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Signature ✍️
- Acute anemia 🩸 : ⊕ symptoms (i.e. no time to compensate), ⊕/⊖ tachycardia (hemodynamic compensation, may be absent if rate-controlled vs. senile conduction), ⊕/⊖ transfusion response (i.e. hemoglobin loss may be ongoing), ⊕/⊖ reticulocytosis (marrow compensation, may be absent if concurrent myelosuppression)
- Chronic anemia 🩸 : ⊖ symptoms/HR (i.e. body has adapted, including ↑ plasma volume, ↓ SVR, ↑ O2 extraction), ⊕ transfusion response, ⊖ reticulocytosis
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DDx (MCV) 🏳️🌈
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- Iron deficiency
- Thalassemia
- Lead poisoning
- Sideroblastic anemia
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- Hyperproliferative
- Hemorrhage + Hematoma
- Hemolysis
- Hypersplenism
- Hypoproliferative
- Inflammation
- CKD
- Hypothyroidism
- Marrow failure
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- Megaloblastic*
- Nutrient deficiencies
- B12 & Folate
- Copper
- Medications
- Hydroxyurea (urea analog blocks DNA synthesis)
- Methotrexate (folate depletion + direct precursor toxicity)
- Azathioprine (metabolism into 6-mercaptopurine → ↓ purine synthesis)
- Toxins
- Nitrous oxide (N2O, subacute combined degeneration)
- Non-megaloblastic
- Reticulocytosis (e.g. > 10%)
- EtOH use +/- EtOH cirrhosis
- Chronic liver disease
- MDS
⚪ Pathophysiology of Megaloblastic Anemia: ↓ DNA synthesis → “megaloblastic” marrow changes (hypercellular, large erythroblasts a.k.a megaloblasts, cytosolic sideroblasts) → cytopenias (early) → intramedullary hemolysis +/- TMA (late)
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DDx (Acuity) 🏳️🌈
- Acute (Loss > Production) ⏱️
- Loss ⏱️
- Hemorrhage (External)
- GI bleeding DDx
- Hematoma (Internal)*
- Overt
- Anterior rectus sheath hematoma
- Morel-Lavallée lesion
- Occult
- Retroperitoneal hemorrhage
- Posterior rectus sheath hematoma
- Hemolysis (Internal)
- Hemolysis DDx
- Production ⏱️
- Endogenous
- Sepsis
- Exogenous
- Hydroxyurea
- Methotrexate
- Azathioprine
- Chronic (Production > Loss) ⏱️
- Stratify by MCV
⚪ Note*: the development of overt vs. occult hematomas often leads to the finding of an undetectably low haptoglobin owing to expected RBC breakdown — knowledge of this expected natural history of hematoma breakdown is crucial given the low haptoglobin can otherwise misdirect you toward the hemolysis DDx
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Principles❗️
DDx: Layered Approach (MCV + Acuity + CBC) 🌈
- While the DDx for anemia is most often taught through the lens of the MCV, the real-life work-up often calls for a layered analysis given …
- Concurrent processes affecting RBC size can sway the MCV either direction (ultimately leading to pseudonormalization if concurrent micro- ⊕ macrocytic disease), the acuity of anemia is often more productive
- The tempo of anemia often is the most important filter (e.g. acute, large hemoglobin drop analysis largely requires ignoring the MCV)
- The presence of concurrent cytopenias also largely sways the analysis (i.e. ↑ cytopenias → ↑ probability of production issue)
Helpful Resources 📚
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References 📚
- Principles borrowed from @rabihmgeha
- Framework adapted from @AndreMansoor
- B12 testing principles from @WilliamAird4
