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Hematologic manifestations of rheumatoid arthritis

Michael Ehrenfeld, MD
Yehuda Shoenfeld, MD
Section Editor
Ravinder N Maini, BA, MB BChir, FRCP, FMedSci, FRS
Deputy Editor
Paul L Romain, MD


Patients with rheumatoid arthritis (RA) may exhibit a variety of hematologic abnormalities. Common changes associated with active disease include anemia of chronic disease (ACD; also termed anemia of chronic inflammation), thrombocytosis, and sometimes a mild leukocytosis. There is an increased risk of lymphoproliferative disease, including non-Hodgkin lymphoma. Felty’s syndrome, with neutropenia and splenomegaly, is very infrequent.

An overview of the hematologic manifestations of RA is presented here. The clinical manifestations of RA; clinical manifestations, diagnosis, and treatment of Felty’s syndrome; and large granular lymphocyte (LGL) leukemia in RA are discussed in detail separately. (See "Clinical manifestations of rheumatoid arthritis" and "Clinical manifestations and diagnosis of Felty's syndrome" and "Drug therapy in Felty's syndrome" and "Role of splenectomy for Felty's syndrome" and "Large granular lymphocyte leukemia in rheumatoid arthritis".)


Anemia, which was formerly common in patients with rheumatoid arthritis (RA), has become much less common since the 1990s, mainly since the introduction of the newer drugs. In one analysis, the prevalence of anemia decreased between 2001 and 2007 [1].

Among the most prevalent hematologic abnormalities in patients with rheumatologic disorders are the anemia of chronic disease (ACD), a mild anemia that is generally asymptomatic, and iron deficiency anemia [2,3]. A 2008 study of 111 patients with early RA reported the prevalence of ACD to be 25 percent during the first year of disease [4]. Other forms of anemia occur less commonly. (See 'Anemia of chronic disease' below and 'Iron deficiency anemia' below and 'Macrocytic anemia' below and 'Hemolytic anemia' below and 'Bone marrow hypoplasia with anemia' below and 'Pure red cell aplasia' below.)

Estimates in studies from the early 1980s suggested a prevalence of anemia of about 30 to 70 percent [5,6]. A 2004 analysis of the available data dating back to the 1960s was similar, with an estimated prevalence of 54 percent [7]. In a study from the Ukraine, in which anemia was observed in 46 percent of patients with RA, the presence of anemia was associated with high RA disease activity [8]. Similarly, a study from China found an association in patients with RA of anemia with erosive arthritis [9].

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Literature review current through: Nov 2017. | This topic last updated: Oct 29, 2016.
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  1. Möller B, Scherer A, Förger F, et al. Anaemia may add information to standardised disease activity assessment to predict radiographic damage in rheumatoid arthritis: a prospective cohort study. Ann Rheum Dis 2014; 73:691.
  2. Vreugdenhil G, Wognum AW, van Eijk HG, Swaak AJ. Anaemia in rheumatoid arthritis: the role of iron, vitamin B12, and folic acid deficiency, and erythropoietin responsiveness. Ann Rheum Dis 1990; 49:93.
  3. Baer AN, Dessypris EN, Krantz SB. The pathogenesis of anemia in rheumatoid arthritis: a clinical and laboratory analysis. Semin Arthritis Rheum 1990; 19:209.
  4. Nikolaisen C, Figenschau Y, Nossent JC. Anemia in early rheumatoid arthritis is associated with interleukin 6-mediated bone marrow suppression, but has no effect on disease course or mortality. J Rheumatol 2008; 35:380.
  5. Hansen NE. The anaemia of chronic disorders. A bag of unsolved questions. Scand J Haematol 1983; 31:397.
  6. Rajapakse CN, Holt PJ, Perera B. Diagnosis of true iron deficiency in rheumatoid arthritis. Ann Rheum Dis 1980; 39:596.
  7. Wilson A, Yu HT, Goodnough LT, Nissenson AR. Prevalence and outcomes of anemia in rheumatoid arthritis: a systematic review of the literature. Am J Med 2004; 116 Suppl 7A:50S.
  8. Ganna S. [The prevalence of anemia in rheumatoid arthritis]. Rev Bras Reumatol 2014; 54:257.
  9. Yuan S, Chen D, Xiao Y, et al. Factors Associated with Erosive Arthritis in Rheumatoid Arthritis and Other Connective Tissue Diseases: A Retrospective Study From a Southern Chinese Population. J Clin Rheumatol 2016; 22:22.
  10. Bloxham E, Vagadia V, Scott K, et al. Anaemia in rheumatoid arthritis: can we afford to ignore it? Postgrad Med J 2011; 87:596.
  11. Marx JJ. Iron and infection: competition between host and microbes for a precious element. Best Pract Res Clin Haematol 2002; 15:411.
  12. Boyd HK, Lappin TR. Erythropoietin deficiency in the anaemia of chronic disorders. Eur J Haematol 1991; 46:198.
  13. Hochberg MC, Arnold CM, Hogans BB, Spivak JL. Serum immunoreactive erythropoietin in rheumatoid arthritis: impaired response to anemia. Arthritis Rheum 1988; 31:1318.
  14. Davis D, Charles PJ, Potter A, et al. Anaemia of chronic disease in rheumatoid arthritis: in vivo effects of tumour necrosis factor alpha blockade. Br J Rheumatol 1997; 36:950.
  15. Papadaki HA, Kritikos HD, Valatas V, et al. Anemia of chronic disease in rheumatoid arthritis is associated with increased apoptosis of bone marrow erythroid cells: improvement following anti-tumor necrosis factor-alpha antibody therapy. Blood 2002; 100:474.
  16. Glossop JR, Dawes PT, Hassell AB, Mattey DL. Anemia in rheumatoid arthritis: association with polymorphism in the tumor necrosis factor receptor I and II genes. J Rheumatol 2005; 32:1673.
  17. Porter DR, Sturrock RD, Capell HA. The use of serum ferritin estimation in the investigation of anaemia in patients with rheumatoid arthritis. Clin Exp Rheumatol 1994; 12:179.
  18. Masson C. Rheumatoid anemia. Joint Bone Spine 2011; 78:131.
  19. Peeters HR, Jongen-Lavrencic M, Raja AN, et al. Course and characteristics of anaemia in patients with rheumatoid arthritis of recent onset. Ann Rheum Dis 1996; 55:162.
  20. Hansen OP, Hansen TM, Jans H, Hippe E. Red blood cell membrane-bound IgG: demonstration of antibodies in patients with autoimmune haemolytic anaemia and immune complexes in patients with rheumatic diseases. Clin Lab Haematol 1984; 6:341.
  21. Dessypris EN, Baer MR, Sergent JS, Krantz SB. Rheumatoid arthritis and pure red cell aplasia. Ann Intern Med 1984; 100:202.
  22. Kamper AM, Malbrain M, Zachee P, Chew SL. Parvovirus infection causing red cell aplasia and leukopenia in rheumatoid arthritis. Clin Rheumatol 1994; 13:129.
  23. Doube A, Davis M, Smith JG, et al. Structured approach to the investigation of anaemia in patients with rheumatoid arthritis. Ann Rheum Dis 1992; 51:469.
  24. Mulherin D, Skelly M, Saunders A, et al. The diagnosis of iron deficiency in patients with rheumatoid arthritis and anemia: an algorithm using simple laboratory measures. J Rheumatol 1996; 23:237.
  25. Fitzsimons EJ, Houston T, Munro R, et al. Erythroblast iron metabolism and serum soluble transferrin receptor values in the anemia of rheumatoid arthritis. Arthritis Rheum 2002; 47:166.
  26. Baillie FJ, Morrison AE, Fergus I. Soluble transferrin receptor: a discriminating assay for iron deficiency. Clin Lab Haematol 2003; 25:353.
  27. Pavai S, Jayaranee S, Sargunan S. Soluble transferrin receptor, ferritin and soluble transferrin receptor--Ferritin index in assessment of anaemia in rhaeumatoid arthritis. Med J Malaysia 2007; 62:303.
  28. Takashina N, Kondo H, Kashiwazaki S. Suppressed serum erythropoietin response to anemia and the efficacy of recombinant erythropoietin in the anemia of rheumatoid arthritis. J Rheumatol 1990; 17:885.
  29. Means RT Jr, Krantz SB. Progress in understanding the pathogenesis of the anemia of chronic disease. Blood 1992; 80:1639.
  30. Vreugdenhil G, Löwenberg B, Van Eijk HG, Swaak AJ. Tumor necrosis factor alpha is associated with disease activity and the degree of anemia in patients with rheumatoid arthritis. Eur J Clin Invest 1992; 22:488.
  31. Peeters HR, Jongen-Lavrencic M, Vreugdenhil G, Swaak AJ. Effect of recombinant human erythropoietin on anaemia and disease activity in patients with rheumatoid arthritis and anaemia of chronic disease: a randomised placebo controlled double blind 52 weeks clinical trial. Ann Rheum Dis 1996; 55:739.
  32. Pincus T, Olsen NJ, Russell IJ, et al. Multicenter study of recombinant human erythropoietin in correction of anemia in rheumatoid arthritis. Am J Med 1990; 89:161.
  33. Martí-Carvajal AJ, Agreda-Pérez LH, Solà I, Simancas-Racines D. Erythropoiesis-stimulating agents for anemia in rheumatoid arthritis. Cochrane Database Syst Rev 2013; :CD000332.
  34. Genovese MC, McKay JD, Nasonov EL, et al. Interleukin-6 receptor inhibition with tocilizumab reduces disease activity in rheumatoid arthritis with inadequate response to disease-modifying antirheumatic drugs: the tocilizumab in combination with traditional disease-modifying antirheumatic drug therapy study. Arthritis Rheum 2008; 58:2968.
  35. Martini A, Ravelli A, Di Fuccia G, et al. Intravenous iron therapy for severe anaemia in systemic-onset juvenile chronic arthritis. Lancet 1994; 344:1052.
  36. Rodrigues JF, Harth M, Barr RM. Pure red cell aplasia in rheumatoid arthritis. J Rheumatol 1988; 15:1159.
  37. Bessissow T, Renard M, Hoffman I, et al. Review article: non-malignant haematological complications of anti-tumour necrosis factor alpha therapy. Aliment Pharmacol Ther 2012; 36:312.
  38. Hastings R, Ding T, Butt S, et al. Neutropenia in patients receiving anti-tumor necrosis factor therapy. Arthritis Care Res (Hoboken) 2010; 62:764.
  39. Panush RS, Franco AE, Schur PH. Rheumatoid arthritis associated with eosinophilia. Ann Intern Med 1971; 75:199.
  40. Guellec D, Milin M, Cornec D, et al. Eosinophilia predicts poor clinical outcomes in recent-onset arthritis: results from the ESPOIR cohort. RMD Open 2015; 1:e000070.
  41. Farr M, Scott DL, Constable TJ, et al. Thrombocytosis of active rheumatoid disease. Ann Rheum Dis 1983; 42:545.
  42. Vidal F, Fontova R, Richart C. Severe neutropenia and thrombocytopenia associated with infliximab. Ann Intern Med 2003; 139:W.
  43. Coblyn JS, Weinblatt M, Holdsworth D, Glass D. Gold-induced thrombocytopenia. A clinical and immunogenetic study of twenty-three patients. Ann Intern Med 1981; 95:178.
  44. Thomas D, Gallus AS, Brooks PM, et al. Thrombokinetics in patients with rheumatoid arthritis treated with D-penicillamine. Ann Rheum Dis 1984; 43:402.
  45. Franck H, Rau R, Herborn G. Thrombocytopenia in patients with rheumatoid arthritis on long-term treatment with low dose methotrexate. Clin Rheumatol 1996; 15:266.