Journal of thrombosis and haemostasis : JTH

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.

PMID 26186686


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. To determine the frequency of overt DIC, according to ISTH criteria, in children with fatal and non-fatal CM. Malawian children were recruited into a prospective cohort study in the following diagnostic groups: retinopathy-positive CM (nxa0=xa0140), retinopathy-negative CM (nxa0=xa036), non-malarial coma (nxa0=xa014), uncomplicated malaria (UM), (nxa0=xa091), mild non-malarial febrile illness (nxa0=xa085), and healthy controls (nxa0=xa036). Assays in the ISTH DIC criteria were performed, and three fibrin-related markers, i.e. proteinxa0C, antithrombin, and soluble thrombomodulin, were measured. 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]xa03.068; 95% confidence interval [CI]xa01.085-8.609; Pxa0=xa00.035]. The levels of the three fibrin-related markers and soluble thrombomodulin were higher in CM patients than in UM patients (all Pxa0< 0.001). The mean fibrin degradation product level was higher in fatal CM patients (71.3xa0μgxa0mL(-1) [95% CIxa049.0-93.6]) than in non-fatal CM patients (48.0 μgxa0mL(-1) [95%xa0CIxa037.7-58.2]; Pxa0=xa00.032), but, in multivariate logistic regression, thrombomodulin was the only coagulation-related marker that was independently associated with a fatal outcome (ORxa01.084 for each ng mL(-1) increase [95% CIxa01.017-1.156]; Pxa0= 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.