Causes of Elevated Platelet Count (468 ×10⁹/L)
A platelet count of 468 ×10⁹/L represents mild thrombocytosis that is most commonly secondary (reactive) rather than primary, with the leading causes being infection, inflammation, iron deficiency anemia, malignancy, and recent tissue damage or surgery. 1
Primary vs. Secondary Thrombocytosis: The Critical Distinction
Secondary (reactive) thrombocytosis accounts for the vast majority of cases in clinical practice and rarely causes thrombotic complications, whereas primary thrombocytosis represents a clonal myeloproliferative neoplasm with significant thrombotic risk. 1, 2
Secondary Thrombocytosis Causes (Most Common)
Infection and inflammation are the most frequent triggers, with elevated acute phase reactants (C-reactive protein, fibrinogen, ESR, IL-6) confirming the reactive nature. 1, 3
Iron deficiency anemia is frequently overlooked but accounts for 11% of secondary thrombocytosis cases—check ferritin, iron studies, and mean corpuscular volume. 1
Malignancy (solid tumors and lymphoproliferative disorders) can drive platelet elevation through cytokine production, often accompanied by elevated leukocyte count. 1, 2
Chronic inflammatory disorders including connective tissue diseases and inflammatory bowel disease produce sustained thrombocytosis with evidence of underlying inflammatory process. 1
Post-hemorrhagic states and hemolytic anemia trigger compensatory platelet production. 1
Post-splenectomy or functional hyposplenism removes the splenic platelet reservoir, causing persistent elevation. 1
Tissue damage from recent surgery, trauma, or burns stimulates thrombopoietin release. 1, 4
Rebound thrombocytosis can occur after recovery from bone marrow suppression or chemotherapy. 1
Primary Thrombocytosis (Myeloproliferative Neoplasms)
Essential thrombocythemia (ET) is 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, often with leukocytosis, lower ESR, lower fibrinogen, and lower serum potassium. 1
Primary myelofibrosis and chronic myeloid leukemia are other myeloproliferative disorders that can present with thrombocytosis. 1
Diagnostic Algorithm for Platelet Count 468 ×10⁹/L
Step 1: Confirm True Thrombocytosis
Review the complete blood count with differential to identify isolated thrombocytosis versus other cytopenias or leukocytosis. 1
Examine the peripheral blood smear to exclude pseudothrombocytosis and identify abnormalities suggesting primary versus secondary causes. 1
Step 2: Assess for Obvious Secondary Causes
Obtain targeted history focusing on:
- Recent or current infection (most common cause) 1, 3
- Chronic inflammatory conditions 1
- Recent surgery, trauma, or tissue injury 1, 4
- Symptoms of iron deficiency (menorrhagia, GI blood loss) 1
- Known malignancy or constitutional symptoms (fever, weight loss, night sweats) 1, 2
- Splenectomy history 1
Laboratory evaluation for secondary causes:
- Iron studies (ferritin, serum iron, TIBC, transferrin saturation) 1
- Inflammatory markers (CRP, ESR, fibrinogen) 1, 3
- Complete metabolic panel 1
Step 3: Molecular Testing if No Clear Secondary Cause
At a platelet count of 468 ×10⁹/L with no obvious secondary cause, obtain molecular testing for JAK2V617F, CALR, and MPL mutations to exclude essential thrombocythemia. 1
If platelet count exceeds 1000 ×10⁹/L, molecular testing is mandatory regardless of apparent secondary causes due to higher likelihood of primary thrombocytosis. 1
Step 4: Bone Marrow Biopsy (Selected Cases)
Bone marrow biopsy is indicated if:
- Molecular markers (JAK2V617F, CALR, MPL) are positive 1
- Clinical suspicion remains high for myeloproliferative neoplasm despite negative molecular testing 1
- Platelet count remains persistently elevated without clear secondary cause 1
- Other cytopenias or abnormal blood count parameters are present 1
Risk Stratification and Clinical Implications
Secondary thrombocytosis at this level (468 ×10⁹/L) carries minimal thrombotic risk and requires no specific antiplatelet therapy beyond treating the underlying condition. 2, 3
Primary thrombocytosis (essential thrombocythemia) carries significant thrombotic risk requiring cardiovascular risk factor modification, antiplatelet agents, and potentially cytoreductive therapy in high-risk patients. 2
Common Pitfalls to Avoid
Do not assume thrombocytosis is benign without excluding iron deficiency—this treatable cause is missed in 11% of cases. 1
Do not overlook occult malignancy—thrombocytosis may be the presenting sign of solid tumors or hematological conditions. 1, 2
Do not delay molecular testing in unexplained persistent thrombocytosis—early identification of myeloproliferative neoplasms allows appropriate thrombotic risk stratification and management. 1
Do not initiate antiplatelet therapy for secondary thrombocytosis—treatment should focus on the underlying condition, as reactive thrombocytosis rarely causes vascular complications. 2, 3