What laboratory tests and values are required for a patient with mononucleosis (mono) to safely return to play?

Laboratory Tests for Return to Play After Mononucleosis

Ultrasound assessment of splenic size is the most important laboratory test to determine when a patient with mononucleosis can safely return to play, with normal splenic dimensions required before clearance for contact sports. 1, 2

Splenic Assessment

• Splenic enlargement (splenomegaly) is common in mononucleosis, occurring in most patients, with splenic rupture being a rare but potentially fatal complication 3
• Serial abdominal ultrasound should be performed to assess splenic dimensions before clearing athletes for return to contact sports 1
• Initial ultrasound assessment should be performed at 1 month after diagnosis, as approximately 84% of patients will have normal splenic dimensions by this time 1, 4
• For patients with persistent splenomegaly at 1 month, repeat ultrasound should be performed at 2 months post-diagnosis 1

Timing Considerations

• Current guidelines based on case reports traditionally recommend activity restriction for 3 weeks after symptom onset 3
• However, more recent evidence suggests extending activity restrictions to 31 days after symptom onset, as only 73.8% of splenic injuries occur within 21 days, while 90.5% occur within 31 days 5
• Ultrasound studies show that most patients' spleens return to normal size within approximately 28 days 4

Laboratory Confirmation of Diagnosis

• For diagnostic confirmation of mononucleosis, the following tests are recommended:
  • Heterophile antibody test ("Monospot") as the initial screening test 6, 2
  • For patients with negative heterophile antibody but persistent clinical suspicion, EBV-specific antibody testing should be performed, including Viral Capsid Antigen (VCA) antibodies, Epstein-Barr Nuclear Antigen (EBNA) antibodies, and Early Antigen (EA) antibodies 6
  • Acute primary EBV infection is indicated by positive VCA IgM (with or without VCA IgG) and absence of EBNA antibodies 6

Liver Function Assessment

• Liver function tests should be performed as transaminase elevations are common in mononucleosis 2, 4
• Monitoring AST and LDH levels can help track disease progression, with these parameters typically returning to normal within 28 days 4

Return to Play Algorithm

1. Confirm diagnosis of mononucleosis through appropriate laboratory testing 6, 2
2. Restrict from all contact sports for a minimum of 31 days after symptom onset 5
3. Perform abdominal ultrasound to assess splenic dimensions at 1 month post-diagnosis 1
4. If splenic dimensions are normal, the athlete may be cleared to return to contact sports 1, 4
5. If splenomegaly persists, repeat ultrasound at 2 months post-diagnosis 1
6. Clear for return only when splenic dimensions have normalized 1, 5

Common Pitfalls to Avoid

• Relying solely on clinical examination to detect splenomegaly is inadequate, as many enlarged spleens are not palpable on physical examination 4
• Clearing athletes too early (before 31 days) may increase risk of splenic rupture 5
• Failing to obtain confirmatory EBV-specific antibody testing in patients with negative heterophile antibody tests but persistent clinical suspicion 6
• Not considering alternative diagnoses in patients with mononucleosis-like symptoms but negative EBV testing (CMV, Adenovirus, HIV, Toxoplasma gondii) 6