What is the most likely diagnosis?A 65-year-old African-American woman presented to the emergency room complaining of worsening shortness of breath and palpitations for about 1 week. She reports feeling “dizzy” on and off for the past year; the dizziness is associated with weakness that has been worsening for the past month. She has been feeling “too tired” to even walk to her backyard and water her flower bed that she used to do “all the time.” She has been so dyspneic walking up the stairs at her home that she moved downstairs to the guest room about a week ago. Review of systems is significant for knee pain, for which she frequently takes aspirin or ibuprofen; otherwise the review of systems is negative. She has no significant medical history and has not been to a doctor in several years. She had a normal well-woman examination and screening colonoscopy about 5 years ago. She occasionally has an alcoholic drink and denies tobacco or drug use. She is married and is a retired shopkeeper. On examination, her blood pressure is 150/85 mm Hg; her pulse is 98 beats/min; her respiratory rate is 20 breaths/min; her temperature is 98.7°F (37.1°C); and her oxygen saturation is 99% on room air. Significant findings on examination include conjunctival pallor, mild tenderness with deep palpation in the epigastric and left upper quadrant (LUQ) region of the abdomen with normal bowel sounds, and no organomegaly but a positive stool guaiac test. The remainder of the examination, including respiratory, cardiovascular, and nervous systems, was normal.
What is the most likely diagnosis?
What is your next diagnostic step?
What is the next step in therapy?
Summary: A 65-year-old woman with worsening dyspnea on exertion, fatigue, dizziness, and palpitations. She is found to have conjunctival pallor and guaiac-positive stool.
• Most likely diagnosis: Anemia secondary to gastrointestinal bleeding; other considerations should include new-onset angina, congestive heart failure, and atrial fibrillation.
• Next diagnostic step: A complete blood count (CBC) to evaluate for the anemia. To evaluate for the other conditions on your differential diagnosis list, you should perform an electrocardiogram (ECG) and cardiac enzymes. A prothrombin time (PT) and partial thromboplastin time (PTT) to look for coagulation abnormalities would be helpful as well.
• Next step in therapy: Admission as an inpatient for further workup, including blood transfusion (if needed), completion of two more sets of cardiac enzymes, and ECGs. A gastroenterology consult for esophagogastroduodenoscopy (EGD) and colonoscopy is appropriate because of the positive guaiac findings.
1. Know a diagnostic approach to anemia in geriatrics.
2. Be familiar with a rational workup for anemia of different origins.
A 65-year-old woman who has developed worsening dyspnea and palpitations over 1-week period of time needs to be evaluated for cardiac and respiratory problems despite the gradual onset of symptoms. Specifically, in a postmenopausal woman, signs and symptoms of angina or acute myocardial infarction may not always have a typical presentation. That the patient has been feeling weak and has conjunctival pallor warrants testing for anemia. As evaluation with serial cardiac enzymes and ECGs is part of the workup, admission into the hospital is appropriate.
Assuming that the initial workup for cardiac and pulmonary causes is negative and that the hemoglobin and hematocrit levels are low, a thorough evaluation for the cause of the anemia is necessary. A CBC with peripheral smear, reticulocyte count, iron studies, vitamin B12, and folic acid levels would provide clues to the type of anemia that this patient has. A gastroenterology consult for possible EGD and colonoscopy to further investigate the source of gastrointestinal bleeding should be considered. The presence of epigastric and LUQ pain, along with long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs), should also raise a flag for testing to rule out a bleeding ulcer.
The presence of other findings may direct your workup toward other diagnoses. If this patient were from a developing country, the possibility of intestinal parasites would need to be considered. If the PT and PTT were abnormal, GI bleeding from a coagulopathy or liver disease would be possibilities. Weight loss, lymphadenopathy, and coagulopathy may warrant evaluation for nongastrointestinal malignancies, such as leukemias or lymphomas. In younger patients, sickle cell disease, thalassemias, glucose-6-phosphate dehydrogenase (G6PD) deficiency, and other inherited causes of anemia would be on the differential diagnosis list. These are unlikely to manifest as an initial diagnosis at the age of 65 years.
ANEMIA: According to the World Health Organization (WHO), a hemoglobin level of less than 12 g/dL in women and less than 13 g/dL in men.
NHANES: The National Health and Nutrition Examination Surveys.
The prevalence of anemia in Americans older than age 65 years is estimated at 9% to 45%. There is a wide variation in the rates of anemia in different ethnic and racial groups, with NHANES data showing the highest rates in non-Hispanic blacks and lowest rates in non-Hispanic whites. These differences are reportedly a result of biologic, not socioeconomic, differences. Most studies show the rate of anemia to be higher in men than women and there is increasing evidence for anemia as an independent risk factor for increased morbidity and mortality and decreased quality of life (Level B recommendation).
Fatigue, weakness, and dyspnea are symptoms that are commonly reported by elderly persons with anemia. These vague and nonspecific symptoms are often ignored by both patients and physicians as symptoms of “old age.” Anemia may result in worsening of symptoms of other underlying conditions. For example, the reduced oxygen-carrying capacity of the blood as a consequence of anemia may exacerbate dyspnea associated with congestive heart failure.
Certain signs found on examination may prompt a workup for anemia. Conjunctival pallor is recommended as a reliable sign of anemia in the elderly and commonly noted in patients with hemoglobin <9 g/dL. Other signs may suggest a specific cause of anemia. Glossitis, decreased vibratory and positional senses, ataxia, paresthesia, confusion, dementia, and pearly gray hair at an early age are signs suggestive of vitamin B12-deficiency anemia. Folate deficiency can cause similar signs, except for the neurologic deficits. Profound iron deficiency may produce koilonychias (spoon nails), glossitis, or dysphagia. Other clinical manifestations of anemia include jaundice and splenomegaly. Jaundice can be a clue that hemolysis is a contributing factor to the anemia, while splenomegaly can indicate that a thalassemia or neoplasm may be present.
Initial workup of anemia should include a CBC with measurement of red blood cell (RBC) indices, a peripheral blood smear, and a reticulocyte count. Further laboratory studies would be indicated based on the results of the initial tests and the presence of symptoms or signs suggestive of other diseases.
The most common cause of anemia with a low mean corpuscular volume (MCV), microcytic anemia, is iron deficiency. Iron deficiency could be confirmed by subsequent testing that shows a low serum iron, low ferritin, and high total iron-binding capacity (TIBC). Other causes of microcytic anemia include thalassemias and anemia of chronic disease. In the elderly, iron deficiency is frequently caused by chronic gastrointestinal blood loss, poor nutritional intake, or a bleeding disorder. A thorough evaluation of the gastrointestinal tract for a source of blood loss, usually requiring a gastroenterology consultation for upper and lower GI endoscopy, should be undertaken, as iron-deficiency anemia may be the initial presentation of a GI malignancy.
Anemia with an elevated MCV, macrocytic anemia, is most often a manifestation of folate or vitamin B12 deficiency; other causes include drug effects, liver disease, and hypothyroidism. The presence of macrocytic anemia, with or without the symptoms previously mentioned, should lead to further testing to determine B12 and folate levels. An elevated methylmalonic acid (MMA) level can be used to confirm a vitamin B12 deficiency; an elevated homocysteine level can be used to confirm folate deficiency. Folate deficiency anemia is usually seen in alcoholics, whereas B12-deficiency anemia mostly occurs in people with pernicious anemia, a history of gastrectomy, diseases associated with malabsorption (eg, bacterial infection, Crohn disease, celiac disease), and strict vegans (rare).
In the elderly, anemia of chronic inflammation (formerly known as anemia of chronic disease) is the most common cause of a normocytic anemia. Anemia of chronic inflammation is anemia that is secondary to some other underlying condition that leads to increased inflammation and bone marrow suppression. Along with causing a normocytic anemia, anemia of chronic disease can also present as a microcytic anemia. This type of anemia can easily be confused with iron-deficiency anemia because of its similar initial laboratory picture. In anemia of chronic inflammation, the body’s iron stores (measured by serum ferritin) are normal, but the capability of using the stored iron in the reticuloendothelial system becomes decreased. A lack of improvement in symptoms and hemoglobin level with iron supplementation are important clues indicating that the cause is chronic disease and not iron depletion, regardless of the laboratory picture. Another cause of normocytic anemia is renal insufficiency due to decreased erythropoietin production. Although bone marrow iron store remains the gold standard to differentiate between iron-deficiency anemia and anemia of chronic disease, simple serum testing is still used to diagnose and differentiate these two types of anemia (Table 9–1).
Table 9–1 • LABORATORY VALUES DIFFERENTIATING IRON- DEFICIENCY ANEMIA FROM ANEMIA OF CHRONIC INFLAMMATION
The treatment of anemia is determined based on the type and cause of the anemia. Any cause of anemia that creates a hemodynamic instability can be treated with a red blood cell transfusion. A hemoglobin less than 7 g/dL is a commonly used threshold for transfusion; however, transfusion may be indicated at higher levels if the patient is symptomatic or has a comorbid condition such as coronary artery disease. Iron-deficiency anemia is treated first by identification and correction of any source of blood loss. Most iron deficiency can be corrected by oral iron replacement. Various iron preparations are available; a typical treatment is ferrous sulfate 325 mg (contains 65 mg of elemental iron) three times a day. Parenteral iron preparations are available for those with poor iron absorption and high iron replacement needs. Vitamin B12 deficiency traditionally has been treated by intramuscular B12 therapy with a regimen of 1000 μg IM daily for 7 days, then weekly for 4 weeks, then monthly for the rest of the patient’s life. Newer research shows that many patients can be successfully treated with oral B12 therapy using 1000 to 2000 μg PO in a similar regimen. Folate deficiency can be treated with oral therapy of 1 mg daily until the deficiency is corrected. Anemia of chronic inflammation is managed primarily by treatment of the underlying condition in order to decrease inflammation and bone marrow suppression. When anemia of chronic inflammation is severe (hemoglobin <10 g/dL), the risks and benefits of two modalities of treatment, blood transfusion and erythropoiesis-stimulating agents, may be considered. To note, the goals of treatment of anemia of chronic inflammation in patients with chronic kidney disease undergoing dialysis are to maintain a hemoglobin level between 10 and 12 g/dL; higher hemoglobin levels in this patient population are associated with increased rates of death and cardiovascular events.
9.1 A 58-year-old woman comes to your office complaining of fatigue. She has also noticed a burning sensation in her feet over the past 6 months. A CBC shows anemia with an increased MCV. Which of the following is the most likely cause of her anemia?
A. Lack of intrinsic factor
B. Inadequate dietary folate
C. Strict vegetarian diet
D. Chronic GI blood loss
9.2 A 65-year-old man with a history of rheumatoid arthritis is found to have a microcytic anemia. He had a colonoscopy 1 year ago which was normal and stool guaiac is negative. Which of the following is the most likely cause of his anemia?
A. Iron deficiency
B. Chronic disease
C. Pernicious anemia
D. Folate deficiency
For questions 9.3 and 9.4 match the following lab pictures (A-D) of patients with anemia:
A. Normal MMA; decreased serum folate level
B. Elevated MMA; decreased serum B12 level
C. Elevated ferritin; normal MCV; decreased serum iron level
D. Decreased ferritin; decreased MCV; decreased serum iron level
9.3 A 68-year-old male is found to have an incidental finding of anemia while in the hospital for alcohol abuse.
9.4 A 67-year-old male with dizziness and a positive stool guaiac test.
9.5 A 68-year-old man is found to have an incidental finding of anemia while hospitalized with pneumonia. His physical examination is normal except for crackles in the left lower lobe. Serum laboratory examinations reveal a normal MMA and a decreased serum folate level. Which of the following is the best next step?
A. Administer CAGE questionnaire
B. Esophagogastroduodenoscopy
C. Serum iron assay
D. Neurology consultation
9.1 A. The clinical presentation and CBC findings are consistent with macrocytic anemia due to B12 deficiency. Pernicious anemia (lack of intrinsic factor) is the most common cause. B12 deficiency can also be seen in patients who follow a strict vegetarian diet; however, the body’s B12 stores can last several years before they are depleted.
9.2 B. Anemia of chronic disease can cause normocytic or microcytic anemia, and may be secondary to rheumatoid arthritis in the patient. Iron deficiency anemia is less likely with a normal colonoscopy and negative stool guaiac, and serum iron studies could be used to help differentiate the two.
9.3 A. Alcohol abuse is a common cause of folate deficiency. A normal MMA level essentially rules out a concomitant vitamin B12 deficiency.
9.4 D. Low serum iron, low MCV, and low ferritin levels, along with a finding of blood in the stool, are consistent with iron-deficiency anemia. A workup for the source of the GI blood loss should ensue.
9.5 A. Alcohol abuse, which may be assessed by the CAGE questionnaire, is a common cause of folate deficiency. CAGE is an acronym which stands for Cut back, Annoyed, Guilty, and Eye-opener. A normal MMA level essentially rules out a concomitant vitamin B12 deficiency. Gastric endoscopy—to look for atrophic gastritis—would be indicated for pernicious anemia. A serum iron assay would likely be high because of increased turnover of iron in patients with megaloblastic anemia due to either B12 or folate deficiency. A neurology consultation would be needed if the patient had neurologic signs or symptoms of B12 deficiency.
Conjunctival pallor is an indication for anemia workup in elderly patients.
Clinical findings of anemia require investigation for underlying causes.
GI bleeding is an important cause of iron-deficiency anemia in both female and male geriatric patients; this type of anemia mandates a GI workup in this patient population.
Investigating for vitamin B12 and folate deficiency is of high importance in a patient with a history of heavy EtOH (ethyl alcohol) intake and/or abuse.
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NHANES 2007-2008 Clinical Data Analysis, available at: http://www.cdc.gov/nchs/about/major/nhanes/nhanes2007-2008/nhanes07_08.htm. Accessed October 2, 2011.
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