What are the signs and symptoms of plasma leakage in a patient with dengue fever?

Signs and Symptoms of Plasma Leakage in Dengue

Plasma leakage in dengue manifests through specific warning signs that require immediate recognition: persistent vomiting, abdominal pain or tenderness, clinical fluid accumulation (pleural effusion, ascites), mucosal bleeding, lethargy or restlessness, hepatomegaly (>2 cm), and rising hematocrit with concurrent thrombocytopenia. 1

Clinical Warning Signs

The critical indicators of plasma leakage typically appear around days 3-7 of illness, coinciding with defervescence (when fever breaks): 1

• Persistent vomiting - inability to tolerate oral fluids, strongly associated with progression to severe dengue 1, 2
• Abdominal pain or tenderness - particularly right upper quadrant pain due to liver involvement, with pooled prevalence of 3.6% overall 1, 3, 2
• Lethargy or restlessness - indicating potential progression to shock 1, 2
• Mucosal bleeding - including epistaxis, gum bleeding, and gastrointestinal bleeding 1, 2
• Hepatomegaly >2 cm - palpable liver enlargement 1, 2

Laboratory and Imaging Evidence

Hematological changes:

• Rising hematocrit (>20% increase from baseline) with concurrent thrombocytopenia - the hallmark laboratory finding of plasma leakage 1, 4
• Severe thrombocytopenia (<20 × 10⁹/L) - develops in 57% of patients with plasma leakage 3

Ultrasonographic findings (often detectable before hematocrit changes): 5, 6

• Pleural effusion - most common sign, detected in 62% of dengue hemorrhagic fever cases one day after defervescence 6
• Gallbladder wall thickening - detected in 43% of cases, resolves more rapidly than pleural effusion 6, 7, 2
• Ascites - detected in 52% of cases 6, 2
• Pericardial effusion - less common but significant 5

Clinical Fluid Accumulation

Physical examination findings indicating plasma leakage: 1

• Detectable pleural effusion on chest examination
• Ascites on abdominal examination
• Clinical signs of third-spacing

Hemodynamic Manifestations

Signs of progression to dengue shock syndrome: 1

• Narrow pulse pressure ≤20 mmHg - earlier and more sensitive indicator than absolute hypotension 1
• Systolic blood pressure <90 mmHg for >30 minutes 1
• Signs of end-organ hypoperfusion:
  • Cold, clammy extremities or livedo reticularis 1
  • Capillary refill time ≥3 seconds 1
  • Elevated lactate >2 mmol/L 1

Critical Timing Considerations

Ultrasound can detect plasma leakage starting from 2 days before defervescence and sometimes within 3 days after fever onset - significantly earlier than hematocrit changes. 6 In one study, 84.2% of patients with subclinical plasma leakage detected by ultrasound at initial presentation progressed to dengue with warning signs. 5

Important Clinical Pitfalls

• Minimal agreement exists between hematocrit levels and ultrasound detection of plasma leakage (kappa 0.135), meaning hematocrit alone may miss early plasma leakage 5
• Ultrasound detected plasma leakage in 12 of 17 dengue hemorrhagic fever cases who did not meet criteria for significant hemoconcentration 6
• Plasma leakage typically lasts only 48 hours and resolves spontaneously, but severity varies greatly among patients 7
• The size of pleural effusions, ascites, and gallbladder wall thickness in dengue hemorrhagic fever grades I and II are smaller than grade III patients 6

Risk Stratification

Patients presenting with abdominal pain and cough are significantly more likely to develop plasma leakage syndrome and should be monitored closely. 3 With appropriate recognition and management of these warning signs, mortality can be reduced to <0.5%. 1