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- Bruzelius, M., et al.
(författare)
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Predicting venous thrombosis in women using a combination of genetic markers and clinical risk factors
- 2015
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 13:2, s. 219-227
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundFamily history of venous thromboembolism (VTE) has been suggested to be more useful in risk assessment than thrombophilia testing. ObjectivesWe investigated established genetic susceptibility variants for association with VTE and evaluated a genetic risk score in isolation and combined with known trigger factors, including family history of VTE. Patients/MethodA total of 18 single nucleotide polymorphisms (SNPs) selected from the literature were genotyped in 2835 women participating in a Swedish nationwide case-control study (the ThromboEmbolism Hormone Study [TEHS]). Association with VTE was assessed by odds ratios (ORs) with 95% confidence interval (CI) using logistic regression. Clinical and genetic predictors that contributed significantly to the fit of the logistic regression model were included in the prediction models. SNP-SNP interactions were investigated and incorporated into the models if found significant. Risk scores were evaluated by calculating the area under the receiver-operating characteristics curve (AUC). ResultsSeven SNPs (F5 rs6025, F2 rs1799963, ABO rs514659, FGG rs2066865, F11 rs2289252, PROC rs1799810 and KNG1 rs710446) with four SNP-SNP interactions contributed to the genetic risk score for VTE, with an AUC of 0.66 (95% CI, 0.64-0.68). After adding clinical risk factors, which included family history of VTE, the AUC reached 0.84 (95% CI, 0.82-0.85). The goodness of fit of the genetic and combined scores improved when significant SNP-SNP interaction terms were included. ConclusionPrediction of VTE in high-risk individuals was more accurate when a combination of clinical and genetic predictors with SNP-SNP interactions was included in a risk score.
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- Ekstrand, C., et al.
(författare)
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Increased susceptibility to infections before the diagnosis of immune thrombocytopenia
- 2016
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 14:4, s. 807-814
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Tidskriftsartikel (refereegranskat)abstract
- Background Infections after diagnosis of primary chronic immune thrombocytopenia (cITP) have mostly been connected to the immunomodulation treatment. Infections may trigger autoimmune diseases and may be a complication of an already impaired immune system. Objectives To investigate the association of cITP with infection before diagnosis. We also estimated the incidence of cITP based on the new definition by the International ITP Working Group. Methods We identified 1087 adults with primary cITP between 2006 and 2012 using the Swedish Patient Register. Data on infections not already associated with secondary ITP were also retrieved from the register. The standardized incidence ratios (SIRs), using the rates from the general population, and 95% confidence intervals (CIs) were estimated as a measure of relative risk. We used data from the Prescribed Drug Register to estimate SIR for anti-infective treatment. Results The incidence of cITP was 2.30 per 100 000 person-years (95% CI, 2.15-2.45). cITP was associated with an increased risk of serious infections requiring inpatient or outpatient care within 5 years before cITP diagnosis (SIR = 8.74; 95% CI, 7.47-10.18). Higher magnitude SIRs were observed for candidiasis, viral infection at an unspecified site and acute upper respiratory infections. For anti-infective drugs the SIR was 1.37 (1.25-1.50) and the highest SIRs were observed for amoxicillin, macrolides, nitrofurantoin and antivirals. Conclusion Patients with cITP have increased risks of infection and anti-infective treatments before their cITP diagnosis, with a more marked risk for candidiasis and viral infections. The findings indicate that infection is not only related to the immunomodulation treatment but also to the disease itself.
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