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

J Thromb Haemost. 2015 Sep;13(9):1653-64. doi: 10.1111/jth.13060. Epub 2015 Aug 27.


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.

Keywords: blood coagulation; disseminated intravascular coagulation; endothelial cell protein C receptor; fibrin; malaria, cerebral.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / analysis
  • Blood Glucose / analysis
  • Child
  • Child, Preschool
  • Coma / blood
  • Coma / etiology
  • Disseminated Intravascular Coagulation / etiology*
  • Female
  • Fever / blood
  • Fibrin / biosynthesis
  • Hematologic Tests
  • Humans
  • Infant
  • Lactates / blood
  • Malaria, Cerebral / blood*
  • Malaria, Cerebral / mortality
  • Malaria, Falciparum / blood*
  • Malaria, Falciparum / mortality
  • Malawi
  • Male
  • Parasitemia / blood
  • Parasitemia / mortality
  • Prospective Studies
  • Retinal Hemorrhage / blood
  • Retinal Hemorrhage / parasitology
  • Risk Factors
  • Thrombomodulin / analysis


  • Biomarkers
  • Blood Glucose
  • Lactates
  • THBD protein, human
  • Thrombomodulin
  • Fibrin