Highlights
- •Autoimmune cytopenias diagnosis in the elderly is challenged by several comorbidities.
- •AIHA related complications, particularly thrombosis, are more frequent in the elderly.
- •AA survival and response to standard therapy are age related.
- •Treatment has to be weighed on comorbidities and supportive therapy must be maximal.
- •Bone marrow evaluation may detect underlying disease or neoplastic evolution.
Abstract
The physiology of the immune system involves morphologic and functional changes occurring
along ageing, with a decrease in immune response and an increase in autoimmune phenomena,
even in the absence of overt disese. Autoimmune cytopenias, namely autoimmune hemolytic
anemia (AIHA), chronic idiopathic neutropenia (CIN) and aplastic anemia (AA), show
different epidemiologic predilection, but are increasingly diagnosed in the elderly,
where complications and comorbidities are more frequent. A systematic review of recent
literature, shows that comorbidities as well as underlying deficiencies, medications,
neoplasms, and, pathophysiologic chronic organ failures, frequently challenge the
differential diagnosis in this setting and should always be evaluated and excluded.
Complications, particularly infections and thrombosis for AIHA, and bleeding for AA,
should be monitored and promptly treated. Treatment choice should be carefully weighed
on the individual general condition and comorbidities, granted that intense primary
care and support (including evidence-based transfusion policies) are provided. Finally,
bone marrow histology is highly advisable in the elderly, both at diagnosis to detect
underlying conditions, and along the follow-up to monitor possible bone marrow failure
or neoplastic evolution.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to European Journal of Internal MedicineAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Autoimmunity and geriatrics: clinical significance of autoimmune manifestations in the elderly.Lupus. 2003; 12: 341-355
- Interleukin-6 and aging: blood levels and mononuclear cell production increase with advancing age and in vitro production is modifiable by dietary restriction.Lymphokine Cytokine Res. 1993; 12: 225-230
- Gerontology as oncology. Research on aging as the key to the understanding of cancer.Cancer. 1991; 68: 2496-2501
- Effect of age on the capacity of the bone marrow and the spleen cells to generate B lymphocytes.J Immunol. 1986; 137: 2411-2417
- The effect of aging on human serum immunoglobulin concentrations.J Immunol. 1970; 105: 964-972
- Autoimmune phenomena in the elderly.Rev Med Chil. March, 1991; 119: 287-292
- A novel class of antitumour antibodies: nucleosome-restricted antinuclear autoantibodies (ANA) from healthy aged nonautoimmune mice.Oncol Res. 1997; 9: 439-446
- Anticardiolipin antibodies in two elderly subpopulations.Lupus. 1995; 4: 482-485
- Dementia and antiphospholipid antibodies.Dement Geriatr Cogn Disord. 2000; 11: 36-38
- Anti-erythroblast autoimmunity in early myelodysplastic syndromes.Haematologica. 2007; 92: 19-26
- Increased prevalence of autoimmune phenomena in myelofibrosis: relationship with clinical and morphological characteristics, and with immunoregulatory cytokine patterns.Leuk Res. 2011; 37: 1509-1515
- Immune hemolytic anemias.2nd ed. Churchill Livingstone, Philadelphia2004
- Characterization of direct antiglobulin test-negative autoimmune hemolytic anemia: a study of 154 cases.Am J Hematol. 2013; 88: 93-96
- Serologic findings in autoimmune hemolytic anemia associated with immunoglobulin M warm autoantibodies.Transfusion. 2009; 49: 235-242
- Variability of the erythropoietic response in autoimmune hemolytic anemia: analysis of 109 cases.Blood. 1987; 69: 820-826
- Autoimmune hemolytic anemia with reticulocytopenia. A medical emergency.JAMA. 1980; 244: 1688-1690
- The shadowlands of MDS: idiopathic cytopenias of undetermined significance (ICUS) and clonal hematopoiesis of indeterminate potential (CHIP).Hematology Am Soc Hematol Educ Program. 2015; 2015: 299-307
- Clinical characteristics and long-term outcomes of warm-type autoimmune hemolytic anemia.Hematology. 2016; 21: 368-374
- Unusual co-occurrence of Evans syndrome and pure red cell aplasia in elderly patient with prostate cancer.Ann Hematol. 2016; 95: 1743-1744
- Autoimmune hemolytic anemia in individuals aged 75 and older: a study of 10 individuals.J Am Geriatr Soc. 2016; 64: 1372-1374
- Agewise distribution of idiopathic cold agglutinin disease.Gerontol. 1993; 26: 199-201
- Primary chronic cold agglutinin disease: a population based clinical study of 86 patients.Haematologica. 2006; 91: 460-466
- Cold agglutinin disease.Blood. 2013; 122: 1114-1121
- Primary cold agglutinin-associated lymphoproliferative disease: a B-cell lymphoma of the bone marrow distinct from lymphoplasmacytic lymphoma.Haematologica. 2014; 99: 497-504
- Clinical applications of hemolytic markers in the differential diagnosis and management of hemolytic anemia.Dis Markers. 2015; 2015: 635670
- Retrospective cohort study of 205 cases with congenital dyserythropoietic anemia type II: definition of clinical and molecular spectrum and identification of new diagnostic scores.Am J Hematol. 2014; 89: E169-E175
- Clinical heterogeneity and predictors of outcome in primary autoimmune hemolytic anemia: a GIMEMA study of 308 patients.Blood. 2014; 124: 2930-2936
- Lessons from very severe, refractory, and fatal primary autoimmune hemolytic anemias.Am J Hematol. 2015; 90: E149-E151
- Rituximab for primary chronic cold agglutinin disease: a prospective study of 37 courses of therapy in 27 patients.Blood. 2004; 103: 2925-2928
- Low-dose rituximab in adult patients with idiopathic autoimmune hemolytic anemia: clinical efficacy and biological studies.Blood. 2012; 119: 3691-3697
- A phase III randomized trial comparing glucocorticoid monotherapy versus glucocorticoid and rituximab in patients with autoimmune haemolytic anaemia.Br J Haematol. 2013; 163: 393-399
- How I treat autoimmune hemolytic anemias in adults.Blood. 2010; 116: 1831-1838
- Efficacy and safety of splenectomy in adult autoimmune hemolytic anemia.Open Med (Wars). 2016; 11: 374-380
- Rituximab therapy for autoimmune haematological diseases.Eur J Intern Med. 2011; 22: 220-229
- Low-dose rituximab in adult patients with idiopathic autoimmune hemolytic anemia: clinical efficacy and biologic studies.Blood. 2012; 119: 3691-3697
- Rituximab is an effective and safe treatment of relapse in elderly patients with resistant warm AIHA.Ann Hematol. 2016; 95: 765-769
- How I manage patients with cold agglutinin disease.Br J Haematol. 2018; 181: 320-330
- Tjønnfjord GE diagnosis and treatment of cold agglutinin mediated autoimmune hemolytic anemia.Blood Rev. 2012; 26: 107-115
- Current treatment strategies in autoimmune hemolytic disorders.Expert Rev Hematol. 2015; 8: 681-691
- Clinical evolution of autoimmune cytopenias to idiopathic cytopenias/dysplasias of uncertain significance (ICUS/IDUS) and bone marrow failure syndromes.Am J Hematol. 2017; 92: E26-E29
- Clonal hematopoiesis of indeterminate potential and its distinction from myelodysplastic syndromes.Blood. 2015; 126: 9-16
Fattizzo B, Zaninoni A, Giannotta J, et al. Clinical follow-up of 378 patients with autoimmune hemolytic anemia: prognostic impact of hemoglobin levels, autoantibody class, and reticulocytopenia at onset on the relapse risk and outcome. 22nd European hematology association meeting. Madrid 2017. Poster abstract 616.
- Chronic idiopathic neutropenia. A newly recognized entity?.N Engl J Med. 1968; 279: 1015-1019
- Is chronic neutropenia always a benign disease? Evidences from a 5-year prospective study.Eur J Intern Med. 2015; 26: 611-615
- Non-immune chronic idiopathic neutropenia of adult: an overview.Eur J Haematol. 2001; 67: 35-44
- Patients with chronic idiopathic neutropenia of adults have increased serum concentrations of inflammatory cytokines and chemokines.Am J Hematol. 2000; 65: 271-277
- Activated T-lymphocytes with myelosuppressive properties in patients with chronic idiopathic neutropenia.Br J Haematol. 2005; 128: 863-876
- Impaired megakaryopoiesis in patients with chronic idiopathic neutropenia is associated with increased transforming growth factor beta1 production in the bone marrow.Br J Haematol. 2006; 134: 624-631
- Abnormal telomere shortening of peripheral blood mononuclear cells and granulocytes in patients with chronic idiopathic neutropenia.Haematologica. 2012; 97: 743-750
- Pathophysiologic mechanisms, clinical features and treatment of idiopathic neutropenia.Expert Rev Hematol. 2008; 1: 217-229
- Severe chronic neutropenia: treatment and follow-up of patients in the severe chronic neutropenia international registry.Am J Hematol. 2003; 72: 82-93
- Prevalence of chronic idiopathic neutropenia of adults among an apparently healthy population living on the island of Crete.Ann Hematol. 1999; 78: 293-297
- Detection of anti-neutrophil antibodies in autoimmune neutropenia of infancy: a multicenter study.Isr Med Assoc J. 2010; 12: 91-96
- Autoimmune granulocytopenia: the detection of granulocyte autoantibodies with the immunofluorescence test.Br J Haematol. 1978; 39: 339-350
- Diagnosis and clinical course of autoimmune neutropenia in infancy: analysis of 240 cases.Blood. 1998; 91: 181-186
- How I treat acquired aplastic anemia.Blood. 2017; 129: 1428-1436
- Changes in trabecular bone, hematopoiesis and bone marrow vessels in aplastic anemia, primary osteoporosis, and old age: a comparative histomorphometric study.Bone. 1987; 8: 157-164
- Long term follow-up of severe aplastic anaemia patients treated with antithymocyte globulin.Br J Haematol. 1989; 73: 121-126
- Bone marrow failure and the telomeropathies.Blood. 2014; 124: 2775-2783
- Low frequency clonal mutations recoverable by deep sequencing in patients with aplastic anemia.Leukemia. 2013; 27: 968-971
- Somatic mutations and clonal hematopoiesis in aplastic anemia.N Engl J Med. 2015; 373: 35-47
- Somatic mutations identify a subgroup of aplastic anemia patients who progress to myelodysplastic syndrome.Blood. 2014; 124: 2698-2704
- The drug etiology of agranulocytosis and aplastic anemia.Oxford University Press, New York1991
- Incidence of aplastic anemia in Bangkok. The Aplastic Anemia Study Group.Blood. 1991; 77: 2166-2168
- Distinct clinical outcomes for cytogenetic abnormalities evolving from aplastic anemia.Blood. 2002; 99: 3129-3135
- Selection of patients for bone marrow transplantation in severe aplastic anemia.Blood. 1975; 45: 355-363
- Treatment of acquired severe aplastic anemia: bone marrow transplantation compared with immunosuppressive therapy – The European group for blood and marrow transplantation experience.Semin Hematol. 2000; 37: 69-80
- Telomere length, expression of MRE11 and Ku80 in patients with aplastic anemia and their correlation with pathogenesis.Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2017; 25: 503-509
- Outcome of patients with acquired aplastic anemia given first line bone marrow transplantation or immunosuppressive treatment in the last decade: a report from the European Group for Blood and Marrow Transplantation (EBMT).Haematologica. 2007; 92: 11-18
- How I treat aplastic anemia.Blood. 2012; 120: 1185-1196
- British Society for Standards in Haematology. Guidelines for the diagnosis and management of adult aplastic anaemia.Br J Haematol. 2016; 172: 187-207
- Horse versus rabbit antithymocyte globulin in acquired aplastic anemia.N Engl J Med. 2011; 365: 430-438
- For the European group for blood and marrow transplantation severe aplastic anaemia working party: effectiveness of immunosuppressive therapy in older patients with aplastic anemia.Ann Intern Med. 1999; 130: 193-201
- Predicting response to immunosuppressive therapy and survival in severe aplastic anaemia.Br J Haematol Br J Haematol. 2009; 144: 206-216
Bacigalupo A, Oneto R, Schrezenmeier H, et al. First line treatment of aplastic anemia with thymoglobuline in Europa and Asia: outcome of 976 patients treated 2001–2012. 58th American society of hematology meeting. Abstract 2422.
- Short-term efficacy and safety of antithymocyte globulin treatment in elderly patients with acquired aplastic anaemia.Br J Haematol. October, 2016; 7 ([Epub ahead of print])
- A randomized controlled study in newly-diagnosed severe aplastic anemia patients receiving antithymocyte globulin (ATG), cyclosporine, with or without G-CSF: a study of the SAA working party of the EBMT.Blood. 2011; 117: 4434-4441
- Treatment of aplastic anemia (AA) with antilymphocyte globulin (ALG) and methylprednisolone (MPred) with or without androgens: a randomized trial from the EBMT SAA working party.Br J Haematol. 1993; 83: 145-151
- Sex hormones, acting on the TERT gene, increase telomerase activity in human primary hematopoietic cells.Blood. 2009; 114: 2236-2243
- Danazol treatment for telomere diseases.N Engl J Med. 2016; 374: 1922-1931
- Androgens may boost responses to anti-thymocyte globulin in acquired aplastic anemia.Blood. 2016; 128: 3900
- Eltrombopag added to standard immunosuppression for aplastic anemia accelerates count recovery and increases response rates.Blood. 2015; 126: LBA2
Lengline E, Peffault R. Nationwide survey on the use of eltrombopag in patients with severe aplastic anemia: report on behalf of the French reference center for aplastic anemia. 58th American society of hematology meeting. Abstract 2684.
- New insights into the pathophysiology of acquired cytopenias.Hematology Am Soc Hematol Educ Program. 2000; : 18-38
- Malignant tumors occurring after treatment of aplastic anemia. European bone marrow transplantation-severe aplastic Anaemia working party.N Engl J Med. 1993; 329: 1152-1157
Article info
Publication history
Accepted:
May 28,
2018
Received in revised form:
May 24,
2018
Received:
October 3,
2017
Identification
Copyright
© 2018 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
