Polycythemia differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sadaf Sharfaei M.D.[2]

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Overview

Polycythemia manifests in a variety of clinical forms, differentiation must be established in accordance with the particular subtype. Primary and secondary polycythemia must be differentiated from each other. Primary polycythemia might be seen in patients with various mutations. Iatrogenic causes including medications, athletic drugs, and smoking might cause primary polycythemia. Secondary polycythemia must be differentiated in patients with chronic hypoxemia, erythropoietin producing tumors, or arteriovenous malformations.

Differential Diagnosis of Polycythemia

Polycythemia must be differentiated from a variety of other conditions.[1][2][3]

Category Disease Etiology Mutation Clinical manifestations Laboratory findings Gold standard disgnosis Associated findings
Demography Symptoms Signs CBC EPO level PBS
Fatigue Headache Shortness of breath Bleeding Pain Other symptoms Appearance SaO2 Fever BP Tenderness Splenomegaly Other signs Hb RBC WBC Plt
Mutational causes Polycythemia vera (PV)[4] JAK2 mutation (> 95%) Mean age >60 years old + + + ± Facial plethora Nl + ↑ RBC mass Nl to ↑ Nl to ↑
  • Elevated normochromic, normocytic RBCs
  • Thrombocytosis
  • Rarely immature cells
  • Leukoerythroblastic picture
WHO criteria for PV
Chuvash polycythemia[5] Hypoxia-sensing disorder VHL mutation Russia, Italy

<40 years old

+ + + ± Facial plethora + Nl Nl
  • Elevated normochromic, normocytic RBCs
Molecular genetic testing
Hereditary methemoglobinemia[6] Mutations in globin gene Infants ± ± ± Cyanosis Inaccurately Nl Nl Nl Nl Nl NA RBC enzyme activity + DNA analysis
  • Usually asymptomatic
Primary familial and congenital polycythemia[7] Autosomal dominant inheritance EPOR mutation Very rare + + ± Facial plethora Nl Nl to ↑ Nl Nl Nl to ↓ NA Isolated erythrocytosis + genetic testing
  • Mild manifestations of hyperviscosity
Category Disease Etiology Mutation Demography Fatigue Headache Shortness of breath Bleeding Pain Other symptoms Appearance SaO2 Fever BP Tenderness Splenomegaly Other signs Hb RBC WBC Plt EPO level PBS Gold standard diagnosis Associated findings
Iatrogenic causes Smoking[8][9] Any + Cyanosis Nl Nl Nl to ↑ Nl to ↑ Nl to ↓ NA Clinical manifestation NA
Chronic exposure to carbon monoxide[10]
  • Occupational exposure
Miners, fire fighters + + + Cyanosis, flushed cheeks Nl Nl Nl Nl Nl to ↓ NA Blood level of carboxyhemoglobin
Diuretics[11]
  • Reduced plasma volume
Any Nl Nl Nl to ↓ Nl Nl Nl Nl to ↓ NA Clinical manifestation NA
Use of androgens or anabolic steroids[12][13] Athletes + + Acne and hirsutism Nl Nl to ↑ Nl Nl NA Clinical manifestation
Self−injection of erythropoietin[14] Athletes + + Muscular body Nl Nl NA Erythropoietin level
Secondary causes Secondary polycythemia due to hypoxemia[15] Depends on etiology + + + Depends on etiology Cyanosis Nl to ↑ Nl Nl NA Clinical manifestation + imaging
  • Variable manifestations given the diverse etiologies
Secondary polycythemia due to erythropoietin producing tumor[16] Depends on etiology + Depends on etiology Depends on etiology Chronically ill Nl ± Nl to ↑ ± ± ↑/↓ ↑/↓ Nl NA Clinical manifestation + biopsy
  • Variable manifestations given the diverse etiologies
Hereditary hemorrhagic telangiectasia[17] ACVRL1, ENG, GDF2, SMAD4 mutation Children + + GI bleeding Multiple telangiectasia on face, extremities, and body Nl to ↓ Nl ↑/↓ ↑/↓ Nl Nl ↑/↓ NA Clinical criteria + genomic testing
Category Disease Etiology Mutation Demography Fatigue Headache Shortness of breath Bleeding Pain Other symptoms Appearance SaO2 Fever BP Tenderness Splenomegaly Other signs Hb RBC WBC Plt EPO level PBS Gold standard diagnosis Associated findings

References

  1. Tefferi A, Barbui T (2015). "Polycythemia vera and essential thrombocythemia: 2015 update on diagnosis, risk-stratification and management". Am J Hematol. 90 (2): 162–73. doi:10.1002/ajh.23895. PMID 25611051.
  2. Sanchez S, Ewton A (2006). "Essential thrombocythemia: a review of diagnostic and pathologic features". Arch Pathol Lab Med. 130 (8): 1144–50. doi:10.1043/1543-2165(2006)130[1144:ET]2.0.CO;2. PMID 16879015.
  3. Jabbour E, Kantarjian H (2014). "Chronic myeloid leukemia: 2014 update on diagnosis, monitoring, and management". Am J Hematol. 89 (5): 547–56. doi:10.1002/ajh.23691. PMID 24729196.
  4. Stein, Brady L.; Oh, Stephen T.; Berenzon, Dmitriy; Hobbs, Gabriela S.; Kremyanskaya, Marina; Rampal, Raajit K.; Abboud, Camille N.; Adler, Kenneth; Heaney, Mark L.; Jabbour, Elias J.; Komrokji, Rami S.; Moliterno, Alison R.; Ritchie, Ellen K.; Rice, Lawrence; Mascarenhas, John; Hoffman, Ronald (2015). "Polycythemia Vera: An Appraisal of the Biology and Management 10 Years After the Discovery ofJAK2 V617F". Journal of Clinical Oncology. 33 (33): 3953–3960. doi:10.1200/JCO.2015.61.6474. ISSN 0732-183X.
  5. Zhou, Amy W.; Knoche, Eric M.; Engle, Elizabeth K.; Ban-Hoefen, Makiko; Kaiwar, Charu; Oh, Stephen T. (2016). "Clinical Improvement with JAK2 Inhibition in Chuvash Polycythemia". New England Journal of Medicine. 375 (5): 494–496. doi:10.1056/NEJMc1600337. ISSN 0028-4793.
  6. Da-Silva SS, Sajan IS, Underwood JP (August 2003). "Congenital methemoglobinemia: a rare cause of cyanosis in the newborn--a case report". Pediatrics. 112 (2): e158–61. PMID 12897322.
  7. Bento C, McMullin MF, Percy M, et al. Primary Familial and Congenital Polycythemia. 2016 Nov 10. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2018. Available from: https://www.ncbi.nlm.nih.gov/books/NBK395975/
  8. Hasselbalch, Hans Carl (2015). "Smoking as a contributing factor for development of polycythemia vera and related neoplasms". Leukemia Research. 39 (11): 1137–1145. doi:10.1016/j.leukres.2015.09.002. ISSN 0145-2126.
  9. Malenica, Maja; Prnjavorac, Besim; Bego, Tamer; Dujic, Tanja; Semiz, Sabina; Skrbo, Selma; Gusic, Amar; Hadzic, Ajla; Causevic, Adlija (2017). "Effect of Cigarette Smoking on Haematological Parameters in Healthy Population". Medical Archives. 71 (2): 132. doi:10.5455/medarh.2017.71.132-136. ISSN 0350-199X.
  10. Wu, P. E.; Juurlink, D. N. (2014). "Carbon monoxide poisoning". Canadian Medical Association Journal. 186 (8): 611–611. doi:10.1503/cmaj.130972. ISSN 0820-3946.
  11. Pollak R, Maddux MS, Cohan J, Jacobsson PK, Mozes MF (March 1988). "Erythrocythemia following renal transplantation: influence of diuretic therapy". Clin. Nephrol. 29 (3): 119–23. PMID 3282731.
  12. Krauss DJ, Taub HA, Lantinga LJ, Dunsky MH, Kelly CM (December 1991). "Risks of blood volume changes in hypogonadal men treated with testosterone enanthate for erectile impotence". J. Urol. 146 (6): 1566–70. PMID 1942342.
  13. Morales A, Johnston B, Heaton JP, Lundie M (March 1997). "Testosterone supplementation for hypogonadal impotence: assessment of biochemical measures and therapeutic outcomes". J. Urol. 157 (3): 849–54. PMID 9072584.
  14. Elliott, S (2008). "Erythropoiesis-stimulating agents and other methods to enhance oxygen transport". British Journal of Pharmacology. 154 (3): 529–541. doi:10.1038/bjp.2008.89. ISSN 0007-1188.
  15. Nadeem, Omar; Gui, Jiang; Ornstein, Deborah L. (2012). "Prevalence of Venous Thromboembolism in Patients With Secondary Polycythemia". Clinical and Applied Thrombosis/Hemostasis. 19 (4): 363–366. doi:10.1177/1076029612460425. ISSN 1076-0296.
  16. Da Silva JL, Lacombe C, Bruneval P, Casadevall N, Leporrier M, Camilleri JP, Bariety J, Tambourin P, Varet B (February 1990). "Tumor cells are the site of erythropoietin synthesis in human renal cancers associated with polycythemia". Blood. 75 (3): 577–82. PMID 2297568.
  17. McDonald J, Pyeritz RE. Hereditary Hemorrhagic Telangiectasia. 2000 Jun 26 [Updated 2017 Feb 2]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2018. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1351/

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