Abstract
Although several workers have described numerous changes affecting the hemopoietic system during senescence, the existence of univocal “hematological disease” closely related to the elderly is controversial. Many of the hematological changes described, such as sideropenic or megaloblastic anemia, are frequently the consequence of the different pathological conditions which often affect elderly patients. This review will consider the most important alterations of hemopoiesis and coagulation in the elderly, the causes capable of influencing hematological changes in old people, and their pathogenesis. Some of the major diagnostic problems encountered in the management of elderly subjects with hematological changes are also addressed. In the presence of an elderly patient with hematological alterations, it is necessary to follow a precise diagnostic schedule, which should first of all exclude the presence of a primary hematological disorder, and consider the different extrahematological conditions which frequently occur in elderly subjects (malignancies, malnutrition, chronic infections from immunological abnormalities, hormonal changes, deficiencies of various organs and systems etc.) and are responsible for many different hematological changes. These must be tackled rationally so that treatment may not only be symptomatic, but may also directly intervene on the cause of the disorder.
Similar content being viewed by others
References
Lipschitz D.A., Udupa K.B., Milton K.Y., Thompson C.O.: Effect of age on hematopoiesis in man. Blood 63: 502–509, 1984.
Nilsson-Ehle H., Jagenburg R., Landahl S., Svanborg A., Westin J.: Haematological abnormalities and reference intervals in the elderly. Acta Med. Scand. 224: 595–604, 1988.
Vogel J.M.: Hematologic problems of the aged. Mt. Sinai J. Med. 47: 150–163, 1980.
Lipschitz D.A., Mitchell C.O., Thompson C.: The anemia of senescence. Am. J. Hematol. 11: 47–54, 1981.
Lipschitz D.A., Udupa K.B.: The quantitation of the granu-locytic/macrophage committed progenitor cell (CFUc) in man and the mouse. Exp. Hematol. 9: 723–731, 1981.
Harman S.M., Tsitouras P.D.: Reproductive hormones in aging men. I. Measurement of sex steroids, basal luteinizing hormone, and leydig cell response to human chorionic gonadotropin. J. Clin. Endocrinol. Metab. 51: 35–41, 1980.
Timiras M.L., Brownstein H.: Prevalence of anemia and correlation of hemoglobin with age in a geriatric screening clinic population. J. Am. Geriatr. Soc. 35: 639–643, 1987.
Finch C.A.: Red cell manual. University of Washington, Seattle, 1969, p. 14.
Adler S.S.: Anaemia in the aged: causes and considerations. Geriatrics 33: 49–59, 1980.
Bagicalupo A.: Treatment of severe aplastic anemia. Lectures, XIIIth Meeting of the International Society of Haematology (European & African Division), Istanbul, Turkey, 1995, p.71.
Quaglino D., Hayhoe F.G.J.: Haematological Oncology. Churchill Livingstone, London, Edinburgh, 1992.
Krantz S.B.: Diagnosis and treatment of pure red cell aplasia. Med. Clin. North Am. 60: 945–952, 1976.
Linsk J.A., Murray C.K.: Erythrocyte aplasia and hypogam-maglobulinemia. Ann. Intern. Med. 55: 831–838, 1969.
Mitchell A.B.S., Pinn G., Pegrum G.D.: Pure red cell aplasia and carcinoma. Blood 37: 594–597, 1971.
Marx J.J.M.: Normal iron absorption and decreased red cell iron uptake in the aged. Blood 53: 204–211, 1979.
Dunlop W.M., James G.W., Hume D.M.: Anemia and neu-tropenia caused by copper deficiency. Ann. Intern. Med. 80: 470, 1974.
Badenoch J., Bedford P.D., Evans J.R.: Massive diverticulosis of the small intestine with steatorrhoea and megaloblastic anaemia. Q. J. Med. 24: 321–327, 1955.
Carmel R., Karnaze D.S.: Physician response to low serum cobalamin levels. Arch. Intern. Med. 146: 1161–1165, 1986.
Cooper B.A., Fehedy V., Blanshai P.: Recognition of deficiency of vitamin B12 using measurement of serum concentration. J. Lab. Clin. Med. 107: 447–452, 1986.
Thompson W.G., Babitz L., Cassino C., Freedman M.L., Lipkin M.: Evaluation of current criteria used to measure vitamin B12 levels. Am. J. Med. 82: 291–294, 1987.
Thompson W.G., Freedman M.L.: Vitamin B12 and geriatrics: unanswered questions. Acta Haematol. 82: 169–174, 1989.
Herbert V.: The megaloblastic anemias. Grune and Stratton, New York, 1959.
Herbert V.: Megaloblastic anemias. Lab. Invest. 52: 3–19, 1985.
Lindenbaum J., Healton E.B., Savage D.G., Brust J.G., Garret T.J., Podell E.R., Marcell P.D., Stabler S.P., Allen R.H.: Neuropsychiatric disorders caused by cobalamin deficiency in the absence of anemia or macrocytosis. N. Engl. J. Med. 318: 1720–1728, 1988.
Bergia J.J.: Eva anemia. Postgrad. Med. 77: 253–269, 1985.
Ward H.P., Kurnick J.E., Pisarczyk M.J.: Serum level of erythropoietin in anemia associated with chronic infection malignancy and primary hematologic disease. J. Clin. Invest. 50: 332–336, 1971.
Yawata Y., Howe R., Jacob H.S.: Abnormal red cell metabolism causing hemolysis in uremia: defect potentiated by tap water hemodialysis. Ann. Intern. Med. 79: 362–367, 1973.
Ward H.P., Gordon B., Pickett J.C.: Serum levels of erythropoietin in rheumatoid arthritis. J. Lab. Clin. Med. 74: 93–98, 1969.
Cartwright G.E., Lee G.R.: Annotation: the anemia of chronic disorders. B r. J. Haematol. 21: 147–152, 1971.
Francavilla S.: Alterazioni ematologiche nelle malattie endocrine. In: Quaglino D. (Ed.), Alterazioni ematologiche in Medicina Interna. Piccin Editore, Padova, 1996.
Beregi E., Regius O., Rajczy K.: Comparative study of the morphological changes in lymphocytes of elderly individuals and centenarians. Age Ageing 20: 55–59, 1991.
Traill K.N., Jurgens G., Block G., Huber L., Schonitzer D., Widhalm K., Winter U., Wick G.: Analysis of fluorescent low density lipoprotein uptake by lymphocytes. Paradoxical increase in the elderly. Mech. Ageing Dev. 40: 261–288, 1987.
Hartsock R.J., Smith E.B., Ketter C.S.: Normal variation with aging of the amount of hematopoietic tissue in bone-marrow from anterior iliac crest. Am. J. Clin. Pathol. 43: 325–333, 1965.
Lee M.A., Segal G.M., Bagby G.C.: The hematopoietic microenvironment in the elderly: defects in Il1-induced CSF expression in vitro. Exp. Hematol. 17: 952–956, 1989.
Hellman S., Botnick L.E., Hannon E.C., Vignuelle R.M.: Proliferative capacity of murine hematopoietic stem cells. Proc. Natl. Acad. Sci. USA 75: 490–501, 1978.
Mauch P., Botnick L.E., Hannon E.C., Obbagy J., Hellman S.: Decline in bonemarrow proliferative capacity as a function of age. Blood 60: 245–252, 1982.
Lansdorp P.M.: Telomere length and proliferation potential of hematopoietic stem cells. J. Cell. Sciences 108: 1–6, 1995.
Vaziri H., Schachter F., Uchida I., Wei L., Zhu X., Effros R., Cohen D., Harley C.B.: Loss of telomeric DNA during aging of normal and trisomy 21 human lymphocytes. Am. J. Hum. Genet. 52: 661–667, 1993.
Zsebo K.M., Yuschenkoff V.N., Schiffer S., Chang D., Mc-Call E., Dinarello C.A., Brown M.A., Altrock B., Bagby G.C.: Vascular endothelial cells and granulopoiesis: Interleukin 1 stimulates release of G-CSF and GM-CSF. Blood 71: 99–107, 1988.
Herrmann F., Oster W., Meuer S.C., Lindermann A., Mertelsmann R.H.: Interleukin 1 stimulates lymphocytes to produce granulocyte-monocyte colony-stimulating factor. J. Clin. Invest. 81: 1415–1418, 1988.
Munker R.J., Gasson J., Ogawa M., Koeffler H.P.: Recombinant human TNF induces production of granulocyte-monocyte colony stimulating factor. Nature 323: 79–82, 1986.
Murasko D.M., Weiner P., Kaye D.: Decline in mitogen induced proliferation of lymphocytes with increasing age. Clin. Exp. Immunol. 70: 440–448, 1987.
Gillis S., Kozak R., Durante M., Weksler M.E.: Immunological studies of aging. Decreased production of and response to T cell growth factor by lymphocytes from aged humans. J. Clin. Invest. 67: 937–942, 1981.
Staiano-Coico L., Darzynkiewicz Z., Melamed M.R., Weksler M.E.: Immunological studies of aging. IX. Impaired proliferation of T lymphocytes detected in elderly humans by flow cytometry. J. Immunol. 132: 1788–1792, 1984.
Traill K.N., Ratheiser K., Dietrich M., Sailer S., Zevenbergen J.L., Wicck G.: Lack of correlation between serum cholesterol levels, lymphocyte plasma membrane fluidity and mitogen responsiveness in young and aged chickens. Mech. Ageing Dev. 28: 123–138, 1984.
Gutowski J.K., Innes J., Weksler M.E., Cohen S.: Induction of DNA synthesis in isolated nuclei by cytoplasmic factors. II. Normal generation of cytoplasmic stimulatory factors by lymphocytes from aged humans with depressed proliferative responses. J. Immunol. 132: 559–562, 1984.
Gilman S.C., Rosenberg J.S., Feldman J.D.: T lymphocytes from young and aged rats. II. Functional defects and the role of interleukin 2. J. Immunol. 128: 644–650, 1982.
Cantrell D.A., Smith K.A.: The Interleukin T-cell system: a new cell growth model. Science (Wash. DC) 244: 1312–1316, 1984.
Nagel J.E., Chopra R.K., Chrest F.J., McCoy M.T., Schneider E.L., Holbrook N.J., Adler W.H.: Decreased prolifera-tion, interleukin 2 synthesis, and interleukin 2 receptor expression are accompained by decreased mRNA expression in phytohemagglutinin-stimulated cells from elderly donors. J. Clin. Invest. 81: 1096–1102, 1988.
Rubin L.A., Jay G., Nelson D.L.: The released interleukin 2 receptor binds interleukin 2 efficiently. J. Immunol. 137: 3841–3844, 1986.
Kumar A., Moreau J.L., Baran D., Theze J.: Evidence for negative regulation of T cell growth by low affinity interleukin 2 receptors. J. Immunol. 138: 1485–1493, 1987.
Smith K.A., Cantrell D.A.: Interleukin 2 regulates its own receptors. Proc. Natl. Acad. Sci. USA 82: 864–868, 1985.
Vie H., Miller R.A.: Decline with age, in the proportion of mouse T cells that express Il2 receptors after mitogen stimulation. Mech. Ageing Dev. 33: 313–322, 1986.
Flurkey K., Stadecker M., Miller R.A.: Memory T lymphocyte hyporesponsiveness to non-cognate stimuli: a key factor in age-related immunodeficiency. Eur. J. Immunol. 22: 931–935, 1992.
Krishnaraj R., Blandford G.: Ageassociated alterations in human natural killer cells. I. Increased activity as per conventional and kinetic analysis. Clin. Immunol. Immunopathol. 45: 268–285, 1987.
Crawford J., Cohen H.J.: Aging and neoplasia. Annu. Rev. Gerontol. Geriatr. 4: 3–32, 1984.
Mege J.L., Capo C., Michel B., Gastau J.L., Bongrand P.: Phagocytic cell function in aged subjects. Neurobiol. Aging 9: 217–220, 1988.
Fulop T., Foris G., Worum I., Paragh G., Leovey A.: Age-related variations of some polymorphonuclear leukocyte functions. Mech. Ageing Dev. 29: 1–8, 1985.
Babior B.M.: The respiratory burst of phagocytosis. J. Clin. Invest. 73: 599, 1984.
Lipschitz D.A., Udupa K.B., Indelicato S.R., Das M.: Effect of age on second messenger generation in neutrophils. Blood 78: 1347–1354, 1991.
Beisel W.R.: Single nutrients and immunity. Am. J. Clin. Nutr. 35: 417–468, 1982.
Bogden J.D., Oleske J.M., Munves E.M., Lavenhar M.A., Bruening K.S., Kemp F.W., Holding K.S., Denny T.N., Louria T.B.: Zinc and immunocompetence in the elderly: baseline data on zinc nutriture and immunity in unsupplemented subjects. Am. J. Clin. Nutr. 46: 101–109, 1987.
Bick R.L.: Common bleeding and clotting disorders. Med. Clin. North Am. 78: 3, 1994.
Meade T.W., Vickers M.V., Thrompson S.G., Stirling Y., Haines A.P., Miller G.J.: Epidemiological characteristics of platelet aggregability. B r. Med. J. 290: 428–432, 1985.
Shreiner D.P., Bell W.R.: Pseudothrombocytopenia: manifestation of a new type of platelet agglutinin. Blood 42: 541–547, 1973.
Scott B.D.: Heparin-induced thrombocytopenia. Postgrad. Med. 86: 153–155, 1981.
Ingeberg S., Stofferson E.: Platelet dysfunction in patients with vitamin B12 deficiency. Acta Haematol. 61: 75–79, 1979.
Rutherford C.J., Frenkel E.P.: Thrombocytopenia: issues in diagnosis and therapy. In: R.L. Bick (Ed.), Common bleeding and clotting disorders. Med. Clin. North Am. 78: 555–575, 1994.
Martin J.F., Bath P.M.V., Burr M.L.: Influence of platelet size on outcome after myocardial infarction. Lancet 338: 1409–1411, 1991.
Martin J.F., Shaw T., Heggie J., Penington D.G.: Measurement of the density of human platelets and its relationship to volume. Br. J. Haematol. 54: 337–352, 1983a.
Hendagma P.J., Bainton D.F.: Incorporation of a circulating protein into alpha-granules of megakaryocytes. Blood 15: 59–72, 1989.
Cramer E.M., Debili N., Martin J.F., Gladwin A.M., Breton-Gorius J., Harrison P., Savidge G.F., Vainchenker W.: Uncoordinated expression of fibrinogen compared with thrombos-pondin and von Willebrand factor in maturing human mega-karyocytes. Blood 73:1123–1129, 1989.
Trowbridge E.A., Slater D.N., KishK Y.T., Woodcock B.W.: Platelet production in myocardial infarction and sudden cardiac death. Thromb. Haemost. 52: 2701–2705, 1984.
Martin J.F.: The relationship between platelet volume and megakaryocytes ploidy. Blood Cells 15: 108–117, 1989.
Hoffman R.: Regulation of megakaryocytopoiesis. Blood 74: 1196–1212, 1989.
Arbustini E., Grasso M., Diegli M., Pucci A.: Coronary atherosclerotic plaques with and without thrombus in ischemic heart syndromes: a morphologic, immunohistochemical and biochemical study. Am. J. Cardiol. 68: 36B–49B, 1991.
Smith R.E.A., Martin J.F.: Endogenous mediators and thrombophilia. In: Meade T.W. (Ed.), Thrombophilia. Bailliere’s Clin. Haematol. 7: 485–497, 1994.
Kannel W.B., Wolf P.A., Castelli W.P., D’Agostino R.B.: Fibrinogen and risk of cardiovascular disease. The Framingham study. JAMA 258: 1183–1186, 1987.
Balleisen L., Bailey J., Epping P.H., Shulte H., Van de Loo J.: Epidemiological study on factor VII, factor VIII and fibrinogen in an industrial population. I. Baseline data on the relation to age, gender, body-weight, smoking, alcohol, pillusing and menopause. Thromb. Haemost. 54: 475–479, 1985.
Stegnar M., Keber D., Pentek M.: Age and sex differences in resting and postocclusion values of tissue plasminogen activator in a healty population. Fibrinolysis 2(Suppl. 2): 121–122, 1980.
Bauer K.A., Weiss L.M., Sparrow D., Vokonas P.S., Rosenberg R.D.: Aging associated changes in indices of thrombin generation and protein C activation in humans. Normative Aging Study. J. Clin. Invest. 80: 1527–1534, 1987.
Bauer K.A., Kass B.L., Cate H.C., Hawinger J.J, Rosenberg R.D.: Factor IX is activated in vivo by the tissue factor mechanism. Blood 76: 731–736, 1990.
Cadroy Y., Pierrejean D., Fontan B., Sie P., Boneu B.: Influence of aging on the activity of the haemostatic system: prothrombin fragment 1+2 thrombin-antithrombin III complexes and D-dimers in 80 healthy subjects with age ranging from 20 to 94 years. Nouv. Rev. Fr. Hematol. 34: 43–46, 1992.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Quaglino, D., Ginaldi, L., Furia, N. et al. The effect of age on hemopoiesis. Aging Clin Exp Res 8, 1–12 (1996). https://doi.org/10.1007/BF03340109
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF03340109