Patients with IVF complicated by moderate-to-critical OHSS experience increased thrombosis, GDM and neonatal NICU admission but slightly shorter gestation compared with matched IVF counterparts: A retrospective Chinese cohort study.

BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) is a common disease during controlled ovarian hyperstimulation treatment. However, the obstetric and neonatal outcomes of this group of patients are unknown. The aim of this study was to explore the effects of late moderate-to-critical OHSS on obstetric and neonatal outcomes. METHODS: This prospective observational study included 17,537 patients who underwent IVF/ICSI-fresh embryo transfer (ET) between June 2012 and July 2016 and met the inclusion criteria, including 7,064 eligible patients diagnosed with clinical pregnancy. Ultimately, 6,356 patients were allocated to the control group, and 385 patients who were hospitalized and treated at the center for late moderate-to-critical OHSS were allocated to the OHSS group. Then, propensity score matching analysis was performed, matching nine maternal baseline covariates and the number of multiple gestations; 385 patients with late moderate-to-critical OHSS were compared with a matched control group of 1,540 patients. The primary outcomes were the live birth rate, preterm delivery rate, miscarriage rate, gestational age at birth (weeks), obstetric complications and neonatal complications. RESULTS: The duration of gestation in the matched control group was significantly higher than that in the OHSS group. The live birth delivery rate did not significantly differ between the OHSS and matched control groups. The incidence rates of the obstetric complications venous thrombosis (VT) and gestational diabetes mellitus (GDM), neonatal complications and the number of neonates admitted to the NICU were significantly higher in the OHSS group than in the matched control group. CONCLUSIONS: Pregnant women undergoing IVF with fresh ET whose course is complicated by late moderate-to-critical OHSS appear to experience shortened gestation and increased obstetrical and neonatal complications compared with matched controls whose course is not complicated by OHSS. However, the live birth rate, average neonatal weight, and incidence rates of premature delivery, miscarriage, early abortion, hypertensive disorder of pregnancy (HDP), placenta previa (PP), intrahepatic cholestasis of pregnancy (ICP), and low neonatal birth weight (LBW) did not differ significantly between the two groups.

Perspective: Vitamin D deficiency and COVID-19 severity - plausibly linked by latitude, ethnicity, impacts on cytokines, ACE2 and thrombosis.

BACKGROUND: SARS-CoV-2 coronavirus infection ranges from asymptomatic through to fatal COVID-19 characterized by a 'cytokine storm' and lung failure. Vitamin D deficiency has been postulated as a determinant of severity. OBJECTIVES: To review the evidence relevant to vitamin D and COVID-19. METHODS: Narrative review. RESULTS: Regression modelling shows that more northerly countries in the Northern Hemisphere are currently (May 2020) showing relatively high COVID-19 mortality, with an estimated 4.4% increase in mortality for each 1 degree latitude north of 28 degrees North (P = 0.031) after adjustment for age of population. This supports a role for ultraviolet B acting via vitamin D synthesis. Factors associated with worse COVID-19 prognosis include old age, ethnicity, male sex, obesity, diabetes and hypertension and these also associate with deficiency of vitamin D or its response. Vitamin D deficiency is also linked to severity of childhood respiratory illness. Experimentally, vitamin D increases the ratio of angiotensin-converting enzyme 2 (ACE2) to ACE, thus increasing angiotensin II hydrolysis and reducing subsequent inflammatory cytokine response to pathogens and lung injury. CONCLUSIONS: Substantial evidence supports a link between vitamin D deficiency and COVID-19 severity but it is all indirect. Community-based placebo-controlled trials of vitamin D supplementation may be difficult. Further evidence could come from study of COVID-19 outcomes in large cohorts with information on prescribing data for vitamin D supplementation or assay of serum unbound 25(OH) vitamin D levels. Meanwhile, vitamin D supplementation should be strongly advised for people likely to be deficient.

Long-term antithrombotic management patterns in Asian patients with acute coronary syndrome: 2-year observations from the EPICOR Asia study.

BACKGROUND: Despite guideline recommendations, dual antiplatelet therapy (DAPT) is frequently used for longer than 1 year after an acute coronary syndrome (ACS) event. In Asia, information on antithrombotic management patterns (AMPs), including DAPT post discharge, is sparse. This analysis evaluated real-world AMPs up to 2 years post discharge for ACS. HYPOTHESIS: There is wide variability in AMP use for ACS management in Asia. METHODS: EPICOR Asia (NCT01361386) is a prospective observational study of patients discharged after hospitalization for an ACS in eight countries/regions in Asia, followed up for 2 years. Here, we describe AMPs used and present an exploratory analysis of characteristics and outcomes in patients who received DAPT for ≤12 months post discharge compared with >12 months. RESULTS: Data were available for 12 922 patients; of 11 639 patients discharged on DAPT, 2364 (20.3%) received DAPT for ≤12 months and 9275 (79.7%) for >12 months, with approximately 60% still on DAPT at 2 years. Patients who received DAPT for >12 months were more likely to be younger, obese, lower Killip class, resident in India (vs China), and to have received invasive reperfusion. Clinical event rates during year 2 of follow-up were lower in patients with DAPT >12 vs ≤12 months, but no causal association can be implied in this non-randomized study. CONCLUSIONS: Most ACS patients remained on DAPT up to 1 year, in accordance with current guidelines, and over half remained on DAPT at 2 years post discharge. Patients not on DAPT at 12 months are a higher risk group requiring careful monitoring.

Risk of Major Adverse Cardiovascular Events and Major Hemorrhage Among White and Black Patients Undergoing Percutaneous Coronary Intervention.

Background Data on racial disparities in major adverse cardiovascular events (MACE) and major hemorrhage (HEM) after percutaneous coronary intervention are limited. Factors contributing to these disparities are unknown. Methods and Results PRiME-GGAT (Pharmacogenomic Resource to Improve Medication Effectiveness-Genotype-Guided Antiplatelet Therapy) is a prospective cohort. Patients aged ≥18 years undergoing percutaneous coronary intervention were enrolled and followed for up to 1 year. Racial disparities in risk of MACE and HEM were assessed using an incident rate ratio. Sequential cumulative adjustment analyses were performed to identify factors contributing to these disparities. Data from 919 patients were included in the analysis. Compared with white patients, black patients (n=203; 22.1% of the cohort) were younger and were more likely to be female, to be a smoker, and to have higher body mass index, lower socioeconomic status, higher prevalence of diabetes mellitus and moderate to severe chronic kidney disease, and presentation with acute coronary syndrome and to undergo urgent percutaneous coronary intervention. The incident rates of MACE (34.1% versus 18.2% per 100 person-years, P<0.001) and HEM (17.7% versus 10.3% per 100 person-years, P=0.02) were higher in black patients. The incident rate ratio was 1.9 (95% CI, 1.3-2.6; P<0.001) for MACE and 1.7 (95% CI, 1.1-2. 7; P=0.02) for HEM. After adjustment for nonclinical and clinical factors, black race was not significantly associated with outcomes. Rather, differences in socioeconomic status, comorbidities, and coronary heart disease severity were attributed to racial disparities in outcomes. Conclusions Despite receiving similar treatment, racial disparities in MACE and HEM still exist. Opportunities exist to narrow these disparities by mitigating the identified contributors.

Usefulness of Coronary Artery Calcium to Identify Adults of Sufficiently High Risk for Atherothrombotic Cardiovascular Events to Consider Low-Dose Rivaroxaban Thromboprophylaxis (from MESA).

Low-dose rivaroxaban was effective in secondary prevention of atherosclerotic cardiovascular disease (ASCVD) in the COMPASS trial. There is no established role, however, for oral anticoagulants in primary prevention. We evaluated whether coronary artery calcium (CAC) scoring identifies a high-risk primary prevention adult population who may benefit from low-dose rivaroxaban to prevent ASCVD events. We modeled expected outcomes of low-dose rivaroxaban in 5,196 Multiethnic Study of Atherosclerosis (MESA) cohort participants not already on antiplatelet or anticoagulant therapy. We applied relative risk ratios from COMPASS to absolute MESA event rates in order to estimate number needed to treat (NNT) to avoid a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke, as well as number needed to harm (NNH) to cause 1 hospitalized bleed; with both NNT and NNH stratified by calculated ASCVD risk and by baseline CAC. MESA participants with CAC ≥300 had crude ASCVD event rate of 20 per 1000 patient-years, which is comparable to that observed in the COMPASS control-arm. CAC was independently associated with the composite ASCVD outcome (p <0.001 for trend). However, CAC was not independently associated with adjusted hazard ratio for hospitalized major bleeding. Predicted 5-year NNT (modeled from COMPASS) was 75 in persons with CAC 100-299 and 45 with CAC ≥300 despite NNH values of 252 and 98, respectively. In conclusion, CAC helps to distinguish estimated ASCVD benefit from estimated bleeding harm, thereby identifying very high-risk primary prevention adults without established cardiovascular disease who may derive net-benefit from low-dose rivaroxaban.

Thrombotic risk factors in patients with antiphospholipid syndrome: a single center experience.

Patients with primary or secondary antiphospholipid syndrome (APS) have an increased risk of recurrent venous, arterial thrombosis and pregnancy complications. Therefore, determining thrombotic risk is important when individualizing antithrombotic therapy in patients with APS. To identify thrombotic risk factors in a cohort of APS patients. We conducted a retrospective review of APS patients who received care at a Hematology clinic of a university medical center from 2004 to 2017. Demographics, clinical features, antithrombotic therapy and thrombotic outcomes were collected. Time to event analysis identified clinical risk factors for thrombosis. The time varying effects of antithrombotic treatments on thrombosis outcome were analyzed. We identified 84 subjects with APS with a median age at diagnosis of 40.7 years [interquartile range [IQR] 33.5-57.6]. The majority were female (n = 63, 75%) and White (n = 45, 54%). Twenty-eight (33%) patients had concomitant autoimmune disease (AID) and of these, 15 (54%) had systemic lupus erythematosus. A thrombotic event occurred in 15 (18%) patients during a median follow-up of 48 months. A significantly higher rate of thrombotic events was observed in APS patients with AID compared to those without AID (hazard ratio (HR) 4.93, 95% CI 1.7-14.3, p = 0.04), and in black patients compared to whites (HR 5.94, 95% CI 1.1-32.1, p = 0.039). Patients on therapeutic anticoagulation regardless of type (warfarin, low molecular weight heparin or direct oral anticoagulants) were significantly less likely to have a recurrent thrombotic event compared to those on prophylactic anticoagulation (HR 0.11, 95% confidence interval [CI] 0.031-0.395, p = 0.001). However the numbers are too small to draw conclusions. Our study suggests that APS patients with concomitant AID and of Black race are at increased risk of recurrent thrombotic events.

Investigation of potential biomarkers for thrombosis related diseases in Turkish Cypriot population.

Genetic and environmental factors are involved in development of many diseases. The allelic frequencies may differ in different populations and in different ethnic groups. The aim of this study was to investigate the genotypes of MTHFR and factor VII polymorphisms and to identify biomarkers for thrombosis related diseases in Turkish Cypriot population. The lipid profiles and genotypes of MTHFR polymorphisms (rs1801133, rs1801131) and factor VII (rs6046) genes were investigated for the first time in the Turkish Cypriot population. The heterozygosity for MTHFR (rs1801133, rs1801131) and FVII (rs6046) polymorphisms is high in Turkish Cypriot population. The heterozygosity for MTHFR C677T was 38%, MTHFR A1298C was 40% and factor VII G353A was 37%, respectively. Allelic frequencies between males and females were similar. There were no correlations between the genotypes of polymorphisms and the lipid profiles. This study is the first genetic epidemiology study that investigated the allelic frequencies of MTHFR and FVII polymorphisms associated with metabolic syndromes. This study proves to be a crucial analysis in order to use these polymorphisms as a predictor of disease development in the Turkish Cypriot community.

Influencia de la actividad inflamatoria del trombo mural en los pacientes con aneurisma de aorta abdominal con reparación endoluminal / Influence of inflammatory activity of the mural thrombus in patients with abdominal aortic aneurysms with endoluminal repair

Introducción: Los mecanismos fisiopatológicos que se encuentran implicados en el crecimiento de los aneurismas de aorta abdominal (AAA) son multifactoriales, como cambios inflamatorios, hemostáticos, disfunciones endoteliales y los clásicos factores de riesgo ateroscleróticos. La persistencia de un trombo mural biológicamente activo y del saco aneurismático, al igual que el posible desarrollo de endofugas tipo 2, puede ser el origen de la activación de mediadores inflamatorios, cuyas consecuencias se desconocen. Nuestro objetivo es definir un modelo predictivo de complicaciones después de la reparación endoluminal del aneurisma de aorta abdominal a corto y medio plazo a partir de variables clínicas, serológicas y anatómicas. Material y métodos: Se incluyeron 50 pacientes intervenidos de AAA ateroscleróticos asintomáticos entre enero 2016 y noviembre 2016, en el Servicio de Angiología y Cirugía Vascular del Hospital Clínico Universitario de Valladolid. Se recogieron datos clínicos (edad, sexo, factores de riesgo cardiovascular, comorbilidad y medicación), diámetro basal de los AAA, crecimiento aórtico a los 6 meses y concentraciones basales circulantes de proteína C reactiva, interleucina 2 (IL2), IL6 y homocisteína, en el preoperatorio, a los 7 días del postoperatorio y a los 6 meses. A los pacientes se les realizó una angioTAC en el postoperatorio inmediato y a los 6 meses. Resultados: Se observó un crecimiento medio del diámetro de los AAA con fuga de 6,18 mm, mientras que los AAA correctamente presurizados disminuyeron su diámetro medio en 4,69 mm, siendo esta diferencia estadísticamente significativa (p = 0,001). En relación con los cambios en el trombo del saco aneurismático, en los pacientes con AAA con fuga el trombo se incrementó en 7,74 mm de media, mientras que en los pacientes con AAA correctamente sellados y sin fugas se incrementó solo en 3,08 mm, siendo esta diferencia estadísticamente significativa (p = 0,027). Se estableció una correlación estadísticamente significativa entre la modificación del tamaño del aneurisma postEVAR y los niveles plasmáticos de PCR y homocisteína a los 7 días, y de la modificación del tamaño del trombo intraaórtico y los niveles plasmáticos de IL2 a los 7 días y a los 6 meses. Conclusiones: Los patrones de biomarcadores estudiados a corto y a medio plazo después de EVAR deben ser considerados como indicadores un proceso activo de inflamación que ejerce su influencia en la remodelación aórtica

Introduction: The pathophysiological mechanisms that are involved in the growth of abdominal aortic aneurysms (AAA) are multifactorial, and include inflammatory changes, as well as haemostatic and endothelial dysfunctions and, the classic atherosclerotic risk factors. The persistence of a biologically active mural thrombus and the aneurysmal sac, as well as the possible development of type 2 endoleaks, can be the origin of the activation of inflammatory mediators, the consequences of which are unknown. The aim of this study is to define a predictive model of complications after endoluminal repair of abdominal aortic aneurysm in the short and medium-term using clinical, serological, and anatomical variables. Material and methods: A total of 50 hospital patients with asymptomatic atherosclerotic AAA were included in the study between January 2016 and November 2016, in the Angiology and Vascular Surgery Department of the Hospital Clínico Universitario de Valladolid. Clinical data were collected (age, gender, cardiovascular risk factors, comorbidity, medication), baseline AAA diameter, aortic growth at 6 months, as well as baseline C-reactive protein levels, interleukin-2 (IL2), IL6 and homocysteine, preoperatively, 7 days postoperatively, and 6 months later. The patients had an angioCT scan in the immediate postoperative period, and at 6 months. Results: A mean growth in diameter of 6.18 mm was observed in the AAA with a leak, while the correctly pressurised AAA showed a decrease of 4.69mm in their mean diameter, with this difference being statistically significant (P = .001). As regards the changes in the thrombus of the aneurysmal sac, in patients with AAA with a leak the thrombus increased by a mean of 7.74 mm, while patients with AAA correctly sealed and without leakage only increased by 3.08 mm, with this difference being statistically significant (P = .027). A statistically significant relationship was observed between the change in the size of the post-EVAR aneurysm and the plasma levels of CRP and homocysteine at 7 days, and of the change in the size of the intra-aortic thrombus and the plasma levels of IL2 at 7 days and at 6 months. Conclusions: The biomarker patterns studied in the short and medium term after EVAR should be considered as indicators of an active inflammation process that exerts its influence on aortic remodeling

Increased resistance to tissue plasminogen activator-induced fibrinolysis in healthy subjects from Thailand.

: There is significant variability in blood coagulation among world populations. In particular, there may exist important differences in regulation of the fibrinolytic system in Asian populations that contribute to diseases of thrombosis and hemostasis. To investigate this issue, we compared fibrinogen concentration, plasma clot formation, and fibrinolytic resistance of healthy Asian subjects from Hat Yai, Songkhla, Thailand (Thai) vs. healthy North American subjects from Seattle, Washington, USA (SEA). Citrated plasma samples were obtained from healthy adult volunteers. Fibrinogen concentration was measured in plasma by the method of Clauss to examine for baseline differences of fibrinogen concentration. Samples were then standardized to 2.8 mg/ml fibrinogen using physiological buffer for each sample prior to fibrinolytic testing using rotational thromboelastometry (ROTEM) to examine for differences of clot lysis not attributable to fibrinogen concentration alone. Clot lysis was examined with ROTEM extrinsic pathway activation in the presence of 0, 0.5, and 1.0 µg/ml of tissue plasminogen activator (tPA). Two-way repeated measures analysis of variance was used to determine the effects of tPA and study group on ROTEM parameters. N = 49 Thai samples were compared with N = 58 SEA samples. Mean (SD) fibrinogen concentration was significantly increased for the Thai group at 4.03 (0.79) mg/ml vs. the SEA group at 3.66 (0.70) mg/ml (t test P = 0.014). After standardization of all samples to equivalent fibrinogen concentration, there were no differences in clot formation between groups without tPA. There was a significant effect of increasing tPA concentration on all ROTEM parameters except for clotting time. There were significant individual differences for amplitude at 10 min and lysis onset time, where amplitude at 10 min was significantly increased and lysis onset time was significantly prolonged for Thai vs. SEA at tPA concentrations of 0.5 and 1.0 µg/ml. Variability in thrombosis and hemostasis in Asians vs. other populations is likely to involve differences of fibrinogen concentration and regulation of clot lysis.

Effect of ethnicity on clinical presentation and risk of antiphospholipid syndrome in Roma and Caucasian patients with systemic lupus erythematosus: a multicenter cross-sectional study.

AIM: To determine if there are ethnic differences in the prevalence of antiphospholipid syndrome (APS), clinical presentation and autoantibody profile between Roma and Caucasian patients with systemic lupus erythematosus (SLE). METHOD: A cross-sectional study was conducted including data from Roma and Caucasian SLE patients consecutively attending six hospitals in Spain. Socio-demographic characteristics, prevalence of APS, clinical and analytical features of SLE and APS were compared between ethnic groups. RESULTS: Data from 52 Roma and 98 Caucasian SLE patients were included. Roma SLE patients had a higher risk (odds ratio 2.56, 95% CI 1.02-6.39) and prevalence of APS (28.8% vs. 13.3%, P = 0.027). Furthermore, Roma SLE patients had a statistically significant higher prevalence of abortions (23.5% vs. 10.2%, P = 0.049). In relation to other APS diagnostic criteria, Roma SLE patients had a non-statistically significant higher prevalence of fetal deaths (14.3% vs. 5.1%, P = 0.106) and thrombotic events (21.1% vs. 12.2%, P = 0.160). In relation to SLE clinical features, Roma patients had a significantly higher prevalence of arthritis (75% vs. 57.1%, P = 0.034) and non-significant higher prevalence of serositis (44.2% vs. 29.6%, P = 0.104), discoid lesions (11.5% vs. 5.1%, P = 0.191), oral ulcers (46.1% vs. 34.7%, P = 0.218) and livedo reticularis (21.1% vs. 15.3%, P = 0.374). No statistically significant differences were found in the Systemic Lupus International Collaborating Clinics Damage Index or the autoimmune serological profile. CONCLUSION: Prevalence and risk of APS were significantly higher in Roma SLE patients. Furthermore, Roma patients had a significantly higher prevalence of abortions and a non-significant higher prevalence of fetal deaths and thrombotic events.

VKORC1-1639A allele influences warfarin maintenance dosage among Blacks receiving warfarin anticoagulation: a retrospective cohort study.

AIM: The study objectives were to investigate the association between selected CYP2C9 and VKORC1 single nucleotide polymorphisms with serious bleeding or thrombotic risk, and to estimate mean daily maintenance dose of warfarin and international normalized ratio measurements among Blacks receiving warfarin anticoagulation. METHODS: We conducted a retrospective cohort study among 230 Black adults receiving warfarin for a minimum of three consecutive months with a confirmed date of first dosage. RESULTS: A lower mean daily maintenance dosage of warfarin was required to maintain an international normalized ratio measurement within the therapeutic range among Blacks with the VKORC1-1639G>A variant alleles ([G/A vs G/G, p = 0.02], [A/A vs G/A, p = 0.008] and [A/A vs G/G, p = 0.001]). CONCLUSION: Data indicated that VKORC1-1639A variant allele influenced warfarin daily maintenance dosage among our small, likely admixed Black patient population.

Idarucizumab does not have procoagulant effects: Assessment of thrombosis biomarkers in healthy volunteers.

Idarucizumab, a humanised monoclonal antibody fragment, binds dabigatran with high affinity and immediately, completely and sustainably reverses dabigatran-induced changes on blood coagulation. The present analysis focuses on the evaluation of potential procoagulant properties of idarucizumab when administered in the absence of dabigatran. As part of two Phase I studies conducted in healthy Caucasian and Japanese male volunteers, the effect of idarucizumab (8 g as a 1-hour [h] infusion and 4 g as a 5-minute [min] infusion) and placebo on calibrated automated thrombography (CAT) was assessed using platelet-poor plasma samples. Measures were made before and 15 min after the end of infusion in Caucasian subjects, as well as pre-dose, 15 min, 4 h and 8 h in Japanese subjects. The levels of the thrombosis markers D-dimer and prothrombin fragment 1 + 2 (F1.2) were assessed over time in plasma samples up to 72 h after the end of infusion of idarucizumab and placebo. Idarucizumab had no apparent effect on endogenous thrombin formation as measured by CAT. D-dimer and F1.2 levels were highly variable in all dose groups but did not increase when compared with placebo or pre-dose levels. In conclusion, idarucizumab had no effect on endogenous thrombin generation. Additional markers of thrombosis, F1.2 and D-dimer, did not differ between placebo and idarucizumab, indicating a lack of procoagulant properties of idarucizumab.

A multi-institutional outcome analysis of patients undergoing left ventricular assist device implantation stratified by sex and race.

BACKGROUND: Earlier studies have demonstrated disparities in patients undergoing left ventricular assist device (LVAD) implantation when stratified according to sex and race. Because very few data exist from large investigations, we reviewed data from the registry of the Mechanical Circulatory Support Research Network. METHODS: Between May 2004 and September 2014, 734 patients underwent primary LVAD implantation at our institutions. Median age at implant was 57 (range 18 to 82) years and there were 577 males (80%). Race included Caucasian (C) in 586 patients (82%), African-American (AA) in 112 (16%), and other (O) in 21 (3%). Between sexes, significant pre-operative differences most commonly included median age at implant (males 60 years, females 57 years), ischemic etiology (53% vs 35%) and mean INTERMACS profile (2.9 vs 2.5). Between races, significant pre-operative differences most commonly included median age at implant (C = 61 vs AA = 51 vs O = 51), New York Heart Association functional class (85% vs 100% vs 92%) and ischemic etiology (55% vs 24% vs 40%). RESULTS: There were no significant differences in survival at 1, 3 or 5 years by sex or race. Similarly, there were no differences in time-related freedom from stroke, drive-line infection, gastrointestinal bleeding or pump thrombus by sex or race. After controlling for differences, neither sex nor race was associated with survival (p = 0.09 and p = 0.18, respectively), stroke (p = 0.28 and p = 0.21), drive-line infection (p = 0.9 and p = 0.92), gastrointestinal bleed (p = 0.48 and p = 0.45) or pump thrombus (p = 0.99 and p = 0.8). CONCLUSIONS: In this large, multi-institutional analysis, although some pre-operative clinical characteristics varied, they did not translate into any significant differences in late survival or complications while on LVAD support.

Association between the interleukin-6 genetic polymorphism 174 G/C and thrombosis disorder risk: Meta-analysis of 10,549 cases and 19,316 controls.

Studies investigating the association between interleukin-6 (IL-6) gene-174 G/C polymorphism (rs1800795) and thrombosis disorder risk reported conflicting results. The aim of our study was to assess the association between the IL-6 gene 174 G/C polymorphisms and the risk of thrombosis disorders.Thirty four case-control studies in 29 articles with 29,865 individuals were incorporated in this meta-analysis by searching the public databases including Medline, Embase, and ISI Web of Science databases as of June 1st, 2015. The odds ratio (OR) and 95% confidence interval (95%CI) were used to assess the strength of the association.By pooling all studies, there was marginal association between and the risk of thrombotic disorders (1.09[0.97-1.22]), arterial thrombotic disorders (1.08[0.95-1.23]), and myocardial infarction (MI, 1.14[0.99-1.32]) under dominant genetic effect (C carriers vs GG). In subgroup analyses stratified by ethnicity, study scale, thrombotic category, and country, the results indicated that IL-6 gene-174 G/C polymorphism was significantly associated with increased risk of thrombotic disorders given the conditional such as Asians, large sample-sized, MI, population-based, and Indian studies (C carriers vs GG: 1.39 [1.13-1.72] and C allele vs G allele: 1.36 [1.18-1.56] for Asian; C carriers vs GG: 1.15 [1.01-1.31] and C allele vs G allele: 1.12 [1.01-1.23] for large sample-sized studies; C allele vs G allele: 1.10 [1.03-1.18] for population-based studies; and C carriers vs GG: 1.40 [1.19-1.65] for Indian studies). We did not observe significant association between IL-6-174 G/C and the risk of Caucasians, small sample-sized studies, stroke and venous studies, and other country studies.This meta-analysis suggests that IL-6 gene-174 G/C polymorphism may be marginally associated with risk of thrombotic disorders, arterial disorders, MI especially for Asian, Indian, population-based, and large sample-sized studies. More studies with larger sample size and well-designed studies might be warranted.

A comparative analysis of clinical characteristics of patients with paroxysmal nocturnal hemoglobinuria between Asia and Europe/America.

To accurately analyze the clinical characteristics of paroxysmal nocturnal hemoglobinuria (PNH) in different ethnic backgrounds, we retrieved all retrospective studies on clinical characteristics of PNH with a median follow-up period >60 months published after 2000, analyzed the clinical characteristics of PNH patients in Asia and European/America, and statistically compared enumeration data in these studies. We included 1665 patients in this analysis. The proportion of female patients in Asia was significantly lower than that in Europe/America (P = 0.000). Incidence rates of hemoglobinuria and thromboembolism in Asia were significantly lower than in Europe/America (both P values were 0.000). Within the subgroups of patients with thromboembolism, Asian patients had a higher proportion of arterial thrombosis while Western patients had a higher proportion of abdominal venous thrombosis. Bone marrow failure was not clearly defined in most studies. The proportion of patients with pancytopenia was higher in China than in France (P = 0.048). The total death rates were similar in both ethnic groups (P > 0.05). In Europe/America the major cause of death was thromboembolism and in Asian countries was serious infections. Differences in population characteristics of PNH patients among different ethnic groups indicate the possibility of differential pathogenesis and may be informative for treatment decisions.

Primary thrombophilia in Mexico: a single tertiary referral hospital experience.

Thrombophilia is a complex hypercoagulable state that increases the risk of thrombosis. Most reports in medical literature of the Mexican population with this disease lack statistical validity. Therefore, the aim of this study is to describe the prevalence of primary thrombophilia in a tertiary referral hospital in Mexico. This is a study of patients referred to our hospital because of a hypercoagulable state and who later on were diagnosed with primary thrombophilia. The thrombophilia workup included methylenetetrahydrofolate reductase (MTHFR) C677T, antiphospholipid antibodies, protein C, protein S, antithrombin, factor VIII, factor V Leiden, prothrombin mutation G20210A, activated protein C resistance, JAK2 V617F and homocysteine. Ninety-five individuals were tested. The MTHFR C677T polymorphism was the most frequent anomaly in 84.1% of the tested individuals. There was a relatively low prevalence of factor V Leiden (5.2%) and anticoagulant protein deficiency (8.3%). The MTHFR C677T polymorphism has a very high prevalence compared with the low prevalence of anticoagulant protein deficiency and factor V Leiden mutation in Mexicans.

Three-year changes of prothrombotic factors in a cohort of South Africans with a high clinical suspicion of obstructive sleep apnea.

A hypercoagulable state might be one important mechanism linking obstructive sleep apnea (OSA) with incident myocardial infarction and stroke. However, previous studies on prothrombotic factors in OSA are not uniform and cross-sectional. We longitudinally studied prothrombotic factors in relation to OSA risk, adjusting for baseline levels of prothrombotic factors, demographics, metabolic parameters, aspirin use, and life style factors. The Berlin Questionnaire and/or neck circumference were used to define high OSA risk in 329 South African teachers (48.0% male, 44.6% black) at baseline and at three-year follow-up. Von Willebrand factor (VWF), fibrinogen, D-dimer, plasminogen activator inhibitor-1, clot lysis time (CLT), and soluble urokinase-type plasminogen activator receptor (suPAR) were measured in plasma. At baseline 35.7% of participants had a high risk of OSA. At follow-up, persistently high OSA risk, persistently low OSA risk, OSA risk remission, and new-onset OSA risk were present in 26.1%, 53.2%, 9.4%, and 11.3% of participants, respectively. New-onset OSA risk was associated with a significant and longitudinal increase in VWF, fibrinogen, CLT, and suPAR relative to persistently low OSA risk; in VWF, fibrinogen, and suPAR relative to remitted OSA risk; and in VWF relative to persistently high OSA risk. Persistently high OSA risk was associated with an increase in CLT and suPAR relative to persistently low OSA risk and in D-dimer relative to remitted OSA risk. Remitted OSA risk was associated with D-dimer decrease relative to persistently low OSA risk. In OSA, hypercoagulability is a dynamic process with a most prominent three-year increase in individuals with new-onset OSA risk.

Virgin olive oil, palm olein and coconut oil diets do not raise cell adhesion molecules and thrombogenicity indices in healthy Malaysian adults.

BACKGROUND/OBJECTIVES: Effects of high-protein diets that are rich in saturated fats on cell adhesion molecules, thrombogenicity and other nonlipid markers of atherosclerosis in humans have not been firmly established. We aim to investigate the effects of high-protein Malaysian diets prepared separately with virgin olive oil (OO), palm olein (PO) and coconut oil (CO) on cell adhesion molecules, lipid inflammatory mediators and thromobogenicity indices in healthy adults. METHODS: A randomized cross-over intervention with three dietary sequences, using virgin OO, PO and CO as test fats, was carried out for 5 weeks on each group consisting of 45 men and women. These test fats were incorporated separately at two-thirds of 30% fat calories into high-protein Malaysian diets. RESULTS: For fasting and nonfasting blood samples, no significant differences were observed on the effects of the three test-fat diets on thrombaxane B2 (TXB2), TXB2/PGF1α ratios and soluble intracellular and vascular cell adhesion molecules. The OO diet induced significantly lower (P<0.05) plasma leukotriene B4 (LTB4) compared with the other two test diets, whereas PGF1α concentrations were significantly higher (P<0.05) at the end of the PO diet compared with the OO diet. CONCLUSION: Diets rich in saturated fatty acids from either PO or CO and high in monounsaturated oleic acid from virgin OO do not alter the thrombogenicity indices-cellular adhesion molecules, thromboxane B2 (TXB2) and TXB2/prostacyclin (PGF1α) ratios. However, the OO diet lowered plasma proinflammatory LTB4, whereas the PO diet raised the antiaggregatory plasma PGF1α in healthy Malaysian adults. This trial was registered at clinicaltrials.gov as NCT 00941837.

Thrombosis: a major contributor to the global disease burden.

Thrombosis is a common pathology underlying ischemic heart disease, ischemic stroke, and venous thromboembolism (VTE). The Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study 2010 documented that ischemic heart disease and stroke collectively caused one in four deaths worldwide. GBD 2010 did not report data for VTE as a cause of death and disability. We performed a systematic review of the literature on the global disease burden caused by VTE in low-income, middle-income and high-income countries. Studies from western Europe, North America, Australia and southern Latin America (Argentina) yielded consistent results, with annual incidence rates ranging from 0.75 to 2.69 per 1000 individuals in the population. The incidence increased to between 2 and 7 per 1000 among those aged ≥ 70 years. Although the incidence is lower in individuals of Chinese and Korean ethnicity, their disease burden is not low, because of population aging. VTE associated with hospitalization was the leading cause of disability-adjusted life-years (DALYs) lost in low-income and middle-income countries, and the second most common cause in high-income countries, being responsible for more DALYs lost than nosocomial pneumonia, catheter-related bloodstream infections, and adverse drug events. VTE causes a major burden of disease across low-income, middle-income and high-income countries. More detailed data on the global burden of VTE should be obtained to inform policy and resource allocation in health systems, and to evaluate whether improved utilization of preventive measures will reduce the burden.