Polycythemia Vera BRIAN J

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Polycythemia Vera BRIAN J PRACTICAL THERAPEUTICS Polycythemia Vera BRIAN J. STUART, LT, MC, USNR, and ANTHONY J. VIERA, LCDR, MC, USNR Naval Hospital Jacksonville, Jacksonville, Florida Polycythemia vera is a chronic myeloproliferative disorder characterized by increased red blood cell mass. The resultant hyperviscosity of the blood predisposes such patients to thrombosis. Poly- O A patient informa- cythemia vera should be suspected in patients with elevated hemoglobin or hematocrit levels, tion handout on poly- splenomegaly, or portal venous thrombosis. Secondary causes of increased red blood cell mass (e.g., cythemia vera, written by the authors of this heavy smoking, chronic pulmonary disease, renal disease) are more common than polycythemia article, is provided on vera and must be excluded. Diagnosis is made using criteria developed by the Polycythemia Vera page 2146. Study Group; major criteria include elevated red blood cell mass, normal oxygen saturation, and palpable splenomegaly. Untreated patients may survive for six to 18 months, whereas adequate treatment may extend life expectancy to more than 10 years. Treatment includes phlebotomy with the possible addition of myelosuppressive agents based on a risk-stratified approach. Agents under investigation include interferon alfa-2b, anagrelide, and aspirin. Consultation with a hematologist is recommended. (Am Fam Physician 2004: 69;2139-44,2146. Copyright© 2004 American Academy of Family Physicians.) Members of various olycythemia vera (PV) is a chronic family medicine depart- myeloproliferative disorder char- Diagnosis ments develop articles for “Practical Therapeu- acterized by an increased red blood PV should be suspected when hemoglo- tics.” This article is one in cell mass (RCM), or erythrocytosis, bin and/or hematocrit levels are elevated a series coordinated by which leads to hyperviscosity and (i.e., hemoglobin level greater than 18 g per the Department of Fam- an increased risk of thrombosis. Patients may dL [180 g per L] in white men and 16 g per ily Medicine at Naval P present with complaints of pruritus after bath- dL [160 g per L] in blacks and women; hema- Hospital Jacksonville, Jacksonville, Fla. Guest ing, burning pains in the distal extremities (eryth- tocrit level greater than 52 percent (0.52) editor of romelalgia), gastrointestinal disturbances, or in white men and 47 percent (0.47) in blacks the series is Anthony nonspecific complaints such as weakness, head- and women).3 PV also should be suspected in J. Viera, LCDR, MC, aches, or dizziness. Other patients are diagnosed patients with portal venous thrombosis and USNR. after an incidental finding of an elevated hemo- splenomegaly with or without thrombocytosis globin and/or hematocrit level on a complete and leukocytosis. Other signs and symptoms are blood count. listed in Table 1.1,4 The median age of patients diagnosed with In making the diagnosis of PV, the physician PV is 60 years, although it can occur in per- must first exclude a secondary erythrocy- sons in all age groups.1 PV occurs with a slight tosis.5,6 Once a secondary cause is ruled out predominance in men. A comprehensive review1 (Table 27), the diagnosis of PV is made using reported the incidence of PV to be 2.3 per a combination of major and minor criteria 100,000 persons per year. Therefore, a typical defined by the Polycythemia Vera Study Group family physician can expect to make a diagnosis (PVSG). Although new diagnostic modalities of PV once or twice during his or her career, have been developed, these criteria remain the and will often have at least one patient in his standard method to diagnose PV.8 or her patient panel who carries the diagnosis. Major diagnostic criteria include increased The seriousness of PV is underscored by the RCM, normal oxygen saturation, and the pres- fact that the median survival in untreated ence of splenomegaly. The test for RCM is a symptomatic patients after diagnosis is six to nuclear medicine study involving autologous 2 See page 2134 for 18 months. With treatment, the median sur- infusion of radio-labeled red blood cells fol- 2 definitions of levels of vival is more than 10 years. lowed by serial phlebotomy to determine dis- evidence labels. tribution. Physicians may refer patients to a Downloaded from the American Family Physician Web site at www.aafp.org/afp. Copyright© 2004 American Academy of Family Physicians. For the pri- vate, noncommercial use of one individual user of the Web site. All other rights reserved. Contact [email protected] for copyright questions and/or Evaluation of Polycythemia Vera Hemoglobin level >18 g per dL (180 g per L) or hematocrit level >52 percent (0.52) in white men Hemoglobin level >16 g per dL (160 g per L) or hematocrit level No >47 percent (0.47) in blacks and women Do not pursue work-up for polycythemia vera. Splenomegaly with or without thrombocytosis and leukocytosis Portal venous thrombosis TABLE 1 TABLE 2 Signs and Symptoms of Polycythemia Vera Secondary Causes of Increased Red Cell Mass Yes (Erythrocytosis) Yes More Common Is there a secondary cause of polycythemia vera? Treat underlying problem. Hematocrit level >52 percent Less Common Physiologically appropriate (0.52) in white men, Bruising/epistaxis Chronic pulmonary or cardiac disease No >47 percent (0.47) in blacks Budd-Chiari syndrome Decreased 2,3-diphosphoglycerate and women Erythromelalgia High oxygen affinity hemoglobinopathy Does patient have the three major criteria or the first two major criteria and any two of the four minor criteria? Hemoglobin level >18 g per dL Gout Increased carboxyhemoglobin (in smokers) and methemoglobin (180 g per L) in white men, Major criteria Minor criteria Hemorrhagic events Residence at high altitude >16 g per dL (160 g per L) in • Red blood cell mass >36 mL per kg in men or • Leukocyte alkaline phosphatase >100 U per L Hepatomegaly 3 9 blacks and women) Physiologically inappropriate >32 mL per kg in women • Platelet count >400,000 per mm (400 10 per L) Ischemic digits • Oxygen saturation >92 percent • White blood cell count >12,000 per mm3 (12 109 per L) Plethora Adrenal cortical hypersecretion Thrombotic events • Splenomegaly • Serum vitamin B12 level >900 pg per mL (664 pmol per L) or serum Pruritus after bathing Hydronephrosis unbound vitamin B binding capacity >2,200 pg per mL (1,623 pmol per L) Transient neurologic 12 Splenomegaly Tumors producing erythropoietin or anabolic steroids complaints (headache, Weight loss tinnitus, dizziness, blurred Relative (stress) Yes No Weakness vision, paresthesias) Disorders associated with decreased plasma volume (e.g., Sweating diarrhea, emesis, renal diseases) Atypical chest pain Polycythemia vera Not polycythemia vera Consider hematology consultation. Consider alternate diagnoses and hematologist Information from references 1 and 4. Adapted with permission from Polycythemia: primary and second- Major treatment options: consultation. ary. In: Kjeldsberg CR. Practical diagnosis of hematologic disorders. • Phlebotomy 3d ed. Chicago: ASCP Press, 2000:221. • Hydroxyurea (Hydrea) with or without phlebotomy • Interferon alfa-2b (Intron A) specialty laboratory for this study. FIGURE 1. Algorithm for the evaluation and management of polycythemia vera. Changes to these diagnostic criteria have been proposed. For example, determinations of RCM, classically given in gender, and plasma volume.8-10 [Level of evidence: C, con- milliliters per kilogram (mL per kg), can be misleading if the sensus opinion] A patient with PV could have low oxygen patient is obese, because body fat is relatively avascular. The saturation levels, because it is possible to have both PV and International Council for Standardization in Haematology an unrelated hypoxic disorder.1 Palpable splenomegaly is an (ICSH) has amended the RCM assessment, recommending the important physical finding and major criterion. However, use of formulas incorporating body surface area, weight, palpation is only 58 percent sensitive for diagnosis11 (i.e., if present, it will not be detected by examiners in 42 percent of The Authors cases). Specificity is much better. This lack of sensitivity has BRIAN J. STUART, LT, MC, USNR, is serving with the Second Medical Bat- led to some discussion about the use of imaging techniques talion, Second Flight Support Group, Group Aid Station, at Camp Lejune, to answer the question, although such a finding by imaging N.C. He received his medical degree from Saint Louis University School might be relegated to the status of a minor criterion.10 In of Medicine, St. Louis, and completed his residency in family medicine at Naval Hospital Jacksonville, Jacksonville, Fla. addition, the minor criteria of leukocyte alkaline phosphatase (LAP) and serum vitamin B12 and B12 binding capacity may ANTHONY J. VIERA, LCDR, MC, USNR, is a staff family physician at Naval Hospital Jacksonville, and assistant professor of family medicine at the be dropped in the future because of inter-laboratory error Uniformed Services University of the Health Sciences F. Edward Hébert regarding LAP and the unavailability of vitamin B12 binding School of Medicine, Bethesda, Md. He received his medical degree from capacity.10 Furthermore, neither of these criteria is sensitive the Medical University of South Carolina College of Medicine, Charles- 1 ton, and completed a residency in family medicine at Naval Hospital nor specific. Nonetheless, the PVSG criteria remain the diag- Jacksonville. nostic standard. Address correspondence to Brian J. Stuart, M.D., Naval Hospital Jackson- Serum erythropoietin
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