How should I evaluate and manage thrombocytosis in an adult with leukocytosis (~18 × 10⁹/L) and severe tactile and proprioceptive sensory deficits?

Evaluation and Management of Thrombocytosis with Leukocytosis and Sensory Deficits

In an adult with thrombocytosis, leukocytosis (~18 × 10⁹/L), and severe sensory deficits, immediately obtain a complete blood count with differential and peripheral blood smear to distinguish between primary myeloproliferative neoplasm and secondary reactive thrombocytosis, as the sensory deficits may represent either neurologic complications of thrombosis or unrelated pathology requiring urgent evaluation.

Immediate Risk Assessment

• The WBC count of 18 × 10⁹/L does not constitute hyperleukocytosis (defined as >100 × 10⁹/L) and does not require emergent cytoreduction. 1, 2
• No immediate risk of leukostasis exists at this WBC level; routine hydration and monitoring are sufficient unless symptomatic. 2
• The combination of thrombocytosis with leukocytosis raises concern for a myeloproliferative neoplasm (MPN), particularly polycythemia vera or essential thrombocythemia, which can present with neurologic symptoms including sensory deficits from microvascular thrombosis. 1

Diagnostic Workup

Essential Laboratory Studies

• Obtain peripheral blood smear immediately to evaluate cell morphology, maturity, and rule out acute leukemia or other primary bone marrow disorders. 3
• Examine for left shift, immature cells, and erythrocyte abnormalities (Howell-Jolly bodies, spherocytes, target cells) that may indicate functional asplenia. 4
• Measure hemoglobin/hematocrit to assess for concurrent erythrocytosis, which would strongly suggest polycythemia vera. 3

Molecular and Bone Marrow Testing

• Test for JAK2 V617F mutation, CALR mutation, and MPL mutation, as 86% of patients with primary thrombocytosis have at least one molecular marker indicative of MPNs. 5
• If molecular markers are positive or clinical suspicion for MPN remains high, proceed with bone marrow biopsy with cytogenetics. 1

Evaluation for Secondary Causes

The major causes of secondary thrombocytosis include tissue injury (32.2%), infection (17.1%), chronic inflammatory disorders (11.7%), and iron deficiency anemia (11.1%). 5

• Assess for infection with blood cultures, inflammatory markers (CRP, ESR), and site-specific cultures based on clinical presentation, as infection accounts for nearly half of secondary thrombocytosis cases. 6
• Check iron studies (ferritin, iron, TIBC) to exclude iron deficiency anemia. 5
• Evaluate for tissue injury, recent surgery, or underlying malignancy with appropriate imaging. 5, 7
• Consider autoimmune workup including ANA, antiphospholipid antibodies, particularly if peripheral smear shows Howell-Jolly bodies suggesting autosplenectomy. 4

Neurologic Evaluation

The severe tactile and proprioceptive sensory deficits require urgent neurologic assessment independent of the hematologic findings.

• Obtain brain and spinal cord MRI to evaluate for structural lesions, demyelination, or ischemic changes. 1
• Consider nerve conduction studies and EMG if peripheral neuropathy is suspected.
• If MPN is confirmed, the sensory deficits may represent microvascular thrombosis (erythromelalgia or other vasomotor disturbances), which can occur even with normal platelet counts in JAK2-mutated patients. 1

Risk Stratification for Thrombosis

If Primary Thrombocytosis (MPN) is Confirmed

The median platelet count and incidence of thrombosis are significantly higher in primary versus secondary thrombocytosis. 5

• Classify as high-risk if age >60 years and/or prior history of thrombosis; classify as low-risk if age ≤60 years with no prior thrombosis. 1
• JAK2 mutation presence increases thrombotic risk even in younger patients. 1
• Platelet count >1,000 × 10⁹/L is associated with major hemorrhage risk but paradoxically lower thrombosis rates due to acquired von Willebrand disease. 1

Management Strategy

For Confirmed or Suspected Primary Thrombocytosis

Initiate aspirin 81-100 mg daily immediately for vascular symptoms or thrombosis prevention in high-risk patients. 1

• Start cytoreductive therapy with hydroxyurea 50-60 mg/kg/day if any of the following are present: 1

  • New thrombosis
  • Symptomatic or progressive splenomegaly
  • Progressive leukocytosis
  • Vasomotor/microvascular disturbances not responsive to aspirin (including sensory symptoms)
  • Symptomatic thrombocytosis

• For younger patients or those deferring hydroxyurea, consider interferon alfa-2b, peginterferon alfa-2a, or peginterferon alfa-2b. 1

For Secondary Thrombocytosis

• Treat the underlying cause (infection, inflammation, iron deficiency) as the primary intervention. 5, 6
• Platelet counts typically normalize more rapidly with treatment of secondary causes compared to primary thrombocytosis. 6
• Aspirin is generally not indicated unless there are additional cardiovascular risk factors. 1

Monitoring and Follow-up

• Monitor platelet counts and complete blood counts weekly until stable, then every 3 months if on cytoreductive therapy. 1
• Reassess neurologic symptoms after initiating treatment; improvement suggests microvascular etiology related to MPN. 1
• If platelet count remains >400 × 10⁹/L on three separate occasions despite treatment of secondary causes, reconsider primary thrombocytosis and repeat molecular testing. 5

Critical Pitfalls to Avoid

• Do not assume thrombocytosis is reactive without excluding MPN, especially when combined with leukocytosis and unexplained neurologic symptoms. 7
• Do not delay aspirin therapy in high-risk patients while awaiting molecular testing results, as thrombotic complications can occur rapidly. 1
• Avoid attributing sensory deficits solely to thrombocytosis without neuroimaging, as concurrent structural pathology may be present. 1
• Do not perform invasive procedures (lumbar puncture, bone marrow biopsy) if concurrent severe thrombocytopenia or coagulopathy develops. 2
• Recognize that normal inflammatory markers do not exclude infection as a cause of secondary thrombocytosis. 6