What is the mechanism of deranged activated partial thromboplastin time (aPTT) in dengue fever?

Mechanism of Deranged aPTT in Dengue Fever

The primary mechanism of deranged activated partial thromboplastin time (aPTT) in dengue is due to activation of both coagulation and fibrinolysis pathways, with prolonged aPTT reflecting consumption of coagulation factors during the acute phase of infection. 1

Pathophysiological Mechanisms

• Dengue virus infection triggers a complex coagulopathy characterized by both activation of the coagulation cascade and fibrinolytic system, resulting in prolongation of aPTT during the acute phase of illness 1

• The coagulopathy in dengue involves multiple mechanisms:

  • Consumption of coagulation factors due to ongoing activation of the coagulation system 1
  • Increased tissue plasminogen activator (tPA) levels contributing to enhanced fibrinolysis 1
  • Liver dysfunction affecting synthesis of coagulation factors 2
  • Development of disseminated intravascular coagulation (DIC) in severe cases 2

• The degree of aPTT prolongation correlates with disease severity, with significantly more pronounced abnormalities in dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) compared to uncomplicated dengue fever 1

Clinical Significance and Correlation

• Prolonged aPTT (>30 seconds) serves as a predictor of bleeding risk in dengue patients, with longer times associated with greater bleeding tendency 3

• aPTT typically reaches its maximum prolongation around day 5 of illness, coinciding with the lowest platelet counts and highest risk period for hemorrhagic complications 4

• Multiple studies have identified that aPTT >60 seconds significantly increases bleeding risk in dengue patients 5

• The combination of prolonged aPTT with other coagulation abnormalities (thrombocytopenia, elevated INR) creates a compounded risk for hemorrhagic manifestations 5

Temporal Pattern and Resolution

• aPTT abnormalities follow a predictable pattern during dengue infection:

  • Initial prolongation during early acute phase
  • Maximum prolongation around day 5 of illness
  • Gradual normalization during convalescent phase 1

• The normalization of aPTT during recovery correlates with:

  • Declining tPA levels (reduced fibrinolysis)
  • Rising platelet counts
  • Increasing plasminogen activator inhibitor-1 (PAI-1) levels 1

Contributing Factors

• Monocyte activation and phagocytosis may contribute to both thrombocytopenia and coagulation factor consumption, indirectly affecting aPTT 4

• Prior use of anti-platelet medications can exacerbate the coagulopathy and further prolong aPTT in dengue patients 5

• The presence of lupus anticoagulant antibodies has been observed in some viral infections and can cause aPTT prolongation without necessarily increasing bleeding risk, though this mechanism is less established in dengue compared to other viral infections 2

Monitoring and Management Implications

• Regular monitoring of aPTT along with platelet count, prothrombin time, and fibrinogen levels is essential in evaluating coagulopathy severity in dengue patients 2

• When interpreting aPTT in dengue patients, clinicians should consider:

  • The day of illness (peak abnormalities around day 5)
  • Concurrent medication use (especially anticoagulants or antiplatelets)
  • Presence of active bleeding 5

• Prolonged aPTT should prompt careful assessment for bleeding manifestations and consideration of supportive measures, including possible blood product administration in severe cases 6