eMedicine Specialties > Pediatrics: General Medicine > Hematology

Leukocytosis: Treatment & Medication

Author: Susumu Inoue, MD, Professor of Pediatrics and Human Development, Michigan State University College of Human Medicine; Clinical Professor of Pediatrics, Wayne State University School of Medicine; Director of Pediatric Hematology/Oncology, Associate Director of Pediatric Education, Department of Pediatrics, Hurley Medical Center
Contributor Information and Disclosures

Updated: Nov 3, 2009

Treatment

Medical Care

In most cases, treatment for leukocytosis is not necessary.

  • In extreme instances of hyperleukocytosis syndrome (eg, acute leukemia), leukapheresis, hydration, and urine alkalinization to facilitate uric acid excretion are indicated; however, perform these treatments only in consultation with a hematologist, oncologist, or both. Direct treatment toward the underlying etiology.
  • Leukemic hyperleukocytosis may cause clinically significant complications when the WBC count exceeds 100,000/μ L in acute myelogenous leukemia and 300,000/μ L in acute lymphoblastic leukemia.
    • Therefore, in patients with these findings, measures to rapidly reduce the WBC count are advisable.
    • Leukapheresis or exchange blood transfusion is a treatment of choice for this purpose, with hydration, urine alkalinization, and administration of allopurinol or rasburicase (uric acid oxydase) to reduce serum uric acid and minimize tumor lysis syndrome. When rasburicase is used, urine alkalinization is not recommended.
    • Promptly institute definitive treatment with appropriate chemotherapy.

Medication

Hyperleukocytosis in leukemia is often complicated by a tumor lysis syndrome, which includes a high serum uric acid and uric acid nephropathy. Prompt measures to reduce serum uric acid and prevent uric acid nephropathy are required.

Uric acid inhibitors

These drugs are used to prevent acute uric acid nephropathy associated with leukocytosis in myeloproliferative disease and leukemia.


Allopurinol (Aloprim, Zyloprim)

Inhibits xanthine oxidase, the enzyme that synthesizes uric acid from hypoxanthine. Reduces synthesis of uric acid without disrupting biosynthesis of vital purines. Reduces plasma concentration and urine excretion of uric acid; simultaneously increases plasma concentration and urine excretion of more soluble oxypurine precursors.

Adult

200-300 mg/d PO divided bid/qid; alternatively,
200-400 mg/m2/d IV qd or divided q6-12h; not to exceed 600 mg/m2/d

Pediatric

10 mg/kg/d (or 200-300 mg/m2/d) PO divided bid/qid; alternatively, 200 mg/m2/d IV qd or divided q6-12h

Alcohol decreases effects; increased incidence of rash with concurrent ampicillin and amoxicillin; large amounts of vitamin C acidify urine and may cause kidney stones; inhibits metabolism of azathioprine and mercaptopurine

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

Caution in renal insufficiency (decrease dose), hepatic disease, or dehydration; may cause Stevens-Johnson syndrome; discontinue at first sign of rash


Rasburicase (Elitek)

Recombinant form of urate oxidase (derived from Saccharomyces cerevisiae -synthesized Aspergillus flavus), which oxidizes uric acid to allantoin (soluble and inactive). Indicated for treatment and prophylaxis of severe hyperuricemia associated with treatment of malignancy. Hyperuricemia causes precipitant in kidneys, leading to acute renal failure. Unlike uric acid, allantoin soluble and easily excreted by kidneys. Elimination half-life is 18 h.

Adult

0.15-0.2 mg/kg/d IV infused over 30 min for up to 5 d; dilute in 50 mL 0.9% NaCl

Pediatric

Administer as in adults

Documented hypersensitivity; glucose-6-phosphate dehydrogenase (G-6-PD) deficiency (possible severe acute hemolysis on exposure)

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

May cause hemolytic anemia secondary to hydrogen peroxide produced during uric acid oxidation; may cause methemoglobinemia; other adverse effects include fever, nausea, or vomiting; children <2 y may have increased vomiting, diarrhea, fever, and rash; avoid shaking or vortexing during reconstitution; highly antigenic, multiple administration may produce allergic reaction, anaphylaxis, or death; produces falsely low uric acid levels (accurate levels obtained by collecting blood into prechilled, heparin-containing tubes kept and centrifuged at 4°C); maintain resultant plasma at 4°C and analyze within 4 h of collection

More on Leukocytosis

Overview: Leukocytosis
Differential Diagnoses & Workup: Leukocytosis
Treatment & Medication: Leukocytosis
Follow-up: Leukocytosis
Multimedia: Leukocytosis
References
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References

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  2. Lee GM, Harper MB. Risk of bacteremia for febrile young children in the post-Haemophilus influenzae type b era. Arch Pediatr Adolesc Med. Jul 1998;152(7):624-8. [Medline].

  3. Brown L, Shaw T, Wittlake WA. Does leucocytosis identify bacterial infections in febrile neonates presenting to the emergency department?. Emerg Med J. Apr 2005;22(4):256-9. [Medline].

  4. Hsiao AL, Chen L, Baker D. Incidence and predictors of serious bacterial infections among 57- to 180-day-old infants. Pediatrics. May 2006;117:1695-1701.

  5. Hsiao R, Omar SA. Outcome of extremely low birth weight infants with leukemoid reaction. Pediatrics. Jul 2005;116(1):e43-51. [Medline].

  6. Rosa JS, Schwindt CD, Oliver SR, Leu SY, Flores RL, Galassetti PR. Exercise leukocyte profiles in healthy, type 1 diabetic, overweight, and asthmatic children. Pediatr Exerc Sci. Feb 2009;21(1):19-33. [Medline].

  7. Aydogan M, Aydogan A, Kara B, Basim B, Erdogan S. Transient peripheral leukocytosis in children with afebrile seizures. J Child Neurol. Jan 2007;22(1):77-9. [Medline].

  8. Alioglu B, Ozyurek E, Avci Z, Atalay B, Caner H, Ozbek N. Peripheral blood picture following mild head trauma in children. Pediatr Int. Jun 2008;50(3):281-3. [Medline].

  9. Furlan JC, Krassioukov AV, Fehlings MG. Hematologicl abnormalities within the first week after acute isolated traumatic cervical spinal cord injury: a case-control cohort study. Spine. Nov/2006;31:2674-83. [Medline].

  10. Bonadio WA. Evaluation and management of serious bacterial infections in the febrile young infant. Pediatr Infect Dis J. Dec 1990;9(12):905-12. [Medline].

  11. Dinauer MC. The phagocyte system and disorders of granulopoiesis and granulocyte function. In: Nathan and Oski's Hematology of Infancy and Childhood. Vol 1. 5th ed. Philadelphia, PA: WB Saunders; 1998:889.

  12. Izbicki G, Rudensky B, Na'amad M, Hershko C, Huerta M, Hersch M. Transfusion-related leukocytosis in critically ill patients. Crit Care Med. Feb 2004;32(2):439-42. [Medline].

  13. Lichtman MA, Rowe JM. Hyperleukocytic leukemias: rheological, clinical, and therapeutic considerations. Blood. Aug 1982;60(2):279-83. [Medline].

  14. Shah SS, Shofer FS, Seidel JS, Baren JM. Significance of extreme leukocytosis in the evaluation of febrile children. Pediatr Infect Dis J. Jul 2005;24(7):627-30. [Medline].

  15. Wang, CW, Lukens JN. Sickle cell anemia and other sickling syndromes. In: Wintrobe's Clinical Hematology. Vol 1. 10th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 1999:1346-97.

  16. Wright IM, Skinner AM. Post-transfusion white cell count in the sick preterm neonate. J Paediatr Child Health. Feb 2001;37(1):44-6. [Medline].

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Further Reading

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Keywords

leukocytosis, white blood cell count, WBC count, increased WBCs, neutrophil count, neutrophilia, lymphocyte count, lymphocytosis, monocyte count, monocytosis, eosinophilic granulocyte count, eosinophilia, fever, abdominal pain

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Contributor Information and Disclosures

Author

Susumu Inoue, MD, Professor of Pediatrics and Human Development, Michigan State University College of Human Medicine; Clinical Professor of Pediatrics, Wayne State University School of Medicine; Director of Pediatric Hematology/Oncology, Associate Director of Pediatric Education, Department of Pediatrics, Hurley Medical Center
Susumu Inoue, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Hematology, American Society of Pediatric Hematology/Oncology, International Society for Experimental Hematology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Medical Editor

Gary R Jones, MD, Associate Medical Director, Clinical Development, Berlex Laboratories
Gary R Jones, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Pediatric Hematology/Oncology, and Western Society for Pediatric Research
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Gary D Crouch, MD, Program Director of Pediatric Hematology-Oncology Fellowship, Department of Pediatrics, Associate Professor, Uniformed Services University of the Health Sciences
Gary D Crouch, MD is a member of the following medical societies: American Academy of Pediatrics and American Society of Hematology
Disclosure: Nothing to disclose.

CME Editor

Helen SL Chan, MBBS, FRCP(C), FAAP, Senior Scientist, Research Institute; Professor, Division of Hematology/Oncology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Canada
Helen SL Chan, MBBS, FRCP(C), FAAP is a member of the following medical societies: American Academy of Pediatrics, American Association for Cancer Research, American Society of Hematology, and Royal College of Physicians and Surgeons of Canada
Disclosure: Nothing to disclose.

Chief Editor

Robert J Arceci, MD, PhD, King Fahd Professor of Pediatric Oncology, Professor of Pediatrics, Oncology and the Cellular and Molecular Medicine Graduate Program, Kimmel Comprehensive Cancer Center at Johns Hopkins University School of Medicine
Robert J Arceci, MD, PhD is a member of the following medical societies: American Association for Cancer Research, American Association for the Advancement of Science, American Pediatric Society, American Society of Hematology, and American Society of Pediatric Hematology/Oncology
Disclosure: Nothing to disclose.

 
 
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