The majority of patients with iron deficiency did not have resolution of their condition within three years, according to a statewide retrospective study of more than 13,000 Minnesota residents. Among the individuals who did eventually have normal iron stores, resolution of their iron deficiency took almost two years. These results were published in Blood Advances.1
“We found that in a large cohort of patients with laboratory evidence of iron deficiency, the majority, 58%, did not have documented resolution of their iron deficiency by three years after diagnosis. Further, of the 42% with resolution, the median time to resolution was almost two years,” said lead author Jacob C. Cogan, MD, assistant professor in the Division of Hematology, Oncology, and Transplantation at the University of Minnesota in Minneapolis.
Patients at high risk for iron deficiency include menstruating individuals, patients on long-term anticoagulation therapy, people with bleeding disorders, and individuals with malabsorption including those who have undergone bariatric surgery. The prevalence of iron deficiency in adolescent and young adult women the U.S. may be as high as 39% and is comprised primary of nonanemic iron deficiency, which can be associated with fatigue and cognitive impairment even in the absence of anemia.2
Dr. Cogan and his colleagues analyzed a cohort of 13,084 patients who had a laboratory diagnosis of iron deficiency, with or without anemia, within one of the largest health care provider systems in Minnesota that includes more than 4.5 million patients. Included individuals were age 18 and older, were diagnosed between 2010 and 2020, were tested at least twice, and had at least three years of follow-up to document resolution of the iron deficiency. Iron deficiency was defined as a ferritin value of less than or equal to 25 ng/mL. Iron deficiency resolution was a subsequent ferritin value of at least 50 ng/mL.
More than half of the patients in the cohort (58.1%; n=7,599) did not have resolution of their iron deficiency within three years of diagnosis, despite multiple ferritin measurements. The remaining patients (41.9%; n=5,485) experienced resolution of their deficiency within three years; of these patients, 882 (16.1%) had resolution within one year. The median time to resolution was 1.9 years (interquartile range of 0.8 to 3.9 years).
The majority of patients were female (80.9% with resolved iron deficiency, 90.7% unresolved), identified as white (84.1% and 75.9%, respectively), had private insurance (56.9% and 58.9%, respectively), and received some form of treatment for their iron deficiency (84.7% and 72.5%, respectively).
Patients who had their iron deficiency resolved had a median of four ferritin values measured during the three-year period and had median ferritin levels of 12 ng/mL at diagnosis and 78 ng/mL at resolution. Patients with unresolved iron deficiency had a median of two ferritin values measured and a 10 ng/mL median ferritin level at diagnosis.
The authors identified four main factors associated with higher probability of iron deficiency resolution. Increasing age was associated with a higher likelihood of resolution (adjusted hazard ratio [aHR] = 1.26) with a p-value of less than 0.001 for ages 40 to 59 versus ages 18 to 39, and an aHR of 1.56 and p-value of less than 0.001 for ages 60 or greater versus ages 18 to 59. Male sex was also associated with a greater probability of resolution compared to female sex (aHR=1.58, p<0.001). Medicare was the third factor compared to private insurance (aHR=1.13, p=0.001). Lastly, treatment with intravenous (IV) iron alone (aHR=2.96, p<0.001) and both IV and oral iron (aHR=1.93, p<0.001) were also associated with increased likelihood of resolution compared to oral iron alone.
The authors also found that Black patients were less likely to achieve resolution relative to white patients (aHR=0.73, p<0.001) and that those who were not treated with iron supplementation of any kind were associated with a lower likelihood of resolved iron deficiency compared to those who were treated with oral iron (aHR=0.86, p<0.001).
According to Dr. Cogan, iron deficiency is likely underdiagnosed for two reasons. “First, it is often only thought of when patients are anemic. However, we as hematologists know that patients can be significantly iron deficient long before they become anemic, and this can also result in symptoms such as fatigue, hair loss, mood symptoms, and others. Second, iron deficiency is challenging to diagnose even when suspected, given the multiple laboratory parameters that need to be interpreted, disagreement over the levels for each that constitute iron deficiency, and the need for testing to be done while the patient is fasting.”
A limitation of the study is that it was retrospective in nature and did not allow for detailed understanding of the reasons why patients may not receive the appropriate treatment or follow-up testing after an iron deficiency diagnosis.
“My hope is that this work can elicit investment of resources toward improving iron deficiency care, locally and nationally. It is striking that the patients with iron deficiency resolution took so long, a median of two years, to achieve resolution. Two years is way too long,” Dr. Cogan said. “Efficient iron deficiency treatment can be delivered in approximately six months, including time for a trial of oral iron, time to work out insurance issues around securing IV iron if the oral iron does not work, administration of IV iron, and lab testing to document resolution.
“The high number of unresolved cases suggests the need for systems to help all providers arrive at the correct diagnosis when it is suspected,” Dr. Cogan added. “Health care systems need to agree on ways to identify high-risk patients, protocols for screening, and lab thresholds for diagnosis. Given the large number of patients who are likely walking around with this without knowing it, this is worth the investment.”
Any conflicts of interest declared by the authors can be found in the original article.
References
- Cogan JC, Meyer J, Jiang Z, et al. Iron deficiency resolution and time to resolution in an American health system [published online ahead of print, 2024 Aug. 15]. Blood Advances. doi: 10.1182/bloodadvances.2024013197.
- Weyand AC, Chaitoff A, Freed GL, et al. Prevalence of iron deficiency and iron-deficiency anemia in US females aged 12-21 years, 2003-2020. JAMA. 2023;329(24):2191-2193.
