Page 162 - Williams Hematology ( PDFDrive )

136 Part III: Epochal Hematology Chapter 9: Hematology in Older Persons 137

Inflammation/Coagulation Dysregulation and Frailty 21. Chaves PHM: Functional outcomes of anemia in older adults. Semin Hematol
45(4):255–260, 2008.
Presumably on the basis of chronic inflammatory stimuli, there is an 22. Thein M, Ershler WB, Artz AS, et al: Diminished quality of life and physical function in
age-associated activation of coagulation and fibrinolytic pathways community-dwelling elderly with anemia. Medicine (Baltimore) 88(2):107–114, 2009.
287
232
that favor thrombus formation. Fibrinogen levels are typically high 23. Pawelec G, Larbi A: Immunity and ageing in man: Annual review 2006/2007. Exp Ger-
with more than 80 percent of those age 65 years and older having lev- ontol 43(1):34–38, 2008.
els above 320 mg/dL. Similarly an analysis of D-dimer levels in the 24. Longo DL: Immunology of aging, in Fundamental Immunology, 5th ed, edited by WE
227
Paul, pp 1043–1075. Lippincott, Williams and Wilkins, Philadelphia, 2003.
EPESE, including 1727 community elderly, revealed an age-associated 25. Fulop T, Witkowski JM, Pawelec G, et al: On the immunological theory of aging. Inter-
increase that correlated with declining overall physical function. Fur- discip Top Gerontol 39:163–176, 2014.
215
thermore, when combining D-dimer and IL-6 levels, those individuals 26. Dubrow EL: Reactivation of tuberculosis: A problem of aging. J Am Geriatr Soc
24(11):481–487, 1976.
who had elevations of both were at greatest risk for mortality over a 27. Nagami PH, Yoshikawa TT: Tuberculosis in the geriatric patient. J Am Geriatr Soc
4-year interval. In the Cardiovascular Health Study, which included 31(6):356–363, 1983.
233
relatively healthy elderly, higher fibrinogen and factor VIII levels were 28. Arvin A: Aging, immunity, and the varicella-zoster virus. N Engl J Med 352(22):
2266–2267, 2005.
associated with a greater risk for cardiovascular disease and mortality, 29. Schmader K: Herpes zoster in older adults. Clin Infect Dis 32(10):1481–1486, 2001.
even after adjustment for other cardiovascular risk factors. 232,288 Sum- 30. Arden NH, Patriarca PA, Kendal A: Experiences in the use and efficacy of inactivated
marizing what has now become a robust literature, higher IL-6, TNF-α, influenza vaccine in the nursing home, in Options for the Control of Influenza, edited by
A Kendal, P Patriarca, pp 155–168. Alan Liss, New York, 1986.
D-dimer, and C-reactive protein are each associated with negative phys- 31. Deng Y, Jing Y, Campbell AE, Gravenstein S: Age-related impaired type 1 T cell
iologic consequences, including reduced lower-extremity muscle mass responses to influenza: Reduced activation ex vivo, decreased expansion in CTL culture
and strength, 289,290 cognitive decline, insulin resistance, subclini- in vitro, and blunted response to influenza vaccination in vivo in the elderly. J Immunol
292
291
172(6):3437–3446, 2004.
cal and clinical cardiovascular disease, 293,294 renal insufficiency, loss 32. Hilleman MR: Realities and enigmas of human viral influenza: Pathogenesis, epidemi-
295
of bone mineral density, depression, anemia, dementia, and ology and control. Vaccine 20(25–26):3068–3087, 2002.
235
297
186
296
mortality. As a result, a general consensus has emerged that activated 33. Powers DC, Sears SD, Murphy BR, et al: Systemic and local antibody responses in
289
inflammatory mediators are, at least in part, contributing to the physi- elderly subjects given live or inactivated influenza A virus vaccines. J Clin Microbiol
27(12):2666–2671, 1989.
ology of aging, and to the extent that these pathways are dysregulated, 34. Corthay A: Does the immune system naturally protect against cancer? Front Immunol
important functional outcomes are impaired. 5:197, 2014.
35. Kaesberg PR, Ershler WB. The importance of immunesenescence in the incidence and
malignant properties of cancer in hosts of advanced age. J Gerontol 44(6):63–66, 1989.
REFERENCES 36. Miller RA: The cell biology of aging: Immunological models. J Gerontol 44(1):B4–B8,
1989.
37. Kanapuru B, Simonsick EM, Ershler WB: Is cancer incidence decreased in the frail
1. Kinsella KG: Future longevity-demographic concerns and consequences. J Am Geriatr elderly? Evidence from a prospective cohort study. J Geriatr Oncol 4(1):19–25, 2013.
Soc 53(9 Suppl):S299–S303, 2005. 38. Chan TC, Hung IF, Luk JK, et al: Functional status of older nursing home residents can
2. Olshansky SJ, Goldman DP, Zheng Y, Rowe JW: Aging in America in the twenty-first affect the efficacy of influenza vaccination. J Gerontol A Biol Sci Med Sci 68(3):324–330,
century: Demographic forecasts from the MacArthur Foundation Research Network 2013.
on an Aging Society. Milbank Q 87(4):842–862, 2009. 39. Radl J: Age-related monoclonal gammapathies: Clinical lessons from the aging C57BL
3. Blakely T, Atkinson J, Kvizhinadze G, et al: Health system costs by sex, age and prox- mouse. Immunol Today 11(7):234–236, 1990.
imity to death, and implications for estimation of future expenditure. N Z Med J 40. Korde N, Kristinsson SY, Landgren O: Monoclonal gammopathy of undetermined sig-
127(1393):12–25, 2014. nificance (MGUS) and smoldering multiple myeloma (SMM): Novel biological insights
4. Pallin DJ, Espinola JA, Camargo CA Jr: US population aging and demand for inpatient and development of early treatment strategies. Blood 117(21):5573–5581, 2011.
services. J Hosp Med 9(3):193–196, 2014. 41. Martin GM: The genetics of aging. Hosp Pract (1995) 32(2):47–50, 55–56, 59–61
5. Kinsella K, Velkoff VA: An Aging World. US Government Printing Office, Washington, passim, 1997.
DC, 2001. 42. Burtner CR, Kennedy BK: Progeria syndromes and ageing: What is the connection? Nat
6. Walston J, Hadley EC, Ferrucci L, et al: Research agenda for frailty in older adults: Rev Mol Cell Biol 11(8):567–578, 2010.
Toward a better understanding of physiology and etiology: Summary from the Amer- 43. Yu CE, Oshima J, Fu YH, et al: Positional cloning of the Werner’s syndrome gene.
ican Geriatrics Society/National Institute on Aging Research conference on frailty in Science 272(5259):258–262, 1996.
older adults. J Am Geriatr Soc 54(6):991–1001, 2006. 44. Yu CE, Oshima J, Wijsman EM, et al: Mutations in the consensus helicase domains of
7. Martin GM: The biology of aging: 1985–2010 and beyond. FASEB J 25(11):3756–3762, the Werner syndrome gene. Werner’s Syndrome Collaborative Group. Am J Hum Genet
2011. 60(2):330–341, 1997.
8. Huber KR, Mostafaie N, Stangl G, et al: Clinical chemistry reference values for 75-year- 45. Kudlow BA, Kennedy BK, Monnat RJ Jr: Werner and Hutchinson-Gilford progeria
old apparently healthy persons. Clin Chem Lab Med 44(11):1355–1360, 2006. syndromes: Mechanistic basis of human progeroid diseases. Nat Rev Mol Cell Biol
9. Milman N, Pedersen AN, Ovesen L, Schroll M: Hemoglobin concentrations in 358 8(5):394–404, 2007.
apparently healthy 80-year-old Danish men and women. Should the reference interval 46. Eriksson M, Brown WT, Gordon LB, et al: Recurrent de novo point mutations in lamin
be adjusted for age? Aging Clin Exp Res 20(1):8–14, 2008. A cause Hutchinson-Gilford progeria syndrome. Nature 423(6937):293–298, 2003.
10. Shock NW, Gueulich RC, Andres R: Normal human aging: The Baltimore Longitudinal 47. Cao K, Blair CD, Faddah DA, et al: Progerin and telomere dysfunction collabo-
Study of Aging: NIH Publication No. 84–2450. 1984. rate to trigger cellular senescence in normal human fibroblasts. J Clin Invest 121(7):
11. Harada CN, Natelson Love MC, Triebel KL: Normal cognitive aging. Clin Geriatr Med 2833–2844, 2011.
29(4):737–752, 2013. 48. Kennedy BK, Guarente L: Genetic analysis of aging in Saccharomyces cerevisiae. Trends
12. Lindeman RD: Overview: Renal physiology and pathophysiology of aging. Am J Kidney Genet 12(9):355–359, 1996.
Dis 16(4):275–282, 1990. 49. Szilard L: On the nature of the aging process. Proc Natl Acad Sci U S A 45(1):30–45,
13. Wiggins JE: Aging in the glomerulus. J Gerontol A Biol Sci Med Sci 67(12):1358–1364, 1959.
2012. 50. Morley AA: Is ageing the result of dominant and co-dominant mutations? J Theor Biol
14. Gazit R, Weissman IL, Rossi DJ: Hematopoietic stem cells and the aging hematopoietic 98(3):469–474, 1982.
system. Semin Hematol 45(4):218–224, 2008. 51. Cummings DJ: Mitochondrial DNA in Podospora anserina. A molecular approach to
15. Rossi DJ, Bryder D, Zahn JM, et al: Cell intrinsic alterations underlie hematopoietic cellular senescence. Monogr Dev Biol 17:254–266, 1984.
stem cell aging. Proc Natl Acad Sci U S A 102(26):9194–9199, 2005. 52. Fairweather DS, Fox M, Margison GP: The in vitro lifespan of MRC-5 cells is shortened
16. Sudo K, Ema H, Morita Y, Nakauchi H: Age-associated characteristics of murine by 5-azacytidine-induced demethylation. Exp Cell Res 168(1):153–159, 1987.
hematopoietic stem cells. J Exp Med 192(9):1273–1280, 2000. 53. Burnet M: Intrinsic Mutagenesis: A Genetic Approach for Aging. Wiley, New York, 1974.
17. Beghe C, Wilson A, Ershler WB: Prevalence and outcomes of anemia in geriatrics: A 54. Hart RW, Setlow RB: Correlation between deoxyribonucleic acid excision-repair
systematic review of the literature. Am J Med 116 Suppl 7A:3S-10S, 2004. and life-span in a number of mammalian species. Proc Natl Acad Sci U S A 71(6):
18. Pautas E, Siguret V, Kim TM, et al: Anemia in the elderly: Usefulness of an easy and 2169–2173, 1974.
comprehensive laboratory screen. Ann Biol Clin (Paris) 70(6):643–647, 2012. 55. Orgel LE: The maintenance of the accuracy of protein synthesis and its relevance to
19. Artz AS: Anemia and the frail elderly. Semin Hematol 45(4):261–266, 2008. ageing. Proc Natl Acad Sci U S A 49:517–521, 1963.
20. Makipour S, Kanapuru B, Ershler WB: Unexplained anemia in the elderly. Semin 56. Allsopp RC, Vaziri H, Patterson C, et al: Telomere length predicts replicative capacity of
Hematol 45(4):250–254, 2008. human fibroblasts. Proc Natl Acad Sci U S A 89(21):10114–10118, 1992.
Kaushansky_chapter 09_p0129-0142.indd 137 17/09/15 6:16 pm