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Blood, 15 February 2001, Vol. 97, No. 4, pp. 858-862
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Risk of recurrent venous thrombosis in children with
combined prothrombotic risk factors
Ulrike Nowak-Göttl,
Ralf Junker,
Wolfhart Kreuz,
Arnold von
Eckardstein,
Andrea Kosch,
Natascha Nohe,
Rosemarie Schobess, and
Silke Ehrenforth for the Childhood Thrombophilia
Study Group
From the Department of Pediatric Hematology/Oncology,
University of Münster, Germany; Department of Clinical Chemistry
and Laboratory Medicine, and Department of Arteriosclerosis Research,
University of Münster, Germany; Department of Pediatric
Hematology/Oncology, University of Frankfurt am Main, Germany;
University Children's Hospital, Munich, Germany; Department of
Pediatric Hematology/Oncology, University of Halle an der Saale,
Germany; Department of Internal Medicine, University of Frankfurt,
Germany.
After a first episode of spontaneous venous thromboembolism (VTE),
the risk of recurrence persists for many years. However, comprehensive
data about the risk of recurrence in pediatric patients have hitherto
not been reported. Thus, this study evaluated the risk of recurrent VTE
among children in relation to the presence of single or
combined-inherited and/or acquired causes of thrombophilia. A total of
301 patients aged neonate to 18 years (median, 6 years) who were
referred for an objectively confirmed first episode of spontaneous VTE
were followed prospectively for a median time of 7 years (range, 6 months to 15 years) after withdrawal of anticoagulation. All patients
were studied for established acquired and inherited causes of
thromboembolism. With reference to all 301 patients, one single
prothrombotic risk factor was found in 176 subjects (58.5%), whereas
combined defects were found in 20.6% (n = 62). Recurrent VTE
occurred in 64 patients (21.3%) within a median time of 3.5 years
(range, 7 weeks to 15 years) after withdrawal of anticoagulation, with
a significantly shorter cumulative thrombosis-free survival in children
carrying combined defects (P < .0001; chi-square, 42.2).
The factor V G1691A mutation was present in the majority of patients
with recurrent VTE. Including genetic defects, gender, and acquired
risk factors, multivariate analysis showed that only the presence of
prothrombotic defects increases the risk of recurrent VTE (single
defect: odds ratio [OR], 4.6; 95% confidence interval [CI],
2.3-9.0; P < .0001; combined defect: OR, 24.0; 95% CI:
5.3-108.7; P < .0001). As a consequence of the data
presented here, it is suggested that screening for genetic risk factors
be done among pediatric patients with VTE.
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