What is Reactive Thrombocytosis
Reactive thrombocytosis is a non-clonal elevation of platelet count above 450 × 10⁹/L that occurs secondary to an underlying condition, where increased platelet production is stimulated by cytokines in the bone marrow rather than arising from a primary hematologic malignancy. 1
Definition and Pathophysiology
- Reactive thrombocytosis represents a physiologic response to cytokine-mediated stimulation of megakaryocyte production in the bone marrow, distinguishing it from clonal myeloproliferative disorders 2
- The platelet elevation is secondary to an identifiable underlying cause rather than an autonomous proliferation of the megakaryocytic lineage 1
- This condition lacks clonal markers such as JAK2 V617F mutation, which when present would indicate a primary myeloproliferative neoplasm 1
Common Underlying Causes
The WHO classification identifies specific triggers for reactive thrombocytosis 1:
- Iron deficiency (one of the most common causes)
- Post-splenectomy or functional asplenia
- Acute infections (bacterial, viral)
- Chronic inflammation (connective tissue diseases, inflammatory bowel disease)
- Malignancy (metastatic cancer, lymphoproliferative disorders)
- Tissue damage (surgery, trauma, burns)
- Medications (certain drugs can trigger reactive platelet elevation)
Clinical Significance and Thrombotic Risk
- In children and adults without additional thrombotic risk factors, reactive thrombocytosis carries negligible risk of thromboembolic complications, even with extreme thrombocytosis (>1000 × 10⁹/L) 3
- Patients with reactive thrombocytosis secondary to non-myeloproliferative malignancy have increased thrombotic risk and may benefit from antithrombotic prophylaxis 2, 3
- Thrombotic complications occur in less than 5% of reactive thrombocytosis cases overall 4
- In acute infectious diseases, approximately 8% of hospitalized patients develop reactive thrombocytosis, which correlates with enhanced acute-phase response, longer hospital stays, and more bacteremia, though thrombotic complications remain rare 5
Distinguishing from Primary Thrombocytosis
Critical diagnostic features that exclude primary thrombocythemia 1:
- Absence of JAK2 V617F or other clonal markers (present in ~50% of essential thrombocythemia)
- Normal bone marrow morphology without proliferation predominantly of megakaryocytic lineage with enlarged, mature megakaryocytes
- Does not meet WHO criteria for polycythemia vera, primary myelofibrosis, BCR-ABL1-positive CML, or myelodysplastic syndrome
- Resolves with treatment of the underlying condition
Temporal Pattern and Resolution
- In iron deficiency anemia-induced thrombocytosis, 50% of patients resolve thrombocytosis after 2 weeks of iron supplementation, and all patients normalize within 6 weeks 6
- In acute infections, thrombocytosis may be present on admission (56% of cases) or develop during hospitalization, with timing varying by infection type: 1 day median for pneumonia, 4 days for UTI, 7.5 days for skin/soft tissue infections 5
- Inflammatory conditions like adult-onset Still's disease commonly cause reactive thrombocytosis that correlates with disease activity and normalizes with disease remission 1, 2
Prevalence
- Reactive thrombocytosis occurs in 3-13% of hospitalized children, making it very common in pediatric populations 7
- In adults with acute infectious diseases, approximately 7.6% develop infection-associated thrombocytosis 5
- Primary thrombocythemia is 60 times less common in children than adults, with incidence of one per million children 7