title: Mechanisms of hemorrhage in dengue without circulatory collapse.
abstract: To characterize the molecular basis for the hemostatic defects of dengue infections, a study was conducted in Bangkok, Thailand. Febrile children (n = 68) hospitalized with suspected dengue were enrolled before their clinical syndromes were classified as either dengue fever (DF) or dengue hemorrhagic fever (DHF). Hospital course and outcome were recorded; blood was obtained during the febrile illness (S1), after defervescence (S2), and 1 month after onset of disease (S4). Patients were classified as DF (n = 21) and DHF grades 1, 2, and 3; (DHF1, n = 8; DHF2, n = 30; and DHF3, n = 9). All had marked thrombocytopenia. Bleeding scores were assigned on the basis of bleeding site. Although there was no correlation between bleeding scores and pleural effusion index (a measure of vascular leakage) or bleeding scores and platelet counts, there was a correlation between pleural effusion index and platelet counts. Bleeding scores did not correlate with hemostatic data. Activated partial thromboplastin time was prolonged, with trends toward decreased fibrinogen and increased levels of prothrombin fragment F1.2 in the acute-phase samples. However, no factor level was dramatically decreased. We conclude that most patients with DF or DHF, even without overt hemorrhage, have consumptive coagulopathy. Nevertheless, hemorrhage in dengue without circulatory collapse is most likely due to activation of platelets rather than coagulopathy, which is well compensated. Our data suggest that vascular alteration may be the principal factor involved in the association of thrombocytopenia and hemorrhage with disease severity.
authors.affiliation: Walter Reed Army Institute of Research, Silver Spring, Maryland 20910-7500, USA. chitra.krishnamurti@na.amedd.army.mil
authors.forename: C
authors.initials: C
authors.lastname: Krishnamurti
authors.forename: S
authors.initials: S
authors.lastname: Kalayanarooj
authors.forename: M A
authors.initials: MA
authors.lastname: Cutting
authors.forename: R A
authors.initials: RA
authors.lastname: Peat
authors.forename: S W
authors.initials: SW
authors.lastname: Rothwell
authors.forename: T J
authors.initials: TJ
authors.lastname: Reid
authors.forename: S
authors.initials: S
authors.lastname: Green
authors.forename: A
authors.initials: A
authors.lastname: Nisalak
authors.forename: T P
authors.initials: TP
authors.lastname: Endy
authors.forename: D W
authors.initials: DW
authors.lastname: Vaughn
authors.forename: S
authors.initials: S
authors.lastname: Nimmannitya
authors.forename: B L
authors.initials: BL
authors.lastname: Innis
mesh_terms: D000293:Adolescent; D000410:Alanine Transaminase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D001772:Blood Cell Count; D001777:Blood Coagulation; D002648:Child; D002675:Child, Preschool; D003715:Dengue / Q000097:blood / Q000503:physiopathology; D003716:Dengue Virus / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D010865:Pilot Projects; D011446:Prospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019595:Severe Dengue / Q000097:blood / Q000503:physiopathology*; D012720:Severity of Illness Index
chemical_list: D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase