What is the management and diagnosis for a patient with a blood smear showing thrombocytopenia (low platelet count), mild neutrophilia (elevated neutrophil count), and lymphocytosis (elevated lymphocyte count)?

Diagnostic and Management Approach for Thrombocytopenia with Neutrophilia and Lymphocytosis

The combination of thrombocytopenia with mild neutrophilia and lymphocytosis most commonly suggests an infectious or reactive process, particularly viral infection, and requires immediate exclusion of pseudothrombocytopenia followed by systematic evaluation for secondary causes before considering primary immune thrombocytopenia.

Initial Critical Step: Exclude Pseudothrombocytopenia

• Repeat the platelet count immediately in heparin or sodium citrate tubes, as EDTA-dependent platelet agglutination can falsely lower counts and is a common pitfall 1, 2
• Examine the peripheral blood smear to confirm true thrombocytopenia and assess platelet morphology 3, 1

Peripheral Blood Smear Examination

The blood smear provides critical diagnostic information beyond confirming thrombocytopenia 3, 1:

• Platelet characteristics: Normal to large platelets support immune thrombocytopenia; giant platelets suggest inherited disorders 3
• White blood cell morphology: Atypical lymphocytes strongly suggest viral infection (particularly EBV, CMV, or acute HIV) 3, 4
• Red blood cell morphology: Schistocytes indicate thrombotic microangiopathy requiring emergency intervention 3
• Neutrophil inclusions: Döhle bodies or toxic granulation suggest infection or inflammation 3

Most Likely Diagnoses Given This Presentation

Viral Infection (Primary Consideration)

Acute viral infections are the most common cause of thrombocytopenia with lymphocytosis and mild neutrophilia 1, 4:

• Epstein-Barr virus can cause severe thrombocytopenia with atypical lymphocytosis, even in older adults 4
• HIV, hepatitis C, and CMV must be tested in all adults with this presentation 3, 1
• The neutrophilia may represent early bacterial superinfection or the acute phase response 5, 6

Secondary Immune Thrombocytopenia

If viral serologies are positive, this represents secondary rather than primary ITP 1, 2:

• HIV-associated ITP requires antiviral therapy as first-line treatment 1
• HCV-associated ITP should be treated with antiviral therapy when feasible 1
• H. pylori testing and eradication therapy should be considered 1

Essential Diagnostic Work-Up

Immediate Laboratory Tests

• Complete blood count with differential and reticulocyte count to distinguish isolated thrombocytopenia from pancytopenia 3, 1
• Peripheral blood smear review (already discussed above) 3, 1
• HIV, hepatitis C, and hepatitis B testing in all adults 3, 1
• CMV and EBV serologies given the lymphocytosis 3, 4

Additional Testing Based on Clinical Context

• Direct antiglobulin test to exclude Evans syndrome (concurrent autoimmune hemolytic anemia) 3
• Coagulation studies (PT, aPTT, fibrinogen, D-dimer) if concern for DIC or thrombotic microangiopathy 1, 5
• Bacterial and fungal cultures if fever or signs of infection present 3

When Bone Marrow Examination Is Required

Bone marrow examination is NOT necessary in typical presentations but is mandatory in these situations 1, 2:

• Age >60 years (to exclude myelodysplastic syndromes or leukemia) 1, 2
• Pancytopenia or abnormalities beyond isolated thrombocytopenia 1, 2
• Systemic symptoms (fever, weight loss, bone pain) 1, 2
• Splenomegaly, hepatomegaly, or lymphadenopathy on examination 1, 2
• Atypical peripheral smear findings (schistocytes, abnormal white cells) 1, 2
• Failure to respond to first-line therapies 1, 2

Management Strategy

Observation vs. Treatment Decision

Treatment should be based on bleeding severity, NOT platelet count alone 1, 5:

• Platelet count >50 × 10³/μL with no bleeding: Observation only 1, 5
• Platelet count 20-50 × 10³/μL with mild mucocutaneous bleeding: Consider treatment vs. observation based on bleeding risk 1, 5
• Platelet count <10 × 10³/μL or active bleeding: Immediate treatment required 1, 5

Treatment of Underlying Cause

Treating the underlying infection or condition is the priority 1, 2:

• For viral infections: Supportive care; antiviral therapy for HIV/HCV if indicated 1, 4
• For H. pylori: Eradication therapy 1
• Discontinue any potentially causative medications 5, 7

Immune Thrombocytopenia Treatment (If Required)

For grade 2 thrombocytopenia (platelets 25-50 × 10³/μL) with bleeding 3:

• Prednisone 1 mg/kg/day orally for 2-4 weeks, then taper over 4-6 weeks 3
• IVIG 1 g/kg may be added if rapid platelet increase needed 3

For grade 3-4 thrombocytopenia (platelets <25 × 10³/μL) with bleeding 3:

• Prednisone 1-2 mg/kg/day (oral or IV) 3
• IVIG 1 g/kg as single dose, repeat if necessary 3
• Consult hematology immediately 3

Platelet Transfusion Indications

Prophylactic platelet transfusion is recommended 5, 7:

• Active hemorrhage at any platelet count 5
• Platelet count <10 × 10³/μL even without bleeding 5
• Before invasive procedures if platelets <50 × 10³/μL 5
• Do NOT transfuse in ITP or TTP unless life-threatening bleeding 7

Critical Pitfalls to Avoid

• Missing pseudothrombocytopenia by not repeating the count in non-EDTA tubes 1, 2
• Assuming primary ITP without testing for HIV, HCV, and H. pylori 1, 2
• Overlooking thrombotic microangiopathy when schistocytes are present—this requires emergency plasmapheresis 5, 7
• Delaying hematology consultation in patients with systemic symptoms or age >60 years 3, 1
• Treating based on platelet number alone rather than bleeding severity 1, 5
• Using aspirin or NSAIDs which dramatically increase bleeding risk 1, 5

Activity Restrictions

Patients with platelets <50 × 10³/μL should avoid 5:

• Contact sports and activities with high trauma risk
• Intramuscular injections
• Medications that impair platelet function (aspirin, NSAIDs)