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Pernicious Anemia Diagnostic Panel
Test CodeCPT Codes
82607, 83921, 86340
Includes
Preferred Specimen
Patient Preparation
Samples should not be collected from a patient who has received vitamin B12 injection therapy within the past week.
Minimum Volume
Instructions
Note: Send serum in an amber tube. If amber tube is not available, wrap tube in aluminum foil to protect from light.
Separate serum into three tubes, 1 tube with 2 mL and 2 tubes with 1 mL each.
Red-top tube (preferred): Centrifuge the specimen as soon as possible after complete clot formation has taken place. Transfer the serum to a plastic screw-capped vial and ship it at refrigerated temperature.
Barrier gel separator tube (acceptable): Centrifuge the specimen as soon as possible after complete clot formation has taken place. Do not place barrier tubes in an ice bath as freezing may prevent the barrier gel from adequately separating serum from cells. Transfer the serum to a plastic screw-capped vial and ship it at refrigerated temperature.
Heparin tube (acceptable): Centrifuge the specimen as soon as possible (within one hour after collection) and transfer the plasma to a plastic screw-capped vial and ship it at refrigerated temperature.
Transport Temperature
Specimen Stability
Refrigerated: 7 days
Frozen: 28 days
Reject Criteria (Eg, hemolysis? Lipemia? Thaw/Other?)
Methodology
Immunoassay (IA) • Mass Spectrometry (MS)
Setup Schedule
Clinical Significance
This panel tests for anti-intrinsic factor antibodies, vitamin B12, and methylmalonic acid (MMA) and can be used to identify pernicious anemia as the cause of vitamin B12 deficiency. In patients with clinical suspicion of pernicious anemia, the combination of megaloblastic anemia, presence of anti-intrinsic factor antibodies, low level of vitamin B12, and/or high level of MMA confirms the diagnosis [1,2].
Pernicious anemia is one of many conditions that lead to vitamin B12 deficiency. Pernicious anemia is caused by the immune system targeting intrinsic factors or parietal cells that make intrinsic factors. Lack of intrinsic factors results in decreased absorption of vitamin B12, a vitamin that is essential for erythropoiesis. Initial screening for vitamin B12 deficiency usually starts with a complete blood count and serum vitamin B12 level. MMA levels represent a more direct measure of the physiologic activity of vitamin B12. Therefore, MMA measurement may help in evaluating vitamin B12 deficiency when the vitamin B12 level is normal or low-normal-particularly when macrocytosis is found [1].
Anti-intrinsic factor antibodies, found in 40% to 60% of patients with pernicious anemia, are highly specific for pernicious anemia [2]. Therefore, testing for intrinsic factor antibodies may be helpful when dietary vitamin B12 deficiency or malabsorption cannot be identified as the cause of vitamin B12 deficiency. This is especially true for patients with anemia, neuropathy, glossitis, or other autoimmune disorders (eg, Hashimoto disease, type 1 diabetes, vitiligo, and hypoadrenalism). The presence of intrinsic factor antibodies with confirmed vitamin B12 deficiency has a high positive predictive value (95%) for pernicious anemia [1,2].
The components of this panel can be ordered individually. The intrinsic factor antibodies test has relatively low sensitivity (40%-60%); thus, a negative result does not rule out pernicious anemia [2]. In patients with negative results for intrinsic factor antibodies but confirmed vitamin B12 deficiency and strong clinical suspicion of pernicious anemia, a high serum gastrin level is consistent with the diagnosis [1].
The results of this test should be interpreted in the context of pertinent clinical and physical examination findings.
References
1. Langan RC, et al. Am Fam Physician. 2017;96(6):384-389.
2. Devalia V, et al; British Committee for Standards in Haematology. Br J Haematol. 2014;166(4):496-513.
