Causes of Thrombocytosis with Small Platelet Size
Small platelets in the setting of thrombocytosis are most characteristically seen in Wiskott-Aldrich Syndrome (WAS), where platelet volumes range from 3.8 to 5.0 fL compared to normal 7.1 to 10.5 fL, making this the primary diagnostic consideration when encountering this specific combination. 1
Primary Diagnostic Consideration: Wiskott-Aldrich Syndrome
Thrombocytopenia with small platelet size is the most consistent clinical laboratory abnormality of WAS, and small platelet size confirms the diagnosis in the appropriate clinical context. 1 The homogeneity of the small platelet size distinguishes WAS from other thrombocytopenias where small platelets may occasionally be seen. 1
Key Clinical Features to Assess:
- X-linked inheritance pattern (affects males) 1
- Eczema - often present in classical WAS 1
- Recurrent infections - serious infections occur in approximately 7% of X-linked thrombocytopenia (XLT) cases 1
- Bleeding manifestations - bruising and easy bleeding are initial presentations 1
- Autoimmune phenomena - occurs in 12% of XLT patients, including colitis, vasculitis, and glomerulonephritis 1
- Malignancy risk - lymphomas occur in 5% of XLT patients and 10-15% of classical WAS patients 1
Diagnostic Confirmation:
- Blood smear examination should be performed when automated counters report normal platelet size in suspected cases 1
- Molecular diagnosis by identifying WAS gene mutations is definitive 1
- WAS protein expression analysis via Western blot or flow cytometry can be performed on lymphocytes 1
Important Caveat Regarding Thrombocytosis vs. Thrombocytopenia
It is critical to note that WAS typically presents with thrombocytopenia (low platelet count), not thrombocytosis (high platelet count). 1 However, up to 20% of WAS patients can develop immune thrombocytopenia either before or after splenectomy, which may complicate the clinical picture. 1
Alternative Consideration: Essential Thrombocythemia
If the question refers to thrombocytosis (elevated platelets ≥450 × 10⁹/L) with relatively smaller platelet size compared to typical reactive thrombocytosis:
Essential thrombocythemia (ET) is characterized by bone marrow proliferation of enlarged, mature megakaryocytes, but the circulating platelets themselves may vary in size. 1 The diagnosis requires:
- Sustained platelet count ≥450 × 10⁹/L 1
- Bone marrow biopsy showing megakaryocytic lineage proliferation with enlarged, mature megakaryocytes 1
- JAK2 V617F mutation (present in approximately 50% of ET cases) or other clonal markers (CALR, MPL) 1, 2
- Exclusion of reactive causes including iron deficiency, infection, inflammation, malignancy, and post-splenectomy states 1, 3
Secondary Thrombocytosis Causes:
When thrombocytosis is secondary (reactive), the most common causes include:
- Tissue injury (32.2% of cases) - surgery, trauma, burns 3, 4
- Infection (17.1% of cases) - acute bacterial or viral infections 3, 4
- Chronic inflammatory disorders (11.7% of cases) - inflammatory bowel disease, rheumatoid arthritis 3, 4
- Iron deficiency anemia (11.1% of cases) - frequently overlooked cause 3, 5, 4
- Malignancy - solid tumors and lymphoproliferative disorders 3, 5
- Post-splenectomy or hyposplenism 3
Secondary thrombocytosis generally does not require cytoreductive therapy and resolves with treatment of the underlying condition. 3