What causes a slightly elevated platelet count (thrombocytosis)?

Causes of Slightly Elevated Platelet Count (Thrombocytosis)

A slightly elevated platelet count is most commonly caused by secondary (reactive) thrombocytosis, with tissue injury, infection, chronic inflammation, and iron deficiency being the leading culprits, accounting for over 70% of cases. 1, 2

Primary vs. Secondary Thrombocytosis

Secondary thrombocytosis represents the vast majority of cases (83.1%), while primary thrombocytosis accounts for only 12.5% of patients with elevated platelet counts. 2 This distinction is critical because primary thrombocytosis carries significantly higher thrombotic risk and requires different management. 2

Most Common Causes of Secondary Thrombocytosis

The leading causes, in order of frequency, include:

• Tissue injury (32.2% of cases) - including trauma, surgery, burns, or tissue necrosis 2
• Infection (17.1% of cases) - both acute and chronic infectious processes 2
• Chronic inflammatory disorders (11.7% of cases) - such as connective tissue diseases and inflammatory bowel disease 1, 2
• Iron deficiency anemia (11.1% of cases) - a frequently overlooked but common cause 1, 2
• Malignancy - including solid tumors and lymphoproliferative disorders 1
• Post-splenectomy or functional hyposplenism 1

Primary Thrombocytosis Causes

When thrombocytosis is clonal (primary), the main disorders include:

• Essential thrombocythemia (ET) - the most common primary cause (45% of primary cases), characterized by sustained platelet count ≥450 × 10⁹/L with JAK2V617F, CALR, or MPL mutations 1
• Polycythemia vera - presents with elevated platelets alongside increased red cell mass 1
• Primary myelofibrosis 1
• Chronic myeloid leukemia 1

Diagnostic Algorithm

When encountering slightly elevated platelets, follow this systematic approach:

1. Confirm true thrombocytosis - exclude pseudothrombocytosis from laboratory artifacts, microspherocytes, schistocytes, or cryoglobulins 3

2. Obtain complete blood count with differential - look for isolated thrombocytosis versus other cytopenias or leukocytosis 1

3. Assess for obvious secondary causes - evaluate for infection, inflammation, iron deficiency, malignancy, recent surgery/trauma, or splenectomy 1

4. Check inflammatory markers - elevated C-reactive protein, fibrinogen, erythrocyte sedimentation rate, and interleukin-6 support secondary thrombocytosis 4

5. Molecular testing if indicated - obtain JAK2V617F, CALR, and MPL mutations if no clear secondary cause is identified OR if platelet count >1000 × 10⁹/L 1

6. Bone marrow biopsy - recommended if molecular markers are positive or clinical suspicion is high for myeloproliferative neoplasm 1

Key Clinical Distinctions

Platelet count levels provide important clues:

• Secondary thrombocytosis typically has lower median platelet counts than primary thrombocytosis 2
• Extreme thrombocytosis (>1000 × 10⁹/L) warrants molecular testing regardless of apparent secondary causes 1

Thrombotic risk differs dramatically:

• Primary thrombocytosis carries significantly higher thrombosis incidence 2
• Secondary thrombocytosis rarely causes thrombosis at any platelet count 4
• Paradoxically, extreme thrombocytosis (>1000 × 10⁹/L) in essential thrombocythemia is associated with lower thrombotic risk but higher hemorrhagic risk 5

Common Pitfalls to Avoid

• Don't overlook iron deficiency - check iron studies, as this accounts for 11% of cases and is easily treatable 1, 2
• Don't assume benign reactive cause in young patients - essential thrombocythemia can occur at any age and requires molecular testing if no clear secondary cause exists 1
• Don't order molecular testing prematurely - first exclude obvious secondary causes through history, examination, and basic laboratory work 1
• Don't treat secondary thrombocytosis with cytoreductive therapy - it resolves with treatment of the underlying condition 6