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Episode 3: Diagnostic Dilemma — Severe Anemia

Description 🎙️

Andrew presents a case of anemia that challenges the classic board exam schemas. How can a common lab test trick us and help us at the same time?

Teaching ✍️

  1. Utility of the MCV: MCV stands for mean cell volume, which measures the average size of RBCs. Stratifying the anemia DDx by MCV is helpful for a comprehensive overview, but analyzing anemia using only that stratification is misleading, as the driver of anemia is often multifactorial & therefore may be due to both micro- & macrocytic diseases. For this reason, trending the MCV is important. For a patient with chronically low or high MCV, a MCV trend toward the opposite direction suggests new pathology dragging the MCV in that direction. Mike teaches that considering the tempo of anemia is also highly productive.
  1. Testing for B12 deficiency: Serum B12 measures the level of not one, but BOTH forms of B12-binding proteins in the blood: these are called Haptocorrin & Transcobalamin. Haptocorrin is made mostly by myeloid cells. For this reason, several hematologic diseases/cancers can cause high haptocorrin secretion & therefore high B12 measurement. The other binding protein, transcobalamin, binds to haptocorrin, & this complex is taken up by the liver. Leftover binding proteins are cleared by the kidneys. Therefore, both kidney & liver disease can cause high B12 measurement: kidney disease through low clearance & liver disease through low uptake or release of B12 stores if liver damage. Finally, inflammatory diseases can cause high B12 through increased synthesis of these proteins.
  1. Iron Deficiency & Thrombocytosis: Iron Deficiency usually leads to a reactive thrombocytosis, which is often profound (i.e. platelets can be greater than 1 million). In patients with known Iron Deficiency & new thrombocytopenia, this is a red flag for marrow production issues.
  1. When to obtain bone marrow biopsy for macrocytosis: Can be omitted from workup if obvious cause is identified (B12, folate deficiency) unless not responding to treatment. Bone marrow changes in B12 deficiency can mimic those seen in myelodysplastic syndrome and can lead to needless diagnostic workup and inappropriate treatment. Therefore, it is important to give the bone marrow time to respond to B12 supplementation before obtaining bone marrow aspirate if you still suspect underlying MDS/AML. For “workup negative macrocytosis” the 4 Factor Score can help with risk/benefit discussion of bone marrow biopsy, which includes macrocytosis, age > 65, RDW > 14.5%, and LDH > 250. Of patients with score of >3, around 60% were ultimately found to have MDS/AML on biopsy. Whereas only 30% of those with score of 2 or less were found to have MDS/AML.
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Anemia
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