What causes elevated platelet (thrombocytosis) counts?

Causes of Elevated Platelet Count (Thrombocytosis)

Thrombocytosis (elevated platelet count >450×10^9/L) is primarily caused by secondary conditions (83-88% of cases), with primary hematological disorders accounting for only 12-13% of cases.

Primary Thrombocytosis (12-13% of cases)

• Myeloproliferative neoplasms (MPNs) are the main cause of primary thrombocytosis, with essential thrombocythemia being the most common subtype (45% of primary cases) 1
• Other myeloproliferative disorders include polycythemia vera, primary myelofibrosis, and chronic myeloid leukemia 2
• Primary thrombocytosis is associated with a significantly higher risk of both arterial and venous thromboembolic complications compared to secondary causes 3
• Approximately 86% of patients with primary thrombocytosis have at least one molecular marker indicative of MPNs 1

Secondary Thrombocytosis (83-88% of cases)

Inflammatory Conditions (43-56% of cases)

• Tissue injury/damage (32-42% of cases) - most common cause of secondary thrombocytosis 1, 3
• Infections (17-24% of cases) - bacterial, viral, or fungal 1, 3
• Chronic inflammatory disorders (10-12% of cases) - including autoimmune diseases, rheumatoid arthritis, inflammatory bowel disease 1, 3

Hematologic Disorders

• Iron deficiency anemia (11% of cases) - can cause transient thrombocytosis that resolves with iron supplementation 1, 4
• Hemolytic anemia and post-hemorrhagic states 5
• Post-splenectomy or functional hyposplenism 5

Malignancy

• Non-hematologic malignancies (13% of cases) - solid tumors can cause reactive thrombocytosis 1, 3

Medication-Induced

• Vinca alkaloids have thrombocyte-stimulating properties 4
• Miconazole has been documented to cause thrombocytosis (validated by drug rechallenge) 4
• Adrenaline can cause platelet elevations through demargination of platelets in pulmonary vasculature 4
• Iron supplementation can cause transient thrombocytosis 4
• Beta-lactam antibiotics have been implicated, though difficult to distinguish from acute-phase reactions 4

Other Causes

• Rebound thrombocytosis after treatment of thrombocytopenia 5
• Pregnancy and hormonal influences 5
• Exercise-induced (transient) 5

Clinical Significance and Diagnostic Approach

• Primary thrombocytosis is associated with significantly higher median platelet counts and greater incidence of thrombosis compared to secondary causes 1, 3
• Thrombotic complications in secondary thrombocytosis are typically restricted to the venous system and occur only in the presence of other risk factors 3
• Laboratory parameters that help distinguish primary from secondary thrombocytosis include leukocyte count, hematocrit, erythrocyte sedimentation rate, fibrinogen, serum potassium, and lactate dehydrogenase 3
• Reticulated platelet percentage (RP%) and absolute reticulated platelet counts are significantly higher in thrombocytosis patients with thrombotic complications 6

False Thrombocytopenia (Pseudothrombocytopenia)

• Laboratory artifacts can cause falsely low platelet counts, which must be distinguished from true thrombocytopenia 7
• In conditions with increased hematocrit (polycythemia, cyanotic heart disease), standard amounts of anticoagulant with reduced plasma volume can cause falsely low platelet counts 7

Diagnostic Approach

• Complete blood count with differential to identify isolated thrombocytosis versus other cytopenias 5
• Peripheral blood smear examination to exclude pseudothrombocytopenia and identify abnormalities 5
• Patient history to identify potential secondary causes 5
• Testing for molecular markers (JAK2, CALR, MPL mutations) in suspected primary thrombocytosis 1