Laboratory evidence of disseminated intravascular coagulation is associated with a fatal outcome in children with cerebral malaria despite an absence of clinically evident thrombosis or bleeding

Moxon, C.A. et al. (2015) Laboratory evidence of disseminated intravascular coagulation is associated with a fatal outcome in children with cerebral malaria despite an absence of clinically evident thrombosis or bleeding. Journal of Thrombosis and Haemostasis, 13(9), pp. 1653-1664. (doi: 10.1111/jth.13060) (PMID:26186686) (PMCID:PMC4605993)

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Abstract

Background: A procoagulant state is implicated in cerebral malaria (CM) pathogenesis, but whether disseminated intravascular coagulation (DIC) is present or associated with a fatal outcome is unclear. Objectives: To determine the frequency of overt DIC, according to ISTH criteria, in children with fatal and non‐fatal CM. Methods/patients: Malawian children were recruited into a prospective cohort study in the following diagnostic groups: retinopathy‐positive CM (n = 140), retinopathy‐negative CM (n = 36), non‐malarial coma (n = 14), uncomplicated malaria (UM), (n = 91), mild non‐malarial febrile illness (n = 85), and healthy controls (n = 36). Assays in the ISTH DIC criteria were performed, and three fibrin‐related markers, i.e. protein C, antithrombin, and soluble thrombomodulin, were measured. Results and conclusions: Data enabling assignment of the presence or absence of ‘overt DIC’ were available for 98 of 140 children with retinopathy‐positive CM. Overt DIC was present in 19 (19%), and was associated with a fatal outcome (odds ratio [OR] 3.068; 95% confidence interval [CI] 1.085–8.609; P = 0.035]. The levels of the three fibrin‐related markers and soluble thrombomodulin were higher in CM patients than in UM patients (all P < 0.001). The mean fibrin degradation product level was higher in fatal CM patients (71.3 μg mL−1 [95% CI 49.0–93.6]) than in non‐fatal CM patients (48.0 μg mL−1 [95% CI 37.7–58.2]; P = 0.032), but, in multivariate logistic regression, thrombomodulin was the only coagulation‐related marker that was independently associated with a fatal outcome (OR 1.084 for each ng mL−1 increase [95% CI 1.017–1.156]; P = 0.014). Despite these laboratory derangements, no child in the study had clinically evident bleeding or thrombosis. An overt DIC score and high thrombomodulin levels are associated with a fatal outcome in CM, but infrequently indicate a consumptive coagulopathy.

Item Type:Articles
Additional Information:This work was supported by a Clinical PhD Fellowship from The Wellcome Trust, UK (C. A. Moxon), a project grant from The Wellcome Trust (092668/Z/10/Z) (S. Harding and I. MacCormick), and grants from the NIH (T. E. Taylor, 5R01AI034969-14). The Malawi–Liverpool Wellcome Clinical Research Programme is supported by core funding from The Wellcome Trust (084679/Z/08/Z).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Seydel, Dr Karl and Moxon, Dr Christopher
Authors: Moxon, C.A., Chisala, N.V., Mzikamanda, R., MacCormick, I., Harding, S., Downey, C., Molyneux, M., Seydel, K.B., Taylor, T.E., Heyderman, R.S., and Toh, C.-H.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Journal of Thrombosis and Haemostasis
Publisher:Wiley
ISSN:1538-7933
ISSN (Online):1538-7836
Published Online:17 July 2015
Copyright Holders:Copyright © 2015 The Authors
First Published:First published in Journal of Thrombosis and Haemostasis 13(9): 1653-1664
Publisher Policy:Reproduced under a Creative Commons License

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