Coagulation abnormalities in dengue hemorrhagic Fever: serial investigations in 167 Vietnamese children with Dengue shock syndrome.
The pathophysiological basis of hemorrhage in dengue infections remains poorly understood, despite the increasing global importance of these infections. A large prospective study of 167 Vietnamese children with dengue shock syndrome documented only minor prolongations of prothrombin and partial thromboplastin times but moderate to severe depression of plasma fibrinogen concentrations. A detailed study of 48 children revealed low plasma concentrations of the anticoagulant proteins C, S, and antithrombin III, which decreased with increasing severity of shock, probably because of capillary leakage. Concurrent increases in the levels of thrombomodulin, tissue factor, and plasminogen activator inhibitor type 1 (PAI-1) indicated increased production of these proteins. Thrombomodulin levels suggestive of endothelial activation correlated with increasing shock severity, whereas PAI-1 levels correlated with bleeding severity. Dengue virus can directly activate plasminogen in vitro. Rather than causing true disseminated intravascular coagulation, dengue infection may activate fibrinolysis primarily, degrading fibrinogen directly and prompting secondary activation of procoagulant homeostatic mechanisms.
Wills
Bridget A
BA
Centre for Tropical Diseases and Wellcome Trust Clinical Research Unit, Cho Quan Hospital, Ho Chi Minh City, Vietnam. bridgetw@hcm.vnn.vn
Oragui
Emmanuelle E
EE
Stephens
Alick C
AC
Daramola
Olufunmilayo A
OA
Dung
Nguyen Minh
NM
Loan
Ha Thi
HT
Chau
Nguyen Vinh
NV
Chambers
Mary
M
Stepniewska
Kasia
K
Farrar
Jeremy J
JJ
Levin
Michael
M
D000293:Adolescent; D001777:Blood Coagulation; D001780:Blood Coagulation Tests; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D019595:Severe Dengue / Q000097:blood*; D014744:Vietnam / Q000453:epidemiology; D014944:World Health Organization