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. (27th August 2015)

• Record Type: Journal Article
• 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.; Toh, C.‐H.
• Is Part Of: Journal of thrombosis and haemostasis. Volume 13:Number 9(2015:Sep.)
• Page Start: 1653
• Page End: 1664
• Publication Date: 2015-08-27
• Subjects: Thrombosis -- Periodicals; Hemostasis -- Periodicals; Blood coagulation disorders -- Periodicals; 616.1
• DOI: 10.1111/jth.13060
• Languages: English
• ISSNs: 1538-7933

Abstract

<abstract abstract-type="main" id="jth13060-abs-0001"> <title>Summary</title> <sec id="jth13060-sec-0001" sec-type="section"> <title>Background</title> <p>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.</p> </sec> <sec id="jth13060-sec-0002" sec-type="section"> <title>Objectives</title> <p>To determine the frequency of overt DIC, according to ISTH criteria, in children with fatal and non‐fatal CM.</p> </sec> <sec id="jth13060-sec-0003" sec-type="section"> <title>Methods/patients</title> <p>Malawian children were recruited into a prospective cohort study in the following diagnostic groups: retinopathy‐positive CM (<italic>n</italic> = 140), retinopathy‐negative CM (<italic>n</italic> = 36), non‐malarial coma (<italic>n</italic> = 14), uncomplicated malaria (UM), (<italic>n</italic> = 91), mild non‐malarial febrile illness (<italic>n</italic> = 85), and healthy controls (<italic>n</italic> = 36). Assays in the ISTH DIC criteria were performed, and three fibrin‐related markers, i.e. protein C, antithrombin, and soluble thrombomodulin, were measured.</p> </sec> <sec id="jth13060-sec-0004" sec-type="section"> <title>Results and conclusions</title> <p>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; <italic>P</italic> = 0.035]. The levels of the three fibrin‐related markers and soluble thrombomodulin were higher in CM patients than in UM patients (all <italic>P</italic> < 0.001). The mean fibrin degradation product level was higher in fatal CM patients (71.3 μg mL<sup>−1</sup> [95% CI 49.0–93.6]) than in non‐fatal CM patients (48.0 μg mL<sup>−1</sup> [95% CI 37.7–58.2]; <italic>P</italic> = 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<sup>−1</sup> increase [95% CI 1.017–1.156]; <italic>P</italic> = 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.</p> </sec> </abstract>