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A 39-year-old woman was referred to our institution for evaluation of anemia. She was known to have multiple comorbidities and had a baseline hemoglobin concentration of approximately 10.5 g/dL. About 6 months before her referral, the patient began having recurrent episodes of severe anemia, with hemoglobin values as low as 3.5 g/dL. She had become transfusion-dependent and had received about 30 units of packed red blood cells (RBCs) in the preceding 3 months. The patient denied any history of easy bruisability, menorrhagia, or overt evidence of bleeding from any site. Additionally, she denied any change in the appearance or color of her urine and had no history of jaundice. There was no family history of anemia or any other hematologic disorder. As an outpatient, she had undergone an extensive evaluation at another institution, but results failed to provide an explanation for her anemia.
The patient's medical history was remarkable for severe asthma, thought to be due to Churg-Strauss syndrome. She had a tunneled central venous catheter for self-administration of intravenous corticosteroids at the earliest sign of an asthmatic exacerbation. Her other medications included bronchodilators, weekly erythropoietin injections, intravenous iron therapy, an antidepressant, and an anxiolytic.
At presentation, the patient's vital signs were normal. Physical examination was unremarkable except for mild generalized pallor. A complete blood count on the day of admission revealed the following (reference ranges shown parenthetically): hemoglobin, 4.9 g/dL (12.0-15.5 g/dL); mean corpuscular volume (MCV), 94.4 fL (81.6-98.3 fL); hematocrit, 13.4% (34.9%-44.5%); leukocyte count, 6.0 × 109/L (3.5-10.5 × 109/L); and platelet count, 203 × 109/L (150-450 × 109/L). The patient's partial thromboplastin time and prothrombin time (PT)/international normalized ratio were normal. These results were obtained within 24 hours of her last transfusion.
Several cases of factitious anemia have been reported in the literature.1,2 The patient is seldom caught in the act and usually denies the behavior, making the diagnosis difficult to establish incontrovertibly. Patients with this condition often have underlying psychiatric issues and constantly need to assume the sick role. Once the diagnosis is suspected, the patient should be confronted, and removal of any contributing medical device is essential. Early diagnosis is usually difficult but may prevent repeated hospitalizations and the risks associated with invasive diagnostic procedures.2 Management is usually extremely difficult but should be centered around long-term psychotherapy.2 A multidisciplinary approach is of utmost importance because patients usually become very uncooperative when they are discovered and may make attempts to break off relations with the current medical staff and seek medical attention elsewhere. Providing optimal management to an uncooperative patient may be difficult without violating the patient's autonomy. Therefore, a psychiatric consultation should be arranged as soon as possible, and seeking assistance from the institution's ethics and legal committees may be prudent.
The current case provides an opportunity to highlight an approach to the patient presenting with anemia. Anemia can be classified according to measurement of RBC size, as seen on the peripheral blood smear and as indicated by the MCV. This morphological approach categorizes the anemias as microcytic, normocytic, or macrocytic, providing a useful starting point to narrow the list of differential diagnoses. By definition, the MCV is normal (80-100 fL) in patients with normocytic anemia, low (<80 fL) in patients with microcytic anemia, and high (>100 fL) in patients with macrocytic anemia.3
The presence of a microcytic anemia usually indicates a pathologic process involving hemoglobin synthesis. The most common cause is iron deficiency, but other classic causes include the thalassemias and other hemoglobinopathies, lead poisoning, sideroblastic anemia, and, less commonly, anemia of chronic disease. If microcytosis is identified, the next step would be to differentiate among these common causes, and this can be done by assessing serum iron studies, which include serum ferritin, iron, total iron-binding capacity, and transferrin saturation. In iron deficiency, the classic findings are a low serum ferritin value, which is diagnostic, elevated total iron-binding capacity, and low saturation. Other findings include a peripheral blood smear showing anisocytosis and poikilocytosis. If the serum ferritin level and other iron studies are normal, then thalassemia should be considered, and hemoglobin electrophoresis should be performed for the definitive diagnosis. Caution must be taken in interpreting the iron studies in anemia of chronic disease because findings are often inconsistent. The entire clinical scenario must be taken into account.3 Sideroblastic anemias may be hereditary or acquired, and the latter is characterized by increased RBC distribution width, dimorphic RBCs, and bone marrow ringed sideroblasts.
If the anemia is found to be normocytic, the next step would be to differentiate between RBC destruction/loss and a hypoproliferative state. The presence of an increased reticulocyte response (>100 × 109/L) suggests either loss or destruction of RBCs; thus, differentiation of these 2 conditions must be made. Hemolysis is characterized by elevated indirect bilirubin levels, decreased serum haptoglobin levels, and increased serum LDH levels. Also, the peripheral smear may reveal several abnormalities, such as fragmented RBCs and other abnormally shaped RBCs. If laboratory parameters or the peripheral smear is not suggestive of hemolysis, then a bleeding source should be sought. A normocytic anemia without reticulocytosis indicates an aplastic anemia; myelophthisis in which the bone marrow is replaced by fibrosis, tumor, or other abnormal cells; or lack of erythropoietin, which can be seen classically in renal failure.
The first step in evaluating a macrocytic anemia should be ruling out a marked reticulocytosis (polychromasia). Polychromasia may cause a regenerative macrocytosis. If this is found, evaluation for hemolysis or blood loss should be performed as outlined previously. Macrocytic anemias may be due to defects in DNA synthesis, resulting in oval macrocytes, or increase in the cholesterol/phospholipid ratio in membranes, resulting in round macrocytes.
Oval macrocytosis is classically due to vitamin B12 or folate deficiency. If neither is present, then a bone marrow biopsy is warranted to look for the presence of a myelodysplastic syndrome. Round macrocytes may be due to severe alcoholism, liver disease, or hypothyroidism. Also, tobacco use and advanced age may result in round macrocytosis without anemia.
Factitious disorders are difficult to diagnose. However, our patient presented with several clues, including her previous psychiatric history and the recurrent dramatic decreases in her hemoglobin concentration, usually when she was unsupervised. Heightened suspicion is the first step in arriving at the correct diagnosis. Additionally, if anemia is approached in a logical stepwise manner, as outlined previously, multiple expensive, unnecessary, and invasive investigations can be avoided, and if due to a factitious disorder, necessary psychotherapy can be implemented in a more timely fashion.
We thank J. Michael Bostwick MD, Department of Psychiatry, Mayo Clinic, Rochester MN, for his expertise in the care of this patient and guidance in the preparation of the submitted manuscript.
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Correct answers: 1. d, 2. b, 3. a, 4. c, 5. a