Test Catalog

Test Id : ACASM

Pernicious Anemia Cascade, Serum

Useful For
Suggests clinical disorders or settings where the test may be helpful

Diagnosis of pernicious anemia

 

Diagnosis of vitamin B12 deficiency-associated neuropathy

Reflex Tests
Lists tests that may or may not be performed, at an additional charge, depending on the result and interpretation of the initial tests.

Test Id Reporting Name Available Separately Always Performed
IFBPA Intrinsic Factor Blocking Ab, S Yes, Bill Only No
MMAPA Methylmalonic Acid, QN, S Yes, Bill Only No
GASTR Gastrin, S Yes, Bill Only No

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

If the vitamin B12 concentration is less than 150 ng/L, then the intrinsic factor blocking antibody (IFBA) test is performed at an additional charge.

If IFBA result is negative or indeterminate, then the gastrin test is performed at an additional charge.

If the vitamin B12 concentration is 150 to 400 ng/L, then the methylmalonic acid (MMA) test is performed at an additional charge.

If the MMA result is greater than 0.40 nmol/mL, then the IFBA test is performed at an additional charge.

 

See Vitamin B12 Deficiency Evaluation in Special Instructions.

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Name
A short description of the method used to perform the test

Immunoenzymatic Assay

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

Pernicious Anemia Cascade

Aliases
Lists additional common names for a test, as an aid in searching

B12 Assay

B12 Deficiency

Cobalamin

Cobalamin Deficiency

Cyanocobalamin

Gastrin

Intrinsic Factor Blocking Antibody

Islet Cell Tumor

Methylmalonate

Methylmalonic Acid (MMA)

MMA (Methylmalonic Acid)

Schilling Testing (Alternative Strategy)

Soft-ACASM

Type 1 Intrinsic Factor Antibody

Vitamin B 12

CblC

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

If the vitamin B12 concentration is less than 150 ng/L, then the intrinsic factor blocking antibody (IFBA) test is performed at an additional charge.

If IFBA result is negative or indeterminate, then the gastrin test is performed at an additional charge.

If the vitamin B12 concentration is 150 to 400 ng/L, then the methylmalonic acid (MMA) test is performed at an additional charge.

If the MMA result is greater than 0.40 nmol/mL, then the IFBA test is performed at an additional charge.

 

See Vitamin B12 Deficiency Evaluation in Special Instructions.

Specimen Type
Describes the specimen type validated for testing

Serum

Ordering Guidance

Ask patients if they have received a vitamin B12 injection or radiolabeled vitamin B12 injection within the last 2 weeks. Patient results will not reflect deficiency or malabsorption after recent B12 injection. If patient has received such an injection within the past 2 weeks, this test should not be ordered.

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

Patient Preparation:

1. This test should not be performed on patients who have received a vitamin B12 injection or radiolabeled vitamin B12 injection within the previous 2 weeks.

2. Patient should be fasting for 8 hours.

3. If medically feasible, proton pump inhibitor (omeprazole, lansoprazole, dexlansoprazole, esomeprazole, pantoprazole, and rabeprazole) therapy should be discontinued 1 week before measurement of serum gastrin levels.

4. Drugs that interfere with gastrointestinal motility (eg, opioids) should be discontinued for at least 2 weeks before serum gastrin testing.

Container/Tube:

Preferred: Red top

Acceptable: Serum gel

Specimen Volume: 4 mL

Collection Instructions:

1. Divide specimen into 3 plastic vials, 1 containing 1 mL (label as PAGAS), 1 containing 1.5 mL (label as PAMMA), and 1 containing 1.5 mL (label as B12PA).

2. Band specimens together.

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Forms

If not ordering electronically, complete, print, and send a Benign Hematology Test Request Form (T755) with the specimen.

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

2.3 mL

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

Gross hemolysis Reject
Gross lipemia OK
Gross icterus Reject

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Serum Frozen (preferred) 30 days
Refrigerated 24 hours

Useful For
Suggests clinical disorders or settings where the test may be helpful

Diagnosis of pernicious anemia

 

Diagnosis of vitamin B12 deficiency-associated neuropathy

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

If the vitamin B12 concentration is less than 150 ng/L, then the intrinsic factor blocking antibody (IFBA) test is performed at an additional charge.

If IFBA result is negative or indeterminate, then the gastrin test is performed at an additional charge.

If the vitamin B12 concentration is 150 to 400 ng/L, then the methylmalonic acid (MMA) test is performed at an additional charge.

If the MMA result is greater than 0.40 nmol/mL, then the IFBA test is performed at an additional charge.

 

See Vitamin B12 Deficiency Evaluation in Special Instructions.

Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

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 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.

 

The algorithm is similar to that published,(1) except that the serum gastrin assay is performed in place of the Schilling test. Experience with both Mayo Clinic and Mayo Clinic Laboratories' cases has corroborated that this is a cost-effective alternative to the Schilling test.

 

In our experience, 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

3. It is much less expensive

 

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

Reference Values
Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

180-914 ng/L

Interpretation
Provides information to assist in interpretation of the test results

Vitamin B12 >400 ng/L

Results do not suggest B12 deficiency-no further testing.

Vitamin B12 150 to 400 ng/L

Borderline vitamin B12 level-methylmalonic acid (MMA) is performed. If MMA is >0.40 nmol/mL, then intrinsic factor blocking antibody (IFBA) is performed.

Vitamin B12 <150 ng/L

Vitamin B12 deficiency-IFBA is performed. If IFBA is negative or indeterminate, then gastrin is performed.

MMA < or =0.40 nmol/mL

This value implies that there is no vitamin B12 deficiency at the cellular level.

IFBA positive

Consistent with pernicious anemia, Graves disease, or Hashimoto thyroiditis.

Gastrin >200 pg/mL

Result consistent with pernicious anemia.

Gastrin <200 pg/mL

Result does not suggest pernicious anemia.

 

See Vitamin B12 Deficiency Evaluation in Special Instructions.

Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Patients who have received a vitamin B12 injection or radiolabeled vitamin B12 injection within the previous 2 weeks may have high serum vitamin B12 levels, which can interfere with this assay leading to falsely elevated results.

 

Many other conditions are known to cause an increase or decrease in the serum vitamin B12 concentration and should be considered in the interpretation of the assay results, including:

Increased serum vitamin B12

Decreased serum vitamin B12

Ingestion of vitamin C

Pregnancy

Ingestion of estrogens

Aspirin

Ingestion of vitamin A

Anticonvulsants

Hepatocellular injury

Colchicine

Myeloproliferative disorder

Ethanol ingestion

Uremia

Contraceptive hormones

 

Smoking

 

Hemodialysis

 

Multiple myeloma

 

Some patients exposed to animal antigens, either in the environment or as part of treatment or imaging procedure, may have circulating antianimal antibodies present. These antibodies may interfere with the vitamin B 12 assay reagents to produce unreliable results.

 

Some patients with other autoimmune diseases may have positive intrinsic factor blocking antibody (IFBA) assays without suffering from pernicious anemia (PA). This is reported particularly in patients with autoimmune thyroid disease or type I diabetes mellitus. In the validation of this assay, 24 individuals with these autoimmune endocrine diseases were tested and all were IFBA negative. However, 5 of 15 of patients with rheumatoid arthritis were IFBA positive during the validation of this assay. The literature suggests such individuals may, in fact, be at risk of later development of PA.

 

Since the IFBA test is competitive binding assay, the risk of heterophile antibody interference is low. During validation, 24 human antimouse antibody positive specimens and 25 specimens with other heterophile antibodies were tested and all were IFBA negative. However, if the clinical picture does not agree with the IFBA test result, the laboratory should be consulted for advice.

 

Isolated serum gastrin levels can only be interpreted in fasting patients; nonfasting specimens are uninterpretable.

 

Artifactual hypergastrinemia may be observed in fasting patients who have undergone procedures that result in temporary gastric distention or dysmotility (eg, after gastroscopy).

 

Renal failure prolongs the serum half-life of gastrin and is associated with increased serum gastrin levels.

Clinical Reference
Recommendations for in-depth reading of a clinical nature

1. Green R, Kinsella LJ: Current concepts in the diagnosis of cobalamin deficiency. Neurology. 1995 Aug;45(8):1435-1440

2. Lahner E, Annibale B: Pernicious anemia: new insights from a gastroenterological point of view. World J Gastroenterol. 2009 Nov 7;15(41):5121-5128

3. Bizzaro N, Antico A: Diagnosis and classification of pernicious anemia. Autoimmun Rev. 2014 Apr-May;13(4-5):565-568

4. Toh BH: Pathophysiology and laboratory diagnosis of pernicious anemia. Immunol Res. 2017 Feb;65(1):326-330

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Description
Describes how the test is performed and provides a method-specific reference

The Access Vitamin B12 assay is a competitive-binding immunoenzymatic assay. The sample is added to a reaction vessel along with alkaline potassium cyanide and dithiothreitol. This treatment denatures vitamin B12 binding proteins and converts all forms of vitamin B12 to the cyanocobalamin form. After neutralization, intrinsic factor-alkaline phosphatase conjugate and paramagnetic particles coated with goat anti-mouse IgG:mouse monoclonal anti-intrinsic factor are added to the sample. Vitamin B12 in the sample binds to the intrinsic factor conjugate, preventing the conjugate from binding to the solid phase anti-intrinsic factor. After incubation in a reaction vessel, materials bound to the solid phase are held in a magnetic field, while unbound materials are washed away. A chemiluminescent substrate is added to the vessel, and the light generated by the reaction is measured with a luminometer. The photon production is inversely proportional to the concentration of vitamin B12 in the sample. The amount of analyte in the sample is determined by means of a stored, multipoint calibration curve.(Package insert: ACCESS Vitamin B12. Beckman Coulter, Inc; 04/2020)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Monday through Saturday

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

Same day/1 to 4 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

2 weeks/3 months

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their Regional Manager. For assistance, contact Customer Service.

Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

82607-Vitamin B12 assay

82941-Gastrin (if appropriate)

83921-MMA (if appropriate)

86340-IFBA (if appropriate)

LOINC® Information

Test Id Test Order Name Order LOINC Value
ACASM Pernicious Anemia Cascade 2132-9
Result Id Test Result Name Result LOINC Value
Result LOINC Value Tooltip
B12PA Vitamin B12 Assay, S 2132-9

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports