What is the treatment approach for a 39-year-old patient with anemia (low hemoglobin and hematocrit levels) and thrombocytosis (elevated platelet count)?

Treatment Approach for 39-Year-Old with Anemia and Thrombocytosis

The immediate priority is to identify and treat the underlying cause of this patient's anemia with reactive thrombocytosis, most commonly iron deficiency, while ruling out myeloproliferative neoplasm before considering any cytoreductive therapy. 1

Initial Diagnostic Workup

The diagnostic evaluation must proceed systematically to differentiate reactive thrombocytosis from primary myeloproliferative disease:

• Obtain peripheral blood smear immediately to assess red cell morphology (microcytosis, hypochromia suggesting iron deficiency), platelet morphology, and exclude schistocytes or abnormal cells 1
• Check reticulocyte count to determine if the bone marrow is responding appropriately—a low count suggests production defects or iron deficiency, while an elevated count suggests hemolysis or bleeding 1
• Perform comprehensive iron studies including serum ferritin and transferrin saturation to identify absolute or functional iron deficiency, as this is the most common cause of combined anemia and thrombocytosis 1, 2
• Assess for hemolysis with LDH, haptoglobin, indirect bilirubin, and direct antiglobulin test (Coombs) 1
• Obtain liver function tests including GGT, as elevated GGT with cytopenias may indicate hepatobiliary involvement 1

Critical Differential Diagnosis

Iron Deficiency Anemia (Most Likely)

Iron deficiency is the most common cause of reactive thrombocytosis and can produce extreme elevations:

• Platelet counts can reach 1,953-2,500 × 10⁹/L in severe iron deficiency, representing a four to fivefold increase 2, 3
• The thrombocytosis is reactive and resolves with iron replacement 2, 4, 3
• Microcytic, hypochromic red cells on smear strongly support this diagnosis 5
• Investigate sources of iron loss: menorrhagia, gastrointestinal bleeding, dietary insufficiency, malabsorption (including history of bariatric surgery) 2, 3

Myeloproliferative Neoplasm (Must Exclude)

Bone marrow aspiration and biopsy with cytogenetic analysis is essential to exclude primary myeloproliferative disorders before attributing thrombocytosis to reactive causes 1

• In polycythemia vera, hematocrit is typically elevated (>59%), not reduced as in this patient 5
• Primary thrombocytosis would not typically present with anemia unless there is concurrent bleeding or iron deficiency 5

Treatment Algorithm

If Iron Deficiency Confirmed:

Initiate oral iron supplementation immediately as the definitive treatment:

• Iron replacement will correct both the anemia and thrombocytosis within 1-3 months 2, 4, 3
• Monitor complete blood count weekly initially, then monthly 6
• Do NOT initiate cytoreductive therapy (such as hydroxyurea) for reactive thrombocytosis, as this resolves with iron replacement 2, 3
• Address the underlying cause of iron deficiency (treat menorrhagia, investigate GI bleeding, optimize absorption) 1, 3

If Myeloproliferative Neoplasm Confirmed:

• Supportive care and cytoreductive therapy may be indicated 1
• Consider hydroxyurea or ruxolitinib depending on specific diagnosis 1
• Monitor for myelosuppression as hydroxyurea causes severe bone marrow suppression 6

Thrombotic Risk Management:

While the platelet count is elevated, assess thrombotic risk:

• Iron deficiency with thrombocytosis carries thrombotic risk, including cerebral venous thrombosis, particularly in young patients 7
• Anemia itself (hemoglobin <9.2 g/dL) is a bleeding risk factor and modifies thrombotic risk 5
• Do NOT routinely anticoagulate for reactive thrombocytosis alone unless there are additional risk factors or thrombotic events 1
• Ensure adequate hydration and early mobilization 1

Transfusion Considerations:

• Red blood cell transfusion is indicated if the patient is symptomatic or hemodynamically unstable 5
• For asymptomatic patients with hemoglobin 10 g/dL, transfusion can be deferred while initiating iron replacement 5
• Maintain platelet count >50 × 10⁹/L if invasive procedures are planned, though this patient's thrombocytosis exceeds this threshold 1

Common Pitfalls to Avoid

• Do not assume primary thrombocytosis without bone marrow evaluation—reactive thrombocytosis from iron deficiency can be extreme 2, 3
• Do not initiate cytoreductive therapy empirically—this can worsen anemia and is unnecessary for reactive thrombocytosis 6
• Do not overlook iron deficiency in patients with extreme thrombocytosis—the degree of elevation does not distinguish primary from secondary causes 2, 3
• Do not forget to investigate the source of iron loss—particularly menorrhagia in women and GI bleeding in all patients 1, 3
• Do not delay iron supplementation while awaiting bone marrow results if iron deficiency is strongly suspected clinically 1

Monitoring Plan

• Weekly complete blood counts during initial treatment phase 6
• Expect platelet count normalization within 1-3 months of iron replacement 2, 4, 3
• Hemoglobin should improve within 1 month of adequate iron supplementation 5
• If counts do not normalize with iron replacement, reconsider bone marrow evaluation for primary disorder 1