|
|
Blood, Vol. 113, Issue 10, 2336-2341, March 5, 2009
Association of the protein Z ATG haplotype with symptomatic nonvascular stroke or thromboembolism in white children: a family-based cohort study
Blood Nowak-Göttl et al.
113: 2336
Supplemental materials for: Nowak-Gottl et al
Study design and study endpoints: The present case-control study comprises an analysis in which 165 pediatric patients with either non-vascular stroke (n=101) or children with venous thromboembolism (n=64) were compared to 266 unrelated healthy children to assess the association between elevated protein Z (PZ) antigen levels and the onset of first non-vascular stroke/venous thromboembolism (TE). Patients were consecutively enrolled between January 2000 and December 2007 in the Münster stroke/venous thrombosis database. The control group included 266 healthy white children. These controls, who had no history of chronic disease or of thromboembolic events and were not on medication at the time of recruitment, presented as outpatients (same catchment area) for evaluation prior to minor surgery (planned circumcisions and hernias) or bone marrow donation. Healthy children with a positive family history of early thromboembolism/myocardial infarction or stroke were excluded as controls. Laboratory analyses: Total protein Z concentrations were measured with ELISA technique (Asserachrom protein Z, Stago) six to twelve months after the acute TE onset and after withdrawal of oral anticoagulation. Further evaluation included testing for the FII G120210A variant and the FV G1691A mutation, antiphospholipid antibodies (including the lupus anticoagulant at minimum), and levels of antithrombin, protein C, and free protein S-antigen, and lipoprotein (a) in all cases. As an acute phase reactant, fibrinogen was measured according to Clauss (Dade Behring BCS analyser). Statistics: A multivariate logistic regression analysis was performed to compare the rate of elevated PZ antigen levels > 90th age-dependent percentiles between patients and controls and, further, to evaluate the interaction between elevated PZ and established thrombophilic risk factors FII G20210A variant, the FV G1691A mutation, antiphospholipid antibodies (including the lupus anticoagulant at minimum), antithrombin, protein C, free protein S-antigen, lipoprotein (a). In addition, fibrinogen levels (gradual increase per mg/dl) were incorporated in the multivariate analysis to investigate if an acute phase confounded the thrombotic risk associated with high PZ levels. The primary predictor variable consisted of PZ antigen levels > 90th percentiles and adjustment variables included age, established thrombophilias, and fibrinogen levels. Adjusted risks were expressed as odds ratios (OR) together with 95% CIs. For variables with a non-Gaussian frequency distribution, data were presented as median minimum-maximum values. All evaluations and comparisons between patients and controls were done using the Mann-Whitney test.
Files in this Data Supplement:
|
|
