What can cause anemia and thrombocytosis in patients, particularly those with a history of cancer, inflammatory disorders, or bleeding disorders?

Causes of Anemia and Thrombocytosis

The combination of anemia and thrombocytosis most commonly occurs in three clinical scenarios: active malignancy, chronic inflammatory diseases (particularly Adult-Onset Still's Disease and inflammatory bowel disease), and iron deficiency anemia. 1

Primary Causes

Malignancy

• Cancer is a leading cause of concurrent anemia and thrombocytosis, with thrombocytosis occurring in approximately 34% of patients with malignancy at diagnosis or within the first year. 2
• The anemia results from multiple mechanisms: bone marrow infiltration by cancer cells, cytokine-mediated iron sequestration reducing red blood cell production, chronic blood loss at tumor sites, and chemotherapy-induced myelosuppression. 1
• Thrombocytosis in malignancy represents a paraneoplastic phenomenon, though 74% of cancer patients with elevated platelets have concurrent contributing factors including iron deficiency, anemia itself, inflammatory states, or recent surgical procedures. 2
• Common pitfall: Do not assume thrombocytosis in cancer is purely reactive—35% of these patients experience hemorrhagic or thrombotic complications requiring clinical attention. 2

Chronic Inflammatory Diseases

• Adult-Onset Still's Disease (AOSD) characteristically presents with both anemia of chronic disease and reactive thrombocytosis, with anemia returning to normal when disease activity subsides. 1
• The pathophysiology involves chronic inflammation driving a cytokine cascade that causes leucocytosis, anemia, and thrombocytosis—all markers of increased disease activity. 1
• Inflammatory bowel disease produces anemia through multiple mechanisms (blood loss, iron deficiency, anemia of chronic disease) while inflammation drives reactive thrombocytosis. 1
• Key diagnostic feature: Elevated inflammatory markers (ESR, CRP, fibrinogen, alpha-2 globulins) accompany both the anemia and thrombocytosis in inflammatory conditions. 1, 2

Iron Deficiency Anemia

• Iron deficiency itself causes both anemia and reactive thrombocytosis, making it a critical diagnosis to establish or exclude. 3, 2
• Iron deficiency was significantly associated with secondary thrombocytosis in a 2024 study examining thrombocytosis etiology. 3
• This combination is particularly common in patients with chronic gastrointestinal bleeding, where 60-70% of patients with iron deficiency anemia have an identifiable GI source. 4

Secondary Causes

Bleeding Disorders

• Chronic blood loss produces both anemia (from red cell loss) and reactive thrombocytosis (as a compensatory bone marrow response). 1
• Acute hemorrhage may initially present with elevated reticulocytes and reactive thrombocytosis before anemia fully develops. 1

Post-Splenectomy State

• Splenectomy causes persistent thrombocytosis while any underlying condition (malignancy, inflammatory disease) continues to produce anemia. 1, 3
• This was identified as a significant predictor of secondary thrombocytosis in recent diagnostic algorithms. 3

Medication-Induced

• Hydroxyurea causes both myelosuppression with anemia AND can cause hemolytic anemia, though it typically reduces rather than increases platelet counts. 5
• Other chemotherapeutic agents cause anemia through myelosuppression while reactive thrombocytosis may occur as a compensatory response. 1

Diagnostic Approach

When evaluating anemia with thrombocytosis, prioritize these investigations:

• Screen for malignancy: Active cancer, history of malignancy, constitutional symptoms (fever, weight loss), lymphadenopathy, hepatosplenomegaly. 1, 3
• Assess for inflammation: ESR, CRP, clinical features of inflammatory diseases (arthritis, rash, fever patterns in AOSD). 1
• Evaluate iron status: Ferritin, transferrin saturation, TIBC—recognizing that ferritin may be falsely elevated in inflammatory states. 1
• Identify bleeding sources: Stool guaiac, endoscopy if indicated, particularly in iron deficiency. 1, 4
• Laboratory parameters favoring secondary thrombocytosis: Higher BMI, elevated white blood cells and neutrophils, presence of iron deficiency, active malignancy, or chronic inflammatory disease. 3

Critical distinction: Essential thrombocythemia (requiring molecular testing) is associated with higher hemoglobin, MCV, RDW, and MPV, plus history of arterial thrombosis—the opposite hematologic profile from secondary thrombocytosis with anemia. 3