Severe Dengue Is Associated with Consumption of von Willebrand Factor and Its Cleaving Enzyme ADAMTS-13

Severe dengue infections are characterized by thrombocytopenia, clinical bleeding and plasma leakage. Activation of the endothelium, the inner lining of blood vessels, leads to the secretion of storage granules called Weibel Palade bodies (WPBs). We demonstrated that severe dengue in Indonesian children is associated with a strong increase in plasma levels of the WPB constituents von Willebrand factor (VWF), VWF propeptide and osteoprotegerin (OPG). An increased amount of the hemostatic protein VWF was in a hyperreactive, platelet binding conformation, and this was most pronounced in the children who died. VWF levels at enrollment were lower than expected from concurrent VWF propeptide and OPG levels and VWF levels did not correlate well with markers of disease severity. Together, this suggests that VWF is being consumed during severe dengue. Circulating levels of the VWF-cleaving enzyme ADAMTS-13 were reduced. VWF is a multimeric protein and a subset of children had a decrease in large and intermediate VWF multimers at discharge. In conclusion, severe dengue is associated with exocytosis of WPBs with consumption of VWF and low ADAMTS-13 activity levels. This may contribute to the thrombocytopenia and complications of dengue

Unfurling the Rationale Use of Platelet Transfusion in Dengue Fever

Dengue fever and dengue haemorrhagic fever have emerged as a global public health problem in recent decades. The practice of platelet transfusion has been adapted into the standard clinical practice in management of hospitalized dengue patients. The exact indications and situations in which platelet have to be transfused may vary greatly. Blood components especially platelet concentrates due to their short shelf life are frequently in limited supply. Hence, appropriate use of blood is required to ensure the availability of blood for patients in whom it is really indicated, as well as to avoid unnecessary exposure of the patients to the risk of transfusion reactions and transmission of blood borne infection. The present study was conducted to evaluate the appropriateness of platelet transfusion done in dengue patients with thrombocytopenia. The present study was conducted on 343 serologically confirmed dengue patients admitted at JSS University Hospital between 1st January and 30th August 2009. Clinical data, platelet count and platelet requirements were analyzed. Among the 343 serologically confirmed cases, the prevalence of thrombocytopenia (platelet count < 100,000/cumm) was 64.72% (222 patients) and bleeding manifestations were recorded in 6.12% (21 patients). 71 (20.7%) patients of dengue cases received platelet transfusion. Among them 34 (47.89%) patients had a platelet count <20,000/cumm, 28 patients (39.44%) had platelet counts in the range of 21–40,000/cumm while the remaining 9 (12.67%) patients had platelet count between 41–100,000/cumm. Out of 37 patients with a platelet count >20,000/cumm 11 patients had haemorrhagic manifestations such as petechiae, gum bleeding, epistaxis etc., which necessitates the use of platelet transfusion. However, the remaining 26 patients with platelet count >20,000/cumm and with no haemorrhagic manifestations received inappropriate platelet transfusion. Transfusion of 36.62% of platelet concentrate was inappropriate. The study emphasizes the need for development of specific guidelines for transfusion of blood components, constant interaction and co-ordination amongst clinicians and transfusion centre for implementation of these guidelines and a regular medical audit to review the optimal utilization of blood components