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Anemia: not just an outpatient problem anymore

February 2010

A 64-year-old woman presents to the ED complaining of substernal chest pain for the past five days. She’s also been fatigued for six months and has increasing dyspnea on exertion.

Routine blood work shows that her hemoglobin is 8.7 g/dL, which, according to her chart, is a drop from 9.9 g/dL a year or so ago, and that her serum creatinine is elevated at 1.5 g/dL. The patient is on a statin, baby aspirin, an ACE inhibitor, HCTZ and iron for documented iron deficiency anemia (six months ago). Otherwise, she is a standard chest pain admission.

When treating this patient, many hospitalists would follow the basic protocol to rule out active ischemia, determine whether a stress modality is required and then try to discharge the patient in as close to 24 hours as possible. You would probably mention concerns about anemia in the discharge summary, but because there is no need for urgent transfusion, anemia will be left for the next physician to sort out.

It’s a standard approach, but in this case it’s flawed for several reasons. For one, you’ve missed a critical opportunity to jumpstart treatment for a disease state that affects quality of life and readmission rates. This patient has ongoing dyspnea with worsening anemia that has not yet been addressed in other care settings “and the problem is likely to go unaddressed until something worse occurs.

Evaluating iron deficiency anemia in adults. Updated practice guidelines from the AAFP (August 2021).

Patients with anemia, particularly those with chronic kidney disease (CKD), face an increased risk of adverse clinical outcomes, especially when the patient has other common comorbidities such as cardiovascular disease, CHF and diabetes. And anemic patients have higher admission and readmission rates and greater cardiovascular events over time.

These findings have led me to reassess how I approach these patients in the hospital.

Addressing anemia in the hospital
For chronic conditions like hypertension and diabetes, I have always felt that hospitalists should make every effort to talk with a patient’s primary care physician, even when that patient was admitted for another reason. I have recently applied that same philosophy to anemic patients, particularly those with chronic kidney disease, as a hospitalist at Cooper University Hospital in Camden, N.J.

Like many physicians, hospitalists have historically considered hemodynamically stable anemia to be a chronic, outpatient problem that is a normal part of aging. But sending patients home without first specifically addressing their anemia and chronic kidney disease has some major downsides.

This became apparent during a discussion last September, when I chaired a panel of seven physicians to examine how hospitalists should approach the care of anemic patients. The panel, funded by an unrestricted educational grant from American Regent Inc., included several hospitalists, along with representatives of the nephrology, hematology and pharmacy communities.

The first thing that panel members agreed on was the need to define anemia. While multiple definitions were presented, the one favored by the nephrologists comes from the National Kidney Foundation, which defines anemia as a hemoglobin of less than 13.5 g/dL in men and less than 12 g/dL in women.

While the conventional wisdom holds that anemia is a sign of poor health, data from studies presented during our panel discussion actually point to a different interpretation of what it means to have anemia. Although there are many etiologies of anemia, virtually all patients who undergo hemodialysis can be considered anemic due to overwhelming iron malabsorption and erythropoietin deficiency. In addition, occult infections can make iron stores unavailable, even in otherwise seemingly healthy individuals.

Greater LOS, more readmissions
In the U.S., 3.4 million Americans have been diagnosed with anemia, and millions more likely have the condition but haven’t received an official diagnosis. Research has shown that untreated anemia increases LVH, which is an independent risk for cardiac death.

Researchers with the OPTIMIZE HF study, which was published in the July 23, 2007, Archives of Internal Medicine, found that half of the 50,000 hospitalized patients with CHF studied were anemic, and that one-quarter were very anemic and had a hemoglobin of between 5 and 10.7. The study also found higher in-hospital mortality for anemic patients, a greater length of stay and a higher 90- day readmission rate.

Another study published in the June 2008 issue of the Journal of the American Medical Directors Association found that as the amount of time patients had been living with anemia increased, their chances of being admitted to the hospital rose as well. The study also found that anemic patients had longer lengths of stay, and that length of stay increased with anemia severity.

Other studies have found that anemia multiplies patients’ risk factors for poor outcomes. A study in the Nov. 19, 2009, New England Journal of Medicine suggests that patients who received IV iron reported significant or moderate improvement in symptoms, functional capacity and quality of life.

Rethinking ESA use
Panel member Richard Mazey, MD, a nephrologist who has co-authored several studies on iron, presented data from the CHOIR study, which appeared in the Nov. 16, 2006, New England Journal of Medicine. That study found that patients with anemia and CKD treated with an erythropoiesis stimulating agent (ESA) to a target hemoglobin of 13.5 g/dL faced an increased risk of serious, life-threatening cardiovascular complications when compared to treatment with an ESA to a target hemoglobin of 11.3 g/dL.

ESAs are not the only solution for patients with anemia and CKD. As Dr. Mazey explained, ESAs typically tap patients’ iron stores from multiple sites; and if the body is short on iron, ESAs will cause iron stores to plummet. This in turn limits the effectiveness of the ESA to stimulate production of red blood cells needed to treat the anemia.

As a result, many patients with anemia related to CKD stand to benefit more from iron repletion than an ESA. According to Dr. Mazey, he’s been able to stop giving patients ESAs once he has given them enough iron to replete their stores.

“It’s impressive how well people can make red blood cells,” said Dr. Mazey, “when you make their iron kinetics in target range.”

The potential to decrease or eliminate the use of ESAs has a ripple effect because these drugs carry such an enormous price tag. They are among the biggest cost centers for hospital pharmacies.

Issues with transfusions
Another common therapy for anemia “transfusions ” likewise has significant downsides. Blood costs more than $400 to $600 per unit, but that pales in comparison to the total costs of transfusions, which can run as high as $2,200.

Studies have also shown that length of stay can be longer for patients who receive transfusions. And data from the critical care literature associate transfusions with increased postop and surgical-site infections.

But perhaps the biggest problem with transfusions is that the therapy doesn’t address the anemia’s underlying cause. A transfusion will just boost the patient’s red blood cells for the moment, and the problem will resurface over the next few months.

While oral iron is an option, the panel reviewed the challenges of this therapy. Studies have shown that a large percent of patients don’t tolerate oral iron well because of GI side effects. Diet can also hinder the absorption of oral iron, making it less predictable than IV iron.

In addition, we see patients on oral iron who show no signs of improvement. Commonly, these are patients who are already on an ESA and have chronic kidney disease. This is most likely due to a molecule called hepcidin, which is an important regulatory protein for iron homeostasis.

Hepcidin binds to the iron channels in the duodenal enterocyte when iron stores are at appropriate levels, blocking further absorption from the gut. Patients with renal impairment have inappropriately high levels of hepcidin, which interferes with their normal absorption of oral iron.

The case for IV iron
The panel concluded that to address many of these issues, patients suffering from iron deficiency anemia in the presence of CKD that is not due to acute blood loss and without hypotension or tachycardia should be strongly considered for IV iron therapy during their inpatient stay or shortly after discharge. This recommendation not only challenges the hospitalist’s paradigm of passing anemic patients on to a primary care physician, but it raises questions about how to deliver care to hospitalized patients, particularly short stay patients.

Patients require a certain amount of iron over time to achieve their target hemoglobin. Once there, they often can be maintained at a lower dose. In patients with CKD ” and patients with hepcidin issues “achieving that target can take a few doses of IV iron.

Subsequently, patients may be able to be maintained by oral iron as there is some absorption. This approach is commonly used for patients on hemodialysis, but a similar phenomenon is found in earlier stages of CKD.

While panel members agreed that hospitalists need to address anemia in the acute care setting, the reality is that much of patients’ therapy will continue long after discharge. Guidelines from the National Kidney Foundation, for example, recommend that iron levels in CKD patients with anemia be monitored every three months.

If hospitalists do their job well, patients won’t be returning to the hospital within that timeframe. While we will obviously mention the diagnosis and treatment of anemia in a discharge summary, is that enough to ensure that patients receive appropriate follow-up?

Nephrology follow-up
In considering that dilemma, panel members decided that the best route would be to get a nephrologist involved in the patient’s care while in the hospital. I personally think that bringing in a specialist who will follow up on an outpatient basis is the best way to guarantee continuity of care. If patients meet these physicians in the hospital, they’re more likely to go see them in the office.

If the patient has iron deficiency anemia and CKD, I call for a renal consult. I try to give ownership of anemia to a specialist, who is in a much better position to follow up with the patient and make decisions regarding the need for outpatient administration of IV iron (and prevent progression of their kidney disease).

In the case of our 64-year old with chronic anemia and CKD, I would see the patient in our observation unit. I would not only apply the appropriate work-up for chest pain, but care for her anemia. Remember, this patient has received a trial of oral iron without success. While compliance is a possible issue, I would nonetheless choose a more aggressive treatment plan. I would want to rule out other causes of anemia first (GI bleeding or bone marrow issues, for example) by checking old records and reviewing the hemoccult and peripheral blood smear.

Then I would call in the cavalry “our nephrology group “for consideration of IV iron now, and again in follow-up over the next few months. I would not give this patient a transfusion, but if time permitted, I would administer IV iron before she left. If that wasn’t possible, I would set her up as an outpatient in the short procedure unit or a nephologist’s office.

Observation patients or those who move quickly from hospitalist to hospitalist over a weekend often have their anemia overlooked. This is partly due to pressure for an early discharge. For these patients, it may not be feasible (or even necessary, if early follow-up is ensured) to administer IV iron in the hospital, but plugging them in with nephrology is essential.

Cost considerations
The panel raised the issue of the cost of giving patients inpatient IV iron as opposed to prescribing oral iron that patients pay for themselves. While 1 gram of IV iron will cost your hospital about $400 “and may lead to grumbling from the pharmacy department “those concerns are short-sighted if patients can be kept from bouncing back.

In any discussion of anemic patients, then, a key question for me is: Would giving patients IV iron in the hospital, and not waiting for a primary care physician to take action, help keep patients out of the hospital?

Most of the data the panel reviewed seemed to indicate a solid “yes.” Jump-starting patients’ iron stores while they’re hospitalized appears to be a significant first step in not only improving quality of life, but in reducing the chance that those patients will return to the hospital in the very near future.

What if we do nothing to treat the anemia that we see? The medical literature is fairly clear that complications are likely to occur and readmission rates may ultimately rise. Aren’t those what we as hospitalists are trying to avoid?

Eric Kupersmith, MD, is head of the division of hospital medicine at Cooper University Hospital in Camden, N.J., and assistant professor of medicine at UMDNJ Robert Wood Johnson Medical School.

Members of the anemia panel

  • George R. Bailie, PharmD, PhD
    Albany College of Pharmacy Albany, N.Y.
  • Vijay Gandla, MD
    High Point Regional Health System High Point, N.C.
  • Eric Kupersmith, MD
    Cooper University Hospital Camden, N.J.
  • Neil A. Lachant, MD
    Cooper Cancer Institute Camden, N.J.
  • Richard Mazey, MD
    Physicians’ Health and Wellness Mobile, Ala.
  • Robert Perkins, MD
    Geisinger Medical Center Danville, Pa.
  • John E. Reed, MD
    Baptist Memorial Hospital Columbus, Miss.

Published in the February 2010 issue of Today’s Hospitalist