What causes thrombocytosis (high platelet count)?

Causes of High Platelet Count (Thrombocytosis)

Thrombocytosis is broadly divided into primary (clonal myeloproliferative disorders) and secondary (reactive) causes, with secondary thrombocytosis accounting for approximately 88% of cases and being far more common in clinical practice. 1

Primary Thrombocytosis (Clonal Disorders)

Primary thrombocytosis represents clonal bone marrow disorders where platelet production is intrinsically dysregulated:

• Essential thrombocythemia (ET) is characterized by sustained platelet count ≥450 × 10⁹/L, bone marrow proliferation of enlarged mature megakaryocytes, and presence of JAK2V617F mutation (found in ~50% of cases) or other clonal markers. 2, 3
• Polycythemia vera can present with elevated platelet counts as part of the myeloproliferative process. 2
• Primary myelofibrosis causes thrombocytosis through megakaryocyte proliferation with abnormal nuclear morphology (bulbous or irregularly folded nuclei). 2, 3
• Chronic myeloid leukemia is another myeloproliferative disorder that can manifest with thrombocytosis. 2

Primary thrombocytosis is extremely rare in children (incidence of 1 per million) but more common in adults, with median diagnosis age around 11 years in pediatric cases. 4

Secondary (Reactive) Thrombocytosis

Secondary thrombocytosis is a reactive process and represents the vast majority of cases encountered clinically:

Tissue Damage and Trauma

• Surgery, burns, and trauma are the most frequent causes of secondary thrombocytosis (42% of cases). 1
• Post-operative thrombocytosis is common and expected. 2

Infections

• Acute bacterial or viral infections account for 24% of secondary thrombocytosis cases. 1
• HIV and hepatitis C can cause thrombocytosis indistinguishable from primary forms. 3
• Helicobacter pylori infection should be evaluated as a potential cause. 3

Malignancy

• Solid tumors and lymphoproliferative disorders cause thrombocytosis through inflammatory cytokine production (13% of cases). 2, 1
• Erythropoiesis-stimulating agents in cancer patients are associated with thrombocytosis. 2

Chronic Inflammatory Conditions

• Inflammatory bowel disease and rheumatoid arthritis cause sustained platelet elevation through chronic inflammation (10% of cases). 2, 1

Hematologic Causes

• Iron deficiency anemia is an important cause that must be excluded before diagnosing essential thrombocythemia, as occult polycythemia vera may be masked. 2
• Post-splenectomy or hyposplenism leads to thrombocytosis due to loss of splenic platelet sequestration. 2

Drug-Induced

• Corticosteroids and epinephrine can cause drug-induced thrombocytosis. 2

Critical Diagnostic Distinction: Primary vs Secondary

The key clinical difference is that primary thrombocytosis carries significantly higher risk of thromboembolic complications, while secondary thrombocytosis poses minimal thrombotic risk unless additional risk factors are present. 1

Features Suggesting Primary Thrombocytosis:

• Higher platelet counts (typically >1,000 × 10⁹/L, though not absolute). 4, 1
• Splenomegaly on examination. 5
• Both arterial and venous thrombotic events without other risk factors. 1
• Paradoxical bleeding despite high platelets due to qualitative platelet defects. 5
• Laboratory findings: Lower erythrocyte sedimentation rate, lower fibrinogen, different leukocyte count and hematocrit patterns compared to secondary causes. 1

Features Suggesting Secondary Thrombocytosis:

• Identifiable underlying condition (infection, inflammation, malignancy, trauma). 1
• Venous thrombosis only, and only when additional risk factors present. 1
• Mild to moderate elevation (72-86% of pediatric cases have platelet counts 500-700 × 10⁹/L). 4

Special Consideration in Cancer-Associated DIC

In malignancy-related disseminated intravascular coagulation, a decreasing platelet trend from an initially elevated level may be the only sign of DIC, even if the absolute count remains in the normal range—this is a crucial observation that is often discounted as unimportant. 6