Megaloblastic Macrocytic Anemia: Sensitivity and Specificity

Introduction: This is one of the principal mainfestations of Vitamin B12 (cobalamin) deficiency. It is the sole manifestation of Folate Deficiency in the adult. The other major manifestation of B12 deficiency is neurological: subacute combined degeneration of the spinal column and/or dementia. One common cause of B12 deficiency is Pernicious Anemia.

Other causes of macrocytic anemia include Alcoholism, reticulocytosis, and MDS.

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The sensitivity and specificity of findings for Megaloblastic Macrocytic Anemia are listed below. See the left navigation bar to change the display.

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Finding	Sensitivity	Specificity	Comments, Study
Anisocytosis	90%	59%	>2+ by scoring system. In patients with MCV > 100. Study: Am J Med Sci. 2000 Jun;319(6):343-52. PMID: 10875288
Either Low Serum B12 or Low Serum Folate	84%	92%	In patients with MCV > 100. (B12 < 200pg/ml, Folate < 2.1ng/ml) Study: Am J Med Sci. 2000 Jun;319(6):343-52. PMID: 10875288
Elevated Serum Methylmalonic Acid or Homocysteine	89%	73%	either elevated: MMA > 376 nM, HCys > 21.3 uM. In patients with MCV > 100. Extreme elevations found solely in B12 deficiency. False positives occur often from renal failure or hypovolemia. Study: Am J Med Sci. 2000 Jun;319(6):343-52. PMID: 10875288
High LDH	22%	98%	>1000 U/L. In patients with MCV > 100. Study: Am J Med Sci. 2000 Jun;319(6):343-52. PMID: 10875288
Increased MCV Duplicate	74%	75%	>110 fL. In patients with MCV > 100 fL. Study: Am J Med Sci. 2000 Jun;319(6):343-52. PMID: 10875288
Increased MCV Duplicate	16%	99%	>120 fL. In patients with MCV > 100. Study: Am J Med Sci. 2000 Jun;319(6):343-52. PMID: 10875288
Macroovalocytes	100%	82%	In patients with MCV > 100. Study: Am J Med Sci. 2000 Jun;319(6):343-52. PMID: 10875288
Neutrophil Hypersegmentation	90%	97%	in patients with MCV > 100 Study: Am J Med Sci. 2000 Jun;319(6):343-52. PMID: 10875288
RDW, increased	75%	33%	>14.5%. In patients with MCV > 100. Study: Am J Med Sci. 2000 Jun;319(6):343-52. PMID: 10875288
Serum B12	100%	95%	< 200pg/ml. In patients with MCV > 100. For a diagnosis of B12 deficiency specifically. In other series, sensitivity is not 100% - per PMID 2339684, a series of pernicious anemia patients who were receiving less than the proper maintenance dose had elevated MMA levels in 95% of the case while decreased cobalamin was only present in 69%. In the same study, a series of 400 patients with "clinically significant" B12 deficiency had a 97% sensitivity for low B12 levels. Study: Am J Med Sci. 2000 Jun;319(6):343-52. PMID: 10875288