Research Article| Volume 30, ISSUE 9, P784-799, September 1945

Problems of erythrocyte disintegration with particular reference to the life span of the red cell

      This paper is only available as a PDF. To read, Please Download here.


      There are three interdependent factors active in maintaining the normal red cell count: erythrocyte production, disintegration, and the life span of the red cell in the circulation. Shortening of the lifetime may be due to endogenous factors (i.e., faulty structure of the erythrocyte, abnormal hemolyzing activities), or may be caused by removal of erythrocytes from the circulation (hemorrhage).
      With different methods, the true average lifetime was found to be from 100 to 120 days in dogs, monkeys, and man. Under strictly physiologic conditions, the disappearance of the red cells depends on their age. If pathologic mechanisms are at work, they concur with the physiologic processes and destroy the erythrocytes at random, irrespective of their age. The method of cross-determination of the lifetime of the erythrocytes (i.e., the survival time of normal cells in a patient with à hematologic disorder and of this patient's erythrocytes in a normal individual) demonstrates whether the cause of a disorder is due to an extra- or an intracorpuscular abnormality.
      The lifetime of the red cells before and after splenectomy in dogs was found to be practically identical. After splenectomy the red cell population contained numerous target cells with increased resistance to hypotonic saline solutions; the longevity of these abnormally shaped cells is not prolonged.
      Participation of the spleen in physiologic blood destruction seems to be absent or negligible. In certain hemolytic anemias (familial spherocytic jaundice, acquired hemolytic anemia) splenic hemolysis is present; it is selective, conditioned by abnormal properties of the erythrocytes which circulate through the organ. No evidence is available for the existence of a primary hemolytic “hypersplenism.” The diminution of the pigment excretion observed after splenectomy in human beings is not indicative of a decrease of blood destruction.
      The hemolytic syndromes may be classified in two main groups: (1) disorders due to a variety of substances which, by acting on the red cells, injure their structure, and (2) diseases in which there are various and characteristic structural defects present in the red cells at the start of their life. The physicochemical changes responsible for the different structural alterations are unknown. Defective cells usually, but not always, have a shortened life span. Some defects make cells vulnerable to physiologic mechanisms.
      Structural defects manifest themselves morphologically by changes in size, shape, and volume of the red cells, or functionally in such a way that pathologic cells, when injured by different substances, react differently (differential fragility). The many factors which cause pathologic hemolysis seem always to be qualitatively different from those responsible for the physiologic disintegration of the erythrocytes. However, if aging of the cell means physicochemical change in its structure, then physiologic and pathologic disintegration could be correlated in the future when a better knowledge of the characteristics of the various cell alterations may become available.
      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 access
      One-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 to Translational Research
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Singer K.
        • Miller E.B.
        • Dameshek W.
        Hematological Changes Following Splenectomy in Man.
        Am. J. M. Sc. 1941; 202: 171
        • Miller E.B.
        • Singer K.
        • Dameshek W.
        Use of the Daily Fecal Output of Urobilinogen and the Hemolytic Index in the Measurement of Hemolysis.
        Arch. Int. Med. 1942; 70: 722
        • Heath C.W.
        • Daland G.A.
        The Life of the Reticulocyte.
        Arch. Int. Med. 1930; 46: 533
        • Cruz W.O.
        Acetylphenylhydrazine Anemia.
        Am. J. M. Sc. 1941; 202: 781
        • Watson C.J.
        The Average Daily Elimination of Urobilinogen in Health and Disease.
        Arch. Int. Med. 1931; 47: 698
        • Gibson II, J.G.
        • Evans W.A.
        Clinical Studies of the Blood Volume.
        J. Clin. Investigation. 1937; 16: 301
        • Hawkins W.B.
        • Whipple G.H.
        The Life Cycle of the Red Blood Cell in the Dog.
        Am. J. Physiol. 1938; 122: 418
      1. Singer, K., and Weisz, L.: The Life Cycle of the Erythrocyte After Splenectomy and the Problems of Splenic Hemolysis and Target Cell Formation, Am. J. M. Sc. In press.

        • Harne O.G.
        • Lutz J.F.
        • Zimmerman G.J.
        • Davis C.L.
        The Life Duration of the Red Blood Cell in the Macacus Rhesus Monkey.
        J. Lab. & Clin. Med. 1945; 30: 247
        • Callender T.Sh.
        • Powell E.O.
        • Witts L.J.
        The Life Span of the Red Cell in Man.
        J. Path. & Bact. 1945; 57: 129
        • Ashby W.
        Determination of Length of Life of Transfused Blood Corpuscles in Man.
        J. Exper. Med. 1919; 29: 267
        • Wiener A.S.
        Blood Groups and Transfusions.
        ed. 3. Charles C Thomas, Springfield1943
        • Mollison P.L.
        • Young M.
        On Survival of Transfused Erythrocytes of Stored Blood.
        Quart. J. Exper. Physiol. 1941; 30: 313
        • Baar H.S.
        • Lloyd T.W.
        Studies in the Anemias of Infancy and Early Childhood. XIV: The Fate of the Transfused Erythrocyte.
        Arch. Dis. Child. 1943; 18: 124
        • Brown G.M.
        • Hayward O.C.
        • Powell E.O.
        • Witts L.J.
        The destruction of Transfused Erythrocytes in Anemia.
        J. Path. & Bact. 1944; 56: 81
        • Lloyd T.W.
        On the Etiology of Acholuric Family Jaundice.
        in: Thesis. Oxford University, 1941
        • Dacie J.V.
        • Mollison P.L.
        Survival of Normal Erythrocytes After Transfusion to Patients With Familial Hemolytic Anemia.
        Lancet. 1943; 244: 550
        • Dameshek W.
        • Schwartz S.O.
        Acute Hemolytic Anemia.
        Medicine. 1940; 19: 231
        • Krumbhaar E.B.
        Functions of the Spleen.
        Physiol. Rev. 1926; 6: 160-200
        • Krumbhaar E.B.
        Changes Produced in the Blood Picture by Removal of the Normal Mammalian Spleen.
        Am. J. M. Sc. 1932; 184: 215
        • Lauda E.
        Physiologie der Milz.
        Urban & Schwarzenberg, Berlin1933
        • Dacie J.V.
        Familial Hemolytic Anemia.
        Quart. J. Med. 1943; 46: 101
        • Loewy A.
        • Freeman L.W.
        • Marchello A.
        • Johnson V.
        Increased Erythrocyte Destruction on High Fat Diet.
        Am. J. Physiol. 1943; 138: 230
        • Klemperer P.
        The Spleen.
        in: Handbook of Hematology. Paul B. Hoeber, Incorporated, New York1938
        • Knisely M.H.
        Spleen Studies I and II.
        Anat. Rec. 1936; 65: 23
        • Knisely M.H.
        Spleen Studies I and II.
        Anat. Rec. 1936; 65: 131
        • Singer K.
        Lysolecithin and Hemolytic Anemia.
        J. Clin. Investigation. 1941; 20: 153
        • Farley N.H.
        Quart. J. Med. 1941; 1: 95
        • Farley N.H.
        Quart. J. Med. 1941; 1: 115
        • Watson C.J.
        Bile Pigments.
        New England J. Med. 1942; 227: 665
        • Watson C.J.
        Bile Pigments.
        New England J. Med. 1942; 227: 705
        • Lemberg R.
        Animal Pigments.
        Ann. Rev. Biochem. 1938; 7: 421
        • Drabkin D.L.
        Animal Pigments.
        Ann. Rev. Biochem. 1942; 11: 531
        • Haurowitz F.P.
        • Schwerin P.
        • Yenson M.M.
        Destruction of Hemin and Hemoglobin by the Action of Unsaturated Fatty Acids and Oxygen.
        J. Biol. Chem. 1941; 140: 353
        • Watson C.J.
        Ueber Stercobilin und Porphyrine aus Kot.
        Ztschr. f. physiol. Chem. 1932; 204: 57
        • Eppinger H.
        Die hepatolinealen Erkrankungen.
        Julius Springer, Berlin1920
        • Morawitz P.
        Zur Pathogenese der Anaemia perniciosa.
        Deutsches Arch. f. klin. Med. 1928; 159: 85
        • Heilmeyer L.
        Die haemolytische Hypersplenie.
        Deutsches Arch. f. klin. Med. 1935; 178: 89
        • Ham Th.H.
        • Dingle J.H.
        Studies on Destruction of the Red Blood Cells. II.
        J. Clin. Investigation. 1939; 18: 657
        • Dameshek W.
        • Schwartz S.O.
        Hemolysins as the Cause of Clinical and Experimental Hemolytic Anemia.
        Am. J. Med. Sc. 1938; 196: 769
        • Ponder E.
        The Physical Structure of the Red Cell Membrane With Special Reference to Its Shape.
        Faraday Soc. 1937; 33: 947
        • Ponder E.
        Quantitative Aspects of the Disk-Sphere Transformation Produced by Lecithin.
        J. Exper. Biol. 1942; 19: 220
        • Singer K.
        The Lysolecithin Fragility Test.
        Am. J. M. Sc. 1940; 199: 466
        • Foy H.
        • Kondi A.
        • Moumjidis A.
        Transfusion of Blackwater Fever Blood Into Normal Individuals During Hemolytic Crisis.
        Tr. Roy. Soc. Trop. Med. & Hyg. 1941; 35: 119
        • Bauer J.
        Sickle Cell Disease.
        Arch. Surg. 1940; 41: 1344
        • Haden R.L.
        Hemolytic Anemia.
        J. Lab. & Clin. Med. 1940; 26: 65
        • Whipple A.O.
        Recent Studies in the Circulation of the Portal Bed and of the Spleen in Relation to Splenomegaly.
        Tr. Coll. Phys. Philadelphia. 1941; 8: 203
        • Ham T.H.
        • Castle W.B.
        Relation of Increased Hypotonic Fragility and of Erythrostasis to the Mechanism of Hemolysis in Certain Anemias.
        in: Proc. Am. Phil. Soc. 82. 1938: 411
        • Haden R.L.
        The Mechanism of the Increased Fragility of the Erythrocytes in Congenital Hemolytic Jaundice.
        Am. J. M. Sc. 1934; 188: 441
        • Dameshek W.
        Familial Mediterranean Target Oval Cell Syndromes.
        Am. J. M. Sc. 1943; 205: 643
        • Dameshek W.
        • Schwartz S.O.
        • Singer K.
        Spherocytosis (and Increased Erythrocyte Fragility) as Indicators of Hemolytic Activity, With Consideration of “Differential Fragility”.
        J. Clin. Investigation. 1939; 18: 479
        • Foy H.
        • Kondi A.
        Lysolecithin Fragility in Blackwater Fever and Haemolytic Jaundice.
        Tr. Roy. Soc. Trop. Med. & Hyg. 1943; 37: 1
        • Erlsbacher O.
        • Kindermann F.
        Die saponinresistenz des Erythrocyten bei der Anaemia perniciosa.
        Ztschr. f. d. ges. exper. Med. 1931; 75: 454
        • Ham Th.H.
        Studies on Destruction of Red Blood Cells.
        Arch. Int. Med. 1939; 64: 1271
        • Hegglin R.
        • Maier C.
        Heat Resistance of Erythrocytes.
        Am. J. M. Sc. 1944; 207: 624
        • Minot G.R.
        • Castle W.B.
        Editorial Remark.
        in: Yearbook of General Medicine. The Year Book Publishers, Incorporated, Chicago, Illinois1944: 353
        • Shen S.C.
        • Ham T.H.
        Studies in the Destruction of Red Blood Cells. III. Mechanism and Complications of Hemoglobinuria in Patients With Thermal Burns: Spherocytosis and Increased Osmotic Fragility of Red Blood Cells.
        New England J. Med. 1943; 229: 701
        • Doan C.A.
        The Reticulo-Endothelial System: Its Physiology and Pathology.
        J. Lab. & Clin. Med. 1940; 26: 89
        • Valentine W.N.
        • Neel J.V.
        Hematologic and Genetic Study of the Transmission of Thalassemia.
        Arch. Int. Med. 1944; 74: 185
        • Wintrobe M.M.
        • Matthews E.
        • Pollack R.
        • Dobryns G.M.
        A Familial Hemopoietic Disorder in Italian Adolescents and Adults Resembling Mediterranean Disease (Thalassemia).
        J. A. M. A. 1941; 114: 1530
        • Smith C.H.
        Familial Blood Studies in Cases of Mediterranean (Cooley's) Anemia.
        Am. J. Dis. Child. 1943; 65: 681