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

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.

Author information

1
Institute of Infection and Global Health, University of Liverpool, Liverpool, UK.
2
Malawi-Liverpool Wellcome Clinical Research Programme, University of Malawi College of Medicine, Blantyre, Malawi.
3
University of Malawi College of Medicine, Blantyre, Malawi.
4
Institute of Aging and Chronic Disease, University of Liverpool, Liverpool, UK.
5
Roald Dahl Haemostasis & Thrombosis Centre, Royal Liverpool University Hospital, Liverpool, UK.
6
Liverpool School of Tropical Medicine, Liverpool, UK.
7
College of Osteopathic Medicine, Michigan State University, East Lansing, MI, USA.
8
Blantyre Malaria Project, University of Malawi College of Medicine, Blantyre, Malawi.

Erratum in

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.

KEYWORDS:

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

PMID:
26186686
PMCID:
PMC4605993
DOI:
10.1111/jth.13060
[Indexed for MEDLINE]
Free PMC Article

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