ANN ARBOR, MI — Anemia occurs frequently, and clinicians often underappreciate its importance, even though up to 10% of adults with incident iron deficiency anemia (IDA) could have gastrointestinal cancer, according to a new study.

The report in JAMA Network Open pointed out that anemia is a common problem that affects more than 5% of U.S. adults, but the evaluation of new-onset anemia is not well standardized. The authors from the Ann Arbor, MI, VA Healthcare System and the University of Michigan argued that incident anemia requires prompt evaluation to prevent diagnostic delays.1

In addition, because current practices for evaluation of incident anemia are unknown, they sought to characterize incident anemia evaluation in a national integrated health care system.

The national retrospective cohort study included nearly 50,000 patients who received regular VA care—defined as two or more primary care visits in two years—and had incident anemia; average age was 71.8 and nearly all were men. Anemia was determined by: (1) two or more normal hemoglobin (Hb) levels between Jan. 1, 2013, and Dec. 31, 2014; and (2) followed by anemia on two laboratory studies within six months of each other. The World Health Organization criteria were used for Hb levels: less than 12 g/dL for women and less than 13 g/dL for men.

Defined as the primary outcome was appropriate testing within one year. Testing consisted of iron studies (ferritin, iron saturation, or both) in patients with microcytic anemia (mean corpuscular volume, < 80 μm3 [to convert to femtoliters, multiply by 1]); vitamin B12 and folate studies in patients with macrocytic anemia (mean corpuscular volume, >100 μm3); iron studies (ferritin, iron saturation, or both); and vitamin B12 and folate studies in patients with normocytic anemia (mean corpuscular volume, 80-100 μm3). Anemia was classified as mild, moderate, or severe using World Health Organization criteria (mild, Hb ≥11 g/dL; moderate, Hb ≥8 but <11 g/dL; or severe, Hb <8 g/dL). Iron deficiency anemia was determined using established likelihood ratios of ferritin.

In the year after the diagnosis of incident anemia, appropriate laboratory testing was performed in 15 592 of the 49 648 patients (31.4%), according to researchers. Results indicated that, among these patients, 2,676 of 4,013 (66.7%) had appropriate laboratory evaluation for microcytic anemia, 11,533 of 42,593 (27.1%) for normocytic anemia, and 1,383 of 3042 (45.5%) for macrocytic anemia.

The authors pointed out that the “initial anemia severity, or alternatively, the change from the prior baseline normal hemoglobin value, was significantly associated with appropriate testing.” Those with mild anemia were less likely to undergo additional evaluation (odds ratio, 0.53; 95% CI, 0.50-0.56; P < .001).

The study found no statistically significant difference in appropriate laboratory testing by race or sex when controlling for anemia severity.

“For those with IDA (ferritin level <35 ng/mL [to convert to micrograms per liter, multiply by 1) without recent endoscopic assessment, 3,447 of 5,050 patients (68.3%) did not undergo esophagogastroduodenoscopy or colonoscopy within one year of the diagnosis of incident anemia,” researchers advised. “Even with a lower ferritin cutoff value for IDA (<15 ng/mL; with an established likelihood ratio, 51.9; 95% CI, 41.5-62.3), 1777 of 2822 patients (63.0%) did not undergo endoscopic evaluation.”

They noted that patients aged 50 to 75 years were more likely to undergo endoscopic evaluation for incident IDA compared with those younger than 50 or older than age 75 years (odds ratio, 2.1; 95% CI, 1.9-2.4; P < .001).

“In this national retrospective cohort study, undertesting for incident anemia was common, and most patients with newly diagnosed IDA did not undergo endoscopic evaluation,” the authors concluded. However, this finding was attenuated by anemia severity; those with mild anemia were less likely to undergo evaluation, a finding similar to those in previous studies and health care settings.

The study added, “It is important to note that the VA has made substantial efforts to assess and address potential diagnostic delays, such as those identified in this analysis. Future studies should examine variation in testing at the clinician level and identify further opportunities for intervention.”


  1. Read AJ, Waljee AK, Chen CS, Holleman R, Kumbier KE, Saini SD. Prevalence of Appropriate Testing for Incident Anemia in the US Department of Veterans Affairs. JAMA Netw Open. 2021 Jan 4;4(1):e2034406. doi: 10.1001/jamanetworkopen.2020.34406. PMID: 33496793; PMCID: PMC7838922.