profile, risk factors for cerebral venous thrombosis (CVT) and the role of transcranial color-coded duplex (TCCD) in CVT prognosis among Egyptian patients. Methods: Eighty CVT patients and 80 normal healthy individuals were included. Magnetic resonance imaging, magnetic resonance venography, and genetic thrombophilia tests were done for patients. Deep cerebral venous system was evaluated using B-mode transcranial color-coded duplex (TCCD) for both groups. Results: Showed female predominance with gender specific risk factors being the most common etiology. The most common hereditary thrombophilia was homozygous factor V Leiden mutation and anti-thrombin III (AT III). Headache was the most common presentation. Forty-three patients had transverse sinus thrombosis. Regarding TCCD, there was an increase in mean blood flow velocities, peak flow velocities and end diastolic flow velocities in deep middle cerebral vein and basal veins in CVT group compared to control group. There was a positive correlation not reaching statistical significance between flow velocities in the deep venous system and modified Rankin Scale. Conclusion: Clinical presentation is extremely variable. In our population, homozygous factor V Leiden mutation and AT III deficiency were the most common. Increased deep cerebral venous system flow velocities using TCCD in patients with CVT reflect their venous hemodynamic state. [ABSTRACT FROM AUTHOR]

Factor V (FV) Leiden and prothrombin G20210A are the most common hereditary thrombophilias. While their role in venous thromboembolism is well known, there are still uncertainties regarding their relationship with arterial thrombotic events, especially coronary ones. Our research, based on an in-depth analysis of the available literature, provides up-to-date information on the relationship between FV Leiden and prothrombin G20210A and acute myocardial infarction. FV Leiden and prothrombin G20210A screening should be implemented only in select cases, such as acute coronary syndrome in young individuals and/or in the absence of traditional cardiovascular risk factors and/or in the absence of significant coronary artery stenosis at angiography. Their identification should be followed by the implementation of optimal control of modifiable traditional cardiovascular risk factors to reduce the risk of recurrent events and genotyping and genetic counseling of all family members of affected cases for proper prophylaxis. An extended dual antiplatelet therapy (DAPT) may be considered, given the lower risk of bleeding under DAPT conferred by FV Leiden. [ABSTRACT FROM AUTHOR]

(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. [ABSTRACT FROM AUTHOR]

Objective: To elucidate the possible role of unfractionated heparin in patients with failed repeated in in vitro fertilization and embryo transfer (IVF-ET) and thrombophilia. Methods: This case control study evaluated the efficacy of the unfractionated heparin in increasing the pregnancy and implantation ratio in women with recurrent IVF-ET failures. Eighty-six women received in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) with a record of three or more previous IVF-ET failures. Participants were randomly distributed into two groups. Group A (n=43) received unfractionated heparin 5 000 IU twice daily, and group B (n=43) did not take any antithrombotic drugs. Coagulation abnormalities such as factor V Leiden (FVL) mutation, methylene tetra hydro folate reductase (MTHFR) mutation and prothrombin mutation (FII) were evaluated. Age, body mass index, basal follicular stimulating hormone, basal estradiol, duration of infertility, and number of IVF-ET failures were compared between two groups. Results: 45.0% and 17.4% of women were pregnant with and without MTHFR and prothrombin mutation, respectively, when they received unfractionated heparin treatment. The implantation rate was more in group A (12.5%) than group B (4.3%) and differences in the fertilization rate of the two groups were observed (27.7% vs. 35.9%). The clinical pregnancy rate per cycle was remarkably more in group A (30.2%) than group B (14.0%). Conclusions: Heparin is a safe and valuable treatment for patients with repeated IVF-ET failures. The clinical pregnancy and implantation rates are higher in the heparin-treated group in contrast with the control group. Trial registration: The trial registration was done with clinical registration number of “ IRCT138807202575N1”.