BACKGROUND: A number of coagulation defects have been implicated as risk factors in thrombo-embolic disease. Of these, high levels of clotting factor VIII have been shown to be associated with a five- to six-fold increased risk of thrombosis, compared to levels < 100 IU/dL in adults. The objective of this study was to investigate the prevalence of elevated plasma levels of factor VIII in a pediatric population with thrombo-embolism (TE). METHODS: Forty-two children (17 female, 25 male) with TE and 165 healthy controls without familial history of thrombosis or stroke were included in the present study. Doppler ultrasonography with or without angiography, computed tomography, magnetic resonance imaging or echocardiography was utilized to establish the diagnosis. One-stage clotting assay with factor VIII-deficient plasma for measurement of factor VIII and immunoturbidometric assay for von Willebrand factor (vWF) levels were utilized. All measurements were performed in duplicate. Plasma levels of factor VIII were assessed in parents of nine patients to establish whether high levels of factor VIII were genetically determined. RESULTS: The median age at onset of TE was 7 years (range 0-17 years). Among patients with TE compared to controls, the prevalence of high factor VIII levels was 59.5% versus 12.1% (odds ratio 10.6, 95% CI: 4.9-23.1). The prevalence of high factor VIII levels was detected in at least one of nine families. CONCLUSION: The data in the present study provide evidence that elevated plasma factor VIII levels are associated with increased risk of thrombosis in children: thus, plasma concentration of factor VIII should be measured in all children with TE.
BACKGROUND: A number of coagulation defects have been implicated as risk factors in thrombo-embolic disease. Of these, high levels of clotting factor VIII have been shown to be associated with a five- to six-fold increased risk of thrombosis, compared to levels < 100 IU/dL in adults. The objective of this study was to investigate the prevalence of elevated plasma levels of factor VIII in a pediatric population with thrombo-embolism (TE). METHODS: Forty-two children (17 female, 25 male) with TE and 165 healthy controls without familial history of thrombosis or stroke were included in the present study. Doppler ultrasonography with or without angiography, computed tomography, magnetic resonance imaging or echocardiography was utilized to establish the diagnosis. One-stage clotting assay with factor VIII-deficient plasma for measurement of factor VIII and immunoturbidometric assay for von Willebrand factor (vWF) levels were utilized. All measurements were performed in duplicate. Plasma levels of factor VIII were assessed in parents of nine patients to establish whether high levels of factor VIII were genetically determined. RESULTS: The median age at onset of TE was 7 years (range 0-17 years). Among patients with TE compared to controls, the prevalence of high factor VIII levels was 59.5% versus 12.1% (odds ratio 10.6, 95% CI: 4.9-23.1). The prevalence of high factor VIII levels was detected in at least one of nine families. CONCLUSION: The data in the present study provide evidence that elevated plasma factor VIII levels are associated with increased risk of thrombosis in children: thus, plasma concentration of factor VIII should be measured in all children with TE.