A Febrile Woman With Unusual Blood Cell Counts

A Febrile Woman With Unusual Blood Cell Counts

A 41-year-old woman presents to the emergency department with chest pain and dysphagia. Routine laboratory studies reveal profound neutropenia. She denies recent fever, chills, or weight loss.

HISTORY

The patient has a history of hepatitis B, hepatitis C, schizophrenia, and recent keratoplasty. Current medications include brimonidine eye drops, bacitracin and polymyxin B ophthalmic ointment, and famotidine. She lives alone, is unemployed, and smokes tobacco (4 or 5 cigarettes a day) and crack cocaine (2 or 3 times a week).

Two months earlier, the patient underwent a workup for agranulocytosis. A bone marrow examination showed normocellular bone marrow with trilineage hematopoiesis without blasts. She was given growth factor support, and her blood cell counts recovered by the time of discharge. Routine laboratory studies performed before her eye surgery 1 month later revealed a normal white blood cell (WBC) count and normal red blood cell (RBC) indices.

PHYSICAL EXAMINATION

This petite woman is in no apparent distress. Heart rate is 107 beats per minute; blood pressure, 98/60 mm Hg; and temperature, 39.27°C (102.5°F). Examination of the oral mucosa reveals thrush and poor dentition. No cervical, axillary, inguinal, or supraclavicular lymphadenopathy is noted. Results of cardiovascular, respiratory, and abdominal examinations are normal.

LABORATORY RESULTS

WBC count is 2200/μL; absolute neutrophil count (ANC), 300/μL; hemoglobin level, 12.3 g/dL; and mean corpuscular volume, 83 fL. Platelet count is normal. Basic metabolic, hepatic, and renal function panels are all within normal limits. An HIV test is negative. Vitamin B12 and folate levels are normal. A peripheral blood smear reveals a normocytic RBC population, normal platelets, and a decreased WBC population. There are no blasts or abnormal white cells.

(Answer and discussion on next page)

CORRECT ANSWER: E

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Neutropenia is often categorized as mild, moderate, or severe on the basis of the ANC. Mild neutropenia corresponds to an ANC between 1000 and 1500/μL; moderate, between 500 and 1000/µL; and severe, less than 500/µL. The risk of infection begins to increase at an ANC below 1000/µL. Neutrophil counts may be lower in some ethnic and racial groups, such as African Americans, Africans, and Yemenite Jews.¹ Neutropenia may be acute or chronic (of more than 3 months’ duration) depending on the length of the illness.

THE TAKE-HOME MESSAGE:

When neutropenia occurs in a known cocaine user, consider levamisole as a possible cause. In patients with unexplained severe neutropenia/agranulocytosis, urine should be tested for cocaine and levamisole if possible.

Causes of neutropenia. The numerous causes of neutropenia can roughly be categorized as either problems in the production of the cells by the bone marrow or conditions that involve destruction of the cells. Neutropenia is a common manifestation of bone marrow defects associated with a reduction in RBC and platelet counts, such as aplastic anemia, leukemia, myelodysplasia, megaloblastic anemia caused by vitamin B12 or folate deficiency, and the administration of chemotherapy. However, the neutropenia in patients with these conditions is usually not an isolated finding; varying degrees of anemia and thrombocytopenia are also present. Examination of a peripheral smear and a bone marrow aspirate with biopsy are helpful in making these diagnoses. Because this patient’s hemoglobin level and platelet count were normal, she is less likely to have aleukemic leukemia (B) or aplastic anemia (C).

Cyclic neutropenia is a form of primary neutropenia that usually manifests in early childhood. It is characterized by recurrent mouth infections and neutropenia at 2- to 3-week intervals. This patient’s neutropenia occurred in adulthood, and she denied a previous history of recurrent infections; therefore, cyclic neutropenia (D) is unlikely.

Hepatitis C may also lead to neutropenia; however, as in the case of bone marrow disorders, this is usually associated with anemia and thrombocytopenia. Further, the depressed counts are not as severe as those seen here. In the absence of these findings, choice A is a less likely culprit.

In 2008, cases of severe neutropenia associated with exposure to cocaine and levamisole were identified in Alberta.² Later that year, similar cases of neutropenia were found in the United States in patients who had used cocaine. Levamisole was detected in clinical specimens in a majority of patients tested. According to the Drug Enforcement Administration, as of July 2009, 69% of seized cocaine lots coming into the United States contained levamisole as an added agent.³ This potentially dangerous practice has also been reported in the lay press.⁴

Levamisole is an anthelmintic; it was used as a chemotherapeutic agent for colon cancer in the 1990s. Agranulocytosis occurs as an idiosyncratic reaction in 2.5% to 13% of patients who take levamisole.^5,6 The drug indirectly increases the number of dopamine receptors in the brain and affects acetylcholine receptors, which may accentuate the stimulatory effects of cocaine. These effects, coupled with its relative inertness, make it an ideal agent to combine with cocaine.

Clinicians need to be aware of the possible relationship between levamisole, agranulocytosis, and use of cocaine. In suspected cases, urine should be collected promptly for detection of levamisole because the likelihood of finding the drug decreases markedly after 48 hours.

Outcome of this case. In this patient, neutropenia coincided with bouts of cocaine abuse. She was treated with growth factor support, with good results.

References:

REFERENCES:

1.

Haddy TB, Rana SR, Castro O. Benign ethnic neutropenia: what is a normal absolute neutrophil count?

J Lab Clin Med.

1999;133:15-22.

2.

Knowles L, Buxton JA, Skuridina N, et al. Levamisole tainted cocaine causing severe neutropenia in Alberta and British Columbia.

Harm Reduct J.

2009;6:30.

3.

Agranulocytosis associated with cocaine use-four states, March 2008-November 2009.

MMWR.

2009;58:1381-1385.

4.

Szalavitz M. A common cut in cocaine may prove deadly.

Time Magazine.

January 20, 2010.

5.

Thompson JS, Herbick JM, Klassen LW, et al. Studies on levamisole-induced agranulocytosis.

Blood.

1980;56:388-396.

6.

Kinzie E. Levamisole found in patient using cocaine.

Ann Emerg Med.

2009;53:546-547.