Can mononucleosis (mono) cause thrombocytopenia?

Thrombocytopenia in Infectious Mononucleosis

Yes, infectious mononucleosis (mono) can cause thrombocytopenia, occurring in approximately 30% of cases, though severe thrombocytopenia (platelets <50 × 10^9/L) is rare, affecting only about 1.5% of patients with mono. 1

Epidemiology and Presentation

• Thrombocytopenia is a relatively common hematologic complication of Epstein-Barr virus (EBV) mononucleosis:

  • Present in 29.7% of patients with infectious mononucleosis 1
  • Moderate thrombocytopenia (platelets <100 × 10^9/L) occurs in 8% of cases 1
  • Severe thrombocytopenia (platelets <50 × 10^9/L) is rare, occurring in only 1.5% of cases 1

• Clinical presentation of mono-associated thrombocytopenia:

  • Patients with thrombocytopenia often have atypical presentations of mono with:
    • Lower frequency of typical symptoms like sore throat and lymphadenopathy
    • Lower frequency of positive heterophil antibodies
    • Higher serum bilirubin concentration
    • Larger spleen size
    • Lower blood leukocyte and lymphocyte counts 1

Pathophysiology

The mechanism of thrombocytopenia in infectious mononucleosis appears to be immune-mediated in most cases:

• Antiplatelet antibodies have been detected in some patients with severe thrombocytopenia during acute EBV infection 2, 3
• Bone marrow examination typically shows normal or increased megakaryocytes, suggesting peripheral destruction rather than production defect 4
• The process resembles immune thrombocytopenia (ITP) triggered by the viral infection

Natural History and Management

• Most cases of mono-associated thrombocytopenia are self-limiting:

  • Platelet counts typically normalize quickly during follow-up 1
  • Even severe cases often show spontaneous recovery within 7 days 5
  • Significant hemorrhagic complications are rare 1

• Management approach based on severity:

  1. Mild to moderate thrombocytopenia (>50 × 10^9/L):

     • Observation and monitoring are usually sufficient
     • No specific treatment required as spontaneous resolution is common

  2. Severe thrombocytopenia (<50 × 10^9/L) or with bleeding:

     • Corticosteroids (prednisone 1 mg/kg/day) may be considered as first-line therapy 4, 2
     • Intravenous immunoglobulin (IVIG) at 400 mg/kg/day for 2-5 days can be effective when:
       • Response to steroids is slow (platelets remain <20,000/μL after 8-13 days)
       • Bleeding symptoms increase 4

Important Clinical Considerations

• Differential diagnosis: Always rule out other causes of thrombocytopenia:

  • Drug-induced thrombocytopenia
  • Primary ITP
  • Other viral infections (HIV, HCV)
  • Hematologic malignancies 6, 7

• Diagnostic pitfalls:

  • Mono-associated thrombocytopenia can be misdiagnosed as primary ITP or leukemia 3
  • Always screen for EBV infection in patients presenting with isolated thrombocytopenia, especially young adults 2

• Treatment considerations:

  • Most cases resolve spontaneously without specific therapy
  • For severe cases requiring treatment, monitor for rapid response
  • Some patients may require "booster" doses of IVIG if relapse occurs 4

Follow-up

• Monitor platelet counts until normalization
• Avoid contact sports or activities with high bleeding risk until platelets recover
• No long-term follow-up is typically needed as the condition is transient

In conclusion, while thrombocytopenia is a recognized complication of infectious mononucleosis, severe cases are rare and typically resolve spontaneously or with short-term immunomodulatory therapy without long-term sequelae.