Thrombophilic Factors Research Articles

The Role of Chromosome Analysis in Patients with Recurrent Pregnancy Loss

Purpose: Recurrent pregnancy loss (RPL) is called as loss of two or more clinically defined pregnancies. The causes of RPL include chromosomal abnormalities, endocrinological disorders, autoimmune problems, uterine anomalies, and thrombophilic factors. In this study, we aimed to discuss the results of chromosomal analysis of couples who had experienced RPL in central Anatolia and their relationship with RPL. Materials and Methods: A total of 1420 subjects, 721 females and 699 males with two or more RPL, were included in the study. Chromosome analysis was performed using standard cytogenetic GTG banding technique using peripheral blood lymphocytes. All chromosomes were examined for numerical and structural chromosomal abnormalities. Results: Normal chromosome formation,46, XX in 698 people and 46, XY in 680 people, was detected in a total of 1378 people (97%). Normal chromosome variant was detected in 15 patients (1%), most commonly 46,XX,9qh+ (0.28%) in 4 patients and 46,XY,9qh+ (0.21%) in 3 patients. In addition, 12 patients had balance reciprocal translocation (0.8%), 6 patients had robertsonian translocation (0.4%), 45,XX,rob (13;14) (q10;q10) in 4 patients, and 45,XY,rob(13;14)(q10;q10) in 2 patients. Conclusion: In this study, chromosomal translocations were the most important cause of RPL in the chromosomal analysis of the parents (n=18; 1.2%). Approximately 2% of individuals with RPL have numerical and structural chromosomal abnormalities such as reciprocal or robertsonian translocations, inversions, and sex chromosomal abnormalities. In order to have healthy babies, preimplantation genetic diagnostic tests should be recommended to the patients by obstetricians, medical geneticists and clinical embryologists who are involved in reproductive medicine.

Diagnosis and management of cerebral venous sinus thrombosis in children: a single-center retrospective analysis.

Cerebral venous thrombosis (CVT) is a rare disease in children, characterized by partial or total occlusion of blood flow in the cerebral venous system. The aim of this study is to describe clinical presentation, neuroimaging features, therapeutic management, and outcome of children with CVT. We retrospectively analyzed the data, including clinical manifestations, laboratory data, neurological findings, and treatment of children with radiologically confirmed CVT, admitted between January 2010 and March 2020 to our hospital. Cases of CVT complicating brain surgery were excluded. We enrolled 24 children with CVT. Infection was the main etiology (58.3%), followed by trauma in 16.7% of cases. In the remaining 25% of cases, the cause was identified only in one patient presenting a thrombophilic factor. The most frequent site of thrombosis was the superficial venous system (86.8%), with multiple localizations disclosed in 79% of patients. All children received anticoagulant therapy with low molecular weight heparin (LMWH). One patient died for systemic complications of an underlying disease. No patient developed hemorrhagic events during the therapy, lasting from 35 to 360 days (mean 86 days). In all but one surviving patients (22 out of 24), recanalization of the sinus was observed at AngioMRI performed during follow-up. No neurological complications of CVT were recorded (mean follow-up: 1.5 year). CVT may present with subtle and unspecific clinical manifestations in children. High level of suspicion should be kept in trauma and sinusitis. Anticoagulation treatment is safe and effective and should be promptly started to improve outcome.

Prevalence of thrombophilia and antiphospholipid syndrome in myocardial infarction with non-obstructive coronary arteries and cryptogenic stroke

Abstract The role of thrombophilia in myocardial infarction without obstructive coronary artery disease (MINOCA) is unclear. We investigated thrombophilic factors in patients with MINOCA in comparison with a group of patients with cryptogenic stroke. Methods 92 patients (mean age: 52.5 years) were evaluated at least 2 months after hospitalization for I MINOCA. The control group was age-comparable patients with cryptogenic stroke (n=90) and the group of patients with myocardial infarction with obstructive coronary artery disease (MI-CAD) (n=80). Thrombophilia screening included hereditary thrombophilia (factor V Leiden, prothrombin mutation G20210A, protein C, protein S or antithrombin deficiency), antiphospholipid syndrome (APS), along with factor VIII >150%, homocysteine ≥15 μm and lipoprotein (a) ≫30 mg/dl. Results Compared to cryptogenic stroke, in the MINOCA group, men were more common among patients (56.2 vs. 33.3%, P<0.001), obesity was more common among risk factors (31.5 vs. 16.9%, P=0.014), smoking (54.2 vs. 39.7%, P=0.042), as well as a burdened family history (18.4 against 7.0%, P=0.004). Hereditary thrombophilia occurred in 25.8% of patients with MINOCA and in 17.1% with cryptogenic stroke (P=0.17). APS was found in 15.5% of MINOCA. APS was diagnosed less frequently in patients with NSTEMI, (2.9 versus 21.3% P=0.002) and in patients with MINOCA aged ≤55 years (4.1 versus 36.3% for the elderly, P=0.005). Conclusions In patients with MINOCA, there is a high prevalence of thrombophilia, including APS, similar to cryptogenic stroke. Our first comprehensive study of thrombophilia in MINOCA confirms its clinical significance. Funding Acknowledgement Type of funding source: None

Acute coronary syndrome and thrombophilia in young patients:clinical data, experience

Abstract Introduction There is an increasing number of young patients with acute coronary syndromes. The gold standard for diagnosis and treatment remains coronary angiography and primary percutaneous coronary intervention (PPCI). Especially in young individuals there are cases with large thrombus burden and almost none angiographically visible coronary atherosclerosis, which raises major concerns about the etiological cause for such events. Thrombophilia can lead to repeated and unexplained thrombus formation and that is why recently there is an increasing interest in the relationship between thrombophilia and acute coronary syndrome (ACS) in early age. Still there's no precise treatment algorithm. Purpose To diagnose and evaluate the frequency of thrombophilia in patients presenting with first ACS in young age and to alter future treatment in order to prevent further events and improve prognosis. Methods We evaluated all patients with first ACS from age<40 for men and women <50 in our hospital for 3 years. All patients were diagnosed and treated with PPCI. Complete family history was taken. We performed laboratory tests for the most frequent gene mutations, responsible for thrombophilia factor V Leiden, PAI –1 4G/5G, prothrombin G20210A, MTHFR - C677T, MTHFR A 1287C, MTHFR A 1298C and glycoprotein IIb/IIIa in all patients. Results 210 patients with ACS were admitted with 36 young patients (age men <40 and women <50). In all we performed screening for thrombophilia. 32 individuals (5 women and 27 men; mean age of 46) had a distinct genetic variation which can be attributed to thrombophilia. 85% of them had family history for ischemic heart disease. The conventional risk factors for coronary artery disease (CAD), including arterial hypertension, dyslipidemia, smoking, and diabetes were presented respectively in 43%, 57%, 43% and 3% in the group. The most often diseased artery was the left anterior descending artery (LAD). The genetic evaluation results were 20% homozygotes of pathogenic variation of factor V of Leiden, 7% heterozygotes of pathogenic form of factor V of Leiden 25% PAI 1 4G/5G homozygotes, 11% PAI 1 4G/5G heterozygotes, 13% prothrombin G20210A homozygotes and 2% prothrombin G20210A heterozygote. In 28% the index event was a repeated ACS and 4% has had a previous ischemic stroke. We then consulted all of them with haemathologist and altered further discharge treatment (in 100% new oral anticoagulants (NOAC) was added to dual antipatled therapy). In follow up at the first year 70% were left on aspirin 100mg and NOAC and 10% were considered high risk and were left on two NOAC. Conclusion Thrombophilia is an indipendant risk factor for myocardial infarction in young patients and should not be easily overlooked. In them screening for thrombophilia could be beneficial, especially for the follow-up treatment and improvement of the late prognosis. Such detection could prevent subsequent AMI. Funding Acknowledgement Type of funding source: Private hospital(s)

Hypothyroidism In Women With Recurrent Spontaneous Abortion


 
 
 Recurrent miscarriage, defined as loss of two or more consecutive pregnancies, occurs in 1–2% of couples attempting to bear children. The major causes of recurrent pregnancy loss (RPL) based on the literature include parental structural chromosome rearrangement, immunologic factors (i.e. antiphospholipid syndrome), thrombophilic factors (both inherited and acquired), anatomic factors of uterine anomalies, and endocrinologic disorders. Luteal phase defect, polycystic ovarian syndrome (PCOS), diabetes mellitus, thyroid disease and hyperprolactinemia are among the endocrinologic disorders implicated in approximately 17% to 20% of RPL. The prevalence of hypothyroidism in the general population of reproductive age is about 2-3%.
 The aim of this study is to observe the benefit of screening for hypothyroidism amongst women with recurrent spontaneous abortion early in the first trimester.
 The study included one hundred and sixty (160) women, in the reproductive age of life, where there ages ranged from 20 – 33 years, and divided into two groups. Study group which included eighty (80), non pregnant women with a history of two or more consecutive spontaneous abortions early in the first trimester, with no living children and control group which included eighty (80), non pregnant women having one or more living children without any history of abortion.
 Hypothyroidism was noted in ten (10) cases (12.5%) in the study group and noted in two (2) cases (2.5%) in the control group with a statistically significant difference (P < 0.01). The mean levels of TSH in the study group was 22.71  13.13 Iu/ml.
 Conclusion: Screening for hypothyroidism has clinical significance and would help to reduce miscarriage rate in women with recurrent spontaneous abortion.
 
 

Frequency of thrombophilia associated genes variants: population-based study

BackgroundThrombophilia is a hypercoagulable state that may have a genetic basis (inherited) or can be acquired. It is a multifactorial condition and only the mutual interactions between the environment and genes may lead to the development of clinical manifestation. This state is the main factor promoting venous (rarely arterial) thromboembolism (VTE). Inherited thrombophilia is mainly associated with two pathogenic variants in the V coagulation factor (FV) and the prothrombin (FII) genes. The aim of our study was to evaluate the frequency of two pathogenic variants in FII and FV genes as inherited thrombophilia factors in a group within the Polish population in comparison with other described populations.MethodsAll studied groups consisted of 633 unrelated patients aged between 18 and 70. Individuals in the research group come from the Podlasie region of Poland. Genotyping of FII and FV variants was performed using the 7900HT Fast Real-Time PCR System and were genotyped by TaqMan assay.ResultsThe pathogenic allele frequency for A allele was 0.03 (3%) and 0.07 (7%) for FII and FV genes, respectively. The GA/AA genotypes (c.*97G > A variant) were observed in only 33 (5.03%) individuals in the studied group. Additionally, the frequency of GA/AA genotypes was over 17.4% in the coagulation factor V. Co-incidence of heterozygous genotype GA of variants FII and FV genes was observed in only 4 subjects.ConclusionThe FII gene variant shown in our study is less frequent than in other European countries (about 6%). In contrast, the A allele of the FV gene occurs with a frequency similar to that of Northern, Central and South Central Europe (about 5%).

Clinical Outcomes after Biologic Graft Use for the Creation of Blalock-Taussig Shunt in Critically Ill Patients with Thrombophilia.

The modified systemic to pulmonary artery shunt (mSPS) is an effective palliative procedure in children with cyanotic congenital heart disease (CCHD) who are not suited for total correction. Early graft failure related to hereditary thrombophilic disorder is one cause of mortality. The aim of this study is to compare the clinical outcomes and rate of graft failure after mSPS in cyanotic infants with hereditary thrombophilia using bovine mesenteric venous graft (BMVG) and polytetrafluoroethylene (PTFE). 60 cyanotic patients (28 neonates, mean age 19 ± 11.3 days; range 1 to 27) who had thrombophilic risk factors were divided into 2 groups: BMVG (n = 30) and PTFE (n = 30). Preoperative thrombophilic factors were measured for each patient. The most common thrombophilic factors were protein C and S deficiency and Factor V Leiden mutation. We also investigated D-dimer, positivity of prothrombin G20210A, factor XII and antithrombin III deficiency, and homocysteinemia in both groups. The mean age of patients was 4.6 ± 1.09 months (range 1 day to 6 months) in the BMVG group and 3.9 ± 1.02 months (range 2 days to 9 months) in the PTFE group (P = .67). mSPS procedures were performed via left thoracotomy (n = 19 in the BMVG group and n = 22 in the PTFE group) or right anterior thoracotomy (n = 3 in the BMVG group and n = 3 in the PTFE group). Median sternotomy was performed to create a central shunt in 8 neonates in the BMVG group. In the PTFE group, we performed a central shunt in 5 patients via median sternotomy. Low molecular weight heparin in combination with acetylsalicylic acid (aspirin) were administered after surgery in both groups. The patients received aspirin combined with warfarin (Coumadin) after being discharged from hospital. We performed revision surgery to observe whether any patient had a significant drop in saturation with inaudible mSPS murmur. 7 patients died early after surgery (n = 2 in the BMVG group [6.6%] and n = 5 in the PTFE group [16.5%]; P = .022). 53 patients were discharged home in good clinical condition. Early graft thromboses were observed in 2 patients in the BMVG group (6.6%) and 8 patients in the PTFE group (26.6%) (P = .001). In a case from the BMVG group, the reason for graft thrombosis was entanglement of the graft. Revision surgery was performed successfully without any complication. Cil et collegues has been reported a successful percutaneous balloon angioplasty after an acute thrombosis of BMVG previously [Cil 2010]. In another patient who had acute BMVG thrombosis, we performed transluminal graft angioplasty using successful thrombolytic administration in the catheterization laboratory. There were no complications due to graft materials such as hematoma, seroma, or infection in the BMVG group. Bleeding from the needle hole was seen in 1 patient in the BMVG group. PTFE thrombosis developed in 3 patients within 24 hours (10%). We detected total or partial PTFE graft thrombosis in 5 patients during the follow-up period (20%). Revision surgeries in 3 patients were performed immediately after diagnosis. Transluminal balloon angioplasty combined with thrombolysis was performed in infants with partial or total PTFE occlusion in 5 patients. In the PTFE group, perigraft seroma (n = 5 [16.6%)] and hematoma (n = 2 [6.6%]) were detected. We performed revision surgery because of bleeding from the needle hole in 3 patients in the PTFE group (10%) in the early period after surgery. We detected a graft infection in 1 patient (3.3%) 6 months after surgery in the PTFE group. The rate of overall complications including pseudoaneurysm, seroma formation, graft infection, or partial or total graft occlusion in the early and follow-up periods was 6.6% in the BMVG group and 53.3% in the PTFE group (P = .0001). The rate of freedom from shunt failure was 92.6% ± 2.1% and 76.2% ± 4.8% during follow-up in BMVG and PTFE groups, respectively (P = .034). The rate of shunt-related mortality was 10.7% (n = 3) in the BMVG group and 20% in the PTFE group (P = .01). Regular physical examinations, transcutaneous oxygen saturation, and echocardiographic study were performed for shunt control during follow-up. Shunt occlusion or thrombosis was not seen in the BMVG group; 5 patients in the PTFE group (20%) had shunt occlusion during follow-up (P = .001). Our study shows that BMVG, as a biological material, may be used as an alternative material for creating mSPS. It decreases postoperative life-threatening complications after shunt procedures, including graft thrombosis, bleeding from the needle hole, perigraft hematoma, and seroma in patients with hereditary thrombophilia. To our knowledge, we report the first clinical comparison of the 2 grafts in our case series with thrombophilic risk factors.

Inherited thrombophilia in mechanical valve malfunction

Mechanical valve malfunction due to thrombosis is an important and life-threatening complication in patients with prosthetic valves. Our study was performed to determine the prevalence of thrombophilia genes among patients with acute thrombosis of the mechanical pulmonary valves despite acceptable anticoagulation levels. In this cross-sectional comparative study thirthy two consecutive patients with acute thrombosis of pulmonary mechanical valve who had international normalized ratio (INR) levels for prothrombin time of at least 2 at the time of presentation and in the preceding three months were enrolled and the prevalence rates of thrombophilia factor genes among them was assessed. The results showed that 24 patients (75%) had thrombophilia gene mutations. The affected patients had mutations in one gene in 37.5% of cases, two genes in 31.3%, and three genes in 6.3%. Prevalence rate of Factor V Leiden (FVL), prothrombin (PTH), Plasminogen activator inhibitor-1 (PAI-I), Methylenetetrahydrofolate Reductase (MTHFR), and endothelial protein C receptor (EPCR) gene mutations was 3.1%, 6.3%, 50%, 37.5%, and 25%, respectively. In our study the prevalence of thrombophilia factor gene mutations of patients with acute thrombosis of pulmonary valve was higher than that reported in the general population.

Association of Thrombophilic Factors in Pathogenesis of Osteonecrosis of Femoral Head in Indian Population.

Role of heritable blood clotting disorders, both thrombophilias and hypofibrinolysis in causing avascular necrosis (AVN) of femoral head have been studied in regions like Europe and U.S.A. This study was done to investigate the role of heritable thrombophilias in ethnic Indian population. A case control study of 150 patients (100 cases and 50 age and sex matched controls) of Indian Ethnicity with clinico-radiographically documented idiopathic AVNof femoral head was done after ethics committee approval. DNA was extracted from the blood and PCR analysis was used to study heritable thrombophilic gene mutation (G1691A Factor V Leiden). Enzyme-linked immunosorbent assay (ELISA)-based assays, were utilized to measure antigen levels of protein C, antithrombin III levels and protein S. Nine cases out of 100 showed deficiency of Protein C (9%) while no control showed deficiency of Protein C (p value: 0.028-significant, Odds ratio: 9.791) Ten cases showed deficiency of Protein S (10%) in study population as compared to one case (2%) in control population (p value: 0.038-significant, Odds ratio: 5.44). ATIII deficiency was more prevalent in control group i.e. 22% compared to 11% in study group. Factor V mutation was present in 3% cases as compared to one (2%) in control group. (p value is 0.393-not significant). Difference in thrombophilic mutations in various populations indicates possible effect of ethnicity on genetic profile in the development of AVN. This risk stratification will enable in near future early diagnosis and possible role of antithrombotics in disease prevention.

Risk factors including prothrombotic work up in young ischemic stroke Indian patients

Background: Stroke in young poses a major health problem. Various Indian studies have shown the incidence of stroke to be 10-15%. Cerebral venous thrombosis and rheumatic heart disease are the leading causes of stroke in the young in India. Thrombophilic factors have been implicated in 4-8% of the young strokes worldwide. Protein C deficiency is the most common thrombophilia marker followed by a deficiency of protein S, Factor V Leiden mutation, and antithrombin (AT) deficiency. Aims and objectives was the study of stroke in young is important for various reasons. The etiology and risk factors are more diverse and different as compared to the elderly. Therefore, these may indicate separate therapeutic approaches. The aim is to study the profile of ischemic stroke cases among the young.Methods: The study was carried out at a tertiary care defence hospital between December 2018 to December 2019. All cases of fresh ischemic stroke who were more than 15 and less than 45 years of age were included. Following clinical evaluation, patients underwent complete haemogram, blood sugar levels, lipid profile and other metabolic parameters. All patients were subjected to chest radiography, 12 lead ECG, and 2D echocardiography, Non-contrast CT head and MRI brain. Prothrombotic work up was also done.Results: A total of 41 patients (12.69%) presented with ischemic stroke before 45 years of age. Out of these 10 (24%) were females and 31 (76%) were male. None of the women smoked or consumed alcohol. Among the males, 19 (47%) smoked more than 10 cigarettes or bidis per day and 9 (22%) were moderate-to-heavy drinkers of alcohol. Hypertension was present in 7 (18%) and diabetes mellitus in 3 (7%) patients. Serum cholesterol was elevated in 7 (18%) patients and triglycerides in 17 (42%). Protein S deficiency was found in 28.8% patients, while protein C deficiency was detected in 21% patients and antithrombin III deficiency in 12% patients.Conclusions: Although traditional risk factors, such as hypertension, diabetes, and smoking, are associated with stroke in both elderly and young, this study shows that other modifiable risk factors such as alcohol consumption were also prevalent. The most common etiological cause was found to be venous infarction followed by cardio embolic cause. Deficiency of Protein S was the most common prothrombotic defect followed by deficiency of Protein C.

The Association of Hereditary Prothrombotic Risk Factors with ST-Elevation Myocardial Infarction.

ObjectiveThe ST- elevation myocardial infarction (STEMI), a serious health care problem, is commonly a thrombotic complication of coronary artery disease. We compare the STEMI patients and control group in terms of the possible causes of inherited thrombophilia including FactorV Cambridge G1091C, FactorV Leiden G1691A, MTHFRC677T, MTHFR A1298C, FactorII G20210A, Factor XIII (V34L), PAI-1, FGB, ITGB3, APOB, FVHR2, ACE gene variants.MethodsFifty-three patients with STEMI and 47 individuals without diagnosis of acute coronary syndrome were included in the study. Percutaneous coronary intervention was performed for patients with STEMI. Echocardiography was performed and inherited thrombophilia genes were evaluated in all subjects.ResultsThe MTHFR A1298C, Factor XIII (V34L), ITGB, ACE and homozygous or compound heterozygous gene varations of inherited thrombophilia are significantly related with STEMI (p<0.05). Also significantly higher MTHFR A1298C, FactorV Leiden G1691A, PAI and ACE gene variations in MI patients who were smokers; Factor XIII (V34L), PAI and ACE gene variations in MI patients with HT; PAI and ACE gene variation in MI patients with FH and PAI gene variations in MI patients with HL were detected when compared with the control groups with all of the same risk factors (p<0.05).ConclusionHereditary thrombophilia factors may show promise in the prevention and management of STEMI when supported studies with larger case series.

Multiplicity of hereditary thrombophilic factors inherited from both parents results in child catastrophe

Here we present a rare case of hereditary thrombophilia due to transfer of multiple hereditary thrombophilic factors from father and mother with lethal outcome.

A Study on the Role of Thrombophilic Genetic Disorders as a Risk Factor for Thrombotic Complications in Patients with Myeloproliferative Disorders

Summary Myeloproliferative neoplasms (MPN) are haematological diseases, characterized by clonal hematopoiesis. Hemostasis abnormalities are among the most critical and frequent complications, affecting the quality of life and a possible reason for death. Thrombotic complications are common and multifactorial. Our aim was to study some genetic thrombophilia factors – Factor V Leiden (FVL), G20210A mutation in prothrombin gene (PR G20210A) and PLA2 allele polymorphism of glycoprotein IIIa gene (GPIIIa gene), and their frequency and association with thrombotic risk in both Philadelphia-positive and Philadelphia-negative MPN – chronic myelogenous leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET), and primary and secondary myelofibrosis (MF). In our patient population, PLA2 allele polymorphism of GPIIIa gene proved to be the most common and significantly associated with thrombotic complications – 26.85% of our patients were carriers, and 24.14% of them reported thrombotic complications.

Warfarin dose requirement in patients having severe thrombosis or thrombophilia.

Warfarin dose requirement varies significantly. We compared the clinically established doses based on international normalized ratio (INR) among patients with severe thrombosis and/or thrombophilia with estimates from genetic dosing algorithms. Fifty patients with severe thrombosis and/or thrombophilia requiring permanent anticoagulation, referred to the Helsinki University Hospital Coagulation Center, were screened for thrombophilias and genotyped for CYP2C9*2 (c.430C>T, rs1799853), CYP2C9*3 (c.1075A>C, rs1057910) and VKORC1 c.-1639G>A (rs9923231) variants. The warfarin maintenance doses (target INR 2.0-3.0 in 94%, 2.5-3.5 in 6%) were estimated by the Gage and the International Warfarin Pharmacogenetics Consortium (IWPC) algorithms. The individual warfarin maintenance dose was tailored, supplementing estimates with comprehensive clinical evaluation and INR data. Mean patient age was 47years (range 20-76), and BMI 27 (SD 6), 68% being women. Forty-six (92%) had previous venous or arterial thrombosis, and 26 (52%) had a thrombophilia, with 22% having concurrent aspirin. A total of 40% carried the CYP2C9*2 or *3 allele and 54% carried the VKORC1-1639A allele. The daily mean maintenance dose of warfarin estimated by the Gage algorithm was 5.4mg (95% CI 4.9-5.9mg), and by the IWPC algorithm was 5.2mg (95% CI 4.7-5.7mg). The daily warfarin maintenance dose after clinical visits and follow-up was higher than the estimates, mean 6.9mg (95% CI 5.6-8.2mg, P<0.006), with highest dose in patients having multiple thrombophilic factors (P<0.03). In severe thrombosis and/or thrombophilia, variation in thrombin generation and pharmacodynamics influences warfarin response. Pharmacogenetic dosing algorithms seem to underestimate dose requirement.

PB2434 GENETIC AND ACQUIRED THROMBOTIC RISK FACTORS IN CEREBRAL VENOUS THROMBOSIS: A STUDY FROM THE SOUTH OF TUNISIA.

Background:Cerebral Venous Thrombosis (CVT) affecting young adults is considered as an uncommon form of venous thrombosis with a prominent mortality rate (6%). The clinical phenotype may vary among patients as a result of many common prothrombotic risk factors. According to the literature, acquired and inherited thrombophilia should be explored in a constant manner following this thrombotic accident.Aims:Our objectives were to study the incidence of protein S (PS), protein C (PC), antithrombin (AT), factor V Leiden (FVL) G1691A polymorphism, prothrombin G20210A mutation, MTHFR C677T polymorphism and standardized antiphospholipid antibodies in 50 young Tunisian adults who suffered from CVT.Methods:50 patients were carried out in this study and were referred to our laboratory from 2016 to 2018 following the occurrence of a cerebral venous thrombosis. Biological investigation included the PS and PC analysis by coagulometric methods (STACLOT® PROTEIN S ; STACLOT® PROTEIN C) and the AT analysis by a chromogenic method (STA‐CHROM‐AT diagnostica stago).Genotyping for factor V Leiden (FVL) G1691A polymorphism and the prothrombinG20210A mutation was detected by PCR‐AS (allele‐specific polymerase chain reaction) while the MTHFR C677T polymorphism was conducted using PCR‐RFLP (polymerase chain reaction ‐Restriction fragment length polymorphism). Lupus anticoagulant (LA) screening was performed by the STA‐R® using, simultaneously, the PTT‐LA® and the dRVVT Screen®/ dRVVT Confirm® reagents. The anticardiolipin (aCL) and the anti‐beta 2 glycoprotein I (aβ2GPI) antibodies’ assays were performed by the immunological ELISA test.Results:The mean age of our patients was 30 ± 17 years old and the sex ratio was about 1.08. Among 50 patients, 11 cases (22 %) had presented thrombophilic abnormalities. Regarding the common congenital thrombophilia markers, our study revealed as follows: PS deficiency (4%), PC deficiency (4%) and none of the patients had an isolated inherited AT defect. Added to that, two patients had combined deficiencies in AT and PC. Molecular genotyping was explored in six patients, the frequencies of the molecular abnormalities were noticed in this manner: one case of (FVL) G1691A polymorphism (16.6%), two patients presented MTHFR C677T polymorphism (33.3%), all of them were in the heterozygous state, and a total absence of prothrombin G20210A mutation. Concerning the acquired thrombophilic factors, LA screening was positive in 6 cases /42 (14.3%), whereas, no significant levels of aCL and aβ2GPI antibodies were registered.Summary/Conclusion:According to recent Tunisian reports showing high frequencies of prothrombotic states that have reached 39% in CVT's patients, we consider that thrombophilia in our series is rather frequent in the South of Tunisia. The hereditary and acquired prothrombotic markers, have a presumably serious involvement in CVT's occurrence. The most prominent effect is that of MTHFR C677T and FVL polymorphisms, PS and PC deficiencies, while AT defect and prothrombin G20210A mutation remain to be elucidated. It is worth mentioning that combined defects do exist in our series. In regards to LA's positive results, it may necessitate a second positive confirmation after 12 weeks in order to exclude transient antibodies. It would be then interesting to attest the accountability of all these thrombotic risk factors as predisposing factors in CVT, through case‐control studies, in order to reach objective statistical findings.

High prevalence of inherited thrombophilia and antiphospholipid syndrome in myocardial infarction with non-obstructive coronary arteries: Comparison with cryptogenic stroke

BackgroundA role of thrombophilia in myocardial infarction with non-obstructive coronary arteries (MINOCA) is unclear. We investigated thrombophilic factors in MINOCA patients versus those following cryptogenic stroke (CS), a well-established indication for thrombophilia screening. MethodsIn a prospective cross-sectional study, we assessed 84 consecutive patients (median age: 45.5 years) at least 3 months after MINOCA. Age-matched CS patients (n = 84) and published data on general population served as controls. Thrombophilia screening involved inherited thrombophilia (factor V Leiden, prothrombin G20210A mutation, deficiency of protein C, protein S or antithrombin), antiphospholipid syndrome (APS), along with factor VIII >150%, homocysteine ≥15 μM and lipoprotein (a) >30 mg/dl. ResultsCompared to CS, MINOCA were more often males (60.7 vs 33.3%, P < 0.001), obese (34.5 vs 17.9%, P = 0.014), smokers (51.2 vs 35.7%, P = 0.043) and had family history of myocardial infarction (27.4 vs 6.0%, P < 0.001). Inherited thrombophilia occurred in 20 (23.8%) MINOCA patients and in 13 (15.5%) with CS (P = 0.17), without any difference in the parameters except for elevated lipoprotein (a) that was less common in MINOCA (21.4 vs 39.3%, P = 0.012). APS was found in 13 (15.5%) of MINOCA patients, mostly in a single-positive form. APS was diagnosed less frequently in STEMI (2.5 vs 27.3% for NSTEMI, P = 0.002) and MINOCA patients aged ≤50 years (5.7 vs 32.3% for older subjects, P = 0.003). ConclusionsMINOCA patients exhibit high prevalence of thrombophilia including APS, similar to that in CS. Our first comprehensive thrombophilia testing in MINOCA supports its clinical relevance and the need for long-term anticoagulation for some abnormalities, especially APS.

Livedoid vasculopathy: does hyperhomocysteinaemia play an aetiological role?

Livedoid vasculopathy (LV) has been shown to be associated with hypercoagulability. However, relevant genetic and exogenous thrombophilic factors are not fully determined. To evaluate the frequency of hyperhomocysteinaemia (HHCE) and genotypes of hypercoagulative factors in LV patients. Plasma homocysteine level was measured in 42 LV patients. Polymorphism of MTHFR (677C > T and 1298A > C), PAI1 (-675 5G/4G and -844A > G), and F2 (20210G > A), and the F5 Leiden mutation, as well as biochemical parameters for hypercoagulability, were analysed. Of the LV patients, 62% revealed mild HHCE. Polymorphisms of MTHFR were observed in 75% and 56% and the PAI1 -675 5G/4G polymorphism in 100% and 83% of patients with and without HHCE, respectively. All LV patients with renal failure had mild HHCE. A high level of comorbidity of hypertension (99%) and diabetes type 2 (44%) were noted. HHCE seems to play a major pathogenetic role in LV. A high prevalence of further procoagulative factors might support the view that LV is a "complex disease".

Effect of multiple thrombophilic gene mutations on uterine artery blood flow in nonpregnant recurrent pregnancy loss patients: are we searching enough?

Objective: To investigate whether multiple thrombophilic mutations had a significant effect on uterine artery blood flow of nonpregnant recurrent pregnancy loss (RPL) patients.Materials and methods: Among 71 RPL patients, FV Leiden (FV), prothrombin G20210A (PTGM) and MTHFR mutations, deficiency of protein S, protein C and antithrombin III (AT3), association of Val34Leu polymorphism of the FXIII (FXIII), 4G/5G polymorphism of plasminogen activator inhibitor (PAI), −455-G/A polymorphism of β-fibrinogen (fibrinogen), and HPA-1 a/b L33P polymorphism of GPIIIa (GPIIIa) genes were investigated. Doppler flow measurements of RPL patients and healthy controls were performed at mid-luteal phase.Results: Twenty-two patients who had no thrombophilic gene mutations were grouped as unexplained RPL. Also, while 25 patients had multiple mutations, 24 patients had single mutation. In the multiple mutation RPL group, the most frequent mutations were PAI (22%), MTHFR C677T (20%), MTHFR A1298C (19%), and fibrinogen (11%). Only in the multiple mutation RPL group, mean PI and dominant PI values were significantly higher than the control group.Conclusions: Our data showed negative effects of multiple thrombophilic gene mutations on uterine artery blood flow and clarified the different effects of single and multiple thrombophilic factors on uterine artery vasculature. It is concluded that investigating more thrombophilic mutations could ameliorate prognostic factors of RPL and interactions to improve uterine artery blood flow could bring benefit to obstetric outcome.

Effects of Common Thrombophilia Factor Mutations in Central Retinal Vein Occlusion.

Objectives:Central retinal vein occlusion (CRVO) is a severe eye disease that impairs vision. Although numerous systemic conditions have been reported to be a contributor, its exact pathophysiology has not yet been resolved. The purpose of this study was to study the role of some common thrombophilic polymorphisms in CRVO patients.Methods:A total of 33 CRVO patients (25 non-ischemic CRVO and 8 ischemic CRVO) and 30 controls were recruited. Factor V Leiden (G1691A), prothrombin (Factor II G20210A), MTHFR (C677T), MTHFR (A1298C), and PAI-1 5G/4G polymorphisms in venous blood DNA samples were examined, as well as the presence of hypertension, diabetes mellitus, glaucoma, smoking, and history of thrombosis.Results:It was determined that MTHFR C677T polymorphisms, either in heterozygous or homozygous form, might be a risk factor for CRVO and systemic thrombosis. No differences were detected between the CRVO and control groups in terms of diabetes mellitus (p=0.058>0.05), hypertension (p=0.3>0.05), smoking (p=0.923>0.05), glaucoma (p=0.06>0.05) or use of anticoagulant drugs (p=0.4>0.05). Analysis of patient history revealed a statistically significant difference regarding a thrombotic event in the medical history of the CRVO group (p=0.001<0.05; n=4) versus the control group. The ischemic CRVO group had a significantly higher incidence of diabetes mellitus (p=0.002<0.05) and hypertension (p=0.031<0.05) than the non-ischemic CRVO group.Conclusion:The MTHFR C677T mutation appears to be a risk factor for CRVO but factor V Leiden (G1691A), prothrombin (Factor II G20210A), MTHFR (A1298C), and PAI-1 5G/4G mutations were not determined to be specifically related to CRVO in this study. The presence of diabetes mellitus and hypertension was significant in the ischemic CRVO group. Further studies with larger sample sizes should be conducted.

Replicative analysis of hereditary thrombophilia factors in the development of preeclampsia in the Yakut population

Replicative analysis of hereditary thrombophilia factors in the development of preeclampsia in the Yakut population