Browsing by Subject "Thromboembolism"
Now showing items 1-8 of 8
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(2019)Introduction: Thromboembolism is a serious toxicity of acute lymphoblastic leukemia treatment, and contributes to substantial morbidity and mortality. Several single nucleotide polymorphisms have been associated with thromboembolism in the general population; however, their impact in patients with acute lymphoblastic leukemia, particularly in children, remains uncertain. Materials and methods: We collected constitutional DNA and prospectively registered thromboembolic events in 1252 patients, 1-45 years, with acute lymphoblastic leukemia included in the Nordic Society of Pediatric Hematology and Oncology ALL2008 protocol in the Nordic and Baltic countries (7/2008-7/2016). Based on previously published data and a priori power calculations, we selected four single nucleotide polymorphisms: F5 rs6025, F11 rs2036914, FGG rs2066865, and ABO rs8176719. Results: The 2.5 year cumulative incidence of thromboembolism was 7.1% (95% confidence interval (CI) 5.6-8.5). F11 rs2036914 was associated with thromboembolism (hazard ratio (HR) 1.52, 95%CI 1.11-2.07) and there was a borderline significant association for FGG rs2066865 (HR 1.37, 95%CI 0.99-1.91), but no association for ABO rs8176719 or F5 rs6025 in multiple cox regression. A genetic risk score based on F11 rs2036914 and FGG rs2066865 was associated with thromboembolism (HR 1.45 per risk allele, 95%CI 1.15-1.81), the association was strongest in adolescents 10.0-17.9 years (HR 1.64). Conclusion: If validated, a F11 rs2036914/FGG rs2066865 risk prediction model should be tested as a stratification tool for prevention of thromboembolism in patients with acute lymphoblastic leukemia.
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(2017)•Lapsettomuushoidot ovat nykyisin tavallisia ja yleensä varsin turvallisia. •Hoitoja tehdään Suomessa sekä julkisella sektorilla että yksityisillä klinikoilla. •Vakavat komplikaatiot ovat harvinaisia, mutta uhkaavat pahimmillaan henkeä. •Mikäli päivystävä lääkäri epäilee lapsettomuushoitoon liittyvää komplikaatiota, hänen tulee lähettää potilas tarkempiin tutkimuksiin naistentautien päivystykseen.
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(2018)Background: Electrical cardioversion (CV) is essential in rhythm management of atrial fibrillation (AF). However, optimal timing of CV remains unknown. Hypothesis: Timing of CV in AF is associated with risk of adverse events. Methods: We analyzed the effect of AF episode duration on safety and efficacy of electrical CV in a multicenter, multicohort study exploring 4356 CVs in 2530 patients on oral anticoagulation. The composite adverse outcome included unsuccessful CV, acute arrhythmic complications, thromboembolic events, mortality, and AF recurrence within 30-day follow-up. Results: Study groups were stratified according to duration of index AF episode ( 30d), consisting of 1767, 516, 632, and 1441 CVs, respectively. CVs were unsuccessful in 8.5% (30d), respectively (P <0.01). Occurrence of thromboembolic events (0.1%), mortality (0.1%), and asystole >5 seconds (0.7%) within 30-day follow-up was infrequent and comparable in the study groups. AF recurrence within 30 days after initially successful CVs was 29.8% (30d), respectively (P <0.01). Composite adverse outcome occurred in 1669 (38.4%) CVs, and index AF episode >48 hours was an independent predictor for the composite endpoint (OR: 1.49, 95% CI: 1.28-1.74, P <0.01) in multivariate analysis. Conclusions: Optimal timing of CV for AF showed a J-shaped curve, with fewest adverse outcomes in patients with CV performed 24 to 48 hours after onset of AF. In patients with rhythm-control strategy, delaying CV >48 hours is associated with increased risk for adverse outcomes.
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(2020)Introduction: Thromboembolism (TE) is a common and serious toxicity of acute lymphoblastic leukemia (ALL) treatment, but studies of genetic predisposition have been underpowered with conflicting results. We tested whether TE in ALL and TE in the general adult population have a shared genetic etiology. Materials and methods: We prospectively registered TE events and collected germline DNA in patients 1.0-45.9 years in the Nordic Society of Pediatric Hematology and Oncology (NOPHO) ALL2008 study (7/2008-7/2016). Based on summary statistics from two large genome-wide association studies (GWAS) on venous TE in adults (the International Network of VENous Thromboembolism Clinical Research Networks (INVENT) consortium and the UK Biobank), we performed polygenic risk score (PRS) analysis on TE development in the NOPHO cohort, progressively expanding the PRS by increasing the p-value threshold of single nucleotide polymorphism (SNP) inclusion. Results and conclusion: Eighty-nine of 1252 patients with ALL developed TE, 2.5 year cumulative incidence 7.2%. PRS of genome-wide significant SNPs from the INVENT and UK Biobank data were not significantly associated with TE, HR 1.16 (p 0.14) and 1.02 (p 0.86), respectively. Expanding PRS by increasing p-value threshold did not reveal polygenic overlap. However, subgroup analysis of adolescents 10.0-17.9 years (n = 231), revealed significant polygenic overlap with the INVENT GWAS. The best fit PRS, including 16,144 SNPs, was associated with TE with HR 1.76 (95% CI 1.23-2.52, empirical p-value 0.02). Our results support an underlying genetic predisposition for TE in adolescents with ALL and should be explored further in future TE risk prediction models.
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(2018)
