PRACTICE POINTERS
• Obtain a thorough history to aid in narrowing the list of potential causes in pancytopenia’s broad differential.
• Arrange for a peripheral smear and bone marrow biopsy to confirm the cause of pancytopenia.
• Screen any patient with hairy cell leukemia for a second primary malignancy.
• Base a treatment decision on the presence of symptoms and the severity of the pancytopenia.
CASE A 47-year-old man with a history of alcoholism came to our emergency department (ED) with a 3-week history of sore throat and dry cough. He said that for the past 2 months he had experienced worsening shortness of breath, increasing weakness, and episodes of light-headedness. He also said that his gums occasionally bled when he brushed his teeth.
Our patient owned a farm where he was exposed to pesticides and fertilizers, but he reported no contact with sick individuals, new medications, or recent travel. The patient had a 40 pack-year smoking history, but he had quit within the past year. His family history was negative for malignancies or rheumatologic diseases.
On physical exam, we noted splenomegaly (spleen was approximately 3 cm below costal margin); all other exam findings were within normal limits.
Lab results revealed pancytopenia: the patient’s serum white blood cell (WBC) was 900/mcL, the absolute neutrophil count (ANC) was 447/mcL, and the absolute lymphocyte count was 346/mcL. Hemoglobin was 5.4 g/dL and platelet count was 47,000/mcL. (Pancytopenia is defined as hemoglobin <13.5 g/dL [males] or 11.6 g/dL [females], platelet count <150,000/mcL, and WBC count <4000/mcL. Criteria for severe pancytopenia include an ANC <500/mcL, platelet count <20,000 mcL, and corrected reticulocyte count <1%.1,2)
A repeat complete blood count (CBC) showed similar results. Basic metabolic panel, chest x-ray film, and electrocardiogram results were all normal.
Based on the initial lab work, we ordered further testing for human immunodeficiency virus (HIV), Epstein-Barr virus (EBV), cytomegalovirus, hepatitis, parvovirus B19, and antinuclear antibodies. All results were negative. B12 and folate levels were low normal, and the reticulocyte count was 2.31%. We admitted the patient for evaluation of his pancytopenia.
WHAT ADDITIONAL TESTING WOULD YOU PURSUE AT THIS POINT?
We ordered a bone marrow biopsy and peripheral smear, which is protocol in a case such as this. Results showed leukemic and “hairy” cells.
Hairy cell leukemia
Hairy cell leukemia is an uncommon chronic B-cell lymphoproliferative disorder.3 It represents 2% of all adult leukemias; the median age of onset is 52 years, with a male predominance of 4:1. It is 3 times more common in Caucasians than in African Americans. There is still some controversy regarding its cell line, and its pathogenesis is still unknown. Exposures to ionizing radiation, EBV, organic chemicals, woodworking, and farming have been cited as possible causes.4
Symptoms of hairy cell leukemia include fatigue, weakness, and weight loss. Abdominal fullness or discomfort due to splenomegaly is seen in 25% of cases.5,6 Easy bruising and bleeding secondary to severe pancytopenia are also seen in about 25% of cases.5,6 However, 25% of patients are initially asymptomatic and are found to have abnormal lab values during a routine well visit.6
Narrowing in on a diagnosis
The etiology of pancytopenia is broad, but the diagnostic possibilities (TABLE) narrow depending on the pathogenesis of a patient’s condition: decreased bone marrow production, increased destruction or sequestration of cells, inherited/congenital, or idiopathic.
Testing. After an initial CBC, a second CBC should be obtained to confirm the pancytopenia before ordering further tests.1,7 Such testing includes a peripheral blood smear, a reticulocyte count, serum iron studies, and viral studies such as HIV, EBV, or parvovirus, along with an autoimmune profile and liver function tests.8 A hematology consult with probable bone marrow aspirate is also indicated.8
Diagnosis is made based on clinical findings and lab work revealing pancytopenia. A peripheral smear exhibiting leukemic cells and “hairy” cells suffices to make the diagnosis, although bone marrow biopsy—which reveals tartrate-resistant acid phosphatase– positive cells on cytochemical staining in 95% of cases3—is often use to corroborate the diagnosis. More recently, immunotyping using flow cytometry has become the standard for confirming the diagnosis of hairy cell leukemia.3
TABLE
Is it pancytopenia? The differential3
| Decreased bone marrow production | Increased destruction/sequestration of cells | Inherited/congenital |
|---|---|---|
Chemotherapy, radiotherapy Megaloblastic anemia Myelodysplastic syndromes Myelofibrosis Aplastic anemia Paroxysmal nocturnal hemoglobinuria Lymphoma with bone marrow infiltration Leukemia Plasma cell myeloma Infection (eg, parvovirus B19, CMV) Anorexia nervosa | Liver disease Portal hypertension Hypersplenism due to myelo- or lymphoproliferative disorders Evan’s syndrome Infection (eg, brucellosis, leishmaniasis) Heavy metal poisoning | Gaucher disease Fanconi’s anemia |
| Overlap | ||
| Connective tissue disorders (eg, SLE, RA) | ||
| AIDS | ||
| Mycobacterial infection; sepsis; acute viral infection (eg, CMV, HIV, EBV) | ||
| AIDS, acquired immune deficiency syndrome; CMV, cytomegalovirus; EBV, Epstein-Barr virus; HIV, human immunodeficiency virus; RA, rheumatoid arthritis; SLE, systemic lupus erythematosus. | ||