22 • Probe •Vol LXII • No. 3 • May–Aug 2023 The Role of Growth Factors in Dengue and Thrombocytopenia Dengue is one of the most prevalent vector-borne viral infections that affects humans and spreads rapidly. Globally, 3,643,763 dengue cases and 3380 dengue-related deaths have been reported, as of November 2022.1 According to the WHO, thrombocytopenia remains an important predictor of the clinical severity of dengue infection.2 Mechanisms of Thrombocytopenia in Dengue Infection The mechanisms of thrombocytopenia include bone marrow suppression, peripheral immunologic destruction of platelets, and increased platelet activation due to vascular injury.3 Bone marrow suppression The dengue virus (DENV) may influence the bone marrow progenitor cells directly or indirectly by reducing the ability of the hematopoietic cells to proliferate. DENV-mediated bone marrow suppression is caused by direct lesion of the progenitor cells, infection of the stromal cells, and changes in bone marrow regulation.2,3 Platelet destruction Platelet destruction might be caused by DENV nonstructural protein (NS) 1, a viral protein that is secreted into the blood circulation of patients with dengue. DENV NS1 directly activates the platelets via the tolllike receptor 4 (TLR4) and leads to hemorrhage and thrombocytopenia during dengue infection.4 Platelet activation The platelets are activated by the circulating DENV particles in blood and by the immune complex of antibodies during DENV infection. Platelet adhesion to the surface of the vascular endothelial cells drives platelet activation. These activated platelets contribute to thrombi formation on the vascular wall, and the removal of platelets from circulation leads to thrombocytopenia.5 Dysfunctioning of Growth Factors Growth factors (GFs) may lead to a strong inflammatory response and enhanced vascular permeability in cases of severe dengue. Several GFs such as the platelet-derived growth factor (PDGF), epidermal growth factor (EGF), transforming growth factor (TGF), and fibroblast growth factor (FGF) are released by the platelets during the restoration of vascular damage or induction of inflammation. To repair the vascular damage, increased levels of PDGF and EGF are required, but studies have demonstrated that PDGF, EGF, and TGF-β levels are low in severe dengue at the critical phase and are associated with thrombocytopenia.6 Mild-to-moderate thrombocytopenia in dengue infection can cause excessive platelet destruction, followed by plasma leakage or hemorrhage. Therefore, early diagnosis of thrombocytopenia based on clinical and laboratory findings and platelet transfusion can help reduce fatal outcomes.2,4 References 1. Kayesh ME, et al. Trop Med Infect Dis. 2023;8(1):32. 2. Islam A, et al. Trop Med Infect Dis. 2022;7(9):210. 3. de Azeredo EL, et al. Mediators Inflamm. 2015;2015:313842. 4. Faridah IN, et al. Diagnostics. 2022;12(4):950. 5. Raadsen M, et al. J Clin Med. 2021;10(4):877. 6. Fiestas Solórzano VE, et al. Pathogens. 2022;11(10):1179.
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