Medical Policies - Medicine

Serum Holotranscobalamin (holo-TC) as a Marker of Vitamin B12 (Cobalamin) Status


Effective Date:10-15-2017



Measurement of serum holotranscobalamin (holo-TC) is considered experimental, investigational and/or unproven in the diagnosis and management of vitamin B12 deficiency.


Holotranscobalamin (holo-TC) is a transcobalamin-vitamin B12 complex that has been investigated as a diagnostic test for vitamin B12 deficiency in symptomatic and at-risk populations, as well as an assay for monitoring response to therapy.


Vitamin B12 (cobalamin) is an essential vitamin that is required for DNA synthesis affecting red blood cell formation and methionine synthesis affecting neurologic functioning. Cobalamin deficiency can result from nutritional deficiencies or malabsorption. Dietary insufficiency is most common among vegetarians and elderly people. Malabsorption of vitamin B12 may be associated with autoantibodies, as in pernicious anemia, or can occur after gastrectomy, or in other gastrointestinal tract conditions, such as celiac disease, Whipple’s disease, and Zollinger-Ellison syndrome. Clinical signs and symptoms of cobalamin deficiency include megaloblastic anemia, paresthesias and neuropathy, and psychiatric symptoms, such as irritability, dementia, depression, or psychosis. While the hematologic abnormalities promptly disappear after treatment, neurologic disorders may become permanent if treatment is delayed.

The diagnosis of cobalamin deficiency has traditionally been based on low levels of total serum cobalamin, typically less than 200 pg/mL, in conjunction with clinical evidence of disease. However, this laboratory test has been found to be poorly sensitive and specific. Therefore, attention has turned to measuring metabolites of cobalamin as a surrogate marker. For example, in humans, only 2 enzymatic reactions are known to be dependent on cobalamin: the conversion of methylmalonic acid (MMA) to succinyl-CoA, and the conversion of homocysteine and folate to methionine. Therefore, in the setting of cobalamin deficiency, serum levels of MMA and homocysteine are elevated and have been investigated as surrogate markers.

There also is interest in the direct measurement of the subset of biologically-active cobalamin. Cobalamin in serum is bound to 2 proteins, transcobalamin and haptocorrin. Transcobalamin-cobalamin complex (called holotranscobalamin, or holo-TC) functions to transport cobalamin from its site of absorption in the ileum to specific receptors throughout the body. Less than 25% of the total serum cobalamin exists as holo-TC, but this is considered the clinically relevant biologically active form. Serum levels of holo-TC can be measured using a radioimmunoassay or enzyme immunoassay.

Regulatory Status

In January 2004, the device HoloTC RIA (Axis-Shield plc, Dundee, UK) is an example of a radioimmunoassay for holo-TC that was cleared for marketing by the U.S. Food and Drug Administration (FDA) through the 510(k) process (K030655). The FDA determined that this device was substantially equivalent to existing devices for use in: “quantitative measurement of the fraction of cobalamin (vitamin B12) bound to the carrier protein transcobalamin in the human serum or plasma. Measurements obtained by this device are used in the diagnosis and treatment of vitamin B12 deficiency.”

In November 2006, the device Axis-Shield HoloTC Assay (Axis-Shield, Dundee, UK), an enzyme immunoassay for holo-TC, was cleared for marketing by the FDA through the 510(k) process (K062467). The FDA determined that this device was substantially equivalent to existing devices for use in: “quantitative determination of holotranscobalamin…in human serum and plasma on the AxSym® System. HoloTC is used as an aid in the diagnosis and treatment of vitamin B12 deficiency.”

From December 2011 to July 2016 the FDA cleared for marketing additional devices to aid in the diagnosis and treatment of vitamin B12 deficiency. In the table 1 below is a list of these devices (not an all-inclusive list) including the indications for use. (1):

Table 1


510(k) number

Device Name

Intended Use of Device



ARCHITECT Active-B12 (Holotranscobalamin) Reagents (Axis-Shield, Dundee, UK)

The ARCHITECT AB12 (holo-TC) is a chemiluminescent microparticle immunoassay (CMIA) for the quantitative determination of holo-TC in human serum on the ARCHITECT i System. AB12 (holo-TC) is used as an aid in the diagnosis and treatment of vitamin B12 deficiency.



ARCHITECT Active-B12 (Holotrancobalamin) Calibrators (A-F) (Axis-Shield, Dundee, UK)

Calibrators are for the calibration of the ARCHITECT I System when used for the quantitative determination of holo-TC in human serum.



ARCHITECT Active-B12 (Holotranscobalamin) Controls (Low and High) (Axis-Shield, Dundee, UK)

Controls are for the estimation of test precision and the detection of systematic analytical deviations of the ARCHITECT i system (reagents, calibrators, and instrument) when used for the quantitative determination of holo-TC in human serum.



Axis-Shield Active-B12 (Holotranscobalamin) (Axis-Shield, Dundee, UK)

The Axis-Shield AB12 (holo-TC) is used as an aid in the diagnosis and treatment of vitamin B12 deficiency. For in vitro diagnostic use.



ADVIA Centaur Active-B12 (Holotranscobalamin) (AB12) Assay (Axis-Shield, Dundee, UK)

AB12 assay is for in vitro diagnostic use in the quantitative measurement of holo-TC in human serum using the ADVIA Centaur XP system. AB12 holoTC is used as an aid in the diagnosis and treatment of vitamin B12 deficiency.



ADVIA Centaur Active-B12 (AB12) Quality Control (Axis-Shield, Dundee, UK)

Quality control is for in vitro diagnostic use to monitor the precision and accuracy of the ADVIA Centaur AB12 holo-TC assay using the ADVIA Centaur systems.



ADVIA Centaur Active-B12 (AB12) Master Curve Materials (MCM) (Axis-Shield, Dundee, UK)

MCM is for in vitro diagnostic use in the verification of calibration and reportable range of the DAVIA Centaur AB12 holo-TC assay using the ADVIA Centaur systems.

AB12 - Active-B12

holo-TC - Holotranscobalamin


This policy was created in 2005 and updated periodically with searches of the MEDLINE database. There were no clinical trials identified that directly evaluated the utility of testing cobalamin status with serum holotranscobalamin (holo-TC). There were also no trials that evaluated the benefit of treatment in individuals with subclinical cobalamin deficiency. The diagnostic performance and operating characteristics continue to be an area of active research. Several systematic reviews and randomized, controlled trials (RCTs) have been identified addressing this area.

Review articles highlight the analytical aspects and clinical utility of the use of holo-TC. (2, 3)

Validation of the clinical use of any diagnostic test focuses on 3 main principles: 1) technical feasibility of the test; 2) diagnostic performance of the test, such as sensitivity, specificity, and positive and negative predictive value in different populations of patients and compared to the gold standard; and 3) clinical utility of the test, i.e., how the results of the diagnostic test will be used to improve management of the patient.

Technical Feasibility

The serum measurements of holo-TC involve the use of standard laboratory immunoassay techniques. In the first step, holo-TC in the serum sample is separated by magnetic microspheres coated with monoclonal antibodies to human transcobalamin. The cobalamin bound to the holo-TC is then released and measured by a competitive binding radioimmunoassay or by fluorescence, depending on the device used.

Diagnostic Performance

The diagnostic performance must be compared to the established gold standard for measuring cobalamin deficiency. This is particularly problematic since there is currently no established gold standard. As noted in the Description section, serum levels of total cobalamin are considered poorly sensitive and specific, and holo-TC measurements are not independent of total cobalamin measures, leading to a potential bias in the estimate of the test’s diagnostic power. There have been several reports proposing serum measures of methylmalonic acid (MMA) and homocysteine as an alternative gold standard (4-6); however, their specificity has been questioned. (7, 8)

According to the U.S. Food and Drug Administration (FDA) decision summary, the cut-off values for holo-TC were based on a normal population instead of a population of those with known cobalamin deficiency. For example, the low value of holo-TC, 37 pmol/L, was based on a study of 303 normal Finnish individuals. This study has also been published by Loikas and colleagues in the peer-reviewed literature. (9) Participants included 226 normal elderly subjects and 80 normal, non-elderly adult subjects. Patients were excluded from the trial if they had hyperhomocysteinemia, evidence of a possible cobalamin deficiency. In addition, patients in the lowest one-third of holo-TC results underwent additional testing with MMA; those with elevated MMA levels were also excluded. In the normal reference population, the holo-TC range was 25–254 pmol/L with a 95% central reference interval of 37–171 pmol/L. Therefore, the cut-off value for a low result was established at 37 pmol/L. This cut-off value was then applied to the results of 107 patients with presumed cobalamin deficiency, as evidenced by different combinations of an increased plasma homocysteine or MMA level, or a low total serum cobalamin level, defining patients with potential, possible, or probable cobalamin deficiency. A total of 48% of those with presumed deficiency had a holo-TC below 37 pmol/L. The frequencies of low holo-TC levels increased with increasing pretest probability of cobalamin deficiency. For example, among the 16 patients thought to have the highest pretest probability of cobalamin deficiency, based on elevated levels of homocysteine and MMA, 100% had low levels of holo-TC. Therefore, this study used levels of homocysteine and MMA as the gold standard. Based on this standard, the sensitivity of the test was only 48% among those with cobalamin deficiency rated as either potential, possible, or probable. The authors conclude that further studies are needed to confirm the clinical utility and specificity of holo-TC in diagnosis of subclinical cobalamin deficiency. Also, these values for a homogeneous population of Finnish subjects with a diet high in fish might not be able to be extrapolated to the heterogeneous American population and diet. Furthermore, these cut-off points require confirmation in a larger population of patients whose cobalamin status is unknown.

In 2013 Dullemeijer et al. reported on a systematic review and meta-analysis of studies on biomarker responses to B12 supplementation. (10) The authors found doubling the intake of B12 increased serum or plasma levels of B12 by 11% and decreased MMA levels by 7%. However, only 2 small RCTs with 3 holo-TC estimates were identified which showed B12 supplementation significantly increased serum or plasma holo-TC levels. However, the small size of the RCTs precluded meta-analysis. The authors cautioned the heterogeneity of studies limited the interpretation of the results reported.

O’Leary and colleagues in 2012 reported on a systematic review of B12 status and its relationship to cognitive decline and dementia. (11) The authors evaluated 35 cohort studies and found serum B12 levels were not associated with cognitive decline or dementia. However, 4 studies found increased risks of cognitive decline or dementia were associated with MMA and/or holo-TC levels. Nevertheless, the use of underpowered cohort studies of short duration limits interpretation of these results.

In April 2009, Hoey and colleagues published a systematic review of the response of various biomarkers to treatment with vitamin B12. (12) Only one RCT by Eussen and colleagues utilizing holo-TC was identified for the review (13); therefore, the authors concluded that data were insufficient to draw conclusions about the effectiveness of serum holo-TC as a biomarker for vitamin B12 status.

In 2013, Hill and colleagues reported on a double-blind, placebo-controlled, randomized study of 100 elderly patients with poor B12 status. (14) Patients were treated for 8 weeks with vitamin B12 supplements of 10 μg/d, 100 μg/d, or 500 μg/d. Compared to placebo, all B12 dosages had an effect on holo-TC levels (p< 0.01). However, even after receiving 500 μg/d B12 for 56 days, 12% of patients had below threshold (>200pmol/L) plasma B12 levels and 56% still had elevated plasma and urine MMA levels suggesting continued metabolic insufficiency despite supplementation.

In a 2006 double-blind trial to determine the effects of B12 supplementation on cognitive functioning in older adults, Eussen and colleagues measured holo-TC at baseline, 12, and 24 weeks in 195 subjects randomized to 3 groups: cobalamin, cobalamin plus folate supplementation, or placebo. The primary outcome measure was cognitive improvement. (13) The results did not support a significant difference in cognitive functioning. The authors noted a significant time-treatment interaction after 12 weeks in both treatment arms of holo-TC for all biomarkers measured (vitamin B12, MMA, holo-TC, homocysteine, and red blood cell folate [p<0.0002]). Specifically, for holo-TC, in the vitamin B12 group, mean levels increased from 58 +/- 21 to 183 +/- 124 (p<0.05 for difference from baseline). In the folate and vitamin B12 supplementation group, holo-TC increased from 68 +/- 33 to 222 +/- 133 (p<0.05 for difference from baseline). Comparatively, the placebo group’s levels did not significantly change, from 70 +/- 39 to 65 +/-43 (p<0.05 for difference from treatment groups). Further changes did not occur between 12 and 24 weeks of supplementation.

Eussen and colleagues published a smaller trial in 2008. (15) Once again, patients were randomly assigned to cobalamin, cobalamin plus folate, or placebo supplementation in subjects with known mild cobalamin deficiency. Along with serum cobalamin and MMA levels, holo-TC was utilized to assess deficiency status and did rise in response to therapy. Other recent studies have utilized holo-TC as one of a number of measures of cobalamin status. (16-20) However, these studies do not attempt to assess the independent predictive capacity of the test and therefore do not add to the evidence base for this policy.

Valente and colleagues reported on the diagnostic accuracy of holotranscobalamin, MMA, serum cobalamin, and other indicators of tissue vitamin B12 status in an elderly population. (21) Elderly subjects (n=700), age range 63-97 years, were recruited from an ongoing observational cohort study to collect data on 2,000 individuals older than 60 years with mild to moderate cognitive impairment. A separate reference population of 120 healthy volunteers, age 18-62 years, was used to determine a reference interval for the red cell cobalamin assay. The cut-offs for deficiency were defined as 20 pmol/L for holo-TC, 123 pmol/L for serum cobalamin, and less than 33 pmol/L for red cell cobalamin. The red cell lower limit of 33 pmol/L packed red cells was used to dichotomize the concentrations into deficient and nondeficient vitamin B12 status for the construction of receiver operating characteristic (ROC) plots. The areas under the curve (AUC) showed that serum holo-TC was the best predictor with AUC 0.90 (95% confidence interval [CI]: 0.86-0.93), and this was significantly better (p<0.0002) than the next best predictors of serum cobalamin 0.80 (95% CI: 0.75-0.85), and MMA 0.78 (95% CI: 0.72-0.83). For these 3 analytes, the authors constructed a 3-zone partition of positive and negative zones and a deliberate indeterminate zone between. The boundaries were values of each test that resulted in a post-test probability of deficiency of 60% and a post-test probability of no deficiency of 98%. The proportion of indeterminate observations for holo-TC, cobalamin, and MMA was 14%, 45%, and 50%, respectively.

Clinical Utility

Advocates of holo-TC testing suggest that this laboratory test can identify early subclinical stages of cobalamin deficiency or other conditions, permitting prompt initiation of treatment, specifically supplementary cobalamin dietary supplementation. Further, this reasoning suggests that early diagnosis will lead to an improvement in health outcome in patients. This hypothesis was not directly tested in any of the identified published literature. In the absence of a gold standard, the clinical significance of subclinical cobalamin deficiency must be further studied by understanding the natural history of this condition. Does subclinical deficiency inevitably progress to clinical deficiency? Does cobalamin supplementation normalize the values? How variable are cobalamin levels within patients? These clinical issues have not been well-addressed in the literature. Finally, for all patients at risk, i.e., vegetarians, elderly people, and postgastrectomy patients, the recommended treatment of subclinical disease is further dietary supplementation of cobalamin. This recommendation is appropriate, regardless of the level of measured cobalamin.

Heil and colleagues aimed to validate the clinical usefulness of holo-TC as an initial screening assay for metabolic vitamin B12 deficiency in a mixed patient population. (22) Three hundred and sixty blood samples were collected by 5 Dutch hospitals, and vitamin B12 and holo-TC in serum were measured. MMA in serum was measured by tandem mass spectrometry. Receiver-operating-curve analysis demonstrated a greater area under the curve for holo-TC than for vitamin B12 in detecting vitamin B12 deficiency characterized by 3 predefined cut-off levels of MMA. A cut-off value of 32 pmol/L of holo-TC resulted in the highest sensitivity (83%) with acceptable specificity (60%) in detecting MMA concentrations above 0.45 μmol/L. The combination of vitamin B12 and holo-TC did not improve diagnostic accuracy at this cut-off level. The authors concluded that holo-TC has a better diagnostic accuracy than vitamin B12 and can replace the existing vitamin B12 assay as a primary screening test in patients suspected of vitamin B12 deficiency.

Ongoing Clinical Trials

A search of on October 27, 2016 identified no randomized clinical trials on serum holotranscobalamin.


Holotranscobalamin (holo-TC) is a transcobalamin-vitamin B12 complex that has been investigated as a diagnostic test for vitamin B12 deficiency in symptomatic and at-risk populations, as well as an assay for monitoring response to therapy.

There are inadequate data to establish holo-TC testing as an alternative to either total serum cobalamin, or levels of MMA or homocysteine in the diagnosis of vitamin B12 deficiency. While technically feasible, and likely to have diagnostic performance that approaches that of currently utilized tests, no evidence of clinical utility has been demonstrated, neither as a screening tool in the general or at-risk population, nor as a diagnostic tool in symptomatic individuals. Evidence of the clinical utility of the test is currently lacking, and therefore the test remains experimental, investigational and/or unproven.

Practice Guidelines and Position Statements

Many societies have recommended vitamin B12 supplementation for specific clinical conditions or evaluation for vitamin B12 deficiency in the workup for clinical indication without specifying a methodology. An exception is in a practice parameter for peripheral neuropathy by the American Academy of Neurology (AAN) that has specified a methodology (evidence level C): “serum B12 level with metabolites (methylmalonic acid with or without homocysteine)” in the evaluation for vitamin B12 deficiency. (23)

2016 Update

A search of peer reviewed literature through October 27, 2016 identified one additional guideline that supports the use of the Active-B12 assay to aid in the diagnosis and treatment of vitamin B12 deficiency. In 2015, the World Health Organization (WHO) Expert Committee on Biological Standardization recommended that a holotranscobalamin (holo-TC) value of 107 pmol/L is assigned to 03/178 (International Standard for vitamin B12 and serum folate) for use as the 1st International Standard for folate, B12 and holo-TC. No new randomized controlled clinical trial publications were noted that would prompt reconsideration of the coverage statement, which remains unchanged. (24-26)


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1. U.S. Food and Drug Administration (FDA). Center for Devices and Radiological Health. Available at <> (accessed - 2016 October 25).

2. Nexo E, Hoffmann-Lücke. Holotranscobalamin, a marker of vitamin B-12 status: analytical aspects and clinical utility. Am J Clin Nutr 2011; 94(1):359S-65S. PMID 21593496

3. Carmel R. Biomarkers of cobalamin (vitamin B-12) status in the epidemiologic setting: a critical overview of context, applications, and performance characteristics of cobalamin, methylmalonic acid, and holotranscobalamin II. Am J Clin Nutr 2011; 94(1):348S-58S. PMID 21593511

4. Sumner AE, Chin MM, Abrahm JL, et al. Elevated methylmalonic acid and total homocysteine levels show high prevalence of vitamin B12 deficiency after gastric surgery. Ann Intern Med 1996; 124(5):469-76. PMID 8602704

5. Elin RJ, Winter WE. Methylmalonic acid: a test whose time has come? Arch Pathol Lab Med 2001; 125(6):824-7. PMID 11371242

6. Oh R, Brown DL. Vitamin B12 deficiency. Am Fam Physician 2003; 67(5):979-86. PMID 12643357

7. Carmel R. Current concepts in cobalamin deficiency. Annu Rev Med 2000; 51:357-75. PMID 10774470

8. Hvas AM, Ellegaard J, Nexo E. Vitamin B12 treatment normalizes metabolic markers but has limited clinical effect: a randomized placebo-controlled study. Clin Chem 2001; 47(8):1396-404. PMID 11468228

9. Loikas S, Lopponen M, Suominen P, et al. RIA for serum holo-transcobalamin: method evaluation in the clinical laboratory and reference interval. Clin Chem 2003; 49(3):455-62. PMID 12600958

10. Dullemeijer C, Souverein OW, Doets EL, et al. Systematic review with dose-response meta-analyses between vitamin B-12 intake and European Micronutrient Recommendations Aligned’s prioritized biomarkers of vitamin B-12 including randomized controlled trials and observational studies in adults and elderly persons. Am J Clin Nutr 2013; 97(2):390-405. PMID 23269815

11. O’Leary F, Allman-Farinelli M, Samman S. Vitamin B12 status, cognitive decline and dementia: a systematic review of prospective cohort studies. Br J Nutr 2012; 108(11): 1948-61. PMID 23084026

12. Hoey L, Strain JJ, McNulty H. Studies of biomarker responses to intervention with vitamin B-12: a systematic review of randomized controlled trials. Am J Clin Nutr 2009; 89(6):1981S-96S. PMID 19403638

13. Eussen SJ, de Groot LC, Joosten LW, et al. Effect of oral vitamin B-12 with or without folic acid on cognitive function in older people with mild vitamin B-12 deficiency: a randomized, placebo-controlled trial. Am J Clin Nutr 2006; 84(2):361-70.11. PMID 16895884

14. Hill MH, Flatley JE, Barker ME, et al. A vitamin B-12 supplement of 500 µg/d for eight weeks does not normalize urinary methylmalonic acid or other biomarkers of vitamin B-12 status. J Nutr 2013; 143(2):142-7. PMID 23236022

15. Eussen SJ, Ueland PM, Hiddink GJ, et al. Changes in markers of cobalamin status after cessation of oral B-vitamin supplements in elderly people with mild cobalamin deficiency. Eur J Clin Nutr 2008; 62(10):1248-51. PMID 17609694

16. Collin SM, Metcalfe C, Refsum H, et al. Circulating folate, vitamin B12, homocysteine, vitamin B12 transport proteins, and risk of prostate cancer: a case-control study, systematic review, and meta-analysis. Cancer Epidemiol Biomarkers Prev 2010; 19(6):1632-42. PMID 20501771

17. Robinson D, O'Luanaigh C, Tehee E, et al. Associations between holotranscobalamin, vitamin B12, homocysteine and depressive symptoms in community-dwelling elders. Int J Geriatr Psychiatry 2010. PMID 20623775

18. Nexo E, Hvas AM, Bleie O, et al. Holo-transcobalamin is an early marker of changes in cobalamin homeostasis. A randomized placebo-controlled study. Clin Chem 2002; 48(10):1768-71. PMID 12324494

19. Hvas AM, Nexo E. Holotranscobalamin--a first choice assay for diagnosing early vitamin B deficiency? J Intern Med 2005; 257(3):289-98. PMID 15715686

20. Hay G, Clausen T, Whitelaw A, et al. Maternal folate and cobalamin status predicts vitamin status in newborns and 6-month-old infants. J Nutr 2010; 140(3):557-64. PMID 20071650

21. Valente E, Scott JM, Ueland P-M, et al. Diagnostic accuracy of holotranscobalamin, methylmalonic acid, serum cobalamin, and other indicators of tissue vitamin B12 status in the elderly. Clin Chem 2011; 57(6):856-63. PMID 21482749

22. Heil SG, de Jonge R, de Rotte MC et al. Screening for metabolic vitamin B12 deficiency by holotranscobalamin in patients suspected of vitamin B12 deficiency: a multicentre study. Ann Clin Biochem 2012; 49(Pt 2):184-9. PMID 22302152

23. England JD, Gronseth GS, Franklin G, et al. Practice Parameter: evaluation of distal symmetric polyneuropathy: role of laboratory and genetic testing (an evidence-based review). Report of the American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, and American Academy of Physical Medicine and Rehabilitation. Neurology 2009; 72(2):185-92. PMID 19056666

24. Golding PH. Holotranscobalamin (HoloTC, Active-B12) and Herbert’s model for the development of vitamin B12 deficiency: a review and alternative hypothesis. Springerplus 2016; 5(1):668. PMID 27350907

25. The National Institute for Health and Care Excellence (NICE). Active B12 assay for diagnosing vitamin B12 deficiency. (September 2015). Available at <> (accessed - 2016 October 25).

26. The World Health Organization (WHO). International Standard for holotranscobalamin (holoTC) Report of the international collaborative study to assign a holoTC value to the International Standard for folate and B12 (03/178) (October 2015). Available at <> (accessed - 2016 October 25).

27. Serum Holotranscobalamin as a Marker of Vitamin B12 (Cobalamin) Status (Archived). Chicago, Illinois: Blue Cross Blue Shield Association Medical Policy Reference Manual (2013 August) Medicine 2.04.39.

Policy History:

Date Reason
10/15/2017 Reviewed. No changes.
1/1/2017 Document updated with literature review. Coverage unchanged.
5/15/2015 Reviewed. No changes.
5/15/2014 Document updated with literature review. Coverage unchanged
7/15/2013 Document updated with literature review. Coverage unchanged. Title changed from “Serum Holo-Transcobalamin (holo-TC) as a Marker of Vitamin B12 (i.e., Cobalamin) Status”. The statement “This policy is no longer scheduled for routine literature review and update” was removed.
6/1/2008 Policy reviewed without literature review; new review date only. This policy is no longer scheduled for routine literature review and update.
9/1/2007 Revised/updated entire document
7/15/2005 New medical document

Archived Document(s):

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