What are the potential causes of thrombocytosis in a 53-year-old female?

Causes of Elevated Platelets in a 53-Year-Old Female

In a 53-year-old woman with thrombocytosis, secondary (reactive) causes account for approximately 88% of cases, with tissue damage, infection, and malignancy being the most common etiologies, while primary myeloproliferative neoplasms represent only 12% but carry significantly higher thrombotic risk. 1

Algorithmic Approach to Diagnosis

Step 1: Confirm True Thrombocytosis and Assess Severity

• Verify platelet count ≥450×10⁹/L on repeat testing to confirm sustained elevation 2
• Mild thrombocytosis: 500,000-700,000/μL; Moderate: 700,000-900,000/μL; Severe: >900,000/μL 3
• Review peripheral blood smear to exclude pseudothrombocytosis and evaluate for abnormal cells 2

Step 2: Distinguish Primary vs. Secondary Thrombocytosis

Key discriminating features:

Primary thrombocytosis characteristics:

• Platelet count typically >1,000/μL 3
• JAK2V617F mutation present in 86% of essential thrombocythemia cases 2
• Bone marrow shows megakaryocytic proliferation 2
• Significantly higher risk of arterial AND venous thrombosis 1

Secondary thrombocytosis characteristics:

• Usually platelet count <1,000/μL 1
• Venous thrombosis only occurs with additional risk factors 1
• Identifiable underlying condition 1

Step 3: Evaluate for Secondary Causes (Most Common)

Order these specific tests immediately:

Inflammatory/Infectious workup:

• ESR and CRP to identify chronic inflammation 2
• Complete blood count with differential looking for leukocytosis 1
• Infection accounts for 24% of secondary thrombocytosis: evaluate for pneumonia, urinary tract infection, osteomyelitis, abscess 4, 1

Tissue damage assessment (42% of secondary cases):

• Recent surgery, trauma, burns, or tissue injury 1
• Functional or surgical splenectomy 3

Iron deficiency evaluation:

• Serum ferritin, iron studies, transferrin saturation 2
• Iron deficiency causes thrombocytosis even without anemia 2
• Mean corpuscular volume (MCV) may be normal or low 5

Malignancy screening (13% of secondary cases):

• Age-appropriate cancer screening 1
• Solid tumors and lymphoproliferative disorders both cause thrombocytosis 4

Other laboratory parameters that distinguish primary from secondary:

• Leukocyte count (higher in primary) 1
• Hematocrit (higher in primary) 1
• Lactate dehydrogenase (higher in primary) 1
• Serum potassium (different between groups) 1

Step 4: Evaluate for Primary Myeloproliferative Neoplasms

Proceed with this workup if:

• Platelet count >1,000/μL 3
• No identifiable secondary cause 2
• Patient age >60 years 2
• Presence of systemic symptoms (night sweats, weight loss, pruritus) 2

Required testing for primary thrombocytosis:

• JAK2V617F mutation testing (present in >90% of polycythemia vera, 86% of essential thrombocythemia, 50% of primary myelofibrosis) 2, 6
• Bone marrow biopsy showing megakaryocytic proliferation with mature morphology 2
• CALR and MPL mutation testing if JAK2 negative 5
• Exclusion of BCR-ABL1 (chronic myeloid leukemia) 2

WHO diagnostic criteria for Essential Thrombocythemia requires ALL four:

1. Sustained platelet count ≥450×10⁹/L 2
2. Bone marrow biopsy showing megakaryocytic proliferation 2
3. Exclusion of other myeloid neoplasms 2
4. Demonstration of JAK2V617F or other clonal marker 2

Step 5: Risk Stratification for Thrombosis

Primary thrombocytosis (Essential Thrombocythemia) risk factors:

• Age >60 years (intermediate risk) 5, 7
• Prior thrombosis at any age (high risk) 5, 7
• JAK2V617F mutation presence (increases risk) 5, 6
• Cardiovascular risk factors: smoking, hypertension, diabetes 5
• Leukocytosis >11×10⁹/L 5

Paradoxical finding: Extreme thrombocytosis >1,000/μL actually confers LOWER thrombotic risk but higher bleeding risk 5

Secondary thrombocytosis: Thrombotic events restricted to venous system and only occur with additional risk factors present 1

Critical Clinical Pitfalls to Avoid

Do not assume secondary thrombocytosis is benign:

• The presence of a reactive condition does NOT exclude essential thrombocythemia if WHO criteria are otherwise met 2
• Both conditions can coexist 2

Do not delay bone marrow examination in high-risk patients:

• Mandatory in patients >60 years or with systemic symptoms to exclude myelodysplastic syndromes, leukemias, or other malignancies 2

Do not overlook iron deficiency:

• Iron deficiency can cause thrombocytosis even with normal hemoglobin 2
• Microcytosis (MCV <80 fL) indicates iron deficiency requiring supplementation 5

Do not use platelet count alone for risk stratification:

• Primary thrombocytosis carries significantly higher thrombotic risk regardless of absolute platelet count 2, 1
• Leukocytosis confers 60% increase in thrombotic risk in essential thrombocythemia 5

Special Consideration for This Age Group

At 53 years old, this patient falls into an intermediate-risk category if primary thrombocytosis is diagnosed, requiring careful evaluation but not automatically warranting cytoreductive therapy unless additional risk factors present 7. However, the approach to menstruating women differs as pregnancy potential affects treatment choices—interferon-alpha is preferred over hydroxyurea in women of childbearing age 7.