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Test Name:
Pernicious Anemia Cascade, Serum


  • SBMF No:
    42208
  • Performance Lab Name:
    Mayo Medical Laboratories
  • Test Mnemonic:
    ACASM
  • ABN:
    Not required
  • CPT Code:
    82607
    If indicated, add 82941; 83921; 86340
  • LOINC Code:
    19146-0
  • Ref Lab Test No:
    83632
  • Test Includes:
    Vitamin B12
    Gastrin (If indicated)
    Methylmalonic Acid (If indicated)
    Intrinsic Factor Blocking Antibody (If indicated)
  • Also Known As:
    Vitamin B12 Deficiency Panel
    Schilling Testing (Alternative Strategy)
    Cobalamin Deficiency
  • Also See:
    30041 Vitamin B12
    30028 Gastrin
    31403 Methylmalonic Acid, Serum
    44084 Intrinsic Factor Blocking Antibody
  • Spec Type:
    Serum
  • Spec Container:
    Red top (serum) or gold top (SST) tube
  • Pref Vol:
    4.5 mL
  • Min Vol:
    2.5 mL
  • Fasting:
    Yes
  • Patient Prep:
    This test should not be ordered on patients who have received vitamin B12 injection within the last 2 weeks
    Patient should be fasting at least 8 hours
  • Spec Collect:
    Routine venipuncture
  • Spec Process:
    Clot for 30 minutes
    Promptly centrifuge 15 minutes
    Immediately transfer serum into three (3) plastic tubes;
    -One containing 1.0 mL (Min: 0.7 mL)
    -One containing 1.5 mL (Min: 0.8 mL), and
    -One containing 2.0 mL (Min: 1.0 mL)
    Band specimens together and send frozen
  • Spec Store Transport:
    Frozen
  • Spec Reject:
    Specimens other than serum
    Severely hemolyzed sample
    Non-frozen or thawed sample
  • Methodology:
    Vitamin B12: Immunoenzymatic Assay
    Gastrin: Automated Chemiluminescent Immunometric Assay
    Intrinsic Factor Blocking Ab: Competitive-Binding Immunoenzymatic Assay
    Methylmalonic Acid: Liquid Chromatography-Tandem Mass Spectometry (LC-MS/MS)
  • Use:
    Diagnosis of pernicious anemia
    Diagnosis of vitamin B12 deficiency associated neuropathy
  • Clinical Significance:

    Vitamin B12 deficiency can be caused by many factors, one of which is pernicious anemia, a condition resulting in deficient production of intrinsic factor in the parietal cells of the stomach. Intrinsic factor is a protein that is needed to assist in the absorption of vitamin B12 into the small intestine. Vitamin B12 is converted into adenosylcobalamin, which converts L-methylmalonic acid to succinyl coenzyme A; hence, a decrease in vitamin B12 absorption in the intestine can cause an excess of methylmalonic acid within the body.

    Vitamin B12 deficiency may present with any combination of the following: macrocytic anemia, glossitis (painful inflammation of the tongue), peripheral neuropathy, weakness, hyperreflexia, ataxia, loss of proprioception, poor coordination, and/or affective behavioral changes. These manifestations may occur in any combination; many patients present with neurologic symptoms without macrocytic anemia.

    A group of tests is often required to establish the correct diagnosis as determination of vitamin B12 in serum does not detect all cases of vitamin B12 deficiency. Mayo Clinic's Department of Laboratory Medicine and Pathology offers a diagnostic algorithm to expedite the identification of patients with vitamin B12 deficiency. This algorithm takes into account the following facts:
    -The most sensitive test for vitamin B12 deficiency at the cellular level is the assay for methylmalonic acid (MMA).
    -Nearly half of the cases of pernicious anemia can be unambiguously identified if the serum test for intrinsic factor blocking antibody is positive (this is a simpler and less expensive test than the MMA).
    -Serum gastrin is usually markedly increased in pernicious anemia (as a result of gastric atrophy) and this test can be used as a substitute for the more complicated and more expensive Schilling test of intestinal absorption of vitamin B12.

    Greater than 90% of laboratory test costs can be saved by using the algorithm rather than ordering all of the services for a patient suspected of having B12 deficiency. Furthermore, the substitution of the serum gastrin assay for the Schilling test offers 3 advantages: 1) it is an in vitro test that does not require administration of radioisotopes to patients, 2) it can be performed on mailed-in specimens, and 3) it is much less expensive.

    Only those tests that are appropriate, as defined by the algorithm, will be performed.

    Testing Algorithm:
    If vitamin B12 is < 150 ng/L, then intrinsic factor blocking antibody (IFBA) is performed. If IFBA is negative or indeterminate, then gastrin is performed.
    If vitamin B12 is 150 ng/L to 400 ng/L, then methylmalonic acid (MMA) is performed. If methylmalonic acid is > 0.40 umol/L, then IFBA is performed.

  • Reference Range:

    180-914 ng/L

    Interpretation:
    Vitamin B12 > 400 ng/L: Results do not suggest B12 deficiency-no further testing.

    Vitamin B12 150-400 ng/L: Borderline vitamin B12 level- methylmalonic acid (MMA) is performed. If MMA is > 0.40 umol/L, then intrinsic factor blocking antibody (IFBA) is performed.

    Vitamin B12 < 150 ng/L: Vitamin B12 deficiency-an IFBA is performed. If IFBA is negative or indeterminate, then gastrin is performed.

    MMA < 0.4 umol/L: This value implies that there is no vitamin B12 deficiency at the cellular level.

    IFBA positive: Consistent with pernicious anemia, Graves disease, or Hashimoto's thyroiditis.

    Gastrin > 200 pg/mL: Result consistent with pernicious anemia.

    Gastrin < 200 pg/mL: Result does not suggest pernicious anemia.

  • Additional Test Info:

    This test has been cleared or approved by the U.S. Food and Drug Administration and is used per manufacturer's instructions.

    Reference:
    "Pernicious Anemia Cascade, Serum." 2011 Online Test Catalog, Mayo Medical Laboratories, 2011. Web. 30 July 2011 <http://www.mayomedicallaboratories.com/test-catalog/Overview/83632>

  • Day Run:
    Mon-Sat
  • Time Reported:
    2-5 days
  • Test Type:
    CHEMISTRY