What is the mechanism of varicella zoster (chickenpox) induced pulmonary thromboembolism (blood clot in the lungs)?

Mechanism of Varicella Zoster-Induced Pulmonary Thromboembolism

Varicella zoster virus (VZV) causes pulmonary thromboembolism through direct endothelial damage, vasculitis, and acquired protein S deficiency via molecular mimicry, creating a hypercoagulable state that leads to venous thrombosis. 1

Primary Pathophysiologic Mechanisms

The thrombotic complications of VZV infection operate through three interconnected pathways:

Direct Vascular Endothelial Damage

• VZV directly infects and damages vascular endothelium, disrupting the normal anticoagulant properties of blood vessel walls 2
• This endothelial injury exposes prothrombotic surfaces and triggers the coagulation cascade 1
• The virus demonstrates tropism for vascular tissues, leading to endotheliopathy similar to other viral infections 3

Vasculitis and Inflammatory Response

• VZV infection induces vasculitis in affected blood vessels, creating an inflammatory milieu that promotes thrombosis 1
• The inflammatory response generates proinflammatory cytokines that activate the coagulation system 3
• This systemic inflammatory state contributes to hypercoagulability beyond the local vascular damage 2

Acquired Protein S Deficiency

• VZV infection triggers molecular mimicry, producing autoantibodies against protein S that create an acquired protein S deficiency 1
• This antibody-mediated hypercoagulable state specifically impairs natural anticoagulant mechanisms 1
• The resulting protein S deficiency persists during the acute infection and recovery period, maintaining thrombotic risk 1

Clinical Manifestations and Timing

Latency Period

• Thrombotic complications typically occur after a latency period following the initial varicella infection, not during the acute vesicular phase 1
• Deep vein thrombosis can develop during or shortly after the acute illness, with subsequent risk of pulmonary embolism 2, 4

Associated Risk Factors

• Severe pulmonary manifestations of varicella significantly increase thrombotic risk, particularly when varicella pneumonitis is present 2
• Malnourished children and immunocompromised patients face higher risk of thrombotic complications 4
• Adult patients with varicella have increased susceptibility to both pneumonitis and thrombotic events compared to children 5

Virchow's Triad in VZV Infection

The mechanism encompasses all three components of Virchow's triad:

• Hypercoagulability: Acquired protein S deficiency and inflammatory cytokine activation 1
• Endothelial injury: Direct viral damage to vascular endothelium 2, 1
• Stasis: Secondary to severe illness, immobilization, and pulmonary complications 2

Clinical Implications

Diagnostic Considerations

• Maintain high clinical suspicion for venous thromboembolism in patients with severe varicella, particularly those with pulmonary involvement 2
• Consider thrombotic workup for patients presenting with unexplained respiratory deterioration during or after varicella infection 4

Treatment Response

• Anticoagulation therapy effectively treats VZV-associated thrombosis, with good prognosis when recognized and treated promptly 1
• Both deep vein thrombosis and pulmonary embolism respond to standard anticoagulation protocols 2, 1

Long-term Management

• Perform prothrombotic screening after recovery to exclude hereditary prothrombotic states that may have been unmasked by the VZV infection 1
• The acquired protein S deficiency is typically transient, but underlying hereditary conditions require identification 1

Important Caveats

• Cardiovascular complications of varicella are extremely rare but can be life-threatening, including hemorrhagic pericarditis and fatal pulmonary thromboembolism 4
• The severity and risk of complications increase with age, making adult varicella particularly concerning for thrombotic events 5
• Even immunocompetent, healthy adults can develop severe thrombotic complications, though risk is higher in immunocompromised patients 5