Malnourished Elderly Woman With Worsening Anemia

An 83-year-old woman is hospitalized for treatment of deep venous thrombosisin her left leg. She underwent left hip replacement surgery 2 months earlier.At that time, mild anemia (hemoglobin level, 10 g/dL) was noted, and iron therapywas initiated. An iron panel obtained shortly after the hip surgery revealeda serum iron level of 80 μg/dL, a transferrin level of 360 mg/dL, and a ferritinlevel of 50 ng/mL.

HISTORY AND REVIEW OF SYSTEMS
The patient has hypertension, which is treated with metoprolol. She deniesweakness, fatigue, dyspnea with exertion, and chest pain--either at rest or onexertion. Since the hip surgery, she has had difficulty in walking and has beensomewhat housebound. Although she states that her appetitite is good, herfamily reports that her oral intake has been poor for some time. She had gastricsurgery 40 years ago; the reason is unknown.

PHYSICAL EXAMINATION
The patient is thin. Conjunctival and oral mucous membranes are pale, andthe tongue is papillated except for the lateral edges. Chest is clear; neck veinsare not distended. Heart rate is 96 beats per minute and regular, with a grade IIsystolic murmur along the left sternal border. Abdomen is soft, without massesor hepatosplenomegaly; a well-healed laparotomy incision is visible. The leftlower leg is somewhat red and warm, and the left ankle is swollen. Results of aneurologic examination are normal. Stool is negative for occult blood.

LABORATORY AND IMAGING RESULTS
A Doppler study reveals thrombosis in the femoral, popliteal, and peritonealsystems, and an appropriate anticoagulation regimen is initiated. Results of aserum chemistry panel are normal. White blood cell count is 5800/μL; plateletcount, 190,000/μL; hemoglobin level, 8.2 g/dL; and hematocrit, 25%. Mean corpuscularvolume (MCV) is 111 fL with a reticulocyte count of 25,000/μL (1.4%).

Which of the following is the most appropriate next step?A. Increase the current iron dosage, and add vitamin C to the regimen.
B. Measure vitamin B₁₂ and folic acid levels, and start supplementation with both, pending results.
C. Initiate parenteral iron therapy.
D. Obtain a bone marrow aspirate, and start erythropoietin therapy formyelodysplasia.

CORRECT ANSWER: B
The laboratory findings here suggest at least 1 of thecommon nutritional anemias: iron deficiency, folate deficiency,or vitamin B₁₂ deficiency. This evidence is supportedby the patient's history of a poor diet and previous gastricsurgery, either a total or partial resection.

Iron deficiency. The most common type of anemia todevelop after gastric resection is iron deficiency anemia. Itresults from the removal of acid-secreting cells, which areneeded to reduce iron to the absorbable ferrous form.Loss of absorptive surface and the presence of stomal erosionsand bleeding also contribute to this pathophysiology.

However, the patient's serum ferritin level is normal.This strongly suggests that insufficient iron is notthe cause of her deficient erythropoiesis. Moreover, herred blood cell indices show macrocytosis (MCV, 111 fL),which almost certainly indicates that iron-deficient erythropoiesis(characterized by deficient hemoglobin synthesisand microcytosis) is not the cause of her anemia.Thus, increasing the patient's iron dosage and addingascorbic acid to facilitate absorption (choice A) will notreverse her anemia.

Parenteral iron therapy (choice C) can be useful inthe setting of poor iron absorption. The newer forms ofparenteral iron, which do not contain dextran, are lessallergenic than traditional preparations and have madethis therapy safer. However, parenteral therapy requiresa time-consuming infusion and should be resorted toonly after all types of oral iron have been tried. In anyevent, the evidence does not point to iron deficiency asthe primary problem in this patient.

Myelodysplasia (MDS). This has become the mostcommon cause of anemia in elderly persons and is an importantconsideration here. MDS can be classified by examiningbone marrow findings. In about 25% of patients,the anemia responds to pharmacologic doses of erythropoietin(choice D).

However, patients with MDS typically manifest onlyslight macrocytosis--rarely the degree of macrocytosisseen here. Moreover, before MDS can be diagnosed, reversiblecauses of macrocytic anemia, such as vitamin B₁₂and folate deficiency, must be excluded.

Vitamin B₁₂ and folate deficiencies. The appropriatemanagement strategy for this patient is to measure B₁₂and folic acid levels and to initiate therapy based on the results(choice B). Her significant macrocytosis and subtletongue atrophy suggest vitamin B₁₂ deficiency resultingfrom autoimmune gastritis. Autoimmune gastritis, whichinvolves the fundus and body of the stomach, is the classicpathophysiology of pernicious anemia.¹

This patient has had some type of gastric surgery,perhaps as a result of peptic ulcer disease (PUD). Thus,the B₁₂ deficiency may be related to the total gastric resection.(Although it is a less common sequela than iron deficiency,B₁₂ deficiency can affect patients about 10 yearsafter such an operation.) Alternatively, she may have typeB Helicobacter pylori-associated atrophic gastritis, relatedto PUD; this type of gastritis affects fundus, body, andantrum.

A variety of biochemical tests are helpful in this setting.Measurement of serum B₁₂ (by radioimmune assay)and serum methylmalonic acid levels can detect vitaminB₁₂ deficiency. Tests for circulating intrinsic factor autoantibodiescan help determine whether the patient has autoimmunepernicious anemia. If folate deficiency is suspected,the folic acid level must be measured.

An abnormal B₁₂ or methylmalonic acid level and anormal serum folate concentration confirm vitamin B₁₂ deficiencyas the cause of macrocytic anemia. Because neurologicmorbidity related to ongoing B₁₂ deficiency canbecome irreversible, it is important to initiate parenteralB₁₂ therapy while awaiting biochemical confirmation.

A recent, prospective study of cobalamin levels in 729persons older than 60 years found unrecognized and untreateddeficiency in 1.9% of participants; most of those affectedwere women.² It is prudent to consider undiagnosedvitamin B₁₂ deficiency in any elderly patient with anemia.

Outcome of this case. The patient's serum folic acidlevel was normal (16 ng/mL), but her B₁₂ level was 90pg/mL. She was given parenteral B₁₂, and after 1 monthher hemoglobin level had risen to 11 g/dL. After 3 months,her MCV had dropped to 82 fL, but her ferritin level was14 ng/mL. Thus, after the vitamin B₁₂ deficiency was corrected,concomitant iron deficiency was unmasked--acommon finding in patients who have had a gastric resection.The patient was given iron and vitamin C, and at 6months her hemogram was completely normal.

References:

REFERENCES:1. Toh BH, van Driel IR, Gleeson PA. Pernicious anemia. N Engl J Med. 1997;337:1441-1448.
2. Carmel R. Prevalence of undiagnosed pernicious anemia in the elderly. ArchIntern Med. 1996;156:1097-1100.