Thrombocytopenia in Older Adults

Brandon J. McMahon; Hau C. Kwaan

doi:10.1055/s-0034-1389080

Seminars in Thrombosis and Hemostasis, Table of Contents

Semin Thromb Hemost 2014; 40(06): 682-687
DOI: 10.1055/s-0034-1389080

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Thrombocytopenia in Older Adults

Authors

Brandon J. McMahon

¹Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, Chicago, Illinois
Hau C. Kwaan

¹Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, Chicago, Illinois

Abstract

Thrombocytopenia in older patients is associated with several characteristics that are often underrecognized. Among them are the risk of bleeding complications, the senescence of the bone marrow, the increased use of multiple drugs, and greater comorbidity. In this article, the various forms of thrombocytopenia, including primary and drug-associated immune thrombocytopenias, as well as other drug-associated thrombocytopenias, are reviewed. In addition, how age-related changes in platelet function may affect the bleeding risk is discussed.

Keywords

thrombocytopenia - older adults - bleeding - immune thrombocytopenic purpura - drug-induced thrombocytopenia

Full Text

References

References
1 Cines DB, Bussel JB, Liebman HA, Luning Prak ET. The ITP syndrome: pathogenic and clinical diversity. Blood 2009; 113 (26) 6511-6521
2 Frederiksen H, Schmidt K. The incidence of idiopathic thrombocytopenic purpura in adults increases with age. Blood 1999; 94 (3) 909-913
3 Neylon AJ, Saunders PW, Howard MR, Proctor SJ, Taylor PR, Northern Region Haematology G. Northern Region Haematology Group. Clinically significant newly presenting autoimmune thrombocytopenic purpura in adults: a prospective study of a population-based cohort of 245 patients. Br J Haematol 2003; 122 (6) 966-974
4 Schoonen WM, Kucera G, Coalson J , et al. Epidemiology of immune thrombocytopenic purpura in the General Practice Research Database. Br J Haematol 2009; 145 (2) 235-244
5 Segal JB, Powe NR. Prevalence of immune thrombocytopenia: analyses of administrative data. J Thromb Haemost 2006; 4 (11) 2377-2383
6 Neunert C, Lim W, Crowther M, Cohen A, Solberg Jr L, Crowther MA. American Society of Hematology. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood 2011; 117 (16) 4190-4207
7 Grimaldi D, Canouï-Poitrine F, Croisille L , et al. Antiplatelet antibodies detected by the MAIPA assay in newly diagnosed immune thrombocytopenia are associated with chronic outcome and higher risk of bleeding. Ann Hematol 2014; 93 (2) 309-315
8 Smith A, Howell D, Patmore R, Jack A, Roman E. Incidence of haematological malignancy by sub-type: a report from the Haematological Malignancy Research Network. Br J Cancer 2011; 105 (11) 1684-1692
9 Soupir CP, Vergilio JA, Kelly E, Dal Cin P, Kuter D, Hasserjian RP. Identification of del(20q) in a subset of patients diagnosed with idiopathic thrombocytopenic purpura. Br J Haematol 2009; 144 (5) 800-802
10 Lacey JV, Penner JA. Management of idiopathic thrombocytopenic purpura in the adult. Semin Thromb Hemost 1977; 3 (3) 160-174
11 Cortelazzo S, Finazzi G, Buelli M, Molteni A, Viero P, Barbui T. High risk of severe bleeding in aged patients with chronic idiopathic thrombocytopenic purpura. Blood 1991; 77 (1) 31-33
12 Guthrie Jr TH, Brannan DP, Prisant LM. Idiopathic thrombocytopenic purpura in the older adult patient. Am J Med Sci 1988; 296 (1) 17-21
13 Kojouri K, Vesely SK, Terrell DR, George JN. Splenectomy for adult patients with idiopathic thrombocytopenic purpura: a systematic review to assess long-term platelet count responses, prediction of response, and surgical complications. Blood 2004; 104 (9) 2623-2634
14 Ghanima W, Godeau B, Cines DB, Bussel JB. How I treat immune thrombocytopenia: the choice between splenectomy or a medical therapy as a second-line treatment. Blood 2012; 120 (5) 960-969
15 Imbach P, Crowther M. Thrombopoietin-receptor agonists for primary immune thrombocytopenia. N Engl J Med 2011; 365 (8) 734-741
16 Bussel JB, Provan D, Shamsi T , et al. Effect of eltrombopag on platelet counts and bleeding during treatment of chronic idiopathic thrombocytopenic purpura: a randomised, double-blind, placebo-controlled trial. Lancet 2009; 373 (9664) 641-648
17 Arnold DM, Kukaswadia S, Nazi I , et al. A systematic evaluation of laboratory testing for drug-induced immune thrombocytopenia. J Thromb Haemost 2013; 11 (1) 169-176
18 Snoeck HW. Aging of the hematopoietic system. Curr Opin Hematol 2013; 20 (4) 355-361
19 Dykstra B, Olthof S, Schreuder J, Ritsema M, de Haan G. Clonal analysis reveals multiple functional defects of aged murine hematopoietic stem cells. J Exp Med 2011; 208 (13) 2691-2703
20 Beerman I, Bock C, Garrison BS , et al. Proliferation-dependent alterations of the DNA methylation landscape underlie hematopoietic stem cell aging. Cell Stem Cell 2013; 12 (4) 413-425
21 Adams J, Palombella VJ, Sausville EA , et al. Proteasome inhibitors: a novel class of potent and effective antitumor agents. Cancer Res 1999; 59 (11) 2615-2622
22 Aster RH. Drug-induced immune thrombocytopenia: an overview of pathogenesis. Semin Hematol 1999; 36 (1 Suppl 1): 2-6
23 Gerson SL, Kaplan SL, Bruss JB , et al. Hematologic effects of linezolid: summary of clinical experience. Antimicrob Agents Chemother 2002; 46 (8) 2723-2726
24 Attassi K, Hershberger E, Alam R, Zervos MJ. Thrombocytopenia associated with linezolid therapy. Clin Infect Dis 2002; 34 (5) 695-698
25 McCune JS, Liles D, Lindley C. Precipitous fall in platelet count with anagrelide: case report and critique of dosing recommendations. Pharmacotherapy 1997; 17 (4) 822-826
26 Murphy MF, Riordan T, Minchinton RM , et al. Demonstration of an immune-mediated mechanism of penicillin-induced neutropenia and thrombocytopenia. Br J Haematol 1983; 55 (1) 155-160
27 Warkentin TE. HIT paradigms and paradoxes. J Thromb Haemost 2011; 9 (Suppl. 01) 105-117
28 Warkentin TE. Heparin-induced thrombocytopenia and its treatment. J Thromb Thrombolysis 2000; 9 (Suppl. 01) S29-S35
29 Warkentin TE. How I diagnose and manage HIT. Hematology (Am Soc Hematol Educ Program) 2011; 2011: 143-149
30 Warkentin TE, Kelton JG. A 14-year study of heparin-induced thrombocytopenia. Am J Med 1996; 101 (5) 502-507
31 Nand S, Wong W, Yuen B, Yetter A, Schmulbach E, Gross Fisher S. Heparin-induced thrombocytopenia with thrombosis: incidence, analysis of risk factors, and clinical outcomes in 108 consecutive patients treated at a single institution. Am J Hematol 1997; 56 (1) 12-16
32 Tardy-Poncet B, Tardy B. Heparin-Induced thrombocytopenia: minimising the risks in the elderly patient. Drugs Aging 2000; 16 (5) 351-364
33 Prandoni P, Siragusa S, Girolami B, Fabris F. BELZONI Investigators Group. The incidence of heparin-induced thrombocytopenia in medical patients treated with low-molecular-weight heparin: a prospective cohort study. Blood 2005; 106 (9) 3049-3054
34 Aster RH, Bougie DW. Drug-induced immune thrombocytopenia. N Engl J Med 2007; 357 (6) 580-587
35 Aster RH, Curtis BR, McFarland JG, Bougie DW. Drug-induced immune thrombocytopenia: pathogenesis, diagnosis, and management. J Thromb Haemost 2009; 7 (6) 911-918
36 Landrum EM, Siegert EA, Hanlon JT, Currie MS. Prolonged thrombocytopenia associated with procainamide in an elderly patient. Ann Pharmacother 1994; 28 (10) 1172-1176
37 Aster RH, Curtis BR, Bougie DW. Thrombocytopenia resulting from sensitivity to GPIIb-IIIa inhibitors. Semin Thromb Hemost 2004; 30 (5) 569-577
38 Curtis BR, Divgi A, Garritty M, Aster RH. Delayed thrombocytopenia after treatment with abciximab: a distinct clinical entity associated with the immune response to the drug. J Thromb Haemost 2004; 2 (6) 985-992
39 Gentilini G, Curtis BR, Aster RH. An antibody from a patient with ranitidine-induced thrombocytopenia recognizes a site on glycoprotein IX that is a favored target for drug-induced antibodies. Blood 1998; 92 (7) 2359-2365
40 Burgess JK, Lopez JA, Gaudry LE, Chong BH. Rifampicin-dependent antibodies bind a similar or identical epitope to glycoprotein IX-specific quinine-dependent antibodies. Blood 2000; 95 (6) 1988-1992
41 Pereira J, Hidalgo P, Ocqueteau M , et al. Glycoprotein Ib/IX complex is the target in rifampicin-induced immune thrombocytopenia. Br J Haematol 2000; 110 (4) 907-910
42 Ahmed A, Stanley AJ. Acute upper gastrointestinal bleeding in the elderly: aetiology, diagnosis and treatment. Drugs Aging 2012; 29 (12) 933-940
43 Triadafilopoulos G. Management of lower gastrointestinal bleeding in older adults. Drugs Aging 2012; 29 (9) 707-715
44 Pautas E, Gouin-Thibault I, Debray M, Gaussem P, Siguret V. Haemorrhagic complications of vitamin k antagonists in the elderly: risk factors and management. Drugs Aging 2006; 23 (1) 13-25
45 Laurent S. Defining vascular aging and cardiovascular risk. J Hypertens 2012; 30 (Suppl): S3-S8
46 Mohebali D, Kaplan D, Carlisle M, Supiano MA, Rondina MT. Alterations in platelet function during aging: clinical correlations with thromboinflammatory disease in older adults. J Am Geriatr Soc 2014; 62 (3) 529-535
47 Zahavi J, Jones NA, Leyton J, Dubiel M, Kakkar VV. Enhanced in vivo platelet “release reaction” in old healthy individuals. Thromb Res 1980; 17 (3-4) 329-336
48 Johnson M, Ramey E, Ramwell PW. Sex and age differences in human platelet aggregation. Nature 1975; 253 (5490) 355-357
49 Sie P, Montagut J, Blanc M , et al. Evaluation of some platelet parameters in a group of elderly people. Thromb Haemost 1981; 45 (3) 197-199
50 Supiano MA, Hogikyan RV. High affinity platelet alpha 2-adrenergic receptor density is decreased in older humans. J Gerontol 1993; 48 (5) B173-B179
51 Supiano MA, Linares OA, Halter JB, Reno KM, Rosen SG. Functional uncoupling of the platelet alpha 2-adrenergic receptor-adenylate cyclase complex in the elderly. J Clin Endocrinol Metab 1987; 64 (6) 1160-1164
52 Reilly IA, FitzGerald GA. Eicosenoid biosynthesis and platelet function with advancing age. Thromb Res 1986; 41 (4) 545-554
53 Modesti PA, Fortini A, Abbate R, Gensini GF. Age related changes of platelet prostacyclin receptors in humans. Eur J Clin Invest 1985; 15 (4) 204-208
54 Chou TC, Yen MH, Li CY, Ding YA. Alterations of nitric oxide synthase expression with aging and hypertension in rats. Hypertension 1998; 31 (2) 643-648
55 Loscalzo J. Nitric oxide insufficiency, platelet activation, and arterial thrombosis. Circ Res 2001; 88 (8) 756-762
56 Bastyr III EJ, Kadrofske MM, Vinik AI. Platelet activity and phosphoinositide turnover increase with advancing age. Am J Med 1990; 88 (6) 601-606
57 Franchini M. Hemostasis and aging. Crit Rev Oncol Hematol 2006; 60 (2) 144-151
58 Conlan MG, Folsom AR, Finch A , et al. Associations of factor VIII and von Willebrand factor with age, race, sex, and risk factors for atherosclerosis. The Atherosclerosis Risk in Communities (ARIC) Study. Thromb Haemost 1993; 70 (3) 380-385
59 Mari D, Coppola R, Provenzano R. Hemostasis factors and aging. Exp Gerontol 2008; 43 (2) 66-73
60 van Loon JE, Kavousi M, Leebeek FW , et al. von Willebrand factor plasma levels, genetic variations and coronary heart disease in an older population. J Thromb Haemost 2012; 10 (7) 1262-1269
61 Hashimoto Y, Kobayashi A, Yamazaki N, Sugawara Y, Takada Y, Takada A. Relationship between age and plasma t-PA, PA-inhibitor, and PA activity. Thromb Res 1987; 46 (5) 625-633
62 Mehta J, Mehta P, Lawson D, Saldeen T. Plasma tissue plasminogen activator inhibitor levels in coronary artery disease: correlation with age and serum triglyceride concentrations. J Am Coll Cardiol 1987; 9 (2) 263-268
63 Yamamoto K, Takeshita K, Kojima T, Takamatsu J, Saito H. Aging and plasminogen activator inhibitor-1 (PAI-1) regulation: implication in the pathogenesis of thrombotic disorders in the elderly. Cardiovasc Res 2005; 66 (2) 276-285
64 Yamamoto K, Takeshita K, Saito H. Plasminogen activator inhibitor-1 in aging. Sem Thromb Hemost 2014; 40 (6) 652-659
65 Zhou H, Fu R, Wang H , et al. Immune thrombocytopenia in the elderly: clinical course in 525 patients from a single center in China. Ann Hematol 2013; 92 (1) 79-87