Combined Thrombophilia Research Articles

A case of systemic lupus erythematosus with antineutrophil cytoplasmic antibodies, positive skin vasculitis, and concomitant combined thrombophilia.

A case of systemic lupus erythematosus with antineutrophil cytoplasmic antibodies, positive skin vasculitis, and concomitant combined thrombophilia.

Paternal thrombophilia and recurrent implantation failure: an exploratory case-control study.

Many pieces of literature have reported that inherited and acquired thrombophilia might be a risk factor for recurrent implantation failure (RIF), however, most studies have only focused on RIF patients and not their male partners. We studied the possible association of paternal thrombophilia with RIF risk. Forty-two male partners aged 20-45 suffered from RIF compared with 42 males from couples with at least one successful pregnancy. All participants were investigated for thrombophilia markers. The prevalence of coagulation Factor V activity was significantly higher in the case group (42.9%) than in the control group (16.7%) (p=0.008) (OR=3.75; 95% CI, 1.38, 10.12). The prevalence of protein C and protein S deficiencies in RIF patients were 4.8% and 2.4%, respectively, and 0% in the controls. The prevalence of antithrombin III (ATIII) deficiency was significantly higher in the case group (19%) than in the control group (2.4%) (p=0.01). None of MTHFR C677T and MTHFR A1298C were statistically significant between the two groups. Combined thrombophilia was 45.2% in the men of the RIF group when compared with the control, 14.2% (p=0.001) (OR = 4.95; 95% CI, 1.75-13.86). Paternal thrombophilia may be related to recurrent implantation failure, so evaluation of this factor in RIF patients could be used to identify relevant risk groups and may help in the proper management of these cases to enhance the chance of implantation.

The association of thrombophilia in women with severe obstetric complications.

Thrombophilia, where multiple genetic and acquired risk factors interact synergistically, are associated with thrombosis and pregnancy-related complications. Despite being studied profusely, an inconsistent association exists between thrombophilia and pregnancy complications. Between 2018 and 2020, ninety-three women with pregnancy complications were enrolled in the study. Twenty-five healthy pregnant women without pregnancy complications reported to the same hospital were also recruited as controls. Blood samples were tested for homocysteine, coagulation studies, and molecular diagnosis included FVL, PTH and MTHFR genes amplified using PCR strip assay (Vienna Lab Diagnostics, Austria). Other thrombophilia screening, including testing for AT, PC, and LA, were done by chromogenic assays (Dade Diagnostica, Munich, Germany). Homocysteine level was determined by fluorescence polarization immunoassay technology (Axsym, Abbot company, Germany). Overall, 29.03% of women with pregnancy complications had thrombophilia relative to 16% in the control group. However, the difference between the case and control groups did not reach a significant level (p=0.1175). Additionally, combined thrombophilia was more prevalent among cases (10.75%) than in the control group (4%). However, the difference did not reach statistical significance (p=0.1046). Our study demonstrated that the frequency of thrombophilia among healthy women was 16%, and among women with pregnancy-related complications, 29%. Relative to control, all measured thrombophilia markers were more frequent in women with pregnancy-related complications except for LA. Including all the studies on the Saudi population in a meta-analysis study could reveal more information about thrombophilia and pregnancy-related complications in our population.

Inherited and acquired thrombophilia in women of Indian ethnicity with recurrent pregnancy loss: An observational study from North India.

The spectrum of thrombophilia in women with recurrent pregnancy loss (RPL) is different in Indian ethnicity as reported by few studies. We aimed to study the prevalence of thrombophilia in RPL patients referred to hematology department of a tertiary centre. This is an observational study of 112 RPL patients with no apparent cause after extensive workup for non-hematological causes. The investigations performed were routine coagulogram, APLA workup, plasma homocysteine, MTHFRC677T polymorphisms, Protein C, free Protein S, Anti-thrombin III levels, test for Activated Protein C resistance (APC-R) ,Factor V Leiden and Prothrombin gene G20210A mutation. Of 112 patients, at least one thrombophilia was identified in 70.5% and combined thrombophilia in 12.5% patients. Hyperhomocysteinemia (30.4%) and APLA (25.9%) were the commonest thrombophilia whereas anticoagulant defects were seen in 12.5% of the population. Protein C deficiency (5.35%) was the commonest anticoagulant defect followed by APCR (3.6%). Mutational analysis revealed MTHFRC677T polymorphism in 20.5% whereas Factor V Leiden heterozygous in 1.8% patients. None of the patients had homozygous Factor V Leiden or Prothrombin gene G20210A mutation. Hyperhomocysteinemia, MTHFRC677T and Protein C deficiency were more associated with early pregnancy losses whereas Protein S deficiency, Factor V Leiden and APLA caused both early and late losses. Patients with greater number of losses were positive for homozygous MTHFRC677T, factor V Leiden and APLA. The approach to investigating Indian women with RPL should be based on the prevalence of thrombophilia which is unique to Indian ethnicity.

Значимость персонифицированного мониторинга гемостатического потенциала у пациентки с сочетанием комбинированной тромбофилии и тромбоцитопатии в повышении эффективности экстракорпорального оплодотворения

Значимость персонифицированного мониторинга гемостатического потенциала у пациентки с сочетанием комбинированной тромбофилии и тромбоцитопатии в повышении эффективности экстракорпорального оплодотворения

Concomitant pulmonary embolism and myocardial infarction in the presence of underlying major thrombophilia, treated with low-dose systemic alteplase: A Case Report and review of the literature

Background: Pulmonary thromboembolism (PE) and Myocardial Infarction (MI) are lifethreatening conditions witch in rare case could be concomitant. Simultaneous onset is related to a single underlying disease, like paradoxical embolism or hypercoagulable state. Case summary: We report the case of a 78-year patient with recent surgery for prostate cancer, presented for acute onset of dyspnea and angina. Concomitant diagnosis of association of PE and inferior ST-Segment Elevation Myocardial Infarction (STEMI) was done by electrocardiography, troponin I change, Computed Tomography Pulmonary Angiogram (CTPA) and Coronary Angiography (CA). Filling defects were presents in both the main pulmonary artery and its branches and at origin of a bifurcation of marginal branch from coronary right artery. Intravenous tissue plasminogen activator (tPA)-alteplase was administered at a reduced dose (50 mg for 2 hours) due to high risk of bleeding. Clinical recovery was excellent. No Patent Foramen Ovale (PFO) was identified, but laboratory results revealed a combined thrombophilia with an abnormal protein C concentration and a heterozygous factor V Leiden mutation. Patient was discharged with Direct Oral Anticoagulants (DOAC) and is free of adverse events at 18 months follow-up. Conclusion: Early recognition of dual pathologies prompted in this case administration of thrombolytic therapy. Our observation showed that low dose tPA, may be a safe and effective treatment option for massive PE and STEMI, particularly in patients at a high risk of bleeding. Long term treatment with DOACs after Venous Thromboembolism (VTE) is a valuable therapeutic option in the presence of combined thrombophilia.

Role of prothrombin 19911 A>G polymorphism, blood group and male gender in patients with venous thromboembolism: Results of a German cohort study

The role of the A>G polymorphism at position 19911 in the prothrombin gene (factor [F] 2 at rs3136516) as a risk factor for venous thromboembolism [VTE] is still unclear. To evaluate the presence of the F2 polymorphism in VTE patients compared to healthy blood donors and to adjust the results for common inherited thrombophilias [IT], age at onset and blood group [BG], and to calculate the risk of VTE recurrence. We investigated 1012 Caucasian patients with a diagnosis of VTE for the presence of the F2 rs3136516 polymorphism and compared these with 902 healthy blood donors. Odds ratios [OR] together with their 95% confidence intervals were calculated adjusted for F5 at rs6025, F2 at rs1799963, blood group, age and gender. In addition, we evaluated the risk of recurrent VTE during patient follow-up calculating hazard ratios [HR] together with their 95% CI. Compared with the AA wildtype, the F2 GG and AG genotypes (rs3136516) were associated with VTE (OR 1.48 and 1.45). The OR in F5 carriers compared to controls was 5.68 and 2.38 in patients with F2 (rs1799963). BG “non-O” was significantly more often diagnosed in patients compared to BG “O” (OR 2.74). VTE recurrence more often occurred in males (HR 2.3) and in carriers with combined thrombophilia (HR 2.11). Noteworthy, the rs3136516 polymorphism alone was not associated significantly with recurrence. In Caucasian patients with VTE the F2 GG/GA genotypes (rs3136516) were moderate risk factors for VTE. Recurrence was associated with male gender and combined thrombophilia.

Risk Factors, Clinical Manifestations, Treatment Duration and Outcomes in Carriers of Severe Inherited Thrombophilias

Background Severe Inherited thrombophilia comprisses deficiencies of natural anticoagulants (antithrombin (AT), protein C (PC), and protein S (PS), and homozygosity for factor V Leiden (FVL) or prothrombin gene mutation (PGM) or double heterozygosity or other combined thrombophilia. Carriers of AT, PC and PS have a high risk of thrombosis starting at a young age, usually several members of the same family are affected and thrombosis may occur at unusual locations. Conversely homozygotes for either FVL, PGM or double heterozygotes may not have a family history of thrombosis and the first thrombotic event may present later on life. It is also unclear what is the duration and type of anticoagulation and long-term outcomes of these carriers. The purpose of this study was to compare risk factors, clinical manifestations, type and duration of anticoagulation and clinical outcomes between carriers of anticoagulant deficiencies and those with gain of function mutations (homozygosity or double heterozygosity for FVL and PGM). Methods Retrospective evaluation of electronic medical records of patients with severe inherited thrombophilia referred to the Center for Blood Disorders at Weill Cornell Medicine-New York Presbyterian Hospital between January 2009 and June 2019. Severe deficiencies of AT, PC and PS were defined and (AT ≤ 60%, PC ≤ 50% and PS ≤ 40% (2). Patients without confirmatory laboratory results for the anticoagulant deficiencies were excluded from the study. We collected demographic data, risk factors for thrombosis, family history, type of thrombotic events, pregnancy complications in females, type and duration of anticoagulant and outcomes. Statistical analysis was performed using descriptive statistics and chi-square test was applied for comparison of variables between anticoagulant deficiency carriers and gain of function mutation carriers. Results Of a total of 107 patients identified,17 were excluded due to absence of confirmatory results. A total of 90 patients were analyzed; 70 (78%) females; mean age and range 44 (22- 82). There were 34 (38%)patients with anticoagulant deficiencies (10 AT, 6 PC and 18 PS) and 56 (62%) homozygotes for FVL, PGM or double heterozygote. Of those, 23 (39%) homozygote for FVL with one also heterozygote for the PGM, 2 (3.6%) homozygote PGM and 31(55.4%) double heterozygote. Overall risk factors for thrombosis were similar in both groups. There were no identified thrombosis risk factors in 12 and 19 patients in the anticoagulant deficiency and gain of function mutation respectively. The most common type of clinical presentation in both groups was deep vein thrombosis and pulmonary embolism. A positive family history of either thrombosis of thrombophilia in a first degree family member was equal in both groups. Likewise age less than 40 at first thrombotic event was similar. The most frequent anticoagulant prescribed in the patients with anticoagulant deficiency was a direct oral anticoagulant in 26.%% and vitamin K antagonists 22.3% in the ones with gain of function mutation. More patients with anticoagulant deficiencies remain on anticoagulation for more than 1 year than the ones with a gain of function mutation (88.5% vs 64%) and had more recurrent thrombotic events (20.6% vs.5.4%). Within the 70 female patients, 5 (7%) had first trimester pregnancy loss and 14 (20%) had multiple pregnancy losses. Conclusions: Our results suggest that patients with severe inherited antithrombin, protein C and S deficiencies have worse outcomes despite longer duration of anticoagulation than patients homozygote or double heterozygote for gain of function mutations. Disclosures De Sancho: Apellis Pharmaceuticals: Other: Advisory Board; BPL: Other: Advisory Board.

Сочетанная тромбофилия по данным гематологического консультирования

Введение. Диагностическая значимость гомозиготной мутации генов факторов свертывания крови FV Leiden и FII, а также их гетерозиготного полиморфизма в сочетании с маркерами первичного антифосфолипидного синдрома как предикторов тромбоза остается неоднозначной. Цель исследования: представить клинические случаи сочетанных тромбофилий, выявленных в процессе амбулаторного гематологического консультирования. Материалы и методы. В базе данных приема гематолога с января 2012 г. по апрель 2017 г. выявлен 891 пациент (837 женщин и 54 мужчины), которым было проведено обследование и консультирование на предмет тромбофилии и/или наличия активных факторов тромбогенного риска. Результаты. Сочетанная тромбофилия выявлена у 7 (0,8%) из 891 обследованного или у 7 (2,8%) из 246 пациентов с факторами тромбогенного риска. В 4 случаях у 2 мужчин (44 и 28 лет) и у 2 женщин (29 и 33 лет) диагноз установлен в связи с тяжелой и/или рецидивирующей венозной и артериальной тромбоэмболией и у 3 женщин (27, 36 и 39 лет) в связи с синдромом потери плода. Заключение. Анализ наблюдений подтверждает целесообразность поиска сочетанной тромбофилии в случае рецидивирующего тромбоза для выбора оптимальной антикоагулянтной терапии. Introduction. The diagnostic signifi cance of homozygous mutation of FV Leiden and FII clotting factor genes, as well as their heterozygous polymorphism in combination with the markers of the primary antiphospholipid syndrome as predictors of thrombosis remains ambiguous. Aim: to present clinical cases of combined thrombophilia revealed during outpatient hematology counseling. Materials and methods. In hematologist database from January 2012 to April 2017 we found 891 patients (837 women and 54 men) who were examined and consulted for thrombophilia and/or presence of active factors of thrombogenic risk. Results. Combined thrombophilia was identifi ed in 7 (0.8%) of 891 patients or in 7 (2.8%) of 246 patients with thrombogenic risk factors. In 4 cases — 2 men (44 and 28 years) and 2 women (29 and 33 years old) had a diagnosis due to severe and/or recurrent venous and arterial thromboembolism and 3 women (27, 36 and 39 years) had a diagnosis due to fetal loss syndrome. Conclusion. The observations confi rm the practicability of researching for combined thrombophilia in case of recurrent thrombosis for the choice of optimal anticoagulant therapy.

Detection of high-risk thrombophilia with an automated, global test: the Coagulation Inhibitor Potential assay.

: The diagnosis of thrombophilia is a cost-consuming and time-consuming process, as each defect should be separately investigated. The Coagulation Inhibitor Potential (CIP) assay is a promising new global test, sensitive for most of the hereditary thrombophilias, developed for manual methodology. We adapt the original method to an optical coagulation analyser. By this automation, the test will be easier, faster and more precise, and it also allows carrying out 18 measurements simultaneously. The CIP assay was performed in 126 healthy subjects and 193 patients with different types of hereditary thrombophilia conditions. Detected with conventional laboratory tests high-risk thrombophilia was present in 70 patients: deficiencies of antithrombin (AT) (n = 12), protein C (PC) (n = 14), protein S (PS) (n = 6), homozygous factor V Leiden (FVL) mutation (n = 9) and combined types (n = 29). Low-risk thrombophilia was present in 123 patients: heterozygous FVL (n = 115) and FII G2010A mutation (n = 8). Significantly lower median CIP values were found for AT-,PC-, PS deficiencies, homozygous and heterozygous FVL mutations and combined thrombophilias (P < 0.01) as compared with healthy controls. There was no significant difference between the heterozygous FIIG20210A (P = 0.669) thrombophilia group and the healthy controls. The best performance of the test was achieved at the cut-off value of 90.0 U (area: 0.981) with 96% sensitivity and 92% specificity in the high-risk thrombophilia group estimated by receiver operating characteristic analysis. The new method seems to be appropriate and reliable for the detection of AT-, PC- and PS deficiencies, homozygous FVL mutation and also for combined deficiencies. The automated CIP test is insensitive to FII G2010A mutation.

Беременность после экстракорпорального оплодотворения с использованием аллогенных ооцитов у пациентки с синдромом потери плода и сочетанной формой тромбофилии

Беременность после экстракорпорального оплодотворения с использованием аллогенных ооцитов у пациентки с синдромом потери плода и сочетанной формой тромбофилии

Association Between Hypercoagulable Conditions and Calciphylaxis in Patients With Renal Disease

Calciphylaxis is a rare skin disease with high morbidity and mortality that frequently affects patients with renal disease. Hypercoagulable conditions are frequently observed in both patients with calciphylaxis and those with chronic kidney disease (CKD), complicating our understanding of which hypercoagulable conditions are specific to calciphylaxis. To identify hypercoagulable conditions that are risk factors for developing calciphylaxis while controlling for CKD. This was a case-control study, comparing the hypercoagulability status of patients with calciphylaxis and with renal disease with that of a matched control population at 2 large urban academic hospitals in Boston, Massachusetts. Retrospective medical record review of laboratory values was performed to identify patients with hypercoagulable conditions. Case and control patients were further stratified based on both severity of CKD and warfarin. Patients with a dermatologic diagnosis of calciphylaxis between 2006 and 2014 and concomitant CKD were included as cases (n = 38). Three controls (n = 114) per case patient with CKD were included, and were matched by age, sex, and race. The rate of various hypercoagulable states (ie, antithrombin III [ATIII] deficiency, protein C and S deficiency, factor V Leiden mutation, prothrombin gene mutation [G20210A], elevated factor VIII level, lupus anticoagulant, anti-IgG or IgM cardiolipin antibodies, heparin-induced thrombocytopenia antibodies, and elevation of homocysteine) in patients with calciphylaxis compared with their matched controls. Of the calciphylaxis cohort, 28 (58%) were female and 18 (55%) were non-Hispanic white. Among all patients, lupus anticoagulant (13 [48%] positive in cases vs 1 [5%] in controls; P = .001), protein C deficiency (9 [50%] vs 1 [8%]; P = .02), and combined thrombophilias (18 [62%] vs 10 [31%]; P = .02) were found to be significantly associated with calciphylaxis. In a subanalysis of patients with stage 5 CKD, only lupus anticoagulant (12 [53%] vs 9 [0%]; P = .01) and combined thrombophilia (15 [63%] vs 1 [8%]; P = .004) remained significantly associated with calciphylaxis. In a separate subanalysis of warfarin-unexposed patients, only lupus anticoagulant (7 [50%] vs 1 [6%]; P = .01) and protein C deficiency (5 [46%] vs 10 [0%]; P = .04) remained significantly associated with calciphylaxis. Presence of lupus anticoagulant and combined thrombophilias are risk factors for the development of calciphylaxis in patients with late-stage renal disease. Clinicians should be aware of these associations in patients with impaired kidney function and may consider increased screening and appropriate anticoagulation treatment to reduce the risk of calciphylaxis development.

Calciphylaxis: A Disease of Pannicular Thrombosis

ObjectiveTo identify coagulation risk factors in patients with calciphylaxis and the relationship between anticoagulation use and overall survival. Patients and MethodsStudy subjects were 101 patients with calciphylaxis seen at Mayo Clinic from 1999 to September 2014. Data including thrombophilia profiles were extracted from the medical records of each patient. Survival status was determined using patient registration data and the Social Security Death Index. Survival was estimated using the Kaplan-Meier method, and associations were evaluated using Cox proportional hazards models. ResultsSixty-four of the 101 patients underwent thrombophilia testing. Of these, a complete test panel was performed in 55 and a partial panel in 9. Severe thrombophilias observed in 60% (33 of 55) of the patients included antiphospholipid antibody syndrome protein C, protein S, or antithrombin deficiencies or combined thrombophilias. Of the 55 patients, severe thrombophilia (85%, 23 of 27) was noted in patients who were not on warfarin at the time of testing (27). Nonsevere thrombophilias included heterozygous factor V Leiden (n=2) and plasminogen deficiency (n=1). For the comparison of survival, patients were divided into 3 treatment categories: Warfarin (n=63), other anticoagulants (n=20), and no anticoagulants (n=18). There was no statistically significant survival difference between treatment groups. ConclusionLaboratory testing reveals a strikingly high prevalence of severe thrombophilias in patients with calciphylaxis, underscoring the importance of congenital and acquired thrombotic propensity potentially contributing to the pathogenesis of this disease. These findings may have therapeutic implications; however, to date, survival differences did not vary by therapeutic choice.

Impact of high-risk thrombophilia status on recurrence among children with a first non-central-venous-catheter-associated VTE: an observational multicentre cohort study.

Deficiency of antithrombin (AT), protein C (PC) or protein S (PS) constitutes a major risk factor for venous thromboembolism (VTE). Individuals at high risk for recurrence who benefit from screening need to be identified. The primary study objective was to determine the individual recurrence risk among children with a first non-central-venous-catheter-associated VTE with respect to their thrombophilia status and to evaluate if the clinical presentation at first VTE onset differs between children with AT, PC or PS deficiency versus no thrombophilia. We calculated the absolute risk of VTE recurrence and event-free-survival adjusted for thrombophilia, age, sex and positive family VTE history in 161 consecutively enrolled paediatric VTE patients. The presence of a deficiency relative to no thrombophilia was evaluated as a potential predictor of recurrence. Predictors for recurrence were AT deficiency (hazard ratio/95% CI: 6·5/2·46-17·2) and female gender (2·6/1·1-6·35). The annual recurrence rates (95% CIs) were 5·4% (2·6-10) in AT-deficient children, 1·3% (0·3-3·8) in patients with PC deficiency, 0·7% (0·08-2·4) in the PS-deficient cohort and 0·9% (0·4-1·8) in patients with no thrombophilia. Positive family VTE history or combined thrombophilias did not predict recurrence. Given the overall annual incidence rate of recurrence of 1·5% we suggest screening for AT deficiency in children with VTE.

Reduced protein C Global assay level in infertile women prior to IVF-ET treatment

In the last few years more robust evidence is emerging to point out at an increased rate of prematurity and low birth weight in singleton pregnancies following ART. Whether this increased rate is related to ART practice or to infertility per se, is still an open question. Our aim in this study was to explore this question by evaluating Protein C (ProC) Global assay in infertile women before ART treatment. A cohort of 95 unselected and consecutive infertile women, eligible for ART, was prospectively recruited for the study. The control group included 77 matched healthy fertile women with a history of spontaneous conceptions. Pro C Global assay was evaluated in both groups. A full thrombophilic work-up was performed in the study group. ProC Global assay level was found to be significantly lower in the study as compared to the control group, corresponding to 0.78 ± 0.16 and 0.88 ± 0.16, respectively (P < 0.01). As well, abnormal ProC Global assay level of ≤ 0.8 was significantly higher in the study as compared to control group corresponding to 53% and 29%, respectively. ProC Global assay level was significantly lower in women within the study group found to have APCR, factor V Leiden and high factor VIII level, any thrombophilia or combined thrombophilia when compared to women without these thrombophilic risk factors. Reduced ProC Global assay level is encountered in infertile women prior to ART treatment. This finding may suggest a unique anticoagulation Protein C pathway in infertile as compared to fertile women. Further studies are encouraged to explore this finding.

Classification of stillbirths and risk factors by cause of death – a case‐control study

To investigate risk factors for stillbirths by cause, using the Causes of Death and Associated Conditions (CODAC) classification system for perinatal deaths. Case-control study. Two university hospitals in Oslo, Norway, January 1990 through December 2003. Women with stillbirth after 22 gestational weeks (n=377) and controls with live births (n=1215), and a subsample of 105 cases and 262 controls. Socio-demographic, clinical and thrombophilic risk factors for stillbirths were assessed by cause of death in univariate and multivariable logistic regression analyses. Stillbirths were classified according to CODAC based on information from medical records and validated placenta histology. Causes of stillbirths in percentages, prevalence, odds ratios and adjusted odds ratios for potential risk factors. Approximately half of the women (n=190) had placental and 19.4% (n=73) unknown cause of stillbirth. Placental-associated conditions were registered in 18% (n=68) of cases with a non-placental or an unknown cause. Smoking and small-for-gestational age were more prevalent in all causal groups, compared with controls, whereas twin pregnancy, hypertension and diabetes were more prevalent only among women with placental and unknown causes of stillbirth. The F2rs179963 polymorphism and combined thrombophilia were significant risk factors for stillbirth with placental causes and antiphospholipid antibodies for stillbirth with non-placental causes. Two-thirds of all stillbirths (68%) were caused by or associated with placental pathology. Risk factors differed somewhat according to cause, apart from smoking and small-for-gestational age, which were significant risk factors across the causal groups.

The association between poor ovarian response and thrombophilia in assisted reproduction

To investigate the association between thrombophilic risk factors and poor ovarian response in an assisted reproductive technologies (ART) setting. This is a preliminary prospective cohort study in a university affiliated reproductive medicine unit. Eighty-nine infertile women undergoing IVF-ET treatment were recruited. Following IVF-ET treatment, the 28 women that had ≤ 3 oocytes on retrieval were the study group, and the 61 women that had ≥ 4 oocytes on retrieval were the control group. All women underwent ovarian reserve testing and thrombophilia work-up prior to treatment. Patients' characteristics, except for chronological age, were similar between the two groups. Women in the study group had clear manifestations of low ovarian reserve, evident by ovarian reserve testing, controlled ovarian hyper-stimulation and IVF-ET treatment results, as compared to the control group. The incidence of all thrombophilias tested was similar between the study and control group. Moreover, the incidence of any single or combined thrombophilia was also similar between the two groups. Logistic regression model analysis and Pearson correlation tests did not show significant correlation between number of oocytes retrieved and thrombophilia. Furthermore, basal ovarian reserve tests did not differ between women with and without thrombophilia. When only the 48 women ≤ 35 years of were analyzed, the five women in the study group had significantly higher incidence of a single as well as combined thrombophilia as compared to the 43 controls. Thrombophilic risk factors have no correlation with poor ovarian response in the general infertile population undergoing ART. Whether premature low ovarian reserve is linked to thrombophilia remains to be established.

Spontaneous Thrombosis of Basilar Artery Aneurysm After Subarachnoidal Hemorrhage in a Patient With Thrombophilia and Recurrent Deep Venous Thrombosis

We report a patient with combined thrombophilia--protein C deficiency and mild hyperhomocysteinemia with total spontaneous thrombosis of a basilar tip aneurysm after subarachnoid hemorrhage, without neurological deficit. At admission, the patient had headache, drowsiness, and nausea, with no neurological deficit. Computed tomography (CT) did not show the presence of subarachnoid blood, and magnetic resonance examination revealed discrete remains of a subarachnoid hemorrhage in projections of temporal, frontal and occipital lobes, with no vascular abnormalities. Initial angiography showed a small basilar tip aneurysm and the patient was scheduled for endovascular treatment. A second angiography, performed before the planned endovascular treatment, did not show the aneurysm and complete thrombosis was suspected. A follow-up angiogram, 6 months after this event, showed preserved posterior cerebral circulation with no aneurysm present. The patient was discharged in good condition, without neurological deterioration. We did not find any previous reports of similar conditions.

Combined thrombophilic factors increase the risk of recurrent thrombotic events in Behcet’s disease

This retrospective study aims to seek a relationship between the number of thrombotic events and presence of thrombophilic factors in Behcet's disease (BD). Any patient with a vascular problem evaluated for at least one thrombophilic factor was deemed eligible for the present study. Upon an evaluation of their medical records, 96 (23.9%) of the 402 patients diagnosed with BD were determined to have a history of thrombosis. Of these 96 patients, 72 (75%) had only one thrombotic attack, while the remaining 24 (25%) had two or more thrombotic attacks. Thrombophilic parameters were evaluated in only 36 of the 72 patients (50%) who had one thrombotic event (Group I) and in 18 of the 24 patients (75%) who had more than one thrombotic event (Group II). The patients with recurrent thrombotic events had a significantly higher incidence of combined thrombophilias than those patients with only one thrombotic event (8/18, 44%; 4/36, 11%; p < 0.01). The number of the patients free from thrombophilic risk factors was significantly higher in Group I than in Group II (21/36, 58%; 4/18, 22%; p < 0.02). Group II had an increased frequency of combined thrombophilic risk factors (OR 6.4; 95% CI 1.5-25.8) when compared to Group I. No significant differences were found between Groups I and II with respect to clinical features of BD. In conclusion, combined thrombophilias in patients with BD may have a role in the development of recurrent thrombotic events.

Inherited thrombophilia in infertile women: implication in unexplained infertility

Many studies evaluating a possible relationship between inherited thrombophilia and the etiology of unexplained infertility have been performed recently. No significant difference in the prevalence of three genetic mutations associated with the increased risk of thrombophilia (Factor V Leiden G1691A, prothrombin G20210A, and methylenetetrahydrofolate reductase [MTHFR] C677 T) was found in 100 infertile women with unexplained infertility when compared with 200 control fertile women without an infertility history.