What lab values characterize myelodysplastic anemia?

Laboratory Characteristics of Myelodysplastic Syndromes

Myelodysplastic syndromes are characterized by peripheral blood cytopenias (anemia, neutropenia, and/or thrombocytopenia) combined with a normal or hypercellular bone marrow showing dysplastic changes in multiple cell lineages and increased blast cells. 1

Essential Peripheral Blood Findings

Complete Blood Count Abnormalities

• Anemia is the most common finding, typically with hemoglobin <10 g/dL defining cytopenia in prognostic systems 1
• Thrombocytopenia with platelet count <100 × 10⁹/L 1
• Neutropenia with absolute neutrophil count <1.8 × 10⁹/L 1, 2
• Most patients present with one to three cytopenias, though the number and severity directly impact prognosis 1

Reticulocyte Count

• Low or inappropriately normal reticulocyte count despite anemia, reflecting ineffective erythropoiesis 1, 2
• This distinguishes MDS from hemolytic anemia where reticulocytes would be elevated 1

Peripheral Blood Smear Morphology

• Pelger-Huët cells (hyposegmented neutrophils with bilobed nuclei) 2
• Hypogranular or agranular neutrophils 2
• Giant platelets with abnormal granulation 3
• Macrocytic red blood cells (though MCV may be normal) 3
• Circulating blasts may be present: <1% in lower-risk disease, 2-19% in higher-risk MDS 1

Bone Marrow Findings

Cellularity and Blast Percentage

• Normal or hypercellular marrow (cellular marrow) despite peripheral cytopenias—this paradox is pathognomonic 1, 3
• Blast percentage is critical for classification and prognosis:
  • <5% blasts: lower-risk subtypes (MDS-SLD, MDS-MLD, MDS-RS) 1
  • 5-9% blasts: MDS-EB-1 1
  • 10-19% blasts: MDS-EB-2 1
  • ≥20% blasts: reclassified as acute myeloid leukemia 1

Dysplastic Features (≥10% dysplasia required for diagnosis)

• Erythroid lineage: megaloblastoid changes, nuclear-cytoplasmic asynchrony, multinucleated erythroblasts (≥3 nuclei), ringed sideroblasts (≥15% with iron stain) 1, 3
• Myeloid lineage: hypersegmented or hyposegmented neutrophils (pseudo-Pelger-Huët), hypogranulation, peroxidase-negative neutrophils 1, 3
• Megakaryocytic lineage: micromegakaryocytes, hypolobulated nuclei, multiple separated nuclei 1, 3

Iron Studies on Bone Marrow

• Ringed sideroblasts (≥15% or ≥5% if SF3B1 mutation present) define MDS-RS subtypes 1
• Iron staining is mandatory in the initial bone marrow evaluation 1

Biochemical and Supportive Laboratory Values

Iron Parameters

• Elevated serum ferritin (often >1000 ng/mL in transfusion-dependent patients, indicating iron overload) 1, 2
• Elevated transferrin saturation (>45-50%) 1, 2
• These distinguish MDS from iron deficiency anemia and guide iron chelation decisions 1, 2

Exclusion of Other Causes

• Normal or elevated vitamin B12 and folate levels (to exclude megaloblastic anemia) 1, 2
• Normal haptoglobin and indirect bilirubin (to exclude hemolysis) 1
• Normal creatinine (to exclude renal anemia) 1
• Lactate dehydrogenase (LDH): may be normal or mildly elevated; markedly elevated LDH suggests hemolysis or transformation to AML 1

Erythropoietin Level

• Serum erythropoietin should be measured before red blood cell transfusion 1
• Low EPO (<200-500 U/L) predicts better response to erythropoiesis-stimulating agents 1, 4
• High EPO (>500-750 U/L) predicts poor response to ESA therapy 5, 4

Cytogenetic and Molecular Findings

Chromosomal Abnormalities

• Cytogenetic abnormalities present in 50-60% of patients 6
• Common abnormalities: del(5q), monosomy 7 or del(7q), trisomy 8, del(20q) 1, 6
• Complex karyotype (≥3 abnormalities) indicates very poor prognosis 1
• Normal karyotype is intermediate risk 1, 5

Molecular Testing

• SF3B1 mutation: associated with ring sideroblasts 1
• JAK2 mutation: should be tested if thrombocytosis present 1, 2
• TP53, ASXL1, DNMT3A, TET2 mutations: provide prognostic information 2, 5

Additional Specialized Testing

Flow Cytometry

• Evaluation for paroxysmal nocturnal hemoglobinuria (PNH) clone in appropriate cases 1, 2
• Assessment for large granular lymphocytic (LGL) disease 1

HLA Typing

• HLA-DR15 typing to predict response to immunosuppressive therapy 1, 2, 5
• Full HLA typing if allogeneic transplantation is being considered 1

Other Considerations

• Copper deficiency evaluation in cases with unexplained cytopenias 1, 2
• HIV testing if clinically indicated 1, 2

Critical Diagnostic Pitfalls to Avoid

• Do not diagnose MDS based solely on cytopenias—dysplastic morphology in ≥10% of cells in one or more lineages is required 1, 5
• Exclude vitamin B12 deficiency before treating with folic acid, as folic acid >0.1 mg daily can produce hematologic improvement while allowing irreversible neurologic damage from B12 deficiency to progress 2
• Recognize that "normal" serum B12 levels do not exclude functional deficiency—confirm with methylmalonic acid or homocysteine if clinical suspicion exists 2
• Do not assume leukocytosis excludes MDS—chronic myelomonocytic leukemia (CMML) presents with monocytosis and WBC that may exceed 12,000/mcL 2
• Measure EPO before transfusion, as transfusions artificially suppress EPO levels and invalidate prognostic assessment 1
• Review peripheral smear personally—automated counts miss critical dysplastic features like Pelger-Huët cells and hypogranulation 2