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Test ID: ACASM
Pernicious Anemia Cascade

Secondary ID A test code used for billing and in test definitions created prior to November 2011

83632

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

Yes

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 test(s) that may or may not be performed, at an additional charge, depending on the result and interpretation of the initial test(s)

Test IDReporting NameAvailable SeparatelyAlways Performed
IFBPAIntrinsic Factor Blocking Ab, SYes, (order IFBA)No
MMAPAMethylmalonic Acid, QN, SYes, (order MMAS)No
GASTRGastrin, SYes, (order GAST)No

Testing Algorithm Delineates situation(s) when tests are added to the initial order. This includes reflex and additional tests.

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 to 400 ng/L, then methylmalonic acid (MMA) is performed. If methylmalonic acid is >0.40 umol/L, then IFBA is performed.

 

See Pernicious Anemia Testing Cascade in Special Instructions.

Special Instructions and Forms Describes specimen collection and preparation information, test algorithms, and other information pertinent to test. Also includes pertinent information and consent forms to be used when requesting a particular test

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

B12PA/15153: Immunoenzymatic Assay

IFBPA/33050: Competitive-Binding Immunoenzymatic Assay

GASTR/33051: Automated Chemiluminescent Immunometric Assay

MMAPA/33049: Liquid Chromatography-Tandem Mass Spectometry (LC-MS/MS) Stable Isotope Dilution Analysis

Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name

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

Specimen Type Describes the specimen type needed for testing

Serum

Specimen Required Defines the optimal specimen. This field describes the type of specimen required to perform the test and the preferred volume to complete testing. The volume allows automated processing, fastest throughput and, when indicated, repeat or reflex testing.

Container/Tube:

Preferred: Red top

Acceptable: Serum gel

Specimen Volume: 4.5 mL

Collection Instructions:

1. Fasting (8 hours)

2. Divide specimen into 3 plastic vials, 1 containing 1 mL, 1 containing 1.5 mL, and 1 containing 2 mL. 

3. Band specimens together.

Precautions: This test should not be ordered on patients who have received vitamin B12 injection within the last 2 weeks.

Forms: If not ordering electronically, submit a General Request Form (Supply T239) with the specimen.

Specimen Minimum Volume Defines the amount of specimen required to perform an assay once, including instrument and container dead space. Submitting the minimum specimen volume makes it impossible to repeat the test or perform confirmatory or perform reflex testing. In some situations, a minimum specimen volume may result in a QNS (quantity not sufficient) result, requiring a second specimen to be collected.

2.15 mL

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

Hemolysis

Mild OK; Gross reject

Lipemia

Mild OK; Gross OK

Icterus

NA

Other

NA

Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.

Specimen TypeTemperatureTime
SerumFrozen14 days

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, 1 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.

 

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

 

In our experience, >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.

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 ng/L to 400 ng/L

Borderline vitamin B12 level- methylmalonic acid (MMA) is performed. If MMA is >0.40 nmol/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 nmol/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.

 

See Pernicious Anemia Testing Cascade in Special Instructions.

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

See individual test listings.

Clinical Reference Provides recommendations for further in-depth reading of a clinical nature

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

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

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

Monday through Friday 5 a.m.-12 a.m., Saturday 6 a.m. - 6 p.m.

Analytic Time Defines the amount of time it takes the laboratory to setup and perform the test. This is defined in number of days. The shortest interval of time expressed is "same day/1 day," which means the results may be available the same day that the sample is received in the testing laboratory. One day means results are available 1 day after the sample is received in the laboratory.

Same day/1 day

Maximum Laboratory Time Defines the maximum time from specimen receipt at Mayo Medical Laboratories until the release of the test result

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 The location of the laboratory that performs the test

Rochester

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 Medical Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

82607-Vitamin B12 assay

82941-Gastrin (if appropriate)

83921-MMA (if appropriate)

86340-IFBA (if appropriate)

LOINC® Code Information Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the result codes returned for this test or profile.

Result IDReporting NameLOINC Code
B12PAVitamin B12 Assay, S2132-9