How does dengue (Dengue virus) fever lead to thrombocytopenia (low platelet count)?

From the Guidelines

Dengue fever leads to thrombocytopenia through a complex interplay of mechanisms that directly and indirectly target platelets, including suppression of bone marrow production, immune-mediated clearance, complement activation, and platelet sequestration. The dengue virus directly infects megakaryocytes, the precursor cells to platelets, which can lead to a decrease in platelet production 1. Additionally, the immune response triggered by the virus can result in the production of antibodies that mistakenly attack platelets, leading to their increased destruction through immune-mediated clearance. The activation of complement pathways by the virus can also damage platelets and lead to their aggregation and consumption in small blood vessels. Furthermore, dengue infection can cause splenomegaly, resulting in increased platelet sequestration and removal from circulation. These mechanisms combined can lead to significantly decreased platelet counts, often below 100,000/μL, which defines thrombocytopenia.

• Key mechanisms involved in thrombocytopenia include:
  • Suppression of bone marrow production of platelets
  • Immune-mediated clearance of platelets
  • Complement activation and platelet damage
  • Platelet sequestration and removal from circulation due to splenomegaly
• The low platelet count associated with thrombocytopenia can contribute to the hemorrhagic manifestations seen in severe dengue cases, including petechiae, bruising, and potentially life-threatening bleeding, as noted in the context of severe dengue management 1.
• Platelet counts typically begin to recover during the convalescent phase as the viral load decreases and immune responses normalize, highlighting the importance of monitoring and managing thrombocytopenia in patients with dengue fever.

From the Research

Mechanisms of Thrombocytopenia in Dengue Fever

• Thrombocytopenia is a characteristic feature of dengue infection, observed in both mild and severe cases 2
• The decrease in platelet counts may be due to bone marrow suppression or consumption of platelets at the periphery 2
• Bone marrow suppression can occur through the infection of hematopoietic progenitors and stromal cells, including megakaryocytes, which compromises megakaryopoiesis 2
• Peripheral consumption of platelets can occur through direct infection of platelets by DENV, adhesion of platelets to leukocytes and vascular endothelium, and platelet clearance mediated by anti-platelet antibodies 2

Clinical Implications of Thrombocytopenia in Dengue Fever

• Platelet counts do not correlate well with clinical bleeding, and serious bleeding is rare 3
• Patients with severe thrombocytopenia (platelet count < 20,000/μL) are at high risk of bleeding and may require urgent platelet transfusion 4
• Patients with moderate thrombocytopenia (platelet count 21-40,000/μL) may require platelet transfusion only if they have hemorrhagic manifestations or other superadded conditions 4
• Platelet transfusion may not improve outcomes in patients with poor platelet recovery and may actually increase the risk of bleeding 5

Platelet Transfusion in Dengue Patients

• The practice of platelet transfusion has been adapted into the standard clinical practice in the management of hospitalized dengue patients 6
• However, the exact indications and situations in which platelet transfusions are to be given may vary greatly, and inappropriate platelet transfusions are common 6, 4
• There is a need for development of specific guidelines for transfusion of blood components and regular medical audits to review the optimal utilization of blood components 6