What is the best initial management for a 19-year-old woman with thrombocytosis (platelet count 551 × 10⁹/L) and mildly elevated C‑reactive protein and erythrocyte sedimentation rate?

Management of Reactive Thrombocytosis with Inflammatory Markers

For a 19-year-old woman with a platelet count of 551,000/μL and elevated inflammatory markers (CRP 1.7, ESR 31), the priority is to identify and treat the underlying cause of reactive thrombocytosis rather than treating the platelet count itself. 1

Immediate Diagnostic Workup

The first step is to distinguish reactive (secondary) thrombocytosis from a primary myeloproliferative neoplasm (MPN). 1 At age 19 with mildly elevated platelets and clear inflammatory markers, reactive thrombocytosis is far more likely than essential thrombocythemia.

Essential Laboratory Tests

• Complete blood count with differential to assess for leukocytosis, anemia, or other cytopenias 1
• Iron studies (serum iron, ferritin, TIBC, transferrin saturation) – iron deficiency is the most common cause of reactive thrombocytosis in young women and can produce extreme platelet elevations 2, 3
• Peripheral blood smear to evaluate platelet morphology and rule out spurious thrombocytosis 4
• Comprehensive metabolic panel to assess for renal or hepatic disease 1

Targeted Evaluation Based on Inflammatory Markers

The elevated CRP (1.7) and ESR (31) indicate an active inflammatory process that is likely driving the thrombocytosis. 1, 4 Investigate for:

• Infectious causes: chest X-ray, urinalysis with culture, viral serologies if clinically indicated 5
• Inflammatory conditions: ANA, RF, anti-CCP if joint symptoms or rash present 4
• Occult malignancy: age-appropriate cancer screening is generally not indicated at 19 unless specific symptoms suggest malignancy 5
• Menstrual history: assess for menorrhagia causing iron deficiency 3
• Recent surgery or trauma: common triggers for reactive thrombocytosis 5

When to Consider Myeloproliferative Neoplasm Testing

JAK2 V617F mutation testing should be reserved for patients with persistent thrombocytosis after treating secondary causes, or if clinical features suggest primary thrombocytosis. 1 At this platelet level (551,000/μL) with clear inflammatory markers, MPN testing is not indicated initially.

Red flags that would prompt earlier MPN evaluation include:

• Platelet count >1,000/μL 1
• Splenomegaly on examination 1
• Absence of identifiable secondary cause after thorough workup 1
• Persistent thrombocytosis despite treatment of underlying condition 1

Treatment Strategy

Do NOT Treat the Platelet Count

At a platelet count of 551,000/μL without thrombotic or hemorrhagic symptoms, cytoreductive therapy is absolutely not indicated. 6, 1 Reactive thrombocytosis at this level does not increase thrombotic risk and requires no platelet-directed therapy.

Treat the Underlying Cause

Iron deficiency is the most likely diagnosis in a 19-year-old woman with thrombocytosis and should be aggressively treated if confirmed. 2, 3

• If iron deficiency is present: oral iron supplementation (ferrous sulfate 325 mg three times daily) will normalize platelet counts within weeks 2, 3
• If inflammatory condition identified: treat the specific condition (antibiotics for infection, anti-inflammatory therapy for autoimmune disease) 5, 4
• If malignancy discovered: oncology referral and cancer-directed therapy 5

Antiplatelet Therapy Considerations

Aspirin is NOT routinely indicated for reactive thrombocytosis, even at this platelet level. 4 The only scenario where aspirin might be considered is if the patient has:

• Additional cardiovascular risk factors 4
• Documented thrombotic event 4
• Confirmed essential thrombocythemia with JAK2 mutation (not applicable here) 6

For reactive thrombocytosis, aspirin does not reduce thrombotic risk and may increase bleeding risk unnecessarily. 4

Monitoring Plan

• Recheck CBC in 2-4 weeks after initiating treatment for the underlying cause 1
• If platelet count normalizes with treatment, no further hematologic workup is needed 1
• If thrombocytosis persists >3 months despite treating secondary causes, refer to hematology for MPN evaluation including JAK2, CALR, and MPL mutation testing 1

Critical Pitfalls to Avoid

• Do not start hydroxyurea or other cytoreductive therapy – this is only indicated for high-risk essential thrombocythemia or polycythemia vera, not reactive thrombocytosis 6
• Do not prescribe aspirin reflexively – it provides no benefit in reactive thrombocytosis and adds bleeding risk 4
• Do not order expensive MPN mutation panels initially – wait until secondary causes are excluded 1
• Do not overlook iron deficiency – it can cause extreme thrombocytosis (>1,900,000/μL) and is easily treatable 2, 3