What is the management approach for a patient with anemia, leukocytosis, and thrombocytosis?

Management of Anemia with Leukocytosis and Thrombocytosis

The immediate priority is to determine whether this represents reactive changes secondary to iron deficiency anemia versus a primary myeloproliferative neoplasm, as the distinction fundamentally alters management from simple iron supplementation to potential cytoreductive therapy.

Initial Diagnostic Workup

The combination of anemia (Hgb 105 g/L), leukocytosis (WBC 21.5), and thrombocytosis (platelets 416) requires immediate investigation to differentiate reactive from clonal processes:

Essential Laboratory Studies

• Iron studies (serum ferritin, transferrin saturation, TIBC) must be obtained immediately to confirm or exclude iron deficiency 1, 2
• Reticulocyte count to assess bone marrow response and distinguish regenerative from non-regenerative anemia 1, 2
• Peripheral blood smear to evaluate red cell morphology (microcytic vs normocytic), assess for schistocytes, and examine white cell differential 3, 1
• Inflammatory markers (CRP, ESR) to assess for anemia of chronic disease or underlying inflammatory conditions 2, 4
• MCV to classify anemia as microcytic (<80 fL), normocytic (80-100 fL), or macrocytic (>100 fL) 1
• Renal function (creatinine) to exclude renal causes 1, 2
• LDH and indirect bilirubin to evaluate for hemolysis 3

Critical Distinction: Reactive vs Clonal

If iron deficiency is confirmed (low ferritin, low transferrin saturation, microcytic anemia), the leukocytosis and thrombocytosis are likely reactive phenomena that will resolve with iron replacement 5. One case report documented extreme thrombocytosis (2500 × 10⁹/L) and leukocytosis (35 × 10⁹/L) that rapidly resolved with iron supplementation alone 5.

If iron studies are normal or ferritin is elevated, consider myeloproliferative neoplasm and obtain:

• JAK2V617F mutation testing - present in 50-70% of essential thrombocythemia and nearly all polycythemia vera cases 6
• Bone marrow biopsy if JAK2 mutation is positive or clinical suspicion remains high 3, 6

Management Algorithm

Scenario 1: Iron Deficiency Anemia (Most Likely Given Hgb 105 g/L)

Immediate iron replacement:

• Oral iron therapy: Ferrous sulfate 325 mg (65 mg elemental iron) two to three times daily 2
• Continue for three months after hemoglobin correction to replenish stores 2
• Intravenous iron if oral preparations not tolerated or in cancer patients with functional iron deficiency 3, 2

Gastrointestinal evaluation (particularly important in men and postmenopausal women):

• Both upper endoscopy with duodenal biopsies and colonoscopy to exclude GI pathology 2
• Celiac serology in premenopausal women 2

Monitor response:

• Recheck CBC in 2-4 weeks; expect leukocytosis and thrombocytosis to normalize as anemia improves 5
• If counts remain elevated after anemia correction, reassess for myeloproliferative disorder 6

Scenario 2: Myeloproliferative Neoplasm (If JAK2+ or Bone Marrow Confirms)

Risk stratification for thrombosis:

• High-risk: Age >60 years OR prior thrombosis history 6
• Additional risk factors: JAK2V617F mutation, cardiovascular risk factors 6

Treatment approach:

• Low-risk patients: Low-dose aspirin alone 6
• High-risk patients: Hydroxyurea plus low-dose aspirin 6
• Screen for acquired von Willebrand syndrome before aspirin if platelets >1000 × 10⁹/L 6
• Consider cytoreductive therapy (hydroxyurea) for symptomatic leukocytosis or thrombocytosis 3

Scenario 3: Anemia of Chronic Disease

If inflammatory markers elevated with normal/high ferritin but low transferrin saturation:

• Treat underlying inflammatory condition 4
• Supplemental iron, folic acid, vitamin B12 as indicated by deficiency testing 4
• Erythropoiesis-stimulating agents if hemoglobin <10 g/dL in cancer patients receiving chemotherapy 3, 1

Transfusion Threshold

Do not transfuse at current hemoglobin of 105 g/L (10.5 g/dL) unless patient is symptomatic or hemodynamically unstable 1, 2

• Restrictive strategy: Transfuse only if Hgb <7-8 g/dL or patient has cardiovascular instability 3, 1, 2
• Transfuse minimum RBC units necessary to relieve symptoms 3, 1

Critical Pitfalls to Avoid

• Do not assume reactive thrombocytosis/leukocytosis without confirming iron deficiency - missing a myeloproliferative neoplasm delays appropriate cytoreductive therapy and thrombosis prevention 6
• Do not start aspirin with extreme thrombocytosis (>1000 × 10⁹/L) without screening for acquired von Willebrand syndrome due to bleeding risk 6
• Do not overlook GI evaluation in iron deficiency anemia - dual pathology occurs in 10-15% of patients 2
• Do not continue ESA therapy beyond 4-8 weeks if no response in cancer-related anemia 3