Coagulation Abnormalities in Dengue Hemorrhagic Fever: Serial Investigations in 167 Vietnamese Children with Dengue Shock Syndrome

Abstract

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.

Endothelial Cell Sensitization by Death Receptor Fractions of an Anti–Dengue Nonstructural Protein 1 Antibody Induced Plasma Leakage, Coagulopathy, and Mortality in Mice

“…Evidence has suggested that severe DENV infection leads to suppressions on circulating native anticoagulants protein C and antithrombin III (22,23), pathological changes partly in accordance with our warfarinized hypercoagulable mouse model (7). Accordingly, we postulated a "two-hit" model in which DENV-elicited anti-DR4 Igs synergize with the DENV-induced suppression of vascular anticoagulants, exacerbating consumption of coagulant factors.…”

“…Thrombomodulin is crucial in activating vascular anticoagulation processes for preventing the development of a hypercoagulable state (38,39). Soluble circulating thrombomodulin was detected in patients with DHF, potentially contributing to endothelial damage and increasing shock severity (22). In this study, treatments with anti-NS1 Ig, anti-NS1-DR4 Ig, and anti-SP-DR4 Ig suppressed the mRNA and surface expression of thrombomodulin (Fig.…”

Platelet indices evaluation in patients with dengue fever

“…21,22 Reports also show that the activation of complement factor C3 followed by binding of C5b-9 complex to platelet surface is significantly linked with platelet destruction and thrombocytopenia in these patients. [23][24][25] 11 of 61 patients studied by Mitrakul et al, had destruction as a main cause for thrombocytopenia, as revealed by platelet kinetic study. A low MPV implies marrow suppression as a cause of thrombocytopenia and a rising MPV heralds the improvement in platelet count.…”

Autoimmune features caused by dengue fever: a case report

“…7,8 Our patient met the WHO criteria for DHF and showed abnormalities compatible with bone marrow suppression, and DIC, although major hemorrhagic manifestations were not observed. The probable immunological mechanism was suggested by the wide spectrum of laboratorial abnormalities: a low level of C3 complement, positive antinuclear antibodies, positive cryoglobulins and elevated ADA in serositis.…”