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.

Pre-Test Probability (Prevalence): %.	Post-Test Probability (Predictive Value): %.	Switch to display mode.
Note that calculating probabilities from more than one** finding is inherently inaccurate because findings are not independent. (For example, using two positive findings that share a common pathogenesis is likely to overestimate the true probability.)

Sensitive and Specific Findings
Finding	Result	Sensitivity	Specificity
[ + ] Neutrophil Hypersegmentation	+ 0 -	90%	97%
in patients with MCV > 100 Study: Am J Med Sci. 2000 Jun;319(6):343-52. PMID: 10875288
[ + ] Serum B12	+ 0 -	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

Specific Findings
Finding	Result	Sensitivity	Specificity
[ + ] Increased MCV	+ 0 -	16%	99%
>120 fL. In patients with MCV > 100. Study: Am J Med Sci. 2000 Jun;319(6):343-52. PMID: 10875288
[ + ] High LDH	+ 0 -	22%	98%
>1000 U/L. 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	+ 0 -	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

Sensitive Findings
Finding	Result	Sensitivity	Specificity
[ + ] Macroovalocytes	+ 0 -	100%	82%
In patients with MCV > 100. Study: Am J Med Sci. 2000 Jun;319(6):343-52. PMID: 10875288
[ + ] Anisocytosis	+ 0 -	90%	59%
>2+ by scoring system. In patients with MCV > 100. Study: Am J Med Sci. 2000 Jun;319(6):343-52. PMID: 10875288
[ + ] Elevated Serum Methylmalonic Acid or Homocysteine	+ 0 -	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

Poorly Diagnostic Findings
Finding	Result	Sensitivity	Specificity
[ + ] Increased MCV	+ 0 -	74%	75%
>110 fL. In patients with MCV > 100 fL. Study: Am J Med Sci. 2000 Jun;319(6):343-52. PMID: 10875288
[ + ] RDW, increased	+ 0 -	75%	33%
>14.5%. In patients with MCV > 100. Study: Am J Med Sci. 2000 Jun;319(6):343-52. PMID: 10875288