eMedicine Specialties > Pediatrics: General Medicine > Hematology

Polycythemia: Differential Diagnoses & Workup

Author: Sun Choo, MD, Pediatric Resident, University of California Los Angeles
Coauthor(s): Kristin Baird, MD, Staff Clinician, Pediatric Oncology Branch; Kathleen M Sakamoto, MD, PhD, Professor and Chief, Division of Hematology-Oncology, Vice-Chair of Research, Mattel Children's Hospital at UCLA; Department of Pathology and Laboratory Medicine, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA and California Nanosystems Institute and Molecular Biology, UCLA
Contributor Information and Disclosures

Updated: Nov 2, 2009

Differential Diagnoses

Methemoglobinemia
Polycythemia
Polycythemia of the Newborn
Polycythemia Vera

Other Problems to Be Considered

Neonatal considerations (hematocrit >65%)

Normal intrauterine environment
Delayed cord clamping
Twin-twin transfusion
Maternal-fetal transfusion
Infant of a diabetic mother
Maternal smoking
Maternal heart disease
Maternal preeclampsia/eclampsia
Placental insufficiency
Maternal propranolol use
Intrauterine growth retardation
Neonatal thyroid toxicosis
Adrenal hyperplasia
Trisomy 21, trisomy 13, trisomy 18
Beckwith-Wiedemann syndrome

Hypoxia

Altitude
Cardiac disease (right to left shunt)
Lung disease (chronic obstructive lung disease, sleep apnea)
Central hypoventilation

Hemoglobinopathy

High–oxygen affinity variety
Methemoglobin reductase deficiency
Chronic carbon monoxide exposure

Hormones

Malignant tumor (eg, renal carcinoma, Wilms tumor, hepatomas, adrenal tumors, cerebellar hemangioblastomas)
Renal disease (eg, cysts, hydronephrosis, benign renal tumors)
Adrenal disease (eg, virilizing hyperplasia, Cushing syndrome)
Anabolic steroid use

Familial/congenital polycythemia

2,3-Bisphosphoglycerate deficiency
Chuvash polycythemia

Relative erythrocytosis

Secondary to decreased plasma volume as with severe dehydration

Workup

Laboratory Studies

The reference range values for the clinician's laboratory findings in polycythemia should be cross-correlated.

  • Red cell mass: This is less than 25% of predicted values.
  • CBC count: Leukocytosis and thrombocytosis are commonly observed but not universal in patients with polycythemia. Leukocytes are greater than 12 X 109/L; platelets are greater than 400 X 109/L. Large platelets are often observed. Platelets can be morphologically and qualitatively abnormal. Red cell mass is greater than 36 mL/kg in men and greater than 32 mL/kg in women. RBCs often have anisocytosis, basophilic stippling, and polychromatophilia.
  • Serum erythropoietin (Epo): Elevated serum Epo levels can be used to distinguish polycythemia vera (PV) from secondary polycythemia. Elevated Epo levels are observed in secondary polycythemia. Low Epo levels suggest primary familial and congenital polycythemia (PFCP) or polycythemia vera, but Epo levels may be normal.
  • Hemoglobin: Hemoglobin analysis is indicated in patients with inadequately high serum Epo levels. Oxygen dissociation curves and hemoglobin electrophoresis can be used to assess for high oxygen affinity mutants and 2,3-Bisphosphoglycerate deficiency (2,3-BPG) deficiency.
  • Serum B-12: Serum B-12 levels are greater than 900 pg/mL (reference range, 130-785 pg/mL), resulting from transcobalamin release from an increased granulocytic mass.
  • Leukocyte alkaline phosphatase: Activity is greater than 100 U/L (reference range adult levels, 30-120 U/L) because levels vary for age; check pediatric age-specific controls.
  • Uric acid: Uric acid levels are increased (reference range adult levels, 2-8 mg/dL). Because levels vary for age, check pediatric age-specific controls. The uric acid level can be within the reference range.
  • Elevated sedimentation rate
  • Spurious hyperkalemia
  • Increased blood viscosity
  • Artifactual prolongation of coagulation studies
  • Endogenous erythroid colony formation: In vitro, this is characteristic for polycythemia vera; however, its specificity and sensitivity limits its use for diagnosis.
  • Gene testing: Screen for EPOR mutation and JAK2 mutation if primary polycythemia is suspected.
  • Molecular analysis: Consider molecular analysis of the VHL gene.

Imaging Studies

  • Abdominal ultrasonography is indicated to exclude underlying renal and hepatic pathology.
  • CT scanning is indicated if physical examination reveals neurologic deficits.

Other Tests

  • The need for bone marrow biopsy is still controversial. Biopsy is not a part of the diagnostic criteria. It may be helpful when trying to differentiate polycythemia vera from other myeloproliferative disorders and to assess the degree of fibrosis.
  • Cytogenetics are not routinely performed but should be used if the diagnosis is questionable and if the differential includes malignancy, myelodysplastic syndrome, or other myeloproliferative disorders.

Histologic Findings

  • If a bone marrow biopsy is performed, the marrow in polycythemia vera is typically hypercellular, including all marrow elements and displaced marrow fat.
  • The number of megakaryocytes is usually increased with wide variation in size.
  • Stainable iron is decreased or absent, and, later in the disease course, fibrosis and marrow reticulin fibers are increased.23

More on Polycythemia

Overview: Polycythemia
Differential Diagnoses & Workup: Polycythemia
Treatment & Medication: Polycythemia
Follow-up: Polycythemia
Multimedia: Polycythemia
References
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Further Reading

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Keywords

polycythemia vera, PV, polycythemia rubra vera, erythrocytosis, absolute erythrocytosis, relative erythrocytosis, familial erythrocytosis, primary familial and congenital polycythemia, PFCP, primary familial polycythemia, treatment, diagnosis

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Contributor Information and Disclosures

Author

Sun Choo, MD, Pediatric Resident, University of California Los Angeles
Disclosure: Nothing to disclose.

Coauthor(s)

Kristin Baird, MD, Staff Clinician, Pediatric Oncology Branch
Disclosure: Nothing to disclose.

Kathleen M Sakamoto, MD, PhD, Professor and Chief, Division of Hematology-Oncology, Vice-Chair of Research, Mattel Children's Hospital at UCLA; Department of Pathology and Laboratory Medicine, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA and California Nanosystems Institute and Molecular Biology, UCLA
Kathleen M Sakamoto, MD, PhD is a member of the following medical societies: American Society of Hematology, American Society of Pediatric Hematology/Oncology, New York Academy of Sciences, Society for Pediatric Research, and Western Society for Pediatric Research
Disclosure: Nothing to disclose.

Medical Editor

Scott MacGilvray, MD, Clinical Associate Professor of Pediatrics, East Carolina University School of Medicine
Scott MacGilvray, MD is a member of the following medical societies: American Academy of Pediatrics and American Medical Association
Disclosure: MedImmune Speakers Bureau Honoraria Speaking and teaching

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

James L Harper, MD, Associate Professor, Department of Pediatrics, Division of Hematology/Oncology and Bone Marrow Transplantation, Associate Chairman for Education, Department of Pediatrics, University of Nebraska Medical Center; Assistant Clinical Professor, Department of Pediatrics, Creighton University; Director, Continuing Medical Education, Children's Memorial Hospital; Pediatric Director, Nebraska Regional Hemophilia Treatment Center
James L Harper, MD is a member of the following medical societies: American Academy of Pediatrics, American Association for Cancer Research, American Federation for Clinical Research, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Council on Medical Student Education in Pediatrics, and Hemophilia and Thrombosis Research Society
Disclosure: Nothing to disclose.

CME Editor

Samuel Gross, MD, Professor Emeritus, Department of Pediatrics, University of Florida; Clinical Professor, Department of Pediatrics, University of North Carolina; Adjunct Professor, Department of Pediatrics, Duke University
Samuel Gross, MD is a member of the following medical societies: American Association for Cancer Research, American Society for Blood and Marrow Transplantation, American Society of Clinical Oncology, American Society of Hematology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Chief Editor

Max J Coppes, MD, PhD, MBA, Senior Vice President, Children's National Medical Center (Center for Cancer and Blood Disorders); Director, Center for Cancer and Immunology Research, Children's Research Institute, Children's National Medical Center; Professor of Medicine, Oncology, and Pediatrics, Georgetown University
Max J Coppes, MD, PhD, MBA is a member of the following medical societies: American Association for Cancer Research, American Society of Pediatric Hematology/Oncology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

 
 
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