A 54-year-old woman with pancytopenia
Acute myeloid leukemia
Acute myeloid leukemia generally manifests with symptoms related to pancytopenia, with weakness and fatigability being the most common.4
In this condition, genetic alterations in hematopoietic precursor cells result in reduced differentiation capacity and accumulation of leukemic blasts in the bone marrow, peripheral blood, and other tissues.
Peripheral blood analysis usually reveals normocytic normochromic anemia with blasts. To establish a diagnosis of acute myeloid leukemia, one must observe at least 20% myeloblasts in the blood, the bone marrow, or both.
No blasts are seen on our patient’s peripheral blood smear, making acute myeloid leukemia less likely.
Paroxysmal nocturnal hemoglobinuria
Paroxysmal nocturnal hemoglobinuria is a possibility in the setting of intravascular hemolytic anemia, bone marrow failure, and thrombosis.
These processes are due to a defect in the glycosyl phosphatidyl inositol (GPI) anchor caused by an abnormality in the PIG-A gene. Partial or complete absence of the GPI anchor allows for activation of complement-mediated hemolysis. A diminished rate of hematopoiesis is presumably responsible for reticulocytopenia, granulocytopenia, or thrombocytopenia, though reticulocytosis can also be seen.5,6 The highly thrombogenic state is believed to occur because of microparticles rich in phosphatidylserine.7
Our patient’s peripheral smear has rare fragmented red blood cells and lacks teardrop red cells. Although paroxysmal nocturnal hemoglobinuria does not have characteristic morphologic features in the peripheral blood, there are no signs of thrombosis in our patient. Her lactate dehydrogenase level is 395 U/L (reference range 100–220 U/L), and her haptoglobin level is less than 20 mg/dL (33–246). These findings could indicate a low level of intravascular hemolysis.
Myelophthisis
Myelophthisis refers to any disorder in which an abnormal cell process invades the bone marrow, damaging hematopoietic tissue. These processes include neoplastic diseases, storage disorders, and a variety of infections. A decrease in all three cell types may result, depending on the severity of invasion. Documented infectious causes include hepatitis viruses, Epstein-Barr virus, human immunodeficiency virus (HIV), mycobacteria, and fungi.
Our patient’s condition is likely due to a marrow-based process of uncertain etiology. In myelophthisic processes, one may see teardrop red cells, which are not seen in this patient’s smear. However, on her chest imaging, the finding of focal consolidations within the anterior segment of the right upper lobe and both lower lobes raises suspicion of an infectious cause.
CASE CONTINUED: SHE UNDERGOES DIAGNOSTIC TESTING
Let us recap some of the laboratory studies that document the extent of our patient’s pancytopenia and the pattern of her anemia:
- Hemoglobin 10.2 g/dL (reference range 11.5–15.5 g/dL)
- Platelet count 27 × 109/L (150–400)
- Leukopenia with profound T-cell lymphopenia
- Iron 59 μg/dL (30–140)
- Total iron-binding capacity 110 μg/dL (210–415)
- Ferritin 3,004 ng/mL (18–300)
- Transferrin saturation 54% (11%–46%).
2. Which of the following would be the best test to obtain next?
- Bone marrow examination
- Blood cultures
- Tuberculin skin test
- Liver biopsy
- Positron emission tomography and CT
Our patient has unexplained pancytopenia. While all the tests listed above might shed light on her condition, a bone marrow examination would be the best test to obtain next.
Urine histoplasma antigen studies are positive at greater than 39 ng/mL (normal 0, low positive < 0.6–3.9, moderate positive 4.0–19.9, high positive 20–39 ng/mL). A culture of the marrow subsequently grows this organism.
