Evaluating and Treating Active Patients for Anemia
Raymond J. Browne, MD, MPHTHE PHYSICIAN AND SPORTSMEDICINE - VOL 24 - NO. 9 - SEPTEMBER 96
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In Brief: Anemia affects many active patients, from young female recreational athletes to elite male competitors. The treatment may simply be iron supplementation, but the causes of iron-deficiency anemia are many, including poor nutrition, exercise-induced hemoglobinuria or hematuria, gastritis, hemorrhoids, peptic ulcer disease, angiodysplasia, and adenocarcinoma. Therefore, physicians need to do a thorough evaluation that includes a medical history, family medical history, drug history, physical exam, and referral to a gastroenterologist if necessary.
Unequivocally, an athlete with iron deficiency will not perform as well as an athlete with normal iron stores and red blood cell indices. Thus, it is surprising that so many of today's athletes have iron-deficiency anemia. But, as the case below illustrates, it is not enough to simply diagnose anemia and prescribe iron supplements. Physicians must also meticulously search for the cause of the deficiency.
A 25-year-old minor league hockey player sought continuation of his iron therapy. The player had been diagnosed with iron-deficiency anemia the previous year when playing for another team. At that time, his iron deficiency was determined by blood work, and he was started on supplemental iron therapy. No further investigation was done to determine the cause of the deficiency. The player said that he took the supplemental iron whenever he felt fatigued.
The player could relate no obvious source of blood loss. He admitted to having dark stools but attributed them to the iron therapy. He reported no history of peptic ulcer disease or chronic usage of nonsteroidal anti-inflammatory drugs (NSAIDs). The player reported occasional bouts of bilateral cramping in the lower abdomen—but not severe enough to prevent him from playing. He attributed some of his abdominal pain to the iron therapy. He had no family history of inflammatory bowel disease or anemias and no ancestors of Mediterranean descent.
The player's physical exam was remarkable for bilateral lower abdominal discomfort on deep palpation. He had no rebound tenderness, palpable masses, or hepatosplenomegaly. Rectal exam revealed dark, tarry stools that were positive for occult blood. Blood work indicated significant iron deficiency as evidenced by low iron and low ferritin (table 1).
__________________________________________________________________ Table 1. Blood Workup for a 20-Year-Old Hockey Player With Anemia __________________________________________________________________ Patient's Normal Values for Men __________________________________________________________________ Hemoglobin (g/dL) 13.1 14.0 - 18.0 Hematocrit (%) 41.0 42.0 - 52.0 Mean corpuscular volume 80.6 80 - 100 (micrometers3) Iron 20 76 - 198 (micrograms/dL) Total iron-binding capacity 312 213 - 521 (micrograms/dL) Saturation (%) 6 20 - 50 Ferritin* (ng/dL) 28 30 - 300 __________________________________________________________________ *Level increases with inflammation, cancer, and liver disease. __________________________________________________________________
The player was referred to a gastroenterologist. Colonoscopy revealed extensive ulceration and deformity of the ileocecal valve with associated erythema of the intervening normal mucosa (figure 1). The colonoscope could not enter the ileocecal valve because of a stricture. Pathology reports and review of the small bowel follow-through confirmed the diagnosis of Crohn's disease. The gastroenterologist said the stricture was serious enough to warrant surgery. The condition, however, responded to a regimen of high-dose, tapered steroids and azulfidine.
With dissipation of his symptoms and the gastrointestinal bleeding, he was able to finish the last month of the season. (His convalescence lasted about 1 month.) Nevertheless, the player was advised of the serious nature of this disease, its complications, and the potential for increased exacerbations if he continued his hockey career (1).
Anemia: Causes and Effects
The primary role of red blood cells is to transport oxygen from the lungs to tissues and to transport carbon dioxide in the reverse direction. The oxygenation of a particular organ or tissue depends on the oxygen-carrying capacity of the blood, represented by the hemoglobin concentration (2). This function is compromised in a patient who has anemia. Thus, the athlete with chronic anemia may have weakness, lassitude, palpitations, and sometimes exertional dyspnea. These symptoms become more evident in endurance sports.
In addition to the medical concerns related to anemia, an athlete's performance may suffer as well. Obviously, delivery of oxygen to vital tissues during exercise depends on the patient's overall red blood cell mass.
When an athlete has dyspnea on exertion, it's important to ask if it occurs at an activity level previously tolerated. Before embarking on an elaborate and expensive cardiopulmonary work-up, the physician must rule out anemia as a cause of the athlete's worsening fatigue. Baseline anemia studies—hemoglobin, hematocrit, mean corpuscular volume, iron level, total iron-binding capacity, and ferritin level—can help determine if anemia is a potential cause of the athlete's symptoms.
Iron deficiency is a common cause of anemia in athletes. In one study (3), 80% of young female athletes and 30% of elite male athletes were iron deficient. The iron deficiency in females is often attributable to inadequate nutrition and menstruation. Inadequate nutrition as a cause of anemia is rare in male athletes because they don't have the significant and regular blood loss of female athletes. This is reflected in their iron requirements, which are half as much as women's.
Because a typical diet is relatively low in iron, an inactive menstruating female must eat a 3,000-kcal diet to get the 18 mg of daily iron her body needs to absorb its requisite 1.5 mg of iron (nonmenstruating females need only half this much dietary iron). In addition, some studies indicate that iron absorption is less in iron-deficient athletes than in sedentary people (3). To further exacerbate the athlete's plight, many competitors consume little red meat (a major source of dietary iron) and prefer a diet high in natural foods that are not iron supplemented.
Bleeding is the primary cause of iron deficiency, and gastrointestinal bleeding is the most common source of pathologic blood loss and resultant iron-deficiency anemia (2). A complete gastrointestinal work-up is necessary in male and nonmenstruating female athletes in whom iron deficiency has been discovered.
Once the cause is determined (table 2), treatment should address the source so as to prevent further recurrence. Simply prescribing iron for an individual with an apparent iron deficiency may be neglecting a treatable or potentially life-threatening disease. An athlete's poor response to supplemental iron necessitates further evaluation.
__________________________________________________________________ Table 2. Common Causes of Gastrointestinal Blood Loss __________________________________________________________________ Peptic ulcer disease Gastritis Hemorrhoids Angiodysplasia of the colon Colonic adenocarcinoma __________________________________________________________________
Studies have shown that even a slight drop in hemoglobin can adversely affect an athlete's performance. One study (4) comparing the performance of marathon runners revealed that those with a higher hematocrit had faster times than those with lower hematocrits. Even athletes with borderline but acceptable hemoglobin concentrations have diminished performance because of iron deficiency (5). Iron plays a significant role in oxygen transport and is a cofactor in a number of enzyme systems that involve mitochondrial electron transport and oxidative phosphorylation. Animal studies have shown that limitations in treadmill performance and growth depend directly on iron levels and that performance is impaired in iron-deficient rats, independent of hemoglobin concentration (6).
Several causes of anemia are directly related to exercise. Although the amount of iron lost from the gastrointestinal tract and urinary tract during exercise is small, it may be enough to deplete iron stores—especially in a nutritionally compromised athlete. Iron lost through sweat is negligible.
March hemoglobinuria is a well-described intravascular hemolysis caused by exhaustive exercise. Such exercise has been associated with a fall in serum haptoglobin, the presence of free hemoglobin in the urine, a rise in plasma hemoglobin, and an increase in younger red blood cells. The effect is magnified as the intensity of exercise increases. Hemolysis appears to be further influenced by running surface, resilience of shoe insoles, and running technique. In addition, red blood cell fragility may increase with exercise, a rise in body temperature, and the age of the red blood cells (6).
Exertional hematuria can be another cause of anemia and is found not infrequently in long-distance runners. Exercise-induced hematuria may have several causes. "Runner's bladder," which results in gross hematuria, is thought to be due to friction between the posterior bladder wall and the prostatic base (7). Another theory posits the rupture of renal capillaries in connection with increased vascular resistance that occurs during extreme physical exertion (8). Regardless of the cause, greater exercise duration and intensity raise the incidence of exercise-induced hematuria.
Gastrointestinal bleeding directly related to athletics has been described in marathon runners who reported bloody stools after running (6,7). A larger percentage have experienced occult blood loss after races. One cause for the blood loss is ischemic gastritis and colitis secondary to shunting of blood from the gastrointestinal tract to the exercising muscles (7). Stress-induced and NSAID-induced gastritis are also potential sources of gastrointestinal blood loss. Often, the pain associated with gastritis will be masked by the analgesic effect of the NSAID.
The Need for Thoroughness
If an athlete has iron-deficiency anemia, it is typically caused by an inadequate diet or exercise-related occult blood loss. The diagnosis of sport- or exercise-related anemia should be a diagnosis of exclusion. Because bleeding is the primary cause of iron deficiency, many causes of gastrointestinal blood loss must be ruled out. That is why it's so important to do a thorough evaluation that includes medical history, family medical history, drug history, physical exam, and gastrointestinal referral if necessary.
Had we continued to treat our stoic hockey player with supplemental iron, he probably would have developed a small-bowel obstruction. This could have been life-threatening had it occurred on a long bus trip for an away game.
Dr Browne is an internist in private practice in Birmingham, Alabama, an internal medicine consultant with Alabama Sports Medicine and Orthopedic Center in Birmingham, and a member of the American Medical Society for Sports Medicine and the American College of Physicians. Address correspondence to Raymond J. Browne, MD, MPH, 1222 14th Ave S, Suite 310, Birmingham, AL 25205.