Causes of Thrombocytosis
Thrombocytosis (platelet count >450×10^9/L) is most commonly caused by secondary or reactive conditions (83.1%), while primary thrombocytosis accounts for only 12.5% of cases. 1
Primary Thrombocytosis
Primary thrombocytosis refers to clonal disorders where increased platelet production occurs due to abnormal megakaryocyte proliferation:
1. Myeloproliferative Neoplasms (MPNs)
Essential Thrombocythemia (ET)
- Characterized by sustained platelet count ≥450×10^9/L
- Bone marrow shows proliferation of megakaryocytic lineage with enlarged, mature megakaryocytes
- Often positive for JAK2V617F (in ~50% of cases) or other clonal markers (CALR, MPL mutations)
- Diagnosis requires ruling out other myeloid neoplasms 2
Polycythemia Vera (PV)
- JAK2 mutation present in >95% of cases
- Elevated hemoglobin/hematocrit with thrombocytosis 2
Primary Myelofibrosis (PMF)
- Characterized by megakaryocyte proliferation with atypia and fibrosis
- JAK2V617F mutation in ~50% of cases
- Often presents with leukoerythroblastosis, anemia, and splenomegaly 2
Chronic Myeloid Leukemia (CML)
- Presence of Philadelphia chromosome or BCR-ABL fusion gene
- Thrombocytosis may be present at diagnosis 3
Secondary (Reactive) Thrombocytosis
Secondary thrombocytosis is much more common and occurs as a reaction to various underlying conditions:
1. Tissue Injury (32.2% of secondary cases) 1
- Surgical procedures
- Trauma
- Burns
2. Infections (17.1% of secondary cases) 1
- Bacterial, viral, or fungal infections
- Particularly common in children
3. Chronic Inflammatory Disorders (11.7% of secondary cases) 1
- Inflammatory bowel disease
- Rheumatoid arthritis
- Systemic lupus erythematosus
- Vasculitis
4. Iron Deficiency Anemia (11.1% of secondary cases) 1
- Common cause, especially in women and children
5. Other Important Causes
Malignancy
- Solid tumors (lung, breast, gastrointestinal, ovarian)
- Lymphoproliferative disorders 2
Post-splenectomy
- Functional or surgical removal of spleen 3
Drug-induced
- Corticosteroids
- Epinephrine
- Vincristine 2
Rebound thrombocytosis
- Following myelosuppressive chemotherapy
- After resolution of immune thrombocytopenia
Diagnostic Approach
When evaluating thrombocytosis, consider these key factors:
Platelet count severity:
- Mild: 450-700×10^9/L
- Moderate: 700-900×10^9/L
- Severe: >900×10^9/L
- Extreme: >1,000×10^9/L 4
Clinical factors that suggest primary thrombocytosis:
- History of arterial thrombosis
- Higher hemoglobin, MCV, RDW, and MPV 5
- Persistent elevation without obvious cause
- Extreme thrombocytosis (>1,000×10^9/L)
- Family history of blood disorders
Clinical factors that suggest secondary thrombocytosis:
- Active malignancy
- Chronic inflammatory disease
- Recent splenectomy
- Iron deficiency
- Higher BMI, WBC, and neutrophil count 5
- Recent infection or inflammation
Clinical Implications
The distinction between primary and secondary thrombocytosis is critical for patient management:
Primary thrombocytosis carries a significantly higher risk of thrombotic complications and requires specific hematologic management 1
Secondary thrombocytosis rarely causes thrombotic complications and treatment should focus on the underlying cause 4
In children, reactive thrombocytosis accounts for >95% of cases and is usually self-limiting once the underlying condition resolves 4
Important Caveats
The presence of a condition associated with reactive thrombocytosis does not exclude the possibility of essential thrombocythemia if diagnostic criteria are met 2
JAK2V617F or other clonal markers are not universally present in all cases of primary thrombocytosis, nor are they completely specific to any single MPN 6
Bone marrow examination remains a key diagnostic step in distinguishing between different causes of thrombocytosis, particularly when clinical features are ambiguous 6