Racial and ethnic differences in reconstructive surgery for apical vaginal prolapse.

BACKGROUND: There is limited literature identifying racial and ethnic health disparities among surgical modalities and outcomes in the field of urogynecology and specifically pelvic organ prolapse surgery. OBJECTIVE: This study aimed to evaluate the differences in surgical approach for apical vaginal prolapse and postoperative complications by race and ethnicity. STUDY DESIGN: This is a retrospective cohort study of women undergoing surgical repair for apical vaginal prolapse between 2014 and 2017 using data from the American College of Surgeons National Surgical Quality Improvement Program. Patients were eligible for inclusion if they underwent either vaginal colpopexy or abdominal sacrocolpopexy. Abdominal sacrocolpopexy cases were further divided into those performed by laparotomy and those performed by laparoscopy. Multivariable logistic regression models that controlled for age, comorbidities, American Society of Anesthesiologists physical status classification, and concurrent surgery were used to determine whether race and ethnicity are associated with the type of colpopexy (vaginal vs abdominal) or the surgical route of abdominal sacrocolpopexy. Similar models that also controlled for surgical approach were used to assess 30-day complications by race and ethnicity. RESULTS: A total of 22,861 eligible surgical cases were identified, of which 12,337 (54%) were vaginal colpopexy and 10,524 (46%) were abdominal sacrocolpopexy. Among patients who had an abdominal sacrocolpopexy, 2262 (21%) were performed via laparotomy and 8262 (79%) via laparoscopy. The study population was 70% White, 9% Latina, 6% African American, 3% Asian, 0.6% Native Hawaiian or Pacific Islander, 0.4% American Indian or Alaska Native, and 11% unknown. In multivariable analysis, Asian and Native Hawaiian or Pacific Islander women were less likely to undergo abdominal sacrocolpopexy compared with White women (odds ratio, 0.82; 95% confidence interval, 0.68-0.99, and odds ratio, 0.56; 95% confidence interval, 0.39-0.82, respectively). Among women who underwent an abdominal sacrocolpopexy, Latina women and Native Hawaiian or Pacific Islander women were less likely to undergo a laparoscopic approach compared with White women (odds ratio, 0.68; 95% confidence interval, 0.58-0.79, and odds ratio, 0.31; 95% confidence interval, 0.1-0.56, respectively). Complication rates also differed by race and ethnicity. After a colpopexy, African American women were more likely to need a blood transfusion (odds ratio, 3.04; 95% confidence interval, 1.95-4.73; P≤.001) and have a deep vein thrombosis or pulmonary embolus (odds ratio, 2.46; 95% confidence interval, 1.10-5.48; P=.028), but less likely to present with postoperative urinary tract infections (odds ratio, 0.68; 95% confidence interval, 0.49-0.96; P=.028) than White women in multivariable regression models. Using the Clavien-Dindo classification system, Latina women had higher odds of developing grade II complications than White women in multivariable models (odds ratio, 1.25; 95% confidence interval, 1.04-1.51; P=.02). CONCLUSION: There are racial and ethnic differences in the type and route of surgical repair for apical vaginal prolapse. In particular, Latina and Pacific Islander women were less likely to undergo a laparoscopic approach to abdominal sacrocolpopexy compared with White women. Although complications were uncommon, there were several complications including blood transfusions that were higher among African American and Latina women. Additional studies are needed to better understand and describe associated factors for these differences in care and surgical outcomes.

The Diagnostic Value of Serum PIVKA-II Alone or in Combination with AFP in Chinese Hepatocellular Carcinoma Patients.

BACKGROUND: At present, the diagnostic accuracy of alpha-fetoprotein (AFP) for hepatocellular carcinoma (HCC) surveillance is insufficient. It remains controversial whether prothrombin induced by vitamin K absence II (PIVKA-II) has a better diagnostic value than AFP for HCC patients. OBJECTIVE: To investigate the diagnostic role of PIVKA-II alone or in combination with AFP in Chinese HCC patients. METHODS: Serum AFP and PIVKA-II levels were detected and analyzed in 308 HCC afflicted patients and 120 unafflicted controls. The receiver operator curve (ROC) and area under the curve (AUC) were conducted to evaluate the clinical value of AFP and PIVKA-II for diagnosing HCC and early HCC. RESULTS: In the whole HCC cohort, the diagnostic values of PIVKA-II were better than that of AFP. The AUC of PIVKA-II and AFP was 0.90 (95% CI 0.87-0.94) and 0.79 (95% CI 0.74-0.84), respectively. "AFP + PIVKA-II" yielded a high sensitivity of 95.1% and a specificity of 83.3%, with the AUC 0.89 (95% CI 0.85-0.93). In the early stage HCC group, the diagnostic accuracy of PIVKA-II was also better than that of AFP. The AUC of PIVKA-II and AFP was 0.83 (95% CI 0.77-0.89) and 0.75 (95% CI 0.68-0.81), respectively. "AFP + PIVKA-II" achieved the sensitivity of 83.3% and specificity of 89.1%, with an AUC of 0.86 (95% CI 0.81-0.91). Moreover, for AFP-negative HCC patients, serum PIVKA-II showed good diagnostic performance, with an AUC of 0.804 (95% CI 0.720-0.887). Besides, elevated PIVKA-II level was a strong independent risk factor for HCC patients with portal vein tumor thrombus (PVTT) (OR = 4.890, P = 0.020). CONCLUSION: PIVKA-II is superior to AFP in HCC screening, and AFP in combination with PIVKA-II significantly improves the diagnostic value for Chinese HCC patients. PIVKA-II could effectively indicate HCC accompanied by PVTT and help to optimize the therapeutic strategy.

Primary Thrombophilia in Mexico XIII: Localization of the Thrombotic Events in Mexican Mestizos With the Sticky Platelet Syndrome.

The sticky platelet syndrome (SPS) is a common cause of both arterial and venous thrombosis, being a dominant autosomal disease with qualitative platelet alterations and familial occurrence. It is characterized by platelet hyperreactivity with increased platelet aggregability in response to low concentrations of platelet agonists: epinephrine, adenosine diphosphate, or both. The clinical manifestations involve venous or arterial thrombosis, recurrent pregnancy loss, and fetal growth retardation. To analyze the localization of the thrombotic episodes in a cohort of Mexican mestizo patients with SPS. Between 1992 and 2016, 86 Mexican mestizo patients with SPS as the single thrombophilic condition were prospectively identified; all of them had a history of thrombosis. There were 15 males and 71 females. The thrombotic episodes were arterial in 26 cases and venous in 60 (70%). Arterial thrombosis was mainly pulmonary thromboembolism, whereas venous thromboses were identified most frequently in the lower limbs. Mexican mestizo population with SPS is mainly female; the type I of the condition is the most frequent; both arterial and venous thrombosis can occur, and they are mainly pulmonary embolism and lower limbs venous thrombosis, respectively.

Clinical Manifestation and Mutation Spectrum of 53 Unrelated Pedigrees with Protein S Deficiency in China.

Protein S (PS) deficiency is associated with a 10-fold increased risk of venous thromboembolism (VTE), but its diagnosis is quite difficult and complicated. In this study, we identified 53 unrelated pedigrees with PS deficiency in China. Data of their clinical characteristics and laboratory examinations were collected. Genetic analysis of PROS1 including direct sequencing, copy number variant detection and messenger ribonucleic acid analysis was performed in probands and related family members. Of these 53 probands, 52.8% (28/53) experienced multi-site and/or recurrent thrombotic episodes, mainly manifested as deep venous thrombosis and/or pulmonary embolism (82.7%). Additional risk factors of VTE were observed in 39.6% (21/53) probands who exhibited a significantly higher rate of recurrent VTE compared with those not, in which 7 probands were complicated by anti-phospholipid syndrome. Most probands and family members exhibited quantitative PS deficiency with impairment of both activated protein C and tissue factor pathway inhibitor cofactor activities. Note that 87.2% (34/39) PROS1 detectable mutation rate was obtained through comprehensive phenotypic and genetic analysis. A total of 36 PROS1 causative mutations including 16 novel mutations were identified in 48 probands, whereas no PROS1 mutations were detected in the other 5 probands. Three hotspot mutations (Glu67Ala, Arg561Trp and Tyr560*) were identified in the Chinese population for the first time. This article provides a framework for correlating the clinical pathogenesis of PS deficiency to genetic backgrounds in the Chinese population.

Correlations between methylenetetrahydrofolate reductase gene polymorphisms and venous thromboembolism: A meta-analysis of 99 genetic association studies.

We performed this meta-analysis to better assess the relationship between methylenetetrahydrofolate reductase gene ( MTHFR) polymorphisms and the risk of venous thromboembolism. Eligible studies were searched in PubMed, Medline, Embase, and Web of Science. Odds ratios with 95% confidence intervals were used to assess associations of MTHFR polymorphisms with venous thromboembolism. A total of 99 genetic association studies were enrolled for analyses. Although no positive results were detected in overall analyses for the rs1801131 polymorphism. Further subgroup analyses according to ethnicity of participants and type of disease revealed that the rs1801131 polymorphism was significantly correlated with the risk of pulmonary embolism. For the rs1801133 polymorphism, significant association with the risk of venous thromboembolism was found in the dominant, recessive, and allele models. Further subgroup analyses according to ethnicity of participants revealed that the rs1801133 polymorphism was significantly associated with the risk of venous thromboembolism in Caucasians, East Asians, and West Asians. When we stratified available data according to type of disease, we found that the rs1801133 polymorphism was also significantly correlated with the risk of deep vein thrombosis and pulmonary embolism. In conclusion, our findings indicate that the MTHFR rs1801133 polymorphism may serve as a potential biological marker for venous thromboembolism in Caucasians, East Asians, and West Asians. Moreover, the MTHFR rs1801133 polymorphism may be implicated in the development of deep vein thrombosis and pulmonary embolism, while the MTHFR rs1801131 polymorphism may contribute to the development of pulmonary embolism.

Genome-Wide Association Transethnic Meta-Analyses Identifies Novel Associations Regulating Coagulation Factor VIII and von Willebrand Factor Plasma Levels.

BACKGROUND: Factor VIII (FVIII) and its carrier protein von Willebrand factor (VWF) are associated with risk of arterial and venous thrombosis and with hemorrhagic disorders. We aimed to identify and functionally test novel genetic associations regulating plasma FVIII and VWF. METHODS: We meta-analyzed genome-wide association results from 46 354 individuals of European, African, East Asian, and Hispanic ancestry. All studies performed linear regression analysis using an additive genetic model and associated ≈35 million imputed variants with natural log-transformed phenotype levels. In vitro gene silencing in cultured endothelial cells was performed for candidate genes to provide additional evidence on association and function. Two-sample Mendelian randomization analyses were applied to test the causal role of FVIII and VWF plasma levels on the risk of arterial and venous thrombotic events. RESULTS: We identified 13 novel genome-wide significant ( P≤2.5×10-8) associations, 7 with FVIII levels ( FCHO2/TMEM171/TNPO1, HLA, SOX17/RP1, LINC00583/NFIB, RAB5C-KAT2A, RPL3/TAB1/SYNGR1, and ARSA) and 11 with VWF levels ( PDHB/PXK/KCTD6, SLC39A8, FCHO2/TMEM171/TNPO1, HLA, GIMAP7/GIMAP4, OR13C5/NIPSNAP, DAB2IP, C2CD4B, RAB5C-KAT2A, TAB1/SYNGR1, and ARSA), beyond 10 previously reported associations with these phenotypes. Functional validation provided further evidence of association for all loci on VWF except ARSA and DAB2IP. Mendelian randomization suggested causal effects of plasma FVIII activity levels on venous thrombosis and coronary artery disease risk and plasma VWF levels on ischemic stroke risk. CONCLUSIONS: The meta-analysis identified 13 novel genetic loci regulating FVIII and VWF plasma levels, 10 of which we validated functionally. We provide some evidence for a causal role of these proteins in thrombotic events.

Coagulation factor V gene 1691G>A polymorphism as an indicator for risk and prognosis of lower extremity deep venous thrombosis in Chinese Han population.

The purpose of this study was to explore the negative influence coagulation factor V (FV) 1691G>A polymorphism had on the risk and prognosis of lower extremity deep venous thrombosis (LDVT) in Chinese Han population.A total of 348 patients with LDVT (LDVT group) and 398 healthy individuals (control group) were selected to further this study. A polymerase chain reaction-restriction fragment length polymorphism method was used to analyze the FV gene 1691G>A polymorphism; coagulation and anticoagulation indexes of patients with LDVT were detected as a result. A 3-year follow-up and logistic regression analysis were conducted to determine the corresponding correlations between FV gene and LDVT.In comparison with the control group, the frequencies of GA and AA genotypes and A allele of 1691G>A polymorphism significantly increased in the LDVT group. Also, in comparison with patients with LDVT carrying GG genotype of FV gene 1691G>A polymorphism, the following activities reduced significantly: prothrombin time, activated partial thromboplastin time, fibrinogen, protein C, and protein S, while activated protein C resistance and lupus anticoagulant positive rate increased in patients carrying A allele (GA + AA). Logistic regression analysis indicated that FV gene 1691G>A polymorphism, total cholesterol, low-density lipoprotein cholesterol, and LDVT family histories were all closely related with LDVT and were subsequent independent risk factors for LDVT. Moreover, patients with LDVT carrying A allele (GA + AA) had both higher patency and recurrence rates than those carrying GG genotype.FV gene 1691G>A polymorphism may be associated with both the risk and prognosis of LDVT, potentially being a useful index for monitoring LDVT prognosis and risk.

Incidence of clinically suspected venous thromboembolism in British Indian patients.

Introduction Venous thromboembolism (VTE) remains a major public health issue around the world. Ethnicity is known to alter the incidence of VTE. To our knowledge, there are no reports in the literature investigating the incidence of VTE in British Indians. The aim of this study was to investigate the rates of symptomatic VTE in British Indian patients in the UK. Methods Patients referred to our institution between January 2011 and August 2013 with clinically suspected VTE were eligible for inclusion in the study. Those not of British Indian or Caucasian ethnicity were excluded. A retrospective review of these two cohorts was conducted. Results Overall, 15,529 cases were referred to our institution for suspected VTE. This included 1,498 individuals of British Indian ethnicity. Of these, 182 (12%) had confirmed VTE episodes. A further 13,159 of the patients with suspected VTE were coded as Caucasian, including 2,412 (16%) who had confirmed VTE events. VTE rates were a third lower in British Indians with clinically suspected VTE than in the equivalent Caucasian group. The British Indian cohort presented with VTE at a much earlier age than Caucasians (mean 57.0 vs 68.0 years). Conclusions This study suggests that British Indian patients have a lower incidence of VTE and are more likely to present at an earlier age than Caucasians. There was no significant difference in VTE type (deep vein thrombosis vs pulmonary embolism) among the ethnic groups. Clinicians should be aware of variations within ethnicities but should continue to adhere to existing VTE prevention guidance.

Thrombin-Activatable Fibrinolysis Inhibitor Polymorphisms and Cerebral Venous Thrombosis in Mexican Mestizo Patients.

Thrombin-activatable fibrinolysis inhibitor (TAFI) gene polymorphisms have been proposed as a predisposing factor for cerebral venous thrombosis (CVT). We analyzed the association between CVT and TAFI single-nucleotide polymorphisms (rs3742264, rs2146881, and rs1926447) compared to healthy controls. Mexico Mestizo confirmed cases with CVT and age- and sex-matched controls with no history of venous thrombotic events were recruited from July 2006 to July 2015. Demographic, clinical, and imaging information was included in the analysis. Genotyping single-nucleotide polymorphisms were performed by allele-specific polymerase chain reaction. Allelic univariate analysis, haplotype association, and Hardy-Weinberg equilibrium were assessed. A total of 113 CVT cases (94 females [83.2%]; median age 35 years [interquartile range 27-43 years]) and 134 age- and sex-matched controls were included. The main risk factors for CVT were pregnancy/puerperium (30.9%), oral contraceptive use (19.5%), and hereditary thrombophilia (7.1%). We found no significant association for heterozygous and homozygous models for rs3742264 ( P = .30 and P = .69, respectively), rs2146881 ( P = .90 and P = .17, respectively), or rs1926447 ( P = .40 and P = .52, respectively) compared to controls; these findings were consistent in subgroup and haplotype analyses. In conclusion, TAFI rs3742264, rs2146881, and rs1926447 polymorphisms do not increase the risk of CVT in comparison to healthy controls.

Epidemiological updates of venous thromboembolism in a Chinese population.

BACKGROUND/OBJECTIVE: Deep vein thrombosis (DVT) was thought to be uncommon in Asians and routine thromboprophylaxis in the form of anticoagulation for surgical patients was considered to be unnecessary. The current study aims to provide a contemporary epidemiology of venous thromboembolism in a population-based scale. METHODS: Information from January 1, 2010 to December 31, 2011 was retrieved from a centralized computer public healthcare database serving mainly an ethnic Han Chinese population of 7.1 million. The incidence, demographics, and hospital mortality rates of DVT and pulmonary embolism (PE) were obtained, and analyzed for different surgical categories. RESULTS: The overall annual incidences of DVT, PE alone, and PE with DVT were 30.0 per 100,000 population, 8.7 per 100,000 population, and 3.0 per 100,000 population, respectively. Overall male to female ratio was 1:1.24. Venous thromboembolic disease was more common with increasing age in both sexes. Thirty days' mortality rates associated with DVT, PE alone, and PE with DVT were 9.0%, 17.4%, and 13.3% respectively. Among the patients who received 103,023 major and intermediate surgical procedures in the study period, the mean incidence of postoperative DVT, PE alone, and PE with DVT were only 0.20% (203.5 patients), 0.08% (85.5 patients), and 0.04% (40.5 patients) respectively. CONCLUSION: Compared with a similar study 10 years ago, there seemed to be a general increase in incidence of DVT and PE. This study showed that postoperative thromboembolic events were not uncommon, with DVT occurring in up to 0.2% of patients and PE in 0.12% of patients in this longitudinal survey.

African Americans have a lower prevalence of portal vein thrombosis at the time of liver transplantation.

BACKGROUND: Perioperative vascular thrombotic events in patients undergoing liver transplantation (LT) are associated with significant morbidity and mortality. METHODS: In this retrospective UNOS database analysis, we evaluated the prevalence of portal vein thrombosis (PVT) and factors contributing to PVT development in different ethnic groups. RESULTS: Of the 47 953 LT performed between 2002 and 2015, we identified 3642 cases of PVT. African Americans (AA) had a significantly lower prevalence of PVT compared to other ethnic groups (p = 0.0001). Multivariable regression analysis confirmed that AA were less likely than other ethnicities to have PVT (OR = 0.6). AA cohort was more likely to have infectious or autoimmune causes of liver failure (OR = 1.6, 1.7 respectively) as well as higher creatinine and INR compared to other groups (OR = 1.6, 1.3 respectively). AA's were less likely to have encephalopathy, ascites, or variceal bleeding, which might indicate lower portal pressures. AA's were listed for LT later than other ethnicities and had both a lower functional status and higher MELD score at the time of registration. DISCUSSION: AA's had a significantly lower prevalence of preoperative PVT despite having a greater number of factors predisposing to thrombosis. This predisposition should be considered before instituting perioperative antithrombotic therapy.

Clinical characteristics and prognosis of cerebral venous thrombosis in Chinese women during pregnancy and puerperium.

Due to the specific physiology associated with pregnancy and puerperium, cerebral venous sinus thrombosis (CVT) may manifest different characteristics. This study aimed to identify the clinical manifestations and prognosis of pregnancy-associated CVT. A total of 43 pregnancy-associated CVT patients were enrolled. We analysed the clinical presentations of the disease and performed a multivariate logistic regression analysis to determine which variables were associated with prognosis. Our descriptive results showed the following: 1) the incidence was 202 per 100,000 deliveries, and the mortality rate was 11.63%; 2) the most frequent symptom was headache; 3) the most frequent abnormal laboratory findings were increased levels of fibrinogen and several serum lipoproteins (including triglyceride, cholesterol, high-density lipoprotein, low-density lipoprotein, apolipoprotein A1, and apolipoprotein B); and 4) the superior sagittal sinus and transverse sinus were the most frequently affected locations. Moreover, an increased modified Rankin Scale score was positively associated with infection, seizure, intracerebral haemorrhage (ICH) and hypertensive disorders of pregnancy (HDP). Comparably, the occurrence of death was positively and significantly associated with infection, seizure and ICH. Consequently, timely diagnosis and treatment of pregnancy-associated CVT patients with infection, seizure, ICH or HDP are needed. Patients with infection, seizure or ICH have a greater risk of death.

Is there an effect of race/ethnicity on early complications of iliac vein stenting?

Background There have been well-documented implications of race/ethnicity on the outcome of various vascular diseases. Little literature has examined the effect of race/ethnicity on venous disease. Iliac vein stenting is an emerging technology in treating chronic venous insufficiency. To further characterize this disease and its treatment, we chose to study the effect of selected clinical factors including race/ethnicity on the early complications of non-thrombotic iliac vein stenting. Methods In this observational study, data analysis was performed for 623 patients with chronic venous insufficiency who underwent iliac vein stenting during the time period from August 2012 to September 2014. Patients were categorized by Caucasians ( n = 396), African Americans ( n = 89), Hispanics ( n = 138), and others ( n = 23). These were correlated with the age, gender, presenting sign according to CEAP classification, percentage of iliac vein stenosis, post-operative thrombosis and pain score. Pain score was obtained post-operatively on a Likert scale of 0-10. Follow-up was performed after completion of the procedure, through post-operative visits and duplex exams every three months for the first year. Statistical analysis was performed using Chi-square and Student's t-test, Pearson's test and multivariate regression. Results The average age of the study patients was 67.8 years (age range 23-96 years, ± 14.2 SD). Sixty-seven patients were women. The presenting sign according to CEAP classification was (C3 = 331, C4 = 175, C5 = 51, C6 = 66). The average pain score was 2.6 (±2.9 SD). The average degree of stenosis was 64.9% (±3.8 SD). There were insufficient numbers in the "other" race/ethnicity group for further analysis. The number of patients with iliac vein stent thrombosis was 14 (2.2%). When analyzing each race/ethnicity in our dataset with univariate analysis, we found that Caucasians were significantly older than the African Americans and Hispanics ( P < 0.0001). There tended to be more women in the Caucasian group as compared to the Hispanics ( P = 0.04). There were no differences in presenting sign according to CEAP classification or degree of stenosis between the three groups. Hispanics tended to have higher pain scores post-operatively than Caucasians ( P = 0.01). It was found that 1.8% of Caucasians, 3.4% of African Americans and 2.9% of Hispanics had post-operative iliac vein stent thrombosis ( P = 0.55). Men have higher CEAP score than women regardless of race/ethnicity ( P = 0.0001). On the other hand, women tended to have higher pain score than men ( P = 0.04). There were no differences between men and women regarding age, degree of stenosis, and stent thrombosis. Linear multivariate regression test and Pearson's test revealed that age is inversely related to pain score ( P < 0.0001). ANOVA multivariate regression statistical analysis showed no relation between race/ethnicity and pain score ( P = 0.98), and one-way ANOVA showed that the Caucasians were the eldest ethnic group in the study ( P < 0.0001). Linear multivariate regression test and Pearson's correlation test revealed that race/ethnicity is not correlated with thrombosis of iliac vein after stenting ( P = 0.8). Conclusion Race/ethnicity is not significantly associated with CEAP score, degree of iliac vein stenosis, or post-operative thrombosis or pain scores. Age was inversely associated with pain score after iliac vein stenting.

Prevalence of the Factor XIII Val34Leu Polymorphism in Korean Patients with Deep Vein Thrombosis.

OBJECTIVE: According to recent reports, a common polymorphism resulting in Val to Leu substitution, located 3 amino acids (Val34Leu) upstream of the thrombin cleavage site of FXIII A, has been related to a lower incidence of deep vein thrombosis (DVT). And, a different expression pattern has been shown across nations and races. However, the frequency of FXIII polymorphism expression in Koreans has not been reported in normal individuals or DVT-patient groups. DESIGN: Case-control study in Korean population. METHODS: We investigated the distribution of factor XIII Val34Leu polymorphisms in Korean patients of DVT (50 cases) and Korean healthy controls (100 cases), using real-time polymerase chain reaction for single nucleotide polymorphism genotyping. RESULTS: With regard to the frequency of the FXIII polymorphism in DVT patients and in the general control group, all 50 cases in the patient group and 100 cases in the control group were found to be Val34 homozygotes. CONCLUSIONS: The Val34Leu polymorphism of FXIII was not found in Korean people, and compared with Caucasians, a noticeably low incidence of DVT was shown. Thus, the preventive effect of the Val34 allele of FXIII on the formation of thrombi was shown.

VKORC1 and CYP2C9 genotypes in Egyptian patients with warfarin resistance.

Warfarin is the most commonly prescribed anticoagulant drug; however, a narrow therapeutic range and a high risk of bleeding or stroke complicate its clinical use. Warfarin resistance was defined as prolonged warfarin requirements of more than 15 mg/day to achieve therapeutic anticoagulation or failure to achieve therapeutic anticoagulation with more than 20 mg/day. The resistance is associated with polymorphisms of the vitamin K epoxide reductase-oxidase complex (VKORC1) and cytochrome P450-2C9 (CYP2C9) genes, which affect warfarin pharmacodynamics and pharmacokinetics, respectively. Identification of the VKORC1 -1639 (A/G) and CYP2C9 (*1/*2/*3) allelic variants was performed using the PGX-Thrombo Strip in 41 patients with warfarin resistance compared with 30 patients with normal warfarin response out of 352 diagnosed cases of deep vein thrombosis. In warfarin-resistant patients, the VKORC1-1639 genotype frequencies were GG 0.756, GA 0.244 and AA 0.0, whereas in warfarin responder patients, they were: GG 0.333, GA 0.400 and AA 0.276 with P ≤ 0.001. The CYP2C9 genotype frequencies showed nonsignificant difference in both group of patients (P = 0.31). Our results suggest that the VKORC1-1639 GG and the wild type CYP2C9*1*1genotypes are associated with the high-dose requirement for warfarin therapy, and that VKORC1-1639 GG is responsible for warfarin resistance and failure in Egyptian patients.

Association between thrombin-activatable fibrinolysis inhibitor gene polymorphisms and venous thrombosis risk: a meta-analysis.

Thrombin-activatable fibrinolysis inhibitor (TAFI) is an important antifibrinolytic factor that has been shown in increased concentrations to be associated with an increased risk for venous thrombosis. However, the effect of TAFI gene polymorphisms on the risk of venous thrombosis remains debatable. The aim of the current study was to evaluate the association of three single nucleotide polymorphisms: 505G>A (rs3742264), 1040 C>T (rs1926447) and -438G>A (rs2146881) with venous thrombosis risk using a meta-analysis. A systematic literature search for eligible studies published before 20 January 2015 was conducted in PubMed, EMBASE, Web of Science, WanFang database and Chinese National Knowledge Infrastructure. We assessed the possible association by pooled odds ratio and its 95% confidence interval. A total of 14 independent case-control studies including 2970 cases and 3049 controls were enrolled in the final meta-analysis. A significant reduction of venous thrombosis risk in the 505G>A polymorphism was observed under allele comparison, homozygote comparison and recessive models, but opposite results were seen in Asians. Likewise, there was a significant decreased susceptibility to venous thrombosis in the 1040C>T polymorphism in homozygote comparison and recessive models. In the subgroup analysis, the nonvenous thromboembolism disease group showed a significantly increased venous thrombosis risk. Pooled estimates did not show evidence of association between -438G>A and venous thrombosis risk in any genetic model. This meta-analysis suggested that although the -438G>T polymorphism is not correlated with venous thrombosis risk in all models, a trend toward reduced risk still could be observed. The A allele and AA genotype of 505G>A in whites and the TT genotype of 1040C>T were significantly associated with a decreased risk of venous thrombosis, except in the non-venous thromboembolism group.

VEGFR2 Gene Polymorphism Correlates with Deep Venous Thrombosis Risk in Chinese Han Population.

OBJECTIVE: To investigate the correlations between three vascular endothelial growth factor 2 (VEGFR2) gene polymorphisms, +1192C>T, +1719T>A, and -604T>C, and deep venous thrombosis (DVT) in Chinese Han population. METHODS: We conducted a case-control study, between September 2009 and September 2012, in a Chinese Han population with onset of lower extremity DVT. A total of 135 patients were enrolled in the case group and 156 healthy individuals in the control group. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to detect the genotype and allele frequencies of the VEGFR2 gene polymorphisms +1192C>T, +1719T>A, and -604T>C. Haplotype analyses were conducted with SHEsis program. Logistic regression was used to detect the risk factors of DVT. Outpatient review and telephone follow-up were conducted to analyze the long-term treatment of DVT patients. RESULTS: The allele and genotype frequencies of -604T>C VEGFR2 polymorphism exhibited significant differences between the case and control groups (both p < 0.05). Haplotype analyses showed remarkable differences between the case and control groups in the distribution frequency of TAC and CTT haplotypes in the VEGFR2 gene (both p < 0.05). Logistic regression analysis showed independent correlation between the incidence of DVT and TAC haplotype in the VEGFR2 gene (p < 0.05). In addition, the TAC haplotype may be a risk factor for DVT treatment failure. CONCLUSION: Our findings suggest that the VEGFR2 gene -604T>C polymorphism and TAC haplotype are associated with DVT, and the TAC haplotype might affect the efficacy of long-term treatment of DVT patients.

The Incidence of Deep Vein Thrombosis in Asian Patients With Chronic Obstructive Pulmonary Disease.

Most studies have focused on the prevalence of deep vein thrombosis (DVT) and pulmonary embolism in patients with chronic obstructive pulmonary disease (COPD) and acute exacerbation in Caucasian populations. DVT is supposedly less likely to occur among Asians than Caucasians, and the primary purpose of this study was to determine the actual incidence of DVT in patients with COPD in Asian populations.We enrolled patients over the age of 40 with a diagnosis of COPD (International Classification of Diseases, Ninth Revision [ICD-9]: 490-492, 496; A-code: A323 and A325) between 1998 and 2008. The index date was the date of first-time COPD diagnosis. We excluded the patients who had been diagnosed with COPD and DVT (The International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM]: 453.8) before index date. The control group was frequency-matched according to age (3-year stratum), sex, and the year of admission, at a 2:1 ratio. Patients were followed from index date to when either a diagnosis of DVT was made, death occurred, December 31, 2009 was reached, or when the patients withdrew from the National Health Insurance program.The overall incidence rate of DVT was 18.78 per 10,000 person-years in patients with COPD, and the adjusted hazard ration of DVT in patients with COPD was 1.38 (95% confidence interval 1.06-1.80), which was greater than patients without COPD after adjusting for age, sex, atrial fibrillation, hypertension, diabetes, hyperlipidemia, cerebrovascular accident, congestive heart failure, lower leg fracture or surgery, and cancer.Asian patients with COPD had a higher incidence of DVT than non-COPD patients.

Efficacy and safety of edoxaban for treatment of venous thromboembolism: a subanalysis of East Asian patients in the Hokusai-VTE trial.

BACKGROUND: Direct oral anticoagulants have been evaluated for their efficacy and safety in the treatment of venous thromboembolism (VTE), which comprises deep vein thrombosis and pulmonary embolism. The randomized, double-blind Hokusai-VTE trial demonstrated that 60 mg of edoxaban once daily following initial heparin treatment is non-inferior to heparin overlapped with and followed by warfarin for the treatment of VTE, and is associated with significantly fewer bleeding events. OBJECTIVES: To assess the efficacy and safety of edoxaban versus warfarin among East Asian patients enrolled in the Hokusai-VTE trial. PATIENTS/METHODS: The Hokusai-VTE trial enrolled 8292 patients from 439 centers worldwide, including 1109 patients from Japan, China, Korea, and Taiwan. The primary efficacy and safety outcomes were symptomatic recurrent VTE and clinically relevant bleeding, respectively. RESULTS: In the overall East Asian population, the primary efficacy outcome of symptomatic recurrent VTE occurred in 16 of 563 (2.8%) patients in the edoxaban group versus 24 of 538 (4.5%) patients in the warfarin group (hazard ratio [HR] 0.64; 95% confidence interval [CI] 0.34-1.19; P = 0.1601). The primary safety outcome of clinically relevant bleeding occurred in 56 of 563 (9.9%) patients in the edoxaban group versus 93 of 538 (17.3%) patients in the warfarin group (HR 0.56; 95% CI 0.40-0.78; P < 0.001). CONCLUSIONS: Edoxaban is an effective and safer alternative to warfarin in East Asian patients with acute VTE who require anticoagulant therapy, consistent with overall study findings from the Hokusai-VTE trial.