What is the workup for macrocytic anemia and thrombocytosis?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: June 4, 2025View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

From the Guidelines

The workup for macrocytic anemia with thrombocytosis should begin with a complete blood count with peripheral smear, followed by vitamin B12 and folate levels, as these deficiencies are common causes of macrocytic anemia, as suggested by 1. Additional testing should include:

  • Thyroid function tests
  • Liver function tests
  • Reticulocyte count
  • Serum iron studies
  • Hemolysis markers (LDH, haptoglobin, bilirubin) For the thrombocytosis component, JAK2 V617F mutation testing is essential to rule out myeloproliferative disorders, as indicated by 1 and 1. Bone marrow aspiration and biopsy may be necessary if initial tests are inconclusive or if myelodysplastic syndrome is suspected. This combination of findings can occur in various conditions including liver disease, alcoholism, myelodysplastic syndromes, or concurrent vitamin B12/folate deficiency with a reactive thrombocytosis or underlying myeloproliferative disorder. The peripheral smear is particularly important as it can reveal hypersegmented neutrophils (suggesting B12/folate deficiency), teardrop cells or nucleated RBCs (suggesting myelofibrosis), or other morphological abnormalities that help narrow the differential diagnosis. Treatment depends on identifying and addressing the underlying cause rather than simply correcting the laboratory abnormalities. It is also important to consider the potential for copper deficiency, which can mimic many of the peripheral blood and marrow findings seen in myelodysplastic syndromes, as noted by 1. Given the most recent evidence from 1, a thorough and targeted workup is crucial for optimal patient outcomes.

From the Research

Workup for Macrocytic Anemia and Thrombocytosis

The workup for macrocytic anemia and thrombocytosis involves a combination of laboratory tests and physical examinations to determine the underlying cause.

  • A complete blood count (CBC) is typically the first step in evaluating macrocytic anemia, which is defined as a mean corpuscular volume (MCV) greater than 100 fL 2, 3, 4.
  • The following tests are helpful in delineating the underlying cause of macrocytosis:
    • Vitamin B12 level
    • Reticulocyte count
    • Peripheral smear
  • A peripheral smear can indicate megaloblastic anemia, which is characterized by macro-ovalocytes and hyper-segmented neutrophils, suggesting vitamin B12 or folate deficiency as the most likely cause 2, 3.
  • If the peripheral smear is non-megaloblastic, the reticulocyte count can help differentiate between drug or alcohol toxicity and hemolysis or hemorrhage 2.
  • Additional tests that may be required to confirm a diagnosis include:
    • Serum folate levels
    • Serum thyroid studies
    • Liver function studies
    • Bone marrow aspirate and biopsy with cytogenetic analysis 3
  • It is crucial to differentiate nonmegaloblastic from megaloblastic anemia, as treatment is cause-specific 4.
  • In cases where myelodysplastic syndrome (MDS) is suspected, along with leukocytopenia and/or thrombocytopenia with anemia, a hematology consultation may be appropriate 4.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Evaluation of macrocytosis.

American family physician, 2009

Research

Diagnosis and treatment of macrocytic anemias in adults.

Journal of general and family medicine, 2017

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.