What are the next appropriate laboratory tests and evaluations for a patient with leukopenia, thrombocytopenia, elevated liver enzymes, and fatigue?

Diagnostic Approach for Patient with Low WBC Count, Thrombocytopenia, Elevated Liver Enzymes, and Fatigue

The next appropriate laboratory tests should include a complete blood count with differential, peripheral blood smear examination, comprehensive metabolic panel, and specific tests for tickborne illnesses, particularly Anaplasma phagocytophilum and Ehrlichia species. 1

Initial Laboratory Evaluation

Blood Cell Studies

• Complete blood count with differential to confirm and characterize:
  • Leukopenia (assess severity and which cell lines are affected)
  • Thrombocytopenia (quantify severity)
  • Presence of anemia (often mild in tickborne illnesses) 1
• Peripheral blood smear examination to look for:
  • Morulae within granulocytes (characteristic of anaplasmosis) 1
  • Abnormal cell morphology
  • Evidence of hemolysis

Chemistry and Liver Function

• Comprehensive metabolic panel including:
  • Liver enzymes (AST, ALT, alkaline phosphatase, GGT)
  • Total and direct bilirubin
  • Albumin and total protein
  • Renal function (BUN, creatinine)
  • Electrolytes with attention to hyponatremia (common in tickborne illnesses) 1

Specific Testing Based on Clinical Presentation

Infectious Disease Workup

• PCR testing for:
  • Anaplasma phagocytophilum
  • Ehrlichia species (E. chaffeensis, E. ewingii)
  • Other tickborne pathogens based on geographic exposure 1
• Serologic testing for:
  • Rickettsial diseases
  • Lyme disease (Borrelia burgdorferi) - particularly if in endemic area 1
  • Viral hepatitis panel (HBV, HCV) 1
  • HIV testing 1

Additional Testing to Consider

• Ferritin level (to assess for hemophagocytic syndrome) 2
• Lactate dehydrogenase (LDH) - elevated in hemolysis and certain infections
• Coagulation studies (PT/INR, PTT, fibrinogen) 1
• Blood cultures if febrile

Diagnostic Algorithm

1. First tier testing (obtain immediately):

   • CBC with differential and peripheral blood smear
   • Comprehensive metabolic panel
   • Blood cultures if febrile
   • PCR for Anaplasma/Ehrlichia

2. Second tier testing (based on initial results):

   • If peripheral blood smear shows morulae: confirm with specific PCR
   • If liver enzymes are significantly elevated: viral hepatitis panel, ultrasound of liver
   • If pancytopenia is severe: consider bone marrow examination 1
   • If patient has traveled to endemic areas: malaria smear 1

3. Third tier testing (if diagnosis remains unclear):

   • Flow cytometry if hematologic malignancy suspected
   • Autoimmune markers (ANA, ASMA) if autoimmune hepatitis suspected 1
   • Bone marrow biopsy if cytopenias persist without clear cause

Important Clinical Considerations

• The combination of leukopenia, thrombocytopenia, and elevated liver enzymes with fatigue strongly suggests tickborne illness, particularly anaplasmosis or ehrlichiosis 1
• Anaplasmosis typically presents with fever, headache, myalgia, and malaise along with laboratory findings of leukopenia, thrombocytopenia, and elevated liver enzymes 1
• Consider coinfections, as the tick vector for Anaplasma can also transmit Borrelia burgdorferi (Lyme) and Babesia microti 1
• In immunocompromised patients, consider opportunistic infections and broader testing 1
• For patients with recent travel history, consider testing for malaria and other travel-associated infections 1

Common Pitfalls to Avoid

• Failing to obtain a peripheral blood smear, which can provide rapid diagnostic information for tickborne illnesses
• Not considering geographic exposures and travel history when ordering tests
• Delaying empiric treatment for suspected tickborne illness while awaiting test results
• Overlooking the possibility of coinfections in patients with tickborne diseases
• Attributing abnormal liver function solely to medication effects without investigating infectious causes

Early diagnosis and appropriate treatment are essential, as tickborne illnesses like anaplasmosis can progress rapidly but typically respond well to appropriate antibiotic therapy.