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Thrombophilia and first arterial ischaemic stroke: a systematic review
  1. S Haywood1,
  2. R Liesner3,
  3. S Pindora2,
  4. V Ganesan1
  1. 1Neurosciences Unit, Institute of Child Health, University College, London, UK
  2. 2Paediatric Epidemiology and Biostatistics Unit, Institute of Child Health, University College, London, UK
  3. 3Department of Haematology, Great Ormond Street Hospital for Children NHS Trust, London, UK
  1. Correspondence to:
    Dr V Ganesan
    Institute of Child Health, The Wolfson Centre, Mecklenburgh Square, London WC1N 2AP, UK;


Aims: To undertake a systematic review of the literature reporting the prevalence of thrombophilia in children with a first arterial ischaemic stroke (AIS).

Methods: Systematic review of case-control studies reporting data for prevalence of protein C, S, and antithrombin (AT) deficiencies, activated protein C resistance (APCr), total plasma homocysteine >95th centile, the thrombophilic mutations factor V1691 GA, prothrombin 20210GA, and MTHFR C677T in children with first, radiologically confirmed, AIS.

Results: Of 1437 potentially relevant citations, 18 met inclusion criteria. A total of 3235 patients and 9019 controls had been studied. Results of meta-analyses were expressed as pooled odds ratios (OR) relating the prevalence of the thrombophilic condition in children with AIS to that in controls. The pooled OR (and 95% CI) were: protein C deficiency, 6.49 (2.96 to 14.27); protein S deficiency, 1.14 (0.34 to 3.80); AT deficiency, 1.02 (0.28 to 3.67); APCr, 1.34 (0.16 to 11.52); FV1691 GA, 1.22 (0.80 to 1.87); PT20210GA, 1.10 (0.51 to 2.34); MTHFR C677T, 1.70 (1.23 to 2.34); and total plasma homocysteine >95th centile, 1.36 (0.53 to 3.51). There was no statistical heterogeneity within these data.

Conclusions: All factors examined were more common in children with first AIS than in controls, and significantly so for protein C deficiency and the MTHFR C677T mutation. The implications of thrombophilia for prognosis and recurrence need to be established before clinical recommendations can be made regarding investigation and treatment of children with AIS.

  • AIS, arterial ischaemic stroke
  • APCr, activated protein C resistance
  • AT, antithrombin
  • FVL, factor V Leiden
  • thrombophilia
  • stroke
  • meta-analysis
  • systematic review
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  • Funding: Research at the Institute of Child Health and Great Ormond Street Hospital for Children NHS Trust benefits from R&D funding received from the NHS executive

  • Competing interests: none declared

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