A 44-year-old-man comes to the emergency department due to a day of fever, chills, and productive cough. Over the past several weeks, the patient has also had progressive fatigue and dyspnea to the point that he was unable to mow the lawn last weekend. The patient has no prior medical conditions and takes no medications. He does not use tobacco, alcohol, or illicit drugs. Temperature is 38.8 C (102 F), blood pressure is 100/60 mm Hg, pulse is 110/min, and respirations are 24/min. Examination shows mucosal pallor and scattered ecchymoses. Lung auscultation reveals left-sided crackles and bronchial breath sounds. There is no lymphadenopathy or splenomegaly. Laboratory results are as follows:
| Complete blood count | |
| Hemoglobin | 6 g/dL |
| Mean corpuscular volume | 98 µm3 |
| Reticulocytes | 0.3% |
| Platelets | 17,000/mm3 |
| Leukocytes | 2,000/mm3 |
| Serum chemistry | |
| Creatinine | 0.8 mg/dL |
| Calcium | 8.8 mg/dL |
| Coagulation studies | |
| INR | 1.0 (normal: 0.8-1.2) |
| Activated PTT | 23 sec |
| Lactate dehydrogenase, serum | 85 U/L |
Left lower lobe consolidation is seen on chest x-ray. Peripheral blood smear reveals decreased leukocytes, erythrocytes, and platelets but is otherwise unremarkable. Which of the following is the most likely mechanism of this patient's hematologic abnormalities?
Causes of pancytopenia | |
Bone marrow aplasia |
|
Bone marrow infiltration |
|
Mature blood cell destruction |
|
DIC = disseminated intravascular coagulation; TTP = thrombotic thrombocytopenic purpura. | |
Pancytopenia, a decrease in all 3 blood cell lines, is usually caused by damage to hematopoietic stem cells, infiltration of the bone marrow with atypical cells, or peripheral destruction of mature blood cells. Although identifying the underlying cause usually requires additional testing (eg, bone marrow biopsy), a presumptive diagnosis can often be made based upon laboratory and clinical findings.
In this case, the absence of splenomegaly and the presence of diminished, morphologically normal cells on peripheral smear suggest the pancytopenia is due to aplastic anemia (AA), a form of bone marrow failure caused by damage to multipotent hematopoietic stem cells. Most cases are triggered by an alteration to stem cell surface antigens, which leads to subsequent cytotoxic T-cell destruction. Although exposures (eg, drugs, toxins, radiation), viral infections (eg, parvovirus B19), and autoimmune conditions (eg, lupus, eosinophilic fasciitis) can cause AA, most cases are idiopathic.
Patients usually present with complications of pancytopenia, including:
Laboratory evaluation will show inadequate erythropoiesis (eg, low reticulocyte count) and a diminished quantity of morphologically normal cells on peripheral smear. Bone marrow biopsy will demonstrate a hypocellular marrow with a few normal hematopoietic cells, no myeloid infiltration or fibrosis, and increased stroma/adipocytes.
(Choice B) Myelofibrosis is marked by collagen or reticulin deposition in the bone marrow, which can lead to diminished (or increased) peripheral blood counts. However, patients have significant hepatosplenomegaly due to extramedullary hematopoiesis, and peripheral blood smear reveals immature leukocytes and fragmented megakaryocytes.
(Choice C) Nutrient deficiencies (eg, B12, folate) or antimetabolite drugs (eg, azathioprine, methotrexate) can cause impaired DNA synthesis in precursor cells. However, these are associated with megaloblastic anemia and typically lead to macrocytic (MCV > 100 µm3) erythrocytes, mild thrombocytopenia, and multilobed neutrophils on peripheral smear.
(Choice D) Malignant proliferation of mature lymphocytes is seen in chronic lymphocytic leukemia (CLL) and hairy cell leukemia (HCL). Both present with bleeding, anemia, fevers, and splenomegaly. On peripheral smear, HCL has lymphocytes with hairy projections whereas CLL has smudge cells and numerous mature lymphocytes.
(Choice E) Replacement of bone marrow by plasma cells is seen in multiple myeloma, which usually manifests with hypercalcemia, anemia, renal disease, and lytic bone lesions.
Educational objective:
Aplastic anemia is an acquired deficiency of pluripotent hematologic stem cells that can result from certain exposures, viral infections, or autoimmune conditions. Patients have manifestations of pancytopenia. Cellular morphology is normal and splenomegaly is absent.