FREE SHIPPING over $40
OVER 9000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Home / Equine Research Bank / Haematologica / Paroxysmal nocturnal hemoglobinuria clones in severe aplasti...
Haematologica2010; 95(7); 1075-1080; doi: 10.3324/haematol.2009.017889

Paroxysmal nocturnal hemoglobinuria clones in severe aplastic anemia patients treated with horse anti-thymocyte globulin plus cyclosporine.

Abstract: Clones of glycosylphosphatidylinositol-anchor protein-deficient cells are characteristic in paroxysmal nocturnal hemoglobinuria and are present in about 40-50% of patients with severe aplastic anemia. Flow cytometry has allowed for sensitive and precise measurement of glycosylphosphatidylinositol-anchor protein-deficient red blood cells and neutrophils in severe aplastic anemia. Methods: We conducted a retrospective analysis of paroxysmal nocturnal hemoglobinuria clones measured by flow cytometry in 207 consecutive severe aplastic anemia patients who received immunosuppressive therapy with a horse anti-thymocyte globulin plus cyclosporine regimen from 2000 to 2008. Results: The presence of a glycosylphosphatidylinositol-anchor protein-deficient clone was detected in 83 (40%) patients pre-treatment, and the median clone size was 9.7% (interquartile range 3.5-29). In patients without a detectable clone pre-treatment, the appearance of a clone after immunosuppressive therapy was infrequent, and in most with a clone pre-treatment, clone size often decreased after immunosuppressive therapy. However, in 30 patients, an increase in clone size was observed after immunosuppressive therapy. The majority of patients with a paroxysmal nocturnal hemoglobinuria clone detected after immunosuppressive therapy did not have an elevated lactate dehydrogenase, nor did they experience hemolysis or thrombosis, and they did not require specific interventions with anticoagulation and/or eculizumab. Of the 7 patients who did require therapy for clinical paroxysmal nocturnal hemoglobinuria symptoms and signs, all had an elevated lactate dehydrogenase and a clone size greater than 50%. In all, 18 (8.6%) patients had a clone greater than 50% at any given time of sampling. Conclusions: The presence of a paroxysmal nocturnal hemoglobinuria clone in severe aplastic anemia is associated with low morbidity and mortality, and specific measures to address clinical paroxysmal nocturnal hemoglobinuria are seldom required.
Get Full Text
Publication Date: 2010-07-03 PubMed ID: 20595102PubMed Central: PMC2895030DOI: 10.3324/haematol.2009.017889Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Journal Article
  • Research Support
  • N.I.H.
  • Intramural

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research examines the presence and potential significance of abnormal cells related to a disease called paroxysmal nocturnal hemoglobinuria (PNH) in patients with a severe condition known as aplastic anemia. Using a specific technique called flow cytometry, the researchers analyzed more than 200 patients to track any changes in the amount and characteristics of these abnormal cells after being treated with a therapy involving anti-thymocyte globulin and cyclosporine.

Research Background

  • The study is based on severe aplastic anemia, a condition where the body stops producing enough new blood cells. Another associated condition is paroxysmal nocturnal hemoglobinuria (PNH), which is characterized by the presence of cells lacking GPI-anchor proteins – a type of deficiency observed in approximately 40-50% of severe aplastic anemia patients.
  • These abnormal cells or “clones” could be observed through a technique called flow cytometry, enabling the precise measurement of GPI-anchor protein-deficient red blood cells.

Research Methodology

  • The researchers conducted a retrospective analysis of PNH clones in 207 consecutive severe aplastic anemia patients who were treated with a regimen of horse anti-thymocyte globulin and cyclosporine between 2000 and 2008. The aim was to track changes in these clones post treatment.

Key Findings

  • Around 40% of the patients had these abnormal cells before the treatment, and the size of these aberrant cell populations often decreased after the immunosuppressive therapy.
  • In a small number of patients (30), an increase in clone size was observed after the treatment. Additionally, very few of these patients had elevated lactate dehydrogenase levels, experienced hemolysis or thrombosis, or required specific interventions.
  • Only 7 patients needed treatment for clinical PNH symptoms, all of whom had elevated lactate dehydrogenase and a clone size greater than 50%.

Conclusions

  • The presence of PNH clones in severe aplastic anemia patients is associated with low morbidity and mortality, suggesting generally positive outcomes. The need for specific treatment addressing clinical PNH symptoms is rare, implying the disease’s manageable nature after the implementation of immunosuppressive therapy.

Cite This Article

APA
Scheinberg P, Marte M, Nunez O, Young NS. (2010). Paroxysmal nocturnal hemoglobinuria clones in severe aplastic anemia patients treated with horse anti-thymocyte globulin plus cyclosporine. Haematologica, 95(7), 1075-1080. https://doi.org/10.3324/haematol.2009.017889

Publication

Haematologica
ISSN: 1592-8721
NlmUniqueID: 0417435
Country: Italy
Language: English
Volume: 95
Issue: 7
Pages: 1075-1080

Researcher Affiliations

Scheinberg, Phillip
  • Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, 20892-1202, USA. scheinbp@mail.nih.gov
Marte, Michael
    Nunez, Olga
      Young, Neal S

        MeSH Terms

        • Adult
        • Anemia, Aplastic / drug therapy
        • Anemia, Aplastic / pathology
        • Animals
        • Antilymphocyte Serum / therapeutic use
        • Clone Cells / pathology
        • Cyclosporine / therapeutic use
        • Drug Therapy, Combination
        • Female
        • Hemoglobinuria, Paroxysmal / drug therapy
        • Hemoglobinuria, Paroxysmal / pathology
        • Horses
        • Humans
        • Immunosuppressive Agents / therapeutic use
        • Male
        • Middle Aged
        • Prognosis
        • Retrospective Studies
        • Young Adult

        Grant Funding

        • Intramural NIH HHS

        References

        This article includes 20 references
        1. Sanchez-Medal L, Gomez-Leal A, Duarte L, Guadalupe Rico M. Anabolic androgenic steroids in the treatment of acquired aplastic anemia.. Blood 1969 Sep;34(3):283-300.
          pubmed: 5820048
        2. Williams DM, Lynch RE, Cartwright GE. Drug-induced aplastic anemia.. Semin Hematol 1973 Jul;10(3):195-223.
          pubmed: 4577645
        3. Young NS, Calado RT, Scheinberg P. Current concepts in the pathophysiology and treatment of aplastic anemia.. Blood 2006 Oct 15;108(8):2509-19.
          pmc: PMC1895575pubmed: 16778145doi: 10.1182/blood-2006-03-010777google scholar: lookup
        4. Miyata T, Takeda J, Iida Y, Yamada N, Inoue N, Takahashi M, Maeda K, Kitani T, Kinoshita T. The cloning of PIG-A, a component in the early step of GPI-anchor biosynthesis.. Science 1993 Feb 26;259(5099):1318-20.
          pubmed: 7680492doi: 10.1126/science.7680492google scholar: lookup
        5. Dunn DE, Tanawattanacharoen P, Boccuni P, Nagakura S, Green SW, Kirby MR, Kumar MS, Rosenfeld S, Young NS. Paroxysmal nocturnal hemoglobinuria cells in patients with bone marrow failure syndromes.. Ann Intern Med 1999 Sep 21;131(6):401-8.
          pubmed: 10498555doi: 10.7326/0003-4819-131-6-199909210-00002google scholar: lookup
        6. Piedras J, López-Karpovitch X. Flow cytometric analysis of glycosylphosphatidyl-inositol-anchored proteins to assess paroxysmal nocturnal hemoglobinuria clone size.. Cytometry 2000 Aug 15;42(4):234-8.
          pubmed: 10934342doi: 10.1002/1097-0320(20000815)42:4<234::aid-cyto3>3.0.co;2-6google scholar: lookup
        7. Young NS. Paroxysmal nocturnal hemoglobinuria and myelodysplastic syndromes: clonal expansion of PIG-A-mutant hematopoietic cells in bone marrow failure.. Haematologica 2009 Jan;94(1):3-7.
          pmc: PMC2625409pubmed: 19118373doi: 10.3324/haematol.2008.001297google scholar: lookup
        8. Rosenfeld S, Follmann D, Nunez O, Young NS. Antithymocyte globulin and cyclosporine for severe aplastic anemia: association between hematologic response and long-term outcome.. JAMA 2003 Mar 5;289(9):1130-5.
          pubmed: 12622583doi: 10.1001/jama.289.9.1130google scholar: lookup
        9. Rosenfeld SJ, Kimball J, Vining D, Young NS. Intensive immunosuppression with antithymocyte globulin and cyclosporine as treatment for severe acquired aplastic anemia.. Blood 1995 Jun 1;85(11):3058-65.
          pubmed: 7756640
        10. Scheinberg P, Nunez O, Wu C, Young NS. Treatment of severe aplastic anaemia with combined immunosuppression: anti-thymocyte globulin, ciclosporin and mycophenolate mofetil.. Br J Haematol 2006 Jun;133(6):606-11.
          pubmed: 16704434doi: 10.1111/j.1365-2141.2006.06085.xgoogle scholar: lookup
        11. Scheinberg P, Wu CO, Nunez O, Scheinberg P, Boss C, Sloand EM, Young NS. Treatment of severe aplastic anemia with a combination of horse antithymocyte globulin and cyclosporine, with or without sirolimus: a prospective randomized study.. Haematologica 2009 Mar;94(3):348-54.
          pmc: PMC2649367pubmed: 19181786doi: 10.3324/haematol.13829google scholar: lookup
        12. Hall C, Richards S, Hillmen P. Primary prophylaxis with warfarin prevents thrombosis in paroxysmal nocturnal hemoglobinuria (PNH).. Blood 2003 Nov 15;102(10):3587-91.
          pubmed: 12893760doi: 10.1182/blood-2003-01-0009google scholar: lookup
        13. Bourantas K. High-dose recombinant human erythropoietin and low-dose corticosteroids for treatment of anemia in paroxysmal nocturnal hemoglobinuria.. Acta Haematol 1994;91(2):62-5.
          pubmed: 8023644doi: 10.1159/000204254google scholar: lookup
        14. Issaragrisil S, Piankijagum A, Tang-naitrisorana Y. Corticosteroids therapy in paroxysmal nocturnal hemoglobinuria.. Am J Hematol 1987 May;25(1):77-83.
          pubmed: 3578265doi: 10.1002/ajh.2830250108google scholar: lookup
        15. Hillmen P, Young NS, Schubert J, Brodsky RA, Socié G, Muus P, Röth A, Szer J, Elebute MO, Nakamura R, Browne P, Risitano AM, Hill A, Schrezenmeier H, Fu CL, Maciejewski J, Rollins SA, Mojcik CF, Rother RP, Luzzatto L. The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria.. N Engl J Med 2006 Sep 21;355(12):1233-43.
          pubmed: 16990386doi: 10.1056/NEJMoa061648google scholar: lookup
        16. Hillmen P, Muus P, Dührsen U, Risitano AM, Schubert J, Luzzatto L, Schrezenmeier H, Szer J, Brodsky RA, Hill A, Socié G, Bessler M, Rollins SA, Bell L, Rother RP, Young NS. Effect of the complement inhibitor eculizumab on thromboembolism in patients with paroxysmal nocturnal hemoglobinuria.. Blood 2007 Dec 1;110(12):4123-8.
          pubmed: 17702897doi: 10.1182/blood-2007-06-095646google scholar: lookup
        17. Parker C. Eculizumab for paroxysmal nocturnal haemoglobinuria.. Lancet 2009 Feb 28;373(9665):759-67.
          pubmed: 19144399doi: 10.1016/S0140-6736(09)60001-5google scholar: lookup
        18. Maciejewski JP, Rivera C, Kook H, Dunn D, Young NS. Relationship between bone marrow failure syndromes and the presence of glycophosphatidyl inositol-anchored protein-deficient clones.. Br J Haematol 2001 Dec;115(4):1015-22.
          pubmed: 11843844doi: 10.1046/j.1365-2141.2001.03191.xgoogle scholar: lookup
        19. Sugimori C, Chuhjo T, Feng X, Yamazaki H, Takami A, Teramura M, Mizoguchi H, Omine M, Nakao S. Minor population of CD55-CD59- blood cells predicts response to immunosuppressive therapy and prognosis in patients with aplastic anemia.. Blood 2006 Feb 15;107(4):1308-14.
          pubmed: 16179371doi: 10.1182/blood-2005-06-2485google scholar: lookup
        20. Scheinberg P, Wu CO, Nunez O, Young NS. Predicting response to immunosuppressive therapy and survival in severe aplastic anaemia.. Br J Haematol 2009 Jan;144(2):206-16.
          pmc: PMC4149225pubmed: 19036108doi: 10.1111/j.1365-2141.2008.07450.xgoogle scholar: lookup

        Citations

        This article has been cited 34 times.
        1. Rovó A, Gavillet M, Drexler B, Keller P, Schneider JS, Colucci G, Beauverd Y, van Dorland HA, Pollak M, Schmidt A, De Gottardi A, Bissig M, Lehmann T, Duchosal MA, Zeerleder S. Swiss Survey on current practices and opinions on clinical constellations triggering the search for PNH clones.. Front Med (Lausanne) 2023;10:1200431.
          doi: 10.3389/fmed.2023.1200431pubmed: 37564039google scholar: lookup
        2. Rayas J, Hassan M, Hock RA, Nguyen B, Prakash S, Rojas Murguia A, Vahora I, Corral J, Padilla O, Dihowm F. Attack of the Clones: A Patient With Untreated Aplastic Anemia Presenting With Classical Paroxysmal Nocturnal Hemoglobinuria.. Cureus 2023 Jan;15(1):e34093.
          doi: 10.7759/cureus.34093pubmed: 36843778google scholar: lookup
        3. Li H, Hu F, Gale RP, Sekeres MA, Liang Y. Myelodysplastic syndromes.. Nat Rev Dis Primers 2022 Nov 17;8(1):74.
          doi: 10.1038/s41572-022-00402-5pubmed: 36396662google scholar: lookup
        4. Hendricks CL, Naidoo A, Thejpal R, Rapiti N, Neethling B, Goga Y, Buldeo S. Childhood aplastic anaemia with paroxysmal nocturnal haemoglobinuria clones: A retrospective single-centre study in South Africa.. Afr J Lab Med 2022;11(1):1537.
          doi: 10.4102/ajlm.v11i1.1537pubmed: 35811748google scholar: lookup
        5. Atmar K, Ruivenkamp CAL, Hooimeijer L, Nibbeling EAR, Eckhardt CL, Huisman EJ, Lankester AC, Bartels M, Santen GWE, Smiers FJ, van der Burg M, Mohseny AB. Diagnostic Value of a Protocolized In-Depth Evaluation of Pediatric Bone Marrow Failure: A Multi-Center Prospective Cohort Study.. Front Immunol 2022;13:883826.
          doi: 10.3389/fimmu.2022.883826pubmed: 35572556google scholar: lookup
        6. Erkek ET, Nazligul E, Nalcaci M, Yenerel MN. Circulating Endothelial Progenitor Cells and Their Relation to Thrombosis in Paroxysmal Nocturnal Hemoglobinuria and Aplastic Anemia.. Indian J Hematol Blood Transfus 2022 Apr;38(2):319-326.
          doi: 10.1007/s12288-021-01445-6pubmed: 35496969google scholar: lookup
        7. Li J, Zong SY, Yin ZX, Gao YY, Liu LP, Wan Y, Lan Y, Gong XW, Zhu XF. Significance of paroxysmal nocturnal hemoglobinuria clone in immunosuppressive therapy for children with severe aplastic anemia.. Zhongguo Dang Dai Er Ke Za Zhi 2022 Mar 15;24(3):303-308.
          doi: 10.7499/j.issn.1008-8830.2110109pubmed: 35351262google scholar: lookup
        8. Pires da Silva BGP, Fonseca NP, Catto LFB, Pereira GC, Calado RT. The spectrum of paroxysmal nocturnal hemoglobinuria clinical presentation in a Brazilian single referral center.. Ann Hematol 2022 May;101(5):999-1007.
          doi: 10.1007/s00277-022-04797-9pubmed: 35182190google scholar: lookup
        9. Gurnari C, Pagliuca S, Kewan T, Bahaj W, Mori M, Patel BJ, Visconte V, Maciejewski JP. Is nature truly healing itself? Spontaneous remissions in Paroxysmal Nocturnal Hemoglobinuria.. Blood Cancer J 2021 Nov 27;11(11):187.
          doi: 10.1038/s41408-021-00582-5pubmed: 34839350google scholar: lookup
        10. Lan Y, Chang L, Yi M, Cai Y, Feng J, Ren Y, Liu C, Chen X, Wang S, Guo Y, Zhang A, Liu L, Zhang J, Zhu X. Long-term outcomes of 172 children with severe aplastic anemia treated with rabbit antithymocyte globulin and cyclosporine.. Ann Hematol 2021 Jan;100(1):53-61.
          doi: 10.1007/s00277-020-04296-9pubmed: 33033910google scholar: lookup
        11. Naim F, Saraf A, Dass J, Arya V, Langer S, Gupta N, Sharma A, Kotwal J. A Prospective, Cross Sectional Study of PNH Clone in MDS Patients Using High Sensitivity Flowcytometry: A Single Center Experience.. Indian J Hematol Blood Transfus 2020 Jul;36(3):519-525.
          doi: 10.1007/s12288-019-01219-1pubmed: 32647427google scholar: lookup
        12. Sun L, Babushok DV. Secondary myelodysplastic syndrome and leukemia in acquired aplastic anemia and paroxysmal nocturnal hemoglobinuria.. Blood 2020 Jul 2;136(1):36-49.
          doi: 10.1182/blood.2019000940pubmed: 32430502google scholar: lookup
        13. Schrezenmeier H, Röth A, Araten DJ, Kanakura Y, Larratt L, Shammo JM, Wilson A, Shayan G, Maciejewski JP. Baseline clinical characteristics and disease burden in patients with paroxysmal nocturnal hemoglobinuria (PNH): updated analysis from the International PNH Registry.. Ann Hematol 2020 Jul;99(7):1505-1514.
          doi: 10.1007/s00277-020-04052-zpubmed: 32390114google scholar: lookup
        14. Parker CJ. Update on the diagnosis and management of paroxysmal nocturnal hemoglobinuria.. Hematology Am Soc Hematol Educ Program 2016 Dec 2;2016(1):208-216.
          doi: 10.1182/asheducation-2016.1.208pubmed: 27913482google scholar: lookup
        15. Townsley DM, Winkler T. Nontransplant therapy for bone marrow failure.. Hematology Am Soc Hematol Educ Program 2016 Dec 2;2016(1):83-89.
          doi: 10.1182/asheducation-2016.1.83pubmed: 27913466google scholar: lookup
        16. Urbano-Ispizua Á, Muus P, Schrezenmeier H, Almeida AM, Wilson A, Ware RE. Different clinical characteristics of paroxysmal nocturnal hemoglobinuria in pediatric and adult patients.. Haematologica 2017 Mar;102(3):e76-e79.
          doi: 10.3324/haematol.2016.151852pubmed: 27884975google scholar: lookup
        17. Kogiso T, Hashimoto E, Ito T, Hara T, Ikarashi Y, Kodama K, Taniai M, Torii N, Yoshinaga K, Morita S, Takahashi Y, Tanaka J, Sakai S, Yamamoto M, Tokushige K. Successful Treatment of Ascites using a Denver(®) Peritoneovenous Shunt in a Patient with Paroxysmal Nocturnal Hemoglobinuria and Budd-Chiari syndrome.. Intern Med 2016;55(20):2957-2963.
          doi: 10.2169/internalmedicine.55.7087pubmed: 27746432google scholar: lookup
        18. Dal MS, Karakuş A, Ekmen MÖ, Ayyildiz O. Presentation and Management of Paroxysmal Nocturnal Hemoglobinuria: A Single-Center Experience.. Hematol Rep 2016 Mar 17;8(1):6409.
          doi: 10.4081/hr.2016.6409pubmed: 27103981google scholar: lookup
        19. Li Y, Qin T, Xu Z, Zhang Y, Wang J, Li B, Fang L, Pan L, Hu N, Zhang H, Qu S, Liu J, Wang H, Xiao Z. [Clinical and laboratory characteristics in patients of myelodysplastic syndrome with PNH clones].. Zhonghua Xue Ye Xue Za Zhi 2016 Apr;37(4):313-7.
          doi: 10.3760/cma.j.issn.0253-2727.2016.04.013pubmed: 27093995google scholar: lookup
        20. Zhang J, Li X, Shi J, Ge M, Shao Y, Huang J, Huang Z, Nie N, Zheng Y. [Clinical characteristics and evolution of paroxysmal nocturnal hemoglobinuria clones in patients with acquired aplastic anemia].. Zhonghua Xue Ye Xue Za Zhi 2016 Feb;37(2):124-9.
          doi: 10.3760/cma.j.issn.0253-2727.2016.02.008pubmed: 27014982google scholar: lookup
        21. Ishii K, Young NS. Anemia of Central Origin.. Semin Hematol 2015 Oct;52(4):321-38.
          doi: 10.1053/j.seminhematol.2015.07.002pubmed: 26404444google scholar: lookup
        22. DeZern AE, Brodsky RA. Paroxysmal nocturnal hemoglobinuria: a complement-mediated hemolytic anemia.. Hematol Oncol Clin North Am 2015 Jun;29(3):479-94.
          doi: 10.1016/j.hoc.2015.01.005pubmed: 26043387google scholar: lookup
        23. Miano M, Dufour C. The diagnosis and treatment of aplastic anemia: a review.. Int J Hematol 2015 Jun;101(6):527-35.
          doi: 10.1007/s12185-015-1787-zpubmed: 25837779google scholar: lookup
        24. de Azambuja AP, Malvezzi M, Bitencourt MA, Oliveira MM, Medeiros LA, Pasquini R. Paroxysmal nocturnal hemoglobinuria clone in 103 Brazilian patients: diagnosis and classification.. Rev Bras Hematol Hemoter 2015 Mar-Apr;37(2):90-7.
          doi: 10.1016/j.bjhh.2015.01.001pubmed: 25818818google scholar: lookup
        25. Timeus F, Crescenzio N, Longoni D, Doria A, Foglia L, Pagliano S, Vallero S, Decimi V, Svahn J, Palumbo G, Ruggiero A, Martire B, Pillon M, Marra N, Dufour C, Ramenghi U, Saracco P. Paroxysmal nocturnal hemoglobinuria clones in children with acquired aplastic anemia: a multicentre study.. PLoS One 2014;9(7):e101948.
          doi: 10.1371/journal.pone.0101948pubmed: 25007335google scholar: lookup
        26. Townsley DM, Young NS. Blood consult: paroxysmal nocturnal hemoglobinuria and its complications.. Blood 2013 Oct 17;122(16):2795-8.
          doi: 10.1182/blood-2013-07-360081pubmed: 24021672google scholar: lookup
        27. Raghupathy R, Derman O. Response of paroxysmal nocturnal hemoglobinuria clone with aplastic anemia to rituximab.. Case Rep Hematol 2012;2012:106182.
          doi: 10.1155/2012/106182pubmed: 22937317google scholar: lookup
        28. Scheinberg P, Young NS. How I treat acquired aplastic anemia.. Blood 2012 Aug 9;120(6):1185-96.
          doi: 10.1182/blood-2011-12-274019pubmed: 22517900google scholar: lookup
        29. Pu JJ, Hu R, Mukhina GL, Carraway HE, McDevitt MA, Brodsky RA. The small population of PIG-A mutant cells in myelodysplastic syndromes do not arise from multipotent hematopoietic stem cells.. Haematologica 2012 Aug;97(8):1225-33.
          doi: 10.3324/haematol.2011.048215pubmed: 22315493google scholar: lookup
        30. Migdady Y, Olszewski AJ. Paroxysmal nocturnal hemoglobinuria presenting with a left intraventricular thrombus in a patient with prior thymoma and aplastic anemia.. Clin Med Insights Oncol 2011;5:343-8.
          doi: 10.4137/CMO.S8442pubmed: 22174595google scholar: lookup
        31. Scheinberg P, Nunez O, Weinstein B, Scheinberg P, Wu CO, Young NS. Activity of alemtuzumab monotherapy in treatment-naive, relapsed, and refractory severe acquired aplastic anemia.. Blood 2012 Jan 12;119(2):345-54.
          doi: 10.1182/blood-2011-05-352328pubmed: 22067384google scholar: lookup
        32. Risitano AM, Perna F. Aplastic anemia: immunosuppressive therapy in 2010.. Pediatr Rep 2011 Jun 22;3 Suppl 2(Suppl 2):e7.
          doi: 10.4081/pr.2011.s2.e7pubmed: 22053283google scholar: lookup
        33. Dezern AE, Brodsky RA. Clinical management of aplastic anemia.. Expert Rev Hematol 2011 Apr;4(2):221-30.
          doi: 10.1586/ehm.11.11pubmed: 21495931google scholar: lookup
        34. Pu JJ, Mukhina G, Wang H, Savage WJ, Brodsky RA. Natural history of paroxysmal nocturnal hemoglobinuria clones in patients presenting as aplastic anemia.. Eur J Haematol 2011 Jul;87(1):37-45.
          doi: 10.1111/j.1600-0609.2011.01615.xpubmed: 21447004google scholar: lookup
        Subscribe to our newsletter
        Join 99,359 horse owners like you who receive our email updates on horse health and nutrition.