Elevated Levels of IL-6 and IL-8 Are Associated with An Increased Risk of Venous Thromboembolism – a Case Control Study.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2975-2975
Author(s):  
Marinez F Matos ◽  
Dayse M Lourenço ◽  
Cristina M Orikaza ◽  
Maria A E Noguti ◽  
Vânia M Morelli

Abstract Abstract 2975 Poster Board II-953 Background: high levels of some cytokines have been associated with an increased risk of venous thromboembolism (VTE) in some case-control studies, but not in prospective studies. However, data regarding the impact of cytokines levels on the risk of VTE are still limited. The aim of this study was to investigate the association between the risk of VTE and plasma levels of interleukin (IL)-1β, IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-αa and monocyte chemotactic protein (MCP)-1. Materials and Methods: we studied 122 patients (96 women, 79%), with a first objectively confirmed episode of VTE and with a median age of 39.5 years (range: 21-60). Exclusion criteria were malignancy, autoimmune diseases, antiphospholipid syndrome, chronic renal or liver disease and arterial thrombosis. Patients were seen at least 1 month after the discontinuation of the anticoagulant treatment and > 7 months after the event of VTE. Control group was comprised of 131 healthy subjects (105 women, 80%), with median age of 38 years (range: 18-66), recruited via the patients from the same geographic region and ethnic background. Controls were matched for age and sex. Plasma levels of cytokines were measured by commercial ELISA and a highly sensitive assay was used to measure IL-1β, IL-6 and IL-10 levels. Since a high percentage of samples of IL-1β (73%), IL-10 (62%) and TNF-αa (97%) was below the lower limit of detection (LLD) of the assay, levels of these cytokines were categorized as detectable (> LLD) and not detectable (< LLD). Elevated levels of IL-6 (> 2.15pg/mL), IL-8 (> 10.11pg/mL) and MCP-1 (> 84.11pg/mL) were defined by plasma concentration of these cytokines exceeding the 90th percentile of the distribution of the control population. Results: elevated levels of IL-6 were detected in 27% of the patients with VTE in comparison with 10% (by definition) of the controls [odds ratios (OR) = 3.4, 95% Confidence Interval (CI) 1.6 - 7.6]. Elevated levels of IL-8 were detected in 21% of the patients in comparison with 10% of the controls (OR = 2.5, 95%CI 1.1 - 5.6). The risk remained significant for IL-6 (OR = 2.8, 95%CI 1.2 - 6.5) and IL-8 (OR = 2.6, 95%CI 1.1 - 6.7) after adjustment for putative confounders (sex, age, body mass index, smoking and high levels of homocysteine and C-reactive protein). On the other hand, we found no significant association between VTE and elevated levels of MCP-1 (OR = 0.8, 95%CI 0.3 - 1.9) as well as detectable levels of IL-1β (OR = 0.9, 95%CI 0.5-1.6), IL-10 (OR = 1.3, 95%CI 0.8 - 2.2) and TNF-αa (OR = 6.7, 95%CI 0.8 - 56.7). In our study, patients were included at different time intervals after the VTE episode [median: 36 months (range: 7-87)]. No correlation was found between the time since the event of VTE and levels of IL-6 (rs = 0.06, P = 0.54) and IL-8 (rs= 0.07; P = 0.48). Conclusion: this study shows a significant impact of elevated levels of IL-6 and IL-8 on the risk of VTE in a relatively young population of patients. Interestingly, no association was found between the time since the event and the level of these cytokines. Taking into account the importance of the relationship between inflammation and VTE, more epidemiological data including prospective studies are required to elucidate the role of inflammation on the risk of VTE. This study was supported by FAPESP (2005/56799-0). Disclosures: No relevant conflicts of interest to declare.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3987-3987
Author(s):  
Paolo Bucciarelli ◽  
Emanuele Previtali ◽  
Ida Martinelli ◽  
Andrea Artoni ◽  
Serena M Passamonti ◽  
...  

Abstract Abstract 3987 Poster Board III-923 Background Microparticles (MPs) are circulating, submicroscopic fragments (<1 μm of diameter) of membrane-bound cytoplasm that shed from the surface of an activated or apoptotic cell and play a role in coagulation, inflammation, cell remodelling and proliferation. There is increasing evidence that MPs are involved in thrombosis, but whether or not they are an independent risk factor for venous thromboembolism (VTE) is not established. Aim of the study To investigate the association between high plasma levels of MPs and risk of VTE Patients and Methods In a case-control study, 186 patients with a first episode of VTE (deep venous thrombosis and/or pulmonary embolism) and 418 healthy controls were included. MPs were analyzed by flow cytometry with a gate defined by a 1 μm beads and using APC-Annexin V together with FITC anti-CD41 or FITC anti-CD142 antibodies in order to identify platelet MPs (MP-Plts) and MPs exposing tissue factor (MP-TF), respectively. MPs levels were expressed as number/μL. Results Patients had significantly higher median plasma levels of both MPs-Plts and MPs-TF than controls [1942 vs 1519 (p<0.0001) and 579 vs 454 (p<0.0001)]. Higher median levels of MP-Plts and MP-TF were found in 41 patients who underwent blood sampling within 6 months from VTE than in those sampled later [2114 vs 1694 (p=0.086) and 652 vs 543 (p=0.120)]. Sex, age, body mass index and factor VIII plasma levels had no influence on MPs levels, as well as the use of oral contraceptives (this latter evaluated only in controls). In the whole study population, carriership of thrombophilia (antithrombin, protein C or protein S deficiency, factor V Leiden, prothrombin G20210A, antiphospholipid antibodies, hyperhomocysteinemia or combined abnormalities) had higher levels of MP-Plts and MP-TF than non-carriers [1907 vs 1565 (p=0.002) and 532 vs 468 (p=0.011)]. The odds ratio (OR) for VTE, adjusted for sex, age, body mass index and thrombophilia was 2.5-fold higher in individuals with MPs plasma levels >95th percentile of the control group (3633/μL for MPs-Plts and 1113/μL for MPs-TF) than in those with MPs levels ≤95th percentile [for MPs-Plts: OR=2.59 (95%CI 1.23 – 5.45); for MPs-TF: OR=2.38 (1.15 – 4.92)]. The risk increased in a dose-dependent manner for both MPs-Plts and MPs-TF, particularly above the 75th percentile of the distribution in controls. The exclusion of patients whose MPs levels were measured within 6 months from VTE (in order to avoid the possible effect of the acute phase on MPs measurements), did not change the results [adjusted OR: 2.63 (1.18 – 5.89) for MPs-Plts and 2.36 (1.10 – 5.19) for MPs-TF]. The Table shows the relative risks of VTE associated with the presence or absence of high MPs levels and thrombophilia. Individuals with MPs >95th percentile or thrombophilia alone had a 2 to 3-fold increased risk of VTE, whereas those with both MPs-Plts >95th percentile and thrombophilia had a 9-fold increased risk of VTE. This synergistic effect was confirmed also for MPs-TF and remained after the exclusion of patients whose blood sample was collected within 6 months from VTE [OR 7.72 (1.68-35.4) for MP-Plts and 8.14 (2.08-31.8) for MP-TF]. Conclusions Plasma levels of MPs are significantly higher in patients with VTE than in healthy controls. MPs levels >95th percentile are associated with a 2.5-fold increased risk of VTE. There is a synergistic interaction between high levels of MPs and thrombophilia on VTE risk. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1376-1376
Author(s):  
Samir Dalia ◽  
Sheila Pascual ◽  
Jorge Castillo

Abstract Abstract 1376 Poster Board I-398 Introduction: A relationship between red blood cell (RBC) transfusions and the subsequent development of NHL has been suggested from previous observational reports. The mechanism is unclear but could be related to the known immunomodulatory effect of blood transfusion. This report is a meta-analysis of such observational studies and helps clarifying the strength of such an association, if any. Methods: We searched MEDLINE from January 1966 through June 2009 for observational studies on the association between RBC transfusions and NHL in adults using the keywords “transfusion” and “lymphoma”. Prospective studies and case control studies that reported relative risks (RR), hazard ratios or odds ratios with 95% confidence intervals (CI) were included. One author (SD) gathered the data and another (JC) reviewed the data. A fixed-effect model (FEM) was used to assess the combined outcome of individual studies while a random-effects model (REM) was used, if needed, to account for heterogeneity between studies. Heterogeneity was evaluated using the Cochrane Q and I2 statistics. Publication bias was assessed by direct observation of a funnel plot as well as trim-and-fill statistics. Quality of the studies was assessed independently by another author (SP) using the Newcastle-Ottawa scale. Results: Our initial search rendered 1830 articles. After reviewing the abstracts, 21 papers were selected, from which 5 prospective and 9 case-control studies were included in the final analysis. Based on case-control studies, cases receiving RBC transfusions were associated with an RR of 1.37 (95% CI 0.94-1.87) of developing NHL (p=0.11); a REM was used given the heterogeneity found between studies (I2=90%; Q=90.9, p<0.0001). No publication bias was found. Based on prospective studies, RBC transfusions had a RR of 1.57 (95% CI 1.23-1.99) of developing NHL (p=0.0003); a REM was used despite finding minimal heterogeneity (I2=34%; Q=7.7, p=0.17). Publication bias analysis found 2 imputed studies, which would have not altered our results. When pooling data from retrospective and prospective studies, RBC transfusions had a RR of 1.43 (95% CI 1.12-1.84; p=0.005); a REM was used given a high degree of heterogeneity (I2=85%; Q=102.0, p<0.0001). No evidence of publication bias was found when pooling all the studies. Conclusions: In both retrospective and prospective studies, there is an increased risk of developing NHL after getting a RBC transfusion. The possibility that non-diagnosed NHL was the initial indication for transfusions is not addressed by our study, limiting the generalization of our conclusions. After pooling the available data, cases were 43% more likely to develop NHL if they had a RBC transfusion. This risk should be considered non-negligible. Our findings confirm the previously reported association between RBC transfusions and the development of NHL, and further emphasize a conservative approach to RBC transfusions. Disclosures: No relevant conflicts of interest to declare.


Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5654
Author(s):  
Agnieszka Barańska ◽  
Agata Błaszczuk ◽  
Wiesław Kanadys ◽  
Maria Malm ◽  
Katarzyna Drop ◽  
...  

To perform a meta-analysis of case-control studies that addressed the association between oral contraceptive pills (OC) use and breast cancer (BrCa), PubMED (MEDLINE), Embase, and the Cochrane Library were searched to identify case-control studies of OC and BrCa published between 2009 and 2020. We used the DerSimonian–Laird method to compute pooled odds ratios (ORs) and confidence intervals (CIs), and the Mantel–Haenszel test to assess the association between OC use and cancer. Forty-two studies were identified that met the inclusion criteria and we included a total of 110,580 women (30,778 into the BrCa group and 79,802 into the control group, of which 15,722 and 38,334 were using OC, respectively). The conducted meta-analysis showed that the use of OC was associated with a significantly increased risk of BrCa in general, OR = 1.15, 95% CI: 1.01 to 1.31, p = 0.0358. Regarding other risk factors for BrCa, we found that increased risk was associated significantly with early menarche, nulliparous, non-breastfeeding, older age at first parity, postmenopause, obesity, smoking, and family history of BrCa. Despite our conclusion that birth control pills increase the cancer risk being supported by extensive previous studies and meta-analyzes, further confirmation is required.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2560-2560
Author(s):  
Samir Dalia ◽  
Jorge J. Castillo

Abstract Abstract 2560 Introduction: Few risk factors for the development of Hodgkin lymphoma (HL) have been described. A relationship between smoking and the subsequent development of HL has been suggested from previous reports; however, the available data are largely conflicting. The primary objective of this meta-analysis of observational studies is to evaluate the potential epidemiologic relationship, if any, between smoking and HL. Methods: We searched MEDLINE from January 1, 1960 to June 30, 2010 for observational studies on the association between smoking and HL in adults using the keywords “smoking” and “lymphoma”. Prospective cohort studies and case-control studies that reported relative risks (RR), hazard ratios, or odds ratios with 95% confidence intervals (CI) were included. Literature search, study selection and data gathering were performed independently by the two of authors. Cases were subdivided in ever smokers and current smokers and analyzed separately. Fixed-effect model (FEM) and random-effects models (REM) were used to assess the combined outcome of individual studies. The outcome measured in our study is reported as RR (95% CI). REM was used, if needed, to account for heterogeneity between studies. Heterogeneity was evaluated using the Cochrane Q and I2 statistics. Publication bias was assessed by direct observation of a funnel plot as well as trim-and-fill statistics. Quality of the studies was assessed using the Newcastle-Ottawa scale. Results: Our initial search rendered 577 articles. After reviewing the titles and abstracts, 36 papers were selected for full-text retrieval and reference list search, from which 4 prospective and 11 case-control studies were included in the final analysis. All studies were of high quality with both case-control and prospective studies averaging a score of 8 on the Newcastle-Ottawa scale. When pooling all studies, ever smokers had a RR of 1.20 (95% CI 1.07–1.34; p=0.001); there was no heterogeneity between studies or dissemination bias. Current smokers had a RR of 1.42 (95% CI 1.20–1.68; p<0.001, Figure); there was mild heterogeneity between studies (Q=28.5, I2=45.8%, p=0.046) but no dissemination bias was identified. Based on case-control studies, ever smoking was associated with a RR of 1.16 (95% CI 1.02–1.31; p=0.02) while current smoking was associated with a RR of 1.39 (95% CI 1.14–1.69; p<0.001). Based on prospective studies, ever smoking had a RR 1.40 (95% CI 1.10–1.77; p=0.005) while current smoking had a RR 1.49 (1.02-2.18; p=0.04). Conclusions: In both retrospective and prospective studies, there is a 20% increased risk of developing HL in those patients who have ever smoked. However, the risk increases to 42% in those who were current smokers at time of diagnosis of HL. Our findings confirm a previously reported association between smoking and the development of HL, giving additional support in favor of smoking cessation. The lymphomagenic mechanism of smoking is currently unclear but could be related to a direct carcinogenic effect of tobacco-related agents or the immunomodulatory effect of smoking. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 477-477
Author(s):  
Christiane Pereira Gouveia ◽  
Dayse Maria Lourenço ◽  
Marinez Farana Matos ◽  
Cristina Mary Orikaza ◽  
Maria Aparecida Eiko Noguti ◽  
...  

Abstract Abstract 477 Background: abdominal obesity is one of the components of the metabolic syndrome (MS), which is a cluster of cardiovascular risk factors. Recent prospective studies demonstrated that among the components of the MS, abdominal obesity was the only independent risk factor for venous thromboembolism (VTE). However, it remains unclear to what extent inflammation contributes to the risk of VTE from abdominal obesity. The aim of this study was to investigate the association of abdominal obesity and VTE in women and the effect of inflammation on this association. Material and methods: 94 female patients were included with a first objectively confirmed episode of VTE, with a median age of 39 years (range: 21–60). Exclusion criteria were malignancy, autoimmune diseases, chronic renal or liver diseases and arterial thrombosis. Patients were seen at least 1 month after the discontinuation of the anticoagulant treatment and > 7 months after the event of VTE. Controls were comprised of 100 healthy women, with a median age of 37 years (range: 18–63), recruited via the patients from the same geographic region and ethnic background. Controls were matched for age. Waist circumference (WC) was measured at the umbilical line. A WC ≥ 88 cm in women defined abdominal obesity according to the National Cholesterol Education Program. Plasma level of IL-6 was measured by a highly sensitive ELISA, fibrinogen by Clauss method and high-sensitive C-reactive protein (CRP) by immunoturbidimetry. High levels of IL-6 (> 2.01 pg/mL), CRP (> 6.66 mg/L) and fibrinogen (> 3.59 g/L) were dichotomized at the 90th percentile of the control values. Result: median WC was higher in patients (89 cm; range: 65–126) than in controls (84 cm; range: 62–131), P<0.01. In both groups, WC significantly correlated (P<0.01) with body mass index as expected, but also with age, fibrinogen, CRP and IL-6. Fifty-five patients and 43 controls had abdominal obesity, yielding an odds ratio (OR) of 1.87 [95% Confidence Interval (CI) 1.06 – 3.31]. The association of VTE and abdominal obesity was not affected after adjustment for potential confounders, as high levels of CRP (OR 1.86; 95% CI 1.05 – 3.30) and fibrinogen (OR 1.94; 95% CI 1.08 – 3.48), and it was of borderline significance when adjusted for age (OR 1.76; 95% CI 0.97–3.20). However, the risk was no longer significant after adjustment for high levels of IL-6 (OR 1.57; 95% CI 0.87–2.84). Simultaneous adjustment for age and high levels of CRP, fibrinogen and IL-6 yielded an OR of 1.60 (95% CI 0.85 – 3.00). The impact of abdominal obesity on the risk of VTE was more pronouncedly affected when IL-6 entered into the logistic regression model as a continuous variable (OR 1.33; 95% CI 0.72 – 2.47). Conversely, high IL-6 levels increased the risk of VTE even after adjustment for age, abdominal obesity and high levels of CRP and fibrinogen (OR 3.65; 95%CI 1.56 – 8.50). Conclusion: in this study abdominal obesity was associated with VTE in crude analysis in a relatively young population composed of women. However, the association was no longer significant after adjustment for IL-6. There is evidence that visceral adipose tissue, assessed by WC, is metabolic active, releasing cytokines. To our knowledge this is the first study that evaluated in the same population the effect of IL-6 and abdominal obesity on the risk of VTE. More data, including prospective studies, are required to elucidate the role of inflammation in the association of VTE and abdominal obesity. This study was supported by FAPESP (2005/56799-0). Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3348-3348
Author(s):  
Luis Fernando Bittar ◽  
Bruna Mazetto Fonseca ◽  
Silmara Lima Montalvão ◽  
Fernanda Loureiro de Andrade Orsi ◽  
Erich V de Paula ◽  
...  

Abstract Abstract 3348 Introduction: Venous thromboembolism (VTE) is a multifactorial disease, and increased levels of coagulation factor VIII (FVIII) has been demonstrated as risk factor for first and recurrent episodes of VTE. Some authors reported that these high levels of FVIII were still persistent after 4 years of the episode, but median follow-up in these studies are relatively short. The aim of the study was investigate if after a long-term follow-up of 4–15 years (median of 10 years), patients with high levels of FVIII after anticoagulant treatment still showed this alteration. Design and Methods: Previously, we selected 174 adult patients with a first episode of acute VTE between January 1990 and September 2004. One hundred seventy four healthy adult individuals selected from blood donors were chosen as controls, from the same geographic area of origin. Of this group of VTE patients, 68 patients with plasma FVIII: C levels above the 90th percentile were selected. FVIII levels (FVIII:C) were measured by a one-stage clotting assay with FVIII-deficient plasma in duplicate in an automated coagulometer. Levels were measured twice, in 2004 and then in 2011. C-reactive protein (CRP) levels were determined in the same samples by a nephelometric method to evaluate the influence of inflammation on FVIII levels. For individuals with CRP values higher than 1mg/dL, an additional blood sample was analyzed. High FVIII levels were only considered for further analysis when in the presence of normal CRP levels. The presence of post-thrombotic syndrome (PTS) was evaluated and classified clinically by the Clinical-Etiologic-Anatomic-Pathophysiologic (CEAP) classification System. Results: 68 patients with VTE and high levels of FVIII (19M:49F) with a median age of 47 years (range 20–70) were included in the study. The control group consisted of 59 subjects (42M:17F) with a median age of 35 years (range 21–56 years). VTE was spontaneous in 26 (38.2%) patients and secondary to an acquired risk factor in 61.8%. In the 1st evaluation, in 2004, patients with VTE had higher plasma levels of FVIII:C (median 235.8 IU/dL vs. 127.0 IU/dL; p<0.001) compared to controls. In 2011, seven years after the first evaluation and after a median follow-up of 10 years after the first VTE episode, this difference was still present (median 144.6 IU/dL vs. 96.4 IU/dL; p<0.001). Patients with severe PTS (167 IU/dL) showed higher plasma levels of FVIII when compared with patients without PTS (median 141.4 IU/dL), mild PTS patients (median 142.8 IU/dL), and moderate PTS patients (median 143.2); p=0.04. Conclusions: Our results show that even after a median of 10 years of VTE, patients still have increased levels of FVIII. Moreover, there seems to be a relationship between severe post-thrombotic syndrome and increased plasma levels of FVIII. Disclosures: No relevant conflicts of interest to declare.


F1000Research ◽  
2019 ◽  
Vol 7 ◽  
pp. 1725 ◽  
Author(s):  
Carl Heneghan ◽  
Jeffrey K. Aronson ◽  
Elizabeth Spencer ◽  
Bennett Holman ◽  
Kamal R. Mahtani ◽  
...  

Background: Oral hormone pregnancy tests (HPTs), such as Primodos, containing ethinylestradiol and high doses of norethisterone, were given to over a million women from 1958 to 1978, when Primodos was withdrawn from the market because of concerns about possible teratogenicity. We aimed to study the association between maternal exposure to oral HPTs and congenital malformations. Methods: We have performed a systematic review and meta-analysis of case-control and cohort studies that included data from pregnant women and were exposed to oral HPTs within the estimated first three months of pregnancy, if compared with a relevant control group. We used random-effects meta-analysis and assessed the quality of each study using the Newcastle–Ottawa Scale for non-randomized studies. Results: We found 16 case control studies and 10 prospective cohort studies, together including 71 330 women, of whom 4,209 were exposed to HPTs. Exposure to oral HPTs was associated with a 40% increased risk of all congenital malformations: pooled odds ratio (OR) = 1.40 (95% CI 1.18 to 1.66; P<0.0001; I2 = 0%). Exposure to HPTs was associated with an increased risk of congenital heart malformations: pooled OR = 1.89 (95% CI 1.32 to 2.72; P = 0.0006; I2=0%); nervous system malformations  OR = 2.98 (95% CI 1.32 to 6.76; P = 0.0109 I2 = 78%); gastrointestinal malformations, OR = 4.50 (95% CI 0.63 to 32.20; P = 0.13; I2 = 54%); musculoskeletal malformations, OR = 2.24 (95% CI 1.23 to 4.08; P= 0.009; I2 = 0%); the VACTERL syndrome (Vertebral defects, Anal atresia, Cardiovascular anomalies, Tracheoesophageal fistula, Esophageal atresia, Renal anomalies, and Limb defects), OR = 7.47 (95% CI 2.92 to 19.07; P < 0.0001; I2 = 0%). Conclusions: This systematic review and meta-analysis shows that use of oral HPTs in pregnancy is associated with increased risks of congenital malformations.


Author(s):  
Enzo Emanuelli ◽  
Vera Comiati ◽  
Diego Cazzador ◽  
Gloria Schiavo ◽  
Enrico Alexandre ◽  
...  

Case-control studies on malignant sinonasal tumors and occupational risk factors are generally weakened by non-occupational confounders and the selection of suitable controls. This study aimed to confirm the association between sinonasal malignant tumors and patients’ occupations with consideration for sinonasal inverted papillomas (SNIPs) as a control group. Thirty-two patients affected by adenocarcinoma (ADC) and 21 non-adenocarcinoma epithelial tumors (NAETs) were compared to 65 patients diagnosed with SNIPs. All patients were recruited in the same clinical setting between 2004 and 2016. A questionnaire was used to collect information on non-occupational factors (age, sex, smoking, allergies, and chronic sinusitis) and occupations (wood- and leather-related occupations, textile industry, metal working). Odds ratios (OR) with 95% confidence intervals (CI) associated with selected occupations were obtained by a multinomial and exact logistic regression. Between the three groups of patients, SNIP patients were significantly younger than ADC patients (p = 0.026). The risk of NAET increased in woodworkers (OR = 9.42; CI = 1.94–45.6) and metal workers (OR = 5.65; CI = 1.12–28.6). The risk of ADC increased in wood (OR = 86.3; CI = 15.2–488) and leather workers (OR = 119.4; CI = 11.3–1258). On the exact logistic regression, the OR associated to the textile industry was 9.32 (95%CI = 1.10–Inf) for ADC, and 7.21 (95%CI = 0.55–Inf) for NAET. Comparing sinonasal malignant tumors with controls recruited from the same clinical setting allowed demonstrating an increased risk associated with multiple occupations. Well-matched samples of cases and controls reduced the confounding bias and increased the strength of the association.


2010 ◽  
Vol 27 (1) ◽  
pp. 22-26
Author(s):  
Santhana Gunasekaran

AbstractObjective: This study aims to identify and review available evidence in the literature to determine the strength of association between antipsychotic medications and thromboembolism as an adverse effect.Method: Electronic databases were searched for evidence.Results: A total of 15 case reports, 14 case series, two observational studies and three case-control studies were found in the literature. Two case control studies found significantly increased risk of venous thromboembolism (OR 13.3 and 7.1 respectively). The risk was high for low potency antipsychotics. Studies were critically appraised to determine the strength of evidence.Conclusion: The studies reviewed indicate a significant association between antipsychotics and venous thromboembolism. Patients using the antipsychotics and those who prescribe them should be aware of this association.


Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4669-4669 ◽  
Author(s):  
Bei Hu ◽  
Qingyun Wang ◽  
Liang Tang ◽  
Yu Hu ◽  
Han Liu

Abstract Background Antithrombin (AT) is a critical physiological anticoagulant in haemostasis. SERPINC1, the gene encoding antithrombin, is 13.5kb in length and located on chromosome 1q23-25. Mutations in the SERPINC1 gene may cause antithrombin deficiency and are supposed to confer a high risk for venous thrombosis. However, most mutations reported so far are located in the coding or splicing region of this gene. Therefore, we investigate SERPINC1 gene to identify possible regulatory variants that would increase susceptibility of thrombosis in Chinese people. Methods and Results The potential promoter and 5'-untranslated region of SERPINC1 was screened by direct DNA sequencing in 100 individuals diagnosed with unprovoked venous thrombosis. Further genotyping was performed by Restriction Fragment Length Polymorphism (RFLP) analysis in case-control populations (1750 vs 1900). By DNA sequencing, we identified a c.-11.G>A transition, located 11bp upstream from the transcription initiation codon. Next case-control study showed that this mutation was present in ten individuals of thrombosis group and two of control group. All the mutation carriers we identified were heterozygotes. Therefore, individuals carrying the mutant A allele conferred a 5.42-fold increased risk for venous thrombosis (p<0.05) . Conclusion The c.-11G>A mutation of SERPINC1 gene is a risk factor for venous thrombosis in the Chinese population. It's the first time that a predominant mutation in the regulatory region of SERPINC1 gene reported to be associated with venous thrombosis in a large population. Disclosures No relevant conflicts of interest to declare.


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