What is the diagnosis and management for a patient with erythrocytosis, thrombocytopenia, and elevated bilirubin levels?

Diagnosis and Management of Erythrocytosis with Thrombocytopenia and Elevated Bilirubin

The patient's laboratory findings are most consistent with polycythemia vera (PV) complicated by hyperhemolysis, requiring therapeutic phlebotomy to maintain hematocrit below 45% and further investigation of the cause of thrombocytopenia.

Interpretation of Laboratory Findings

The patient presents with:

• Erythrocytosis: Elevated RBC (5.60), hemoglobin (16.0), and hematocrit (51.6)
• Thrombocytopenia: Low platelets (82)
• Elevated bilirubin (1.8)
• Normal WBC count and differential
• Normal liver enzymes and renal function

Primary Diagnosis Considerations

1. Polycythemia Vera (PV):

   • Elevated hemoglobin and hematocrit are consistent with PV 1
   • Approximately 95% of PV patients have a JAK2 gene variant 1
   • Thrombocytopenia is atypical for early PV (typically presents with thrombocytosis) 2

2. Secondary Erythrocytosis with Concurrent Hemolysis:

   • Elevated bilirubin with normal liver enzymes suggests hemolysis
   • Thrombocytopenia with hemolysis suggests possible immune-mediated process 3

Diagnostic Algorithm

1. Confirm erythrocytosis:

   • Measure red cell mass to differentiate true erythrocytosis from spurious polycythemia 4
   • Rule out plasma volume contraction (dehydration)

2. JAK2 mutation testing:

   • Essential for differentiating PV from secondary erythrocytosis 1, 2

3. Evaluate thrombocytopenia and hemolysis:

   • Peripheral blood smear examination 3
   • Direct antiglobulin test (Coombs)
   • Reticulocyte count
   • LDH and haptoglobin levels
   • Bone marrow examination (aspirate and biopsy) 3

4. Secondary causes assessment:

   • Cardiopulmonary evaluation (echocardiogram, sleep study)
   • Abdominal imaging to evaluate splenomegaly and portal circulation
   • Screen for hyperviscosity symptoms

Management Approach

Immediate Management

1. Therapeutic phlebotomy:

   • For hemoglobin >20 g/dL or hematocrit >65% with symptoms of hyperviscosity 3
   • Target hematocrit <45% to reduce thrombotic risk 1, 2
   • Caution: Avoid aggressive phlebotomy in the setting of thrombocytopenia 3

2. Hydration:

   • Ensure adequate hydration to prevent further hemoconcentration
   • Particularly important before any procedures involving contrast media 3

Ongoing Management

1. For confirmed PV:

   • Low-dose aspirin (81mg daily) if platelets recover above 50,000/μL 1, 2
   • Consider cytoreductive therapy (hydroxyurea or interferon-α) for high-risk patients (age >60 or history of thrombosis) 2
   • Monitor for progression to myelofibrosis or acute leukemia 2

2. For hemolysis:

   • If immune-mediated, consider immunosuppressive therapy 3
   • Serial monitoring of hemoglobin, hematocrit, reticulocyte count, bilirubin, and LDH 3

3. For thrombocytopenia:

   • If severe (<20,000/μL) or with bleeding, consider platelet transfusion
   • Investigate for immune thrombocytopenia, drug effects, or hypersplenism 3

Important Considerations and Pitfalls

1. Avoid repeated routine phlebotomies without clear indication as they can lead to iron depletion, decreased oxygen-carrying capacity, and increased stroke risk 3

2. Monitor for iron deficiency which can develop with repeated phlebotomies and may require judicious iron supplementation 3

3. Be cautious with medications affecting renal function (ACE inhibitors, diuretics, NSAIDs) as patients with PV may have compromised renal function 3

4. Consider eryptosis (programmed death of red blood cells) as a potential mechanism for the concurrent thrombocytopenia and elevated bilirubin in liver disease 3

5. Evaluate for hyperviscosity symptoms including headache, visual disturbances, and cognitive changes that may require urgent intervention 3

6. Don't overlook secondary causes of erythrocytosis that may coexist with thrombocytopenia, such as cardiopulmonary disease with concurrent immune thrombocytopenia 5

7. Consider bone marrow examination especially in patients over 60 years or with abnormal findings to rule out other myeloproliferative disorders 3

The combination of erythrocytosis, thrombocytopenia, and elevated bilirubin represents a complex hematologic picture requiring careful evaluation and management to prevent thrombotic and hemorrhagic complications.