eMedicine Specialties > Hematology > Red Blood Cells and Disorders

Agranulocytosis: Treatment & Medication

Author: Ariel Distenfeld, MD, Clinical Professor, Department of Medicine, New York University School of Medicine
Contributor Information and Disclosures

Updated: Dec 11, 2008

Treatment

Medical Care

Medical care is based on the etiology of the agranulocytosis. In most cases in which drug exposure is involved, the most important step is to discontinue the offending agent. If the identity of the causative agent is not known, stop administration of all drugs until the etiology is established.

  • Start specific antibiotic therapy to combat infections. This often involves the use of third-generation cephalosporins or equivalents.
  • Treat areas of stomatitis and skin infections with local cleaning, antisepsis, and dental care. These infections should be managed by someone who has experience in the treatment of infections in neutropenic patients.
  • Control oral and gingival lesion pain with saline and hydrogen peroxide rinses and local anesthetic gels and gargles.
  • The availability of the recombinant neutrophil cytokine, filgrastim (ie, G-CSF), has altered the management of agranulocytosis.
    • When administered before infection is established, filgrastim shortens the period to recovery and the duration of infection.
    • The agent is especially indicated in the management of congenital neutropenia, idiopathic severe chronic neutropenia, and cyclic neutropenia when serious infections are involved.
    • If the condition is mild, with only neutropenia without a serious infection, filgrastim may be withheld.
  • Granulocyte transfusions have undergone a cycle of popularity followed by disfavor, although they may be useful in patients with life-threatening infections whose conditions are not responding to antibiotics.
    • These transfusions are accompanied by many complications, including severe febrile reactions.
    • The use of granulocyte transfusions remains controversial.
  • In cases caused by heavy metals such as gold, chelation with British anti-Lewisite (dimercaprol) may be needed.

Surgical Care

  • Surgical care is generally not indicated for patients with agranulocytosis.
  • Systemic lupus associated with autoimmune agranulocytosis may respond to splenectomy.11
  • Splenectomy has also been used in Felty syndrome, but the response is often short lived.

Consultations

  • Patients with agranulocytosis are seriously ill, and several consultations are indicated.
  • A hematologist reviews the bone-marrow slides and peripheral blood smears to confirm the diagnosis and to assist in G-CSF dosing and evaluation.
  • An infectious disease specialist advises and assists in the selection of appropriate antibiotics.

Diet

  • All foods must be thoroughly cooked. Raw fruits and vegetables may contain large numbers of bacteria and should be avoided.
  • In patients with periodontitis and stomatitis, a soft or full liquid diet is indicated. Spicy and acidic foods should be avoided until recovery is complete.

Activity

Patient activity is permitted as tolerated.

Medication

Antibiotics are used to treat infections. The antibiotics of choice are those shown by culture and sensitivity studies to be the most effective for the organism causing the infection. If no causative organism is identified, use empirical broad-spectrum antibiotic coverage. Granulocyte growth factors and general supportive care should also be provided. Cytokines (growth factors) are used to stimulate production of neutrophils by acting on precursor cells.

Colony-Stimulating Factors

Colony-stimulating factors are used to stimulate production of neutrophils by acting on precursor cells.


Filgrastim (Neupogen)

A human G-CSF produced by recombinant DNA technology. Glycoprotein acts on hematopoietic cells in a lineage-specific fashion. Stimulates proliferation, differentiation, and some end-cell functional activation.

Adult

5 mcg/kg SC qd; titrate to effect; continue until ANC = 1000/µL; continuous administration may be required for chronic conditions

Pediatric

Administer as in adults.

Do not use 12-24 h before or 24 h after cytotoxic chemotherapy (increases the sensitivity of rapidly dividing myeloid cells to cytotoxic chemotherapy).

Documented hypersensitivity to drug or proteins derived from E coli

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

MDS or AML in certain patients; leukocytosis; possible tumor growth; confirm the diagnosis before use; allergic reactions may occur, but they are not common; bone pain observed in 24% of patients, but it is usually controlled with mild, nonopiate analgesics


Pegfilgrastim (Neulasta)

Long-acting filgrastim created by the covalent conjugate of recombinant G-CSF (ie, filgrastim) and monomethoxypolyethylene glycol. As with filgrastim, acts on hematopoietic cells by binding to specific cell-surface receptors, activating and stimulating production, maturation, migration, and cytotoxicity of neutrophils.

Adult

6 mg SC once

Pediatric

<45 kg: Not established

>45 kg: Administer as in adults.

Do not administer between 14 d before and 24 h after cytotoxic chemotherapy or irradiation (increases the sensitivity of rapidly dividing myeloid cells to cytotoxic chemotherapy); lithium may potentiate the release of neutrophils.

Documented hypersensitivity to E coli –derived proteins‚ PEG, or filgrastim

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Splenic rupture is reported rarely; ARDS secondary to the influx of neutrophils to sites of inflammation in lungs may occur; may precipitate sickle cell crisis; may cause bone pain; risk of MDS or AML in certain patients; leukocytosis; possible tumor growth

More on Agranulocytosis

Overview: Agranulocytosis
Differential Diagnoses & Workup: Agranulocytosis
Treatment & Medication: Agranulocytosis
Follow-up: Agranulocytosis
References
Further Reading
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Keywords

agranulocytosis, granulocytopenia, neutropenia, neutrophils, absolute neutrophil count, ANC, stomatitis, periodontitis, pharyngitis, autoimmune hemolytic anemia, idiopathic thrombocytopenic neutropenia, Kostmann syndrome, granulocyte colony-stimulating factor, G-CSF, ELA2

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Contributor Information and Disclosures

Author

Ariel Distenfeld, MD, Clinical Professor, Department of Medicine, New York University School of Medicine
Ariel Distenfeld, MD is a member of the following medical societies: American Academy of Hospice and Palliative Medicine, American College of Physicians-American Society of Internal Medicine, American Medical Association, American Society of Clinical Oncology, American Society of Hematology, International Society of Blood Transfusion, International Society of Hematology, Medical Society of the State of New York, and New York Academy of Sciences
Disclosure: Nothing to disclose.

Medical Editor

Karen Seiter, MD, Professor, Department of Internal Medicine, Division of Oncology/Hematology, New York Medical College
Karen Seiter, MD is a member of the following medical societies: American Association for Cancer Research, American College of Physicians, and American Society of Hematology
Disclosure: Novartis Honoraria Speaking and teaching; Schering Honoraria Speaking and teaching; Cephalon Honoraria Speaking and teaching

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Troy H Guthrie, Jr, MD, Director of Cancer Institute, Baptist Medical Center
Troy H Guthrie, Jr, MD is a member of the following medical societies: American Federation for Medical Research, American Medical Association, American Society of Hematology, Florida Medical Association, Medical Association of Georgia, and Southern Medical Association
Disclosure: Nothing to disclose.

CME Editor

Rajalaxmi McKenna, MD, FACP, Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems
Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis
Disclosure: Nothing to disclose.

Chief Editor

Emmanuel C Besa, MD, Professor, Department of Medicine, Division of Hematologic Malignancies, Kimmel Cancer Center, Thomas Jefferson University
Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, and New York Academy of Sciences
Disclosure: Nothing to disclose.

 
 
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