UNASSIGNED: Inherited thrombophilia, mainly the Factor V Leiden (FVL) and Prothrombin mutation (PTM) are the most risk factors for venous thrombosis especially during pregnancy and was strongly associated with recurrent pregnancy loss (RPL), a devastating reproductive problem that affects more than 1% of couples who are trying to conceive. The frequencies also the correlation among these polymorphisms and RPL have been reported controversially in various populations.
UNASSIGNED: In this study we evaluated the presence inherited thrombophilia amongst 35 Tunisian women with more than 2 miscarriages, referred to our genetic counseling.
UNASSIGNED: DNA was extracted from peripheral blood samples and PCR-RFLP was performed for the molecular diagnosis of mutation.
UNASSIGNED: FVL and PTM were detected in 5.7 % and 2.9% respectively; in women with a particular history of early fetal loss and thrombotic events.
UNASSIGNED: This study emphasizes the importance of testing for FVL and FIIM in women with RPL; mainly in the context of thrombotic events. Multi-center collaboration is necessary to clarify the real impact of thrombotic molecular defects on the pregnancy outcome, to ascertain the effect of inherited thrombophilia on recurrent pregnancy loss and then to evaluate the appropriate therapeutic approach.

In the general population, individuals with an inherited thrombophilia have a higher risk of thrombosis, but the effect of inherited thrombophilia on the risk of cancer-associated venous thromboembolism (VTE) remains controversial. Our objective was to determine the risk of VTE in cancer patients with inherited thrombophilia. We conducted a systematic review and meta-analysis of studies reporting on VTE after a cancer diagnosis in adult patients who were tested for inherited thrombophilia. In September 2022, we searched Medline, EMBASE, and Cochrane Central. Two reviewers screened the abstracts/full texts and assessed study quality using the Quality in Prognostic Studies tool. We used Mantel-Haenszel random-effects models to estimate pooled odds ratios (OR) of VTE and 95% confidence intervals (95%CI). We included 37 and 28 studies in the systematic review and meta-analysis, respectively. Most studies focused on specific cancer types and hematologic malignancies were rare. The risk of VTE was significantly higher in cancer patients with non-O (compared with O) blood types (OR: 1.56 [95% CI: 1.28-1.90]), Factor V Leiden, and Prothrombin Factor II G20210A mutations compared with wild types (OR: 2.28 [95% CI: 1.51-3.48] and 2.14 [95% CI: 1.14-4.03], respectively). Additionally, heterozygous and homozygous methylenetetrahydrofolate reductase C677T had ORs of 1.50 (95% CI: 1.00-2.24) and 1.38 (95% CI: 0.87-2.22), respectively. Among those with Plasminogen-Activator Inhibitor-1 4G/5G, Vascular Endothelial Growth Factor (VEGF) A C634G, and VEGF C2578A mutations, there was no significant association with VTE. In conclusion, this meta-analysis provided evidence that non-O blood types, Factor V Leiden, and Prothrombin Factor II G20210A mutations are important genetic risk factors for VTE in cancer patients.

Statins are powerful lipid-lowering drugs that inhibit cholesterol biosynthesis via downregulation of hydroxymethylglutaryl coenzyme-A reductase, which are largely used in patients with or at risk of cardiovascular disease. Available data on thromboembolic disease include primary and secondary prevention as well as bleeding and mortality rates in statin users during anticoagulation for VTE. Experimental studies indicate that statins alter blood clotting at various levels. Statins produce anticoagulant effects via downregulation of tissue factor expression and enhanced endothelial thrombomodulin expression resulting in reduced thrombin generation. Statins impair fibrinogen cleavage and reduce thrombin generation. A reduction of factor V and factor XIII activation has been observed in patients treated with statins. It is postulated that the mechanisms involved are downregulation of factor V and activated factor V, modulation of the protein C pathway and alteration of the tissue factor pathway inhibitor. Clinical and experimental studies have shown that statins exert antiplatelet effects through early and delayed inhibition of platelet activation, adhesion and aggregation. It has been postulated that statin-induced anticoagulant effects can explain, at least partially, a reduction in primary and secondary VTE and death. Evidence supporting the use of statins for prevention of arterial thrombosis-related cardiovascular events is robust, but their role in VTE remains to be further elucidated. In this review, we present biological evidence and experimental data supporting the ability of statins to directly interfere with the clotting system.

Factor V Leiden is the commonest hereditary prothrombotic allele, affecting 1% to 5% of the world\'s population. The objective of this study was to characterize the perioperative and postoperative outcomes of patients with Factor V Leiden compared to patients without a diagnosis of hereditary thrombophilia. This was a focused systematic review of studies including adult (>18 years) patients with Factor V Leiden (heterozygous or homozygous) undergoing noncardiac surgery. Included studies were either randomized controlled trials or observational. The primary clinical outcomes of interest were thromboembolic events occurring from the perioperative period up to 1 year postoperatively, defined as deep venous thrombosis, pulmonary embolism, or other clinically significant thrombosis occurring during or after a surgical procedure. Secondary outcomes included cerebrovascular events, cardiac events, death, transplant-related outcomes, and surgery-specific morbidity. Pediatric and obstetrical patients were excluded, as were case reports and case series. Databases searched included MEDLINE and EMBASE from inception until August 2021. Study bias was assessed through the CLARITY (Collaboration of McMaster University researchers) Risk of Bias tools, and heterogeneity through analysis of study design and end points, as well as the I 2 statistic with its confidence interval and the Q statistic. A total of 5275 potentially relevant studies were identified, with 115 having full text assessed for eligibility and 32 included in the systematic review. On the whole, the literature suggests that patients with Factor V Leiden have an increased risk of perioperative and postoperative thromboembolic events compared to patients without the diagnosis. Increased risk was also seen in relation to surgery-specific morbidity and transplant-related outcomes, particularly arterial thrombotic events. The literature did not support an increased risk for mortality, cerebrovascular, or cardiac complications. Limitations of the data include predisposition toward bias due in many study designs and small sample sizes across the majority of published studies. Variable outcome definitions and durations of patient follow-up across different surgical procedures resulted in high study heterogeneity precluding the effective use of meta-analysis. Factor V Leiden status may confer additional risk for surgery-related adverse outcomes. Large, adequately powered studies are required to accurately estimate the degree of this risk by zygosity.

Preeclampsia is a multifactorial pathology with negative outcomes in affected patients in both the peripartum and postpartum period. Black patients in the United States, when compared to their White and Hispanic counterparts, have higher rates of preeclampsia. This article aims to review the current literature to investigate how race, social determinants of health, and genetic profiles influence the prevalence and outcomes of patients with preeclampsia. Published studies utilized in this review were identified through PubMed using authors\' topic knowledge and a focused search through a Medline search strategy. These articles were thoroughly reviewed to explore the contributing biosocial factors, genes/biomarkers, as well as negative outcomes associated with disparate rates of preeclampsia. Increased rates of contributing comorbidities, including hypertension and obesity, which are largely associated with low access to care in Black patient populations lead to disparate rates of preeclampsia in this population. Limited research shows an association between increased rate of preeclampsia in Black patients and specific APOL1, HLA-G, and PP13 gene polymorphisms as well as factor V Leiden mutations. Further research is required to understand the use of certain biomarkers in predicting preeclampsia within racial populations. Understanding contributing biosocial factors and identifying genes that may predispose high-risk populations may help to address the disparate rates of preeclampsia in Black patients as described in this review. Further research is required to understand if serum, placental, or urine biomarkers may be used to predict individuals at risk of developing preeclampsia in pregnancy. KEY POINTS: · Prevalence of preeclampsia in the U.S. is higher in Black patients compared to other racial groups.. · Patients with preeclampsia are at risk for poorer health outcomes both during and after delivery.. · Limited research suggests specific biomarkers or gene polymorphisms contribute to this difference; however, explanations for this disparity are multifactorial and further investigation is necessary..

Recurrent pregnancy loss (RPL) is defined as the loss of two or more pregnancies, affecting approximately 1 to 3% of women worldwide. Scientific data highlight a possible correlation between thrombophilic genetic variants and RPL. H1299R variant in the factor V gene would lead to an increased thrombotic risk associated with frequent miscarriages. However, the data are often conflicting, making this an interesting question for further investigations by evaluating genotype-phenotype correlations to improve the clinical management and genetic counseling of couples. A systematic review and meta-analysis will follow the preferred reporting elements for systematic review and meta-analysis protocols (PRISMA-P). The Pubmed (MEDLINE) and Embase (OVID) databases will be explored to identify suitable articles based on inclusion and exclusion criteria. Inclusion criteria are: (a) H1299R genotyping with clear data reported, referred to as Heterozygous (Het) and/or Homozygous (Hom); (b) articles written in English; (c) analyses of only RPL female patients having at least two or more previous pregnancy losses and compared with a control group. This analysis will present selected scientific evidence, addressing the questions concerning the association between the H1299R variant and RPL, hoping to clarify this still unresolved issue. PROSPERO registration number: CRD42022330077.

BACKGROUND: Factor V Leiden (FVL) is a hereditary thrombophilia, which causes the blood to be more hypercoagulable; in essence, the blood tends to clot more easily, especially under certain circumstances. It is the most common genetic mutation, causing thrombophilia in patients of white background. Patients that have FVL are at a higher risk to develop venous thromboembolism (VTE) after surgery and trauma.
OBJECTIVE: The purpose of this review is to identify FVL as a risk factor, which may impede optimum acute cardiopulmonary management which may contribute to a longer length of stay (LOS) in the hospital.
METHODS: This article is a systematic review of the literature involving research printed in peer-reviewed journals from 2015 to 2018. The University of Tennessee Health Science Center online library, PubMed, and Google Scholar were used for the literature search.
RESULTS: The results of this study determined that although FVL is in fact a risk factor, which may impede optimum acute cardiopulmonary management which may contribute to a longer LOS, management of VTE is no different for a person with FVL compared with those without FVL.
CONCLUSIONS: Factor V Leiden is a risk factor for the development of VTE, specifically deep vein thrombosis, in surgical, trauma, pregnant, and hormone replacement therapy patients, thus increasing LOS and recurrence of such events. Regardless of FVL status, management of VTE should be initiated promptly and discontinued when appropriate.

Coagulation factor V (or FV for the purpose of medical safety) is an essential cofactor of coagulation factor X in the common pathway of coagulation; severe FV deficiency leads to a bleeding tendency. Although both congenital and acquired FV deficiencies are widely recognized, FV deficiency also presents as an autoimmune disorder. A nationwide survey on autoimmune coagulation factor deficiencies (AiCFDs) conducted in Japan by our Japanese Collaborative Research Group identified 24 new patients with autoimmune FV deficiency (AiFVD) in the past 5 years. Furthermore, our extensive literature search confirmed that 177 AiFVD cases have been reported in previous articles published from Japan. Patients with AiFVD in Japan were predominantly men, with age similar to those with other AiCFDs. AiFVD was confirmed as a relatively mild type of bleeding diathesis, associated with lower mortality rate than that for AiFVD and other AiCFDs reported in previous studies. Patients with AiFVD had variable FV inhibitor titers and both neutralizing anti-FV autoantibodies and nonneutralizing counterparts. Although spontaneous resolution occurs in some patients, timely initiation of hemostatic and immunosuppressive therapies helps arrest the bleeding and eliminate anti-FV antibodies, resulting in a high cumulative recovery rate. Immunological anti-FV antibody detection is recommended to avoid missing AiFVD cases for the presence of nonneutralizing anti-FV autoantibodies. Further investigation is necessary to clarify the long-term prognosis and optimal management of AiFVD.

Livedoid vasculopathy (LV) is considered a disease of hypercoagulability. Association of LV with genetic variants is poorly characterised and large-scale genetic association studies have not been performed. The aim of the study was to systematically review variants in LV patients and to analyse the available clinical data. A systematic search of the literature in PubMed and Embase databases was performed to identify articles investigating genetic variation in LV patients. Thirty studies or case reports were identified that reported 265 LV patients tested for at least one out of six genetic variations. Among them, PAI-1 -675 4G/5G was the most common, accounting for 85.26% (81/95). Heterozygous 4G/5G was the major genotype. PAI-1 A844G, MTHFR C677T, and MTHFR A1298C were the second, third, and fourth most common variants in LV patients. Prothrombin G20210A and Factor V G1691A were mainly present in LV patients from Europe, North America, and South America. This review highlights the associations between LV and genetic variants. The distribution of variants may be geographically or ethnicity dependent; however, large sample case-control studies are needed to clarify associations.

Hypercoagulable disorders can compromise success of free flap reconstruction. Factor V Leiden is one such disorder for which only one previously reported case of successful free tissue transfer in the head and neck has been described. We report a 70-year-old woman with factor V Leiden treated for stage IVA squamous cell carcinoma of the mandible with a composite resection and reconstruction with an osteocutaneous scapular free tissue transfer. The free tissue transfer occurred without complications, in the setting of intraoperative heparin, postoperative aspirin, and enoxaparin. The free tissue transfer continues to be viable at her most recent follow-up appointment. The hypercoagulable patient represents a diverse presentation of increased coagulation risk in the perioperative period. Considering a patient\'s history and understanding available treatment adjuncts can factor heavily in a patient with factor V Leiden successfully undergoing free tissue transfer for head and neck defects.