Risk factors for recurrent venous thromboembolism in the European collaborative paediatric database on cerebral venous thrombosis: a multicentre cohort study

Gili Kenet, Fenella Kirkham, Thomas Niederstadt, Achim Heinecke, Dawn Saunders, Monika Stoll, Benjamin Brenner, Christoph Bidlingmaier, Christine Heller, Ralf Knöfler, Rosemarie Schobess, Barbara Zieger, Guillaume Sébire, Ulrike Nowak-Göttl, European Thromboses Study Group, Gili Kenet, Fenella Kirkham, Thomas Niederstadt, Achim Heinecke, Dawn Saunders, Monika Stoll, Benjamin Brenner, Christoph Bidlingmaier, Christine Heller, Ralf Knöfler, Rosemarie Schobess, Barbara Zieger, Guillaume Sébire, Ulrike Nowak-Göttl, European Thromboses Study Group

Abstract

Background: The relative importance of previous diagnosis and hereditary prothrombotic risk factors for cerebral venous thrombosis (CVT) in children in determining risk of a second cerebral or systemic venous thrombosis (VT), compared with other clinical, neuroimaging, and treatment variables, is unknown.

Methods: We followed up the survivors of 396 consecutively enrolled patients with CVT, aged newborn to 18 years (median 5.2 years) for a median of 36 months (maximum 85 months). In accordance with international treatment guidelines, 250 children (65%) received acute anticoagulation with unfractionated heparin or low-molecular weight heparin, followed by secondary anticoagulation prophylaxis with low-molecular weight heparin or warfarin in 165 (43%).

Results: Of 396 children enrolled, 12 died immediately and 22 (6%) had recurrent VT (13 cerebral; 3%) at a median of 6 months (range 0.1-85). Repeat venous imaging was available in 266 children. Recurrent VT only occurred in children whose first CVT was diagnosed after age 2 years; the underlying medical condition had no effect. In Cox regression analyses, non-administration of anticoagulant before relapse (hazard ratio [HR] 11.2 95% CI 3.4-37.0; p<0.0001), persistent occlusion on repeat venous imaging (4.1, 1.1-14.8; p=0.032), and heterozygosity for the G20210A mutation in factor II (4.3, 1.1-16.2; p=0.034) were independently associated with recurrent VT. Among patients who had recurrent VT, 70% (15) occurred within the 6 months after onset.

Conclusion: Age at CVT onset, non-administration of anticoagulation, persistent venous occlusion, and presence of G20210A mutation in factor II predict recurrent VT in children. Secondary prophylactic anticoagulation should be given on a patient-to-patient basis in children with newly identified CVT and at high risk of recurrent VT. Factors that affect recanalisation need further research.

Figures

Figure 1
Figure 1
Cumulative thrombosis-free survival with respect to age at first thrombosis onset
Figure 2
Figure 2
Cumulative thrombosis-free survival in children with and without anticoagulation before recurrent VT
Figure 3
Figure 3
Cumulative thrombosis-free survival in children with complete, partial, and no patency at 3–6 months Analysis included only patients for whom full patency data were available (n=266); in the other patients, early second events occurred before completion of patency follow-up. Recurrences in children with full data: four complete, three partial, eight none.

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