A 55-year-old man is being evaluated for constipation. There is no history of prior gastrectomy or of upper GI symptoms. Hemoglobin is 10 g/dL, mean corpuscular volume (MCV) is 72 fL, serum iron is 4 µg/dL (normal 50-150 µg/dL), iron-binding capacity is 450 µg/dL (normal 250-370 µg/dL), saturation is 1% (normal 20%-45%), and ferritin is 10 µg/L (normal 15-400 µg/L).
Which of the following is the best next step in the evaluation of this patient’s anemia?
The patient has a microcytic anemia. A low serum iron, low ferritin, and high iron-binding capacity all suggest iron-deficiency anemia. Most iron-deficiency anemia is explained by blood loss. The patient’s symptoms of constipation point to blood loss from the lower GI tract. Colonoscopy would be the highest-yield procedure. Barium enema misses 50% of polyps and a significant minority of colon cancers. Even patients without GI symptoms who have no obvious explanation (such as menstrual blood loss or multiple prior pregnancies in women) for their iron deficiency should be worked up for GI blood loss. Folate deficiency presents as a megaloblastic anemia with macrocytosis (large, oval-shaped red cells) and hypersegmentation of the polymorpho-nuclear leukocytes. Lead poisoning can cause a microcytic hypochromic anemia, but this would not be associated with the abnormal iron studies and low ferritin seen in this patient. Basophilic stippling or target cells seen on the peripheral blood smear would be important clues to the presence of lead poisoning. Although a bone marrow examination will prove the diagnosis by the absence of stainable iron in the marrow, the diagnosis of iron deficiency is clear from the serum studies. Thalassemia (diagnosed by hemoglobin electrophoresis) is not associated with abnormal iron studies. The most important issue is now to find the source of the iron loss.
A 50-year-old woman complains of pain and swelling in her proximal interphalangeal joints, both wrists, and both knees. She complains of morning stiffness. She had a hysterectomy 10 years ago. Physical examination shows swelling and thickening of the PIP joints. Hemoglobin is 10.3 g/dL, MCV is 80 fL, serum iron is 28 µg/dL, iron-binding capacity is 200 µg/dL (normal 250-370 µg/dL), and saturation is 14%.
Which of the following is the most likely explanation for this woman’s anemia?
Patients with chronic inflammatory or neoplastic disease often develop anemia of chronic disease. Cytokines produced by inflammation cause a block in the normal recirculation of iron from reticuloendothelial cells (which pick up the iron from senescent red blood cells) to the red cell precursors (normoblasts). The peptide hepcidin is felt to be the main mediator of the effect. This defect in iron reutilization causes a drop in the serum iron concentration and a normocytic or mildly microcytic anemia. The inflammatory reaction, however, also decreases the iron-binding capacity (as opposed to iron-deficiency anemia, where the iron-binding capacity is elevated), so the saturation is usually between 10% and 20%. The anemia is rarely severe (Hb rarely < 8.5 g/dL). The hemoglobin and hematocrit will improve if the underlying process is treated. Diseases not associated with inflammation or neoplasia (ie, congestive heart failure, diabetes, hypertension, etc) do not cause anemia of chronic disease. Blood loss causes a lower serum iron level, an elevated iron-binding capacity, and a lower iron saturation. The serum ferritin (low in iron deficiency, normal or high in anemia of chronic disease) will usually clarify this situation. Vitamin B12 and folate deficiencies are associated with macrocytic anemia. Sideroblastic anemia can be either microcytic or macrocytic (occasionally with a dimorphic population of cells, some small and some large), but is associated with an elevated iron level. In addition, this patient’s history (which suggests an inflammatory polyarthritis) would not be consistent with sideroblastic anemia. The diagnosis of sideroblastic anemia is made by demonstrating ringed sideroblasts on bone marrow aspirate. In the anemia of chronic renal insufficiency, the iron studies are normal and the red cells are normocytic.
A 35-year-old woman presents with several days of increasing fatigue and shortness of breath on exertion. She was recently diagnosed with Mycoplasma pneumoniae. Physical examination reveals BP 113/67, HR 114 beats/minute, and respiratory rate 20 breaths/minute. She appears icteric and in mild respiratory distress. Her hemoglobin is 9.0 g/dL and MCV is 110.
Which of the following is the best next diagnostic test?
Macrocytic anemia and indirect hyperbilirubinemia suggest hemolysis, which in this patient is likely due to immune-mediated IgM antibodies which may follow Mycoplasma infections. These antibodies are also called cold-reacting antibodies as they react at temperatures less than 37°C (98°F). Examination of the peripheral blood smear is the first step in evaluation of hemolytic anemia. The young red cells (which would show up as reticulocytes when properly stained) are much larger than mature RBCs, accounting for the macrocytosis (the MCV can be as high as 140 with vigorous reticulocytosis). The presence of microspherocytes suggests immune-mediated hemolysis, while the presence of fragmented RBCs or schistocytes suggest a mechanical cause of hemolysis, as seen in the microangiopathic hemolytic anemias. Serum protein electrophoresis is useful to diagnose multiple myeloma, which is rarely associated with hemolysis, but this would not be the best initial test; the anemia in multiple myeloma is normocytic. Flow cytometry can detect surface proteins like CD55, CD59 on granulocytes, and red blood cells in paroxysmal nocturnal hemoglobinuria (a rare cause of hemolysis), but again is not the best first test. Glucose-6-PD levels might be useful once hemolytic anemia is established by a peripheral smear and negative Coombs test. Bone marrow biopsy would show erythroid hyperplasia, but is usually not required to diagnose hemolytic anemia.
A 70-year-old man complains of 2 months of low back pain and fatigue. He has developed fever with purulent sputum production. On physical examination, he has pain over several vertebrae and rales at the left base. Laboratory results are as follows:
The definitive diagnosis is best made by which of the following?
Multiple myeloma would best explain this patient’s presentation. The onset of myeloma is often insidious. Pain caused by bone involvement, anemia, renal insufficiency, and bacterial pneumonia often follow. This patient presented with fatigue and bone pain, then developed bacterial pneumonia probably secondary to Streptococcus pneumoniae, an encapsulated organism for which antibody to the polysaccharide capsule is not adequately produced by the myeloma patient. There is also evidence for renal insufficiency. Hypercalcemia is frequently seen in patients with multiple myeloma and may be life threatening. Definitive diagnosis of multiple myeloma is made by demonstrating greater than 30% plasma cells in the bone marrow. None of the other findings are specific enough for definitive diagnosis. Seventy-five percent of patients with myeloma will have a monoclonal M spike on serum protein electrophoresis (as shown in the illustration), but 25% will produce primarily Bence-Jones proteins, which, because of their small size, do not accumulate in the serum but are excreted in the urine. Urine protein electrophoresis will identify these patients. Approximately 1% of patients with myeloma will present with a nonsecretory myeloma; the diagnosis can be made only with bone marrow biopsy. The bone scan in myeloma is usually negative. The radionuclide is taken up by osteoblasts, and myeloma is usually a purely osteolytic process. Renal biopsy might show monoclonal protein deposition in the kidney or intratubular casts but would not be the first diagnostic procedure. Rouleaux formation, although characteristic of myeloma, is neither sensitive nor specific.
A 64-year-old man complains of cough, increasing shortness of breath, and headache for the past 3 weeks. He has mild hypertension for which he takes hydrochlorothiazide; he has smoked 1 pack of cigarettes a day for 40 years. On examination you notice facial plethora and jugular venous distension to the angle of the jaw. He has prominent veins over the anterior chest and a firm to hard right supraclavicular lymph node. Cardiac examination is normal and lungs are without rales. Peripheral edema is absent.
What is the most likely cause of his condition?
This patient presents with the superior vena cava (SVC) syndrome. Such patients have jugular venous distension but no other signs of right-sided heart failure. They have prominent facial (especially periorbital) puffiness and may complain of headache, dizziness, or lethargy. SVC syndrome is caused by a malignant tumor 90% of the time. Lung cancer and lymphoma, both of which are often associated with bulky mediastinal lymphadenopathy, predominate. Gastric cancer often metastasizes to the supraclavicular nodes (most often on the left, the so-called Virchow node) but does not usually affect the mediastinal nodes to this degree. Prompt diagnosis is necessary to prevent CNS complications or laryngeal edema. Sensitive tumors (lymphoma, small cell lung cancer) may be treated with chemotherapy, while most other cell types are treated with radiation therapy. Hypertension, emphysema, and nephrotic syndrome do not cause SVC syndrome.
Click to expand