Thrombocytopenia in dengue infection: mechanisms and a potential application

Abstract

Thrombocytopenia is a common symptom and one of the warning signs of dengue virus (DENV) infection. Platelet depletion is critical as it may lead to other severe dengue symptoms. Understanding the molecular events of this condition during dengue infection is challenging because of the multifaceted factors involved in DENV infection and the dynamics of the disease progression. Platelet levels depend on the balance between platelet production and platelet consumption or clearance. Megakaryopoiesis and thrombopoiesis, two interdependent processes in platelet production, are hampered during dengue infection. Conversely, platelet elimination via platelet activation, apoptosis and clearance processes are elevated. Together, these anomalies contribute to thrombocytopenia in dengue patients. Targeting the molecular events of dengue-mediated thrombocytopenia shows great potential but still requires further investigation. Nonetheless, the application of new knowledge in this field, such as immature platelet fraction analysis, may facilitate physicians in monitoring the progression of the disease.

Keywords: immature platelet fraction; megakaryopoiesis; platelet; thrombocytopenia; thrombopoiesis.

Figure 1.

Classification of dengue by the WHO. This information is based on 2009 WHO guideline (Ref. 1). The present work focuses on one of the symptoms of dengue with warning signs which is thrombocytopenia.

Figure 2.

Summary of DENV-mediated thrombocytopenia. DENV causes thrombocytopenia in several ways. (1) DENV impairs megakaryopoiesis. DENV infects and causes apoptosis of megakaryocytes and the progenitor cells. DENV also prevents megakaryocyte maturation. (2) DENV impairs thrombopoiesis by reducing megakaryocytes and interfering with platelet formation. (3) Secondary DENV infection causes elevated platelet activation via IgG–FcR connection in the ADE process. (4) DENV increases platelet activation. (5) DENV causes cytokines, chemokines and other factors to be released from infected platelets and nearby endothelial cells. (6) DENV infects and causes platelet apoptosis. (7) ADE, elevated platelet activation and secretion of various factors cause the platelets to coagulate. (8) Coagulated platelets and apoptotic platelets are cleared from the circulation by phagocytes. Regular arrows (→) in green indicate stimulatory modifications. Blunt-ended arrows (˧) in red indicate inhibitory modifications.