Subacute CareForum

Low White Blood Cell Count-Medication-Induced or Not?

This month's subacute care case involves the possibility of medication-induced leukopenia in an elderly woman newly admitted to the nursing home. The attending physician asked pharmacists from the hospital's subacute care unit to provide a consult on the possible iatrogenic etiology for this woman's blood disorders. The patient's case report is shown in the sidebar on the following page.

Case Analysis

This patient initially presented with pancytopenia-a drop in white blood cells, red blood cells, and platelets. This could have many causes, including autoimmune disorders, viral infections, chemicals, and medications. Within the last group, chloramphenicol, indomethacin, gold preparations, and nitrogen mustard compounds can cause pancytopenia. Chlorpromazine and other antipsychotics, sulfonamides, and anticancer agents can cause leukopenia, a drop in the white cell count. Quinidine, sulfa drugs, and nitrofurantoin may cause a low platelet count. This patient was being treated with furosemide, a possible cause. However, one third of all cases of aplastic anemia are unexplained.¹

Neutropenia is defined as a WBC count less than 4,000/cu mm. Associated conditions include megaloblastic anemia, aplastic anemia, acute leukemia, hypersplenism, certain infections (including overwhelming bacterial infection and disseminated mycobacterial infections), and medications. A long list of the drugs associated with neutropenia is reported in a review article by Young.² Antipsychotics, anticonvulsants, common cardiovascular agents, sulfa agents, penicillins, and antihistaminic agents are among the drugs listed as causing agranulocytosis.

Furosemide, phenytoin, and the cephalosporins have been reported to cause this blood dyscrasia, and this patient had been prescribed all of these medications. This information was communicated to the physician on day 18 of the clinical course. Because the patient needed these medications, was clinically stable, and appeared to be improving, the physician decided not to discontinue any of these medications. During continuing therapy with the agents, the patient's white blood cell counts returned to normal, suggesting that this was not a drug-induced phenomenon.

Overwhelming infection can also cause both the aplastic anemic problem and agranulocytosis. This patient was recovering from a serious diabetic foot infection, and perhaps this was the cause of the neutropenia. The patient remained clinically stable and without signs of progressive infection. Practitioners must continually monitor this type of patient for signs of infection and the trend in white blood cell counts, since an extremely low count could precipitate a life-threatening infection.

Weekly blood counts were used to monitor the patient during this period of exposure to several risk factors for blood dyscrasias. As the patient recovered from her infections, her blood counts improved, suggesting a relationship between the two.

Although agranulocytosis and aplastic anemia are not common, consultant pharmacists must be able to recognize them and know enough about their causes to make useful recommendations to the physicians and other health professionals.

Marie Gardner, Pharm.D.
College of Pharmacy
University of Arizona
Tucson, AZ 85721

Case Presentation: Low White Blood Cell Count

CC: S/P diabetic foot ulcer.

HPI: EM is a 63 yo Native American lady discharged from the hospital with continuing treatment for a right-heel foot infection, type II diabetes mellitus (requiring insulin), cirrhosis, hypertension, chronic anemia, and a seizure disorder.

PMH: None available.

PR: On admission to the subacute care unit, medications included lactulose 15 mL q.i.d. for control of high ammonia, furosemide 20 mg daily with KCl 8 mEq for edema, phenytoin 300 mg h.s., sliding scale insulin for hyperglycemia, and ceftriaxone plus metronidazole for foot infection.

SH: Not applicable.

ROS: None available.

PE: None available.

Labs: Lab tests three days (1/20) after admission showed a white blood cell count of 3,200/mL; H/H was 7.3 g/dL and 22.3% with normal indices, and the platelet count was 92,000/mL. A slight increase in bands was noted. Iron studies revealed a low serum iron, TIBC, and a high ferritin level consistent with anemia of chronic disease and inflammatory processes. No source of bleeding was found. The most striking abnormal chemistry values were a creatinine of 1.7 mg/dL and an albumin of 2.0 g/dL. Phenytoin concentration was 13 µg/mL with a corrected level of 26 µg/mL, but the patient had no signs of toxicity. Ammonia levels were in the normal range.

Other: None available.

HPI: WBC count on 1/27 was 2,400/mL with no left shift, platelet count had increased to 103,000/mL, and H/H remained stable but low. Erythropoeitin level at that time was 67 µU/mL (abnormally low for the patient's hematocrit). Erythropoeitin and iron were begun on 1/26. By 2/1, the Hgb had increased to 9 g/mL, platelets had increased to normal, but the WBCs remained at 3,200/mL. A WBC reading on 2/6 was similar, but on 2/13 it had increased to 3,700/mL with a Hgb of 9.9 g/dL. By 2/27, it was within the normal range at 5,300/mL with a Hgb of 11.6 g/dL. Throughout this time, the patient's vital signs were normal and she had few complaints. Besides the medications noted above, the patient took acetaminophen for pain, multivitamins, and a week of dicloxacillin after the intravenous antibiotics were stopped.

1. Ravel R. Production-deficit anemia in clinical laboratory medicine. 6th ed. St. Louis: Mosby-Year Book, Inc., 1995.

2. Young NS. Agranulocytosis. JAMA 1994; 271:935-8.

The Subacute Care Forum is published monthly. This column contains practice tips, news, and other information that can help consultant pharmacists provide pharmaceutical care to those increasingly common long-term care patients needing a higher level of care and more complex therapies. Contributions, always welcome, should be sent to Academics Editor L. Michael Posey, P. O. Box 6565, Athens, GA 30604; 706/613-0100, 706/613-0200 (fax), mposey@aol.com (e-mail).

Occasionally published in the Subacute Care Forum are case studies, coordinated by Contributing Editor Marie E. Gardner, PharmD, FASCP, of the University of Arizona College of Pharmacy. These case studies provide interesting clinical situations and brief reviews of involved disease states relevant to subacute care and consultant pharmacy.