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Hemostatic Changes in Vietnamese Children with Mild Dengue Correlate with the Severity of Vascular Leakage Rather than Bleeding

The mechanisms underlying the bleeding manifestations and coagulopathy associated with dengue remain unclear, in part because of the focus of much previous work on severe disease without an appropriate comparison group. We describe detailed clinical and laboratory profiles for a large group of children with dengue of all severities, and a group with similar non-dengue febrile illnesses, all followed prospectively from early presentation through to recovery. Among the dengue-infected patients but not the controls, thrombocytopenia, increased partial thromboplastin times and reduced fibrinogen concentrations were apparent from an early stage, and these abnormalities correlated strongly with the severity and timing of vascular leakage but not bleeding. There was little evidence of procoagulant activation. The findings do not support a primary diagnosis of disseminated intravascular coagulation to explain the intrinsic coagulopathy. An alternative biologically plausible hypothesis is discussed.

Received January 6, 2008. Accepted for publication July 15, 2009.

Acknowledgments: We thank the directors of the Hospital for Tropical Diseases for their encouragement, the medical and nursing staff for their care of the patients, and the staff of the Oxford University Clinical Research Unit for laboratory and clerical support.

Financial support: The study was supported by the Wellcome Trust. Bridget Wills is a Wellcome Trust Career Development Fellow.

^* Address correspondence to Bridget Wills, Oxford University Clinical Research Unit, Hospital for Tropical Diseases, 190 Ben Ham Tu, Quan 5, Ho Chi Minh City, Viet Nam. E-mail: bwills{at}oucru.org

Authors’ addresses: Bridget Wills and Jeremy Farrar, Oxford University Clinical Research Unit, Hospital for Tropical Diseases, 190 Ben Ham Tu, Quan 5, Ho Chi Minh City, Viet Nam; and Centre for Clinical Vaccinology and Tropical Medicine, Oxford University, Oxford, UK. Tran Van Ngoc, Nguyen Thi Hong Van, Truong Thi Thu Thuy, Tran Thi Nhu Thuy, Nguyen Minh Dung, Tran Vinh Diet, and Nguyen Van Vinh Chau, Hospital for Tropical Diseases, 190 Ben Ham Tu, Ho Chi Minh City, Viet Nam. Dinh The Trung, Hospital for Tropical Diseases, 190 Ben Ham Tu, Ho Chi Minh City, Viet Nam; and University of Medicine and Pharmacy of Ho Chi Minh City, Viet Nam.