Evidence of Phylogenetic Canalisation of the Circulating Platelet Mass in Man

Summary

Phylogenetically mammalian platelets are an apocrine secretion from nucleated thrombocytes, and biologically the number of circulating fragments is irrelevant compared with their total mass and biochemical function. The literature on human genetic derangements affecting the circulating platelet mass is reviewed. The product of platelet count and platelet volume is shown to be “canalised” since many congenital forms of thrombocytopenia are associated with a reciprocal increase in the mean platelet volume. Considerations of platelet size are essential since macrothrombocytopenia is a racial characteristic of many Mediterranean peoples and probably also occurs frequently in others races. The location of platelet disorders in relation to the phylogenetic canal provides an objective classification which has diagnostic, therapeutic and prognostic significance.

^* Current address : Division of Hematology, AA 512 University Hospital, Seattle, Washington 98105 U.S.A.

• References

• 1 Yamada E. The Fine Structure of the Megakaryocyte in the Mouse Spleen. Acta anat. (Basel) 29: 267 1957;
• 2 Paulus J. Multiple Differentiation in Megakaryocytes and Platelets. Blood 29: 407 1967;
• 3 von Behrens W. E, Lander H. The Log-Normal Distribution with particular reference to platelets. Proc. Aust. Soc. med. Res 02: 380 1970; (Abstract.)
• 4 Lautz E. Statistische Grenzen von Asche und Staub Verteilungen. Braunkohle, Wärme und Energie 19: 233 1967;
• 5 Tocantins L. M. The Mammalian Blood Platelet in Health and Disease. Medicine 17: 155 1938;
• 6 Stahl R. Über die Blutplättchen bei Infektions- und Blutkrankheiten, insbesondere über die unreifen pathologischen Plättchenformen (Thromboblasten). Z. klin. Med 96: 182 1923;
• 7 van Allen G. M. Volume Measurement of Blood Platelets. J. Lab. clin. Med 12: 282 1926;
• 8 Hirsch E. O, Dameshek W. “Idiopathic” Thrombocytopenia: Review of 89 Cases with Particular Reference to Differentiation of Acute (Self-Limited) and Chronic Types. Arch, intern. Med 88: 701 1951;
• 9 Cohen P, Gardner F. H, Barnett G. O. Reclassification of the Thrombocytopenias by the Cr⁵¹-labeling method for Measuring Platelet Life Span. New Engl. J. Med 264: 1294 1961;
• 10 Harker L. A. Platelet Production. New Engl. J. Med 282: 492 1970;
• 11 Quick A. J. Hemostasis as an Evolutionary Development. Thrombos. Diathes. haemorrh. (Stuttg) 18: 1 1967;
• 12 Stokes E. E, Firkin B. G. Studies of the Peripheral Blood of the Port Jackson Shark (Heterodontus portusjacksoni) with Patricular Reference to the Thrombocyte. Brit. J. Haemat 20: 427 1971;
• 13 Betances L. M. Sur l’existence de plaquettes chez l’astacus fluviatilis. C.R. Acad. Sei 171: 320 1920;
• 14 Undritz E, Nusselt-Bohaumilitzky K. Über das Auftreten von diploiden Megakary oblas ten, Promegakaryozyten und Megakaryozyten bei schweren Hämopathien, ein Rückgriff in die Pylogenese. Blut 20: 242 1970;
• 15 Weiner W. Anomalies héréditaires des cellules du sang. Rev. Hémat. (Paris) 05: 644 1950;
• 16 Nakeff A, Ingram M. Platelet Count: Volume Relationship in Four Mammalian Species. J. appl. Physiol 28: 530 1970;
• 17 von Behrens W. E, Lehman R. G, Lander H. Genetic Variations in the Platelet Count. Volume Relationship. (In press.)
• 18 Falconer D. S. Introduction to Quantitative Genetics, ch. 17—20. Oliver and Boyd, Edinburgh. 1960
• 19 von Behrens W. E, Lander H. Observations on Platelet “Anisocytosis”. Proc. Aust. Soc. med. Res 02: 378 1970; (Abstract.)
• 20 Breddin K. I. Thrombozytenzählung und Thrombozytenausbreitung. Ärztl. Lab 14: 338 1968;
• 21 Morley A, King-Smith E. A, Stohlman Jr. F. The Oscillatory Nature of Hemopoiesis. In Hemopoietic Cellular Proliferation. 3 Stohlman Jr. F. (Ed.) Grüne & Stratton Inc; New York: 1970
• 22 Fisher R. A. The Use of Multiple Measurements in Taxonomie Problems. Ann. Eug 07: 179 1936;
• 23 Rodwan A. S, Hake H. W. The discrimination Function as a Model for Perception. Amer. J. Psychol 77: 380 1964;
• 24 Hathaway W. E. Bleeding Disorders Due to Platelet Dysfunction. Amer. J. Dis. Child 121: 127 1971;
• 25 Baldini M. G, Steiner M. Thrombocytopathies with or without Thrombocytopenia. New Engl. J. Med 281: 904 1969;
• 26 Hardisty R. M, Hutton R. A. Bleeding Tendency Associated with a “New” Abnormality of Platelet Behaviour. Lancet I: 983 1967;
• 27 Weiss H. J. Aspirin Ingestion Compared with Bleeding Disorders - Search for a Useful Platelet Antiaggregant. Blood 35: 333 1970;
• 28 Caen J. Thrombopathie et Thrombasthenie. Schweiz, med. Wschr 98: 1641 1968;
• 29 Caen J. P, Castaldi P. A, LeClerc J. C, Inceman S, Larrieu M. J, Probst M, Bernard J. Congenital Bleeding Disorders with Long Bleeding Time and Normal Platelet Count. I. Glanzmann’s Thrombasthenia (Report of Fifteen Patients). Amer. J. Med 41: 4 1966;
• 30 Gross R, Niemeyer G, Reuter H. Ein methodischer Beitrag zur Funktionsprüfung menschlicher Blutplättchen unter standardisierten Bedingungen. Dtsch. med. Wschr 94: 1735 1969;
• 31 Epstein R. D, Lozner E. L, Cobbey T. S, Davidson C. S. Congenital Thrombocytopenic Purpura. Purpura Hemorrhagica in Pregnancy and in the Newborn. Amer. J. Med 09: 44 1950;
• 32 Bonnin J. A. A Serum Anti-Platelet-Thromboplastic Factor in Thrombocytopenia and the Effects of Cortisone. Brit. J. Haemat 02: 160 1956;
• 33 Bonnin J. A. The Management of Thrombocytopenic States with Particular Reference to Platelet Thromboplastic Function I. Idiopathic and Secondary Thrombocytopenic Purpura. Brit. J. Haemat 07: 250 1961;
• 34 Estes J. W. Modern Concepts of the Platelet in Health and Disease. Part II. Boston med. Quart 14: 19 1963;
• 35 Hardisty R. M, Ingram G. I. C. Bleeding Disorders. 217 Blackwell Scientific Publications; Oxford: 1965
• 36 De Gruchy G. C, Dacie J. V. Clinical Haematology in Medical Practice. 549 Blackwell Scientific Publications; Oxford: 1966
• 37 Breckenridge R. T, Moore R. D. O, Ratnoff D. A Study of Thrombocytopenia. New Histologic Criteria for the Differentiation of Idiopathic Thrombocytopenia and Thrombocytopenia Associated with Disseminated Lupus Erythematosus. Blood 30: 39 1967;
• 38 Cullum C, Cooney D. P, Schrier S. L. Familial Thrombocytopenic Thrombocytopathy. Brit. J. Haemat 13: 147 1967;
• 39 Murphy S, Oski F. A, Gardner F. H. Hereditary Thrombocytopenia with an Intrinsic Platelet Defect. New Engl. J. Med 281: 857 1969;
• 40 Dincol K, Aksoy M. On the Platelet Levels in Chronic Iron Deficiency Anaemia. Acta haemat. (Basel) 41: 135 1969;
• 41 Jackson J. M, Knight D. Stomatocytosis in Migrants of Mediterranean Origin. Med. J. Aust 01: 315 1969; (Letter.)
• 42 Duckmanton J. Stomatocytosis in Migrants of Mediterranean Origin. Med. J. Aust 01: 1332 1969; (Letter.)
• 43 Ducrou W, Kimber R. J. Stomatocytosis, Haemolytic Anaemia and Abdominal Pain in Mediterranean Migrants: Some Examples of a New Syndrome ? Med. J. Aust 02: 1087 1969;
• 44 von Behrens W. E, Lander H. Mediterranean Macrothrombocytopenia Masquerading as Acute Idiopathic Thrombocytopenic Purpura. Proc. Aust. Soc. med. Res 02: 378 1970;
• 45 Sterling R. K, Ducrou W, Lander H, von Behrens W. E. The Relationship of Stomatocytosis to the Presence of Macrothrombocytes and Thrombocytopenia in Subjects of Mediterranean Extraction. Proc. Aust. Soc. med. Res 02: 374 1970; (Abstract.)
• 46 von Behrens W. E, Sterling R. K, Lander H. Macrothrombocytes and Thrombocytopenia — A Variant in Healthy Greek and Italian Subjects. Pathology 03: 78 1971; (Abstract.)
• 47 Pembrey R. G, Handley D. A, Kirnber R. J. Causes of Thrombocytopenia in a Hospital Population. A Six Months Survey of 7,570 Patients. Med. J. Aust 01: 583 1971;
• 48 Radkewitsch R. A, Gorkina S. N. Beitrag zur Kenntnis des Ca-Gehalts und der Blutplättchenzahl im Blute von Mongolen. Z. Rassenphysiol 06: 23 1933;
• 49 von Behrens W. E, Lander H. A Geographical or Genetic Gradient in the Platelet Count, Mean Platelet Volume and Spleen Weight of Apparently Healthy Subjects from Northern and Southern Europe. (In press.)
• 50 Rebuck J. W, Riddle J. M, Brown M. G, Johnson M. G, Monto R. W. Volumetric and Ultrastructural Studies of Abnormal Platelets. In: Blood Platelets. 533 Johnson S. A, et a. l. ed. Churchill; London: 1961
• 51 Heqqlin R, Gross R, Löhr G. W. Anomalie Hegglin-May (polyphyle Reifungsstörung). Schweiz, med. Wschr 94: 1357 1964;
• 52 Wassmuth D. R, Hamilton H. E, Shells R. F. May-Hegglin Anomaly. Hereditary Affection of Granulocytes and Platelets. J. Amer. med. Ass 183: 737 1963;
• 53 Jordan S. W, Larsen W. E. Ultrastructural Studies of the May-Hegglin Anomaly. Blood 25: 921 1965;
• 54 Davis J. W, Wilson S. J. Platelet Survival in the May-Hegglin Anomaly. Brit. J. Haemat 12: 61 1966;
• 55 Lusher J. M, Schneider J, Mizukami I, Evans R. K. The May-Hegglin Anomaly: Platelet Function Ultrastructure and Chromosome Studies. Blood 32: 950 1969;
• 56 Lechner K, Breddin K, Moser K, Stockinger L, Wenzel E. May-Hegglinische Anomalie. Acta haemat. (Basel) 42: 303 1969;
• 57 Beck E. A, Baumgartner H. R. Zur Frage der Trombopathie bei May-Hegglin-Anomalie. Schweiz, med. Wschr 100: 330 1970;
• 58 Jenis M. EH, Takeuchi A, Dillon D. E, Ruymann F. B, Rivkin S. The May-Hegglin - Anomaly: Ultrastructure of the Granulocytic Inclusion. Amer. J. clin. Path 55: 187 1971;
• 59 Olef I. The Enumeration of Blood Platelets. J. Lab. clin. Med 20: 416 1934;
• 60 Bigel P, Lellouch J, Mayer S, Waitz R. Les variations pathologiques des diamètres thrombocytaires. Nouv. Rev. franç. Hémat 07: 903 1967;
• 61 Revol L. Etude critique des diathese hémorragiques d’origine plaquettaire. Les thrombo- cytopathies constitionelles. Actualités hémat 01: 165 1950;
• 62 Walther G. Über eine erbliche Thrombopathie mit Neigung zur Thrombopenie. Z. ges. inn. Med 08: 221 1953;
• 63 Quittner H. Hereditary Thrombocytopenia: A New Disease Entity. Proc. 6th Int. Congr. Hematol; Boston: 1956: 901.
• 64 Hemmeler G. Thrombopathie familiale. Schweiz, med. Wschr 88: 1018 1958;
• 65 Krick W, Jürgens R, Hiepler E. Gerinnungsphysiologische Untersuchungen beim familiären Morbus Werlhof. Klin. Wschr 37: 865 1959;
• 66 Larrain G, Etcheverry R. Thrombopenia Thrombopatia Familiar. Rev. méd. Chile 90: 162 1962;
• 67 Lacombe M, D’Angelo G. Études sur une Thrombopathie Familiale. Nouv. Rev. franç. Hémat 03: 611 1963;
• 68 Quick A. J, Hussey G. V. Hereditary Thrombopathie Thrombocytopenia. Amer. J. med. Sei 245: 643 1963;
• 69 Seip M. Hereditary Hypoplastic Thrombocytopenia. Acta pediat. scand 52: 370 1963;
• 70 Bethard W. F, Boyer J. L. Familial Thrombocytopenia. J. Lab. clin. Med 64: 842 1964;
• 71 Bithell T. G, Didisheim P, Cartwright G. E, Wintrobe M. M. Thrombocytopenia Inherited as an Autosomal Dominant Trait. Blood 25: 231 1958;
• 72 Seip M, Kjaerheim A. A Familial Platelet Disease - Hereditary Thromboasthénie Thrombopathie Thrombocytopenia. Scand. J. clin. Lab. Invest. Suppl 84: 159 1965;
• 73 Kurstjens R, Bolt C, Vossen M, Haanen G. Familial Thrombopathie Thrombocytopenia. Brit. J. Haemat 15: 305 1968;
• 74 Harris S, Babcock D. G. Hereditary Thrombopathy Associated with Menorrhagia and Gastrointestinal Bleeding. Ann. Surg 165: 377 1967;
• 75 Stockinger L, Weissei M, Lechner K. Thrombozytenpräparation und Auswertung. Mikroskopie 25: 362 1969;
• 76 Stavem P, Jeremic M, Hjort P. F, WislöjJ F, Vogt E, Öyen R, Abrahamsen A. F, Sövde A. Hereditary Thrombocytopenia with Excessively Prolonged Bleeding Time. Scand. J. Haemat 06: 250 1969;
• 77 Baadenhuysen H, Hirschhäuser R, Kurstjens M, Ewals C. Haanen. Metabolic Observations on Platelets from Patients with Familial Thrombopathie Thrombocytopenia. Brit. J. Haemat 20 4, 11 1971;
• 78 Bernard J, Soulier J. P. Sur une nouvelle variété de dystrophie thrombocytaire hémor- rhagipare congenitale. Sem. Hôp. (Par) 24: 3217 1948;
• 79 Hirsch S, Favre-Gilly J, Dameshek W. Thrombopathie Thrombocytopenia. Successful Transfusion of Blood Platelets. Blood 05: 568 1950;
• 80 Bernard J, Caen J, Maroteau P. La dystrophie thrombocytaire hémorragipare congenitale. Rev. Hémat 12: 222 1957;
• 81 Niewjarowski S, Poplawski A, Prokopowicz J, Kanska B, Lechner K, Stockinger L. Abnormalities of Platelet Function and Ultrastructure in Macrothrombocytic Thrombo- pathia. Scand. J. Haemat 06: 377 1969;
• 82 Gröttum K. A, Solum N. O. Congenital Thrombocytopenia with Giant Platelets: A Defect in the Platelet Membrane. Brit. J. Haemat 16: 277 1969;
• 83 Kashiwagi H, Riddle J. M, Abraham J. P, Frame B. Functional and Ultrastructural Abnormalities of Platelets in Ehlers-Danlos Syndrome. Ann. intern. Med 63: 249 1965;
• 84 Estes J. W, Carey R. J, Desai R. G. Marfan’s Syndrome. Hematological Abnormalities in a Family. Arch, intern. Med. (Chic) 116: 889 1965;
• 85 Hathaway W. E, Solomons C. C, Ott J. Abnormalities of Platelet Function in Osteogenesis Imperfecta. Clin. Res 18: 209 1970;
• 86 Myllylä G, Pelkonen R, Ikkala E, Apajalahti J. Hereditary Thrombocytopenia: Report of Three Families. Scand. J. Haemat 04: 441 1967;
• 87 Sheth N. K, Prankerd T. A. J. Inherited Thrombocytopenia with Thrombasthenia. J. clin. Path 21: 154 1968;
• 88 Roberts M. H, Smith M. H. Thrombopénie Purpura: Report of Four Cases in One Family. Amer. J. Dis. Child 79: 820 1950;
• 89 Ata M, Fisher O. D, Holman C. A. Inherited Thrombocytopenia. Lancet I: 119 1965;
• 90 Schaar F. E. Familial Idiopathic Thrombocytopenic Purpura. J. Pediat 62: 546 1963;
• 91 Vestermark B, Vestermark S. Familial Sex-Linked Thrombocytopenia. Acta pediat. scand 53: 365 1964;
• 92 Canales L, Mauer A. M. Sex-Linked Hereditary Thrombocytopenia as a Variant of Wiskott-Aldrich Syndrome. New. Engl. J. Med 277: 899 1967;
• 93 Shulman I, Pierce M, Lukens A, Currimbhoy Z. Studies on Thrombopoiesis. I. A Factor in Normal Human Plasma Required for Platelet Production; Chronic Thrombocytopenia due to its Deficiency. Blood 16: 943 1960;
• 94 Borsai G, Szentkiralyi I.O, Metz B. Chediak-Steinbrink-Anomalie. Blut 19: 482 1969;
• 95 Dawson J. P. Congenital Pancytopenia Associated with Multiple Congenital Anomalies (Fanconi type) : Review of the Literature and Report of a Twenty-Year Old Female with a Ten-Year Follow-Up and Apparently Good Response to Splenectomy. Pediatrics 15: 325 1955;
• 96 Gross H, Groh C, Weippl G. Kongenitale Hypoplastische Thrombopenie mit Radius- aplasi. Neue öst. Z. Kinderheilk 01: 574 1956;
• 97 Bell D. A, Mold J. W, Oliver R. A. M, Shaw S. Study of Transfused Platelets in a Case of Congenital Hypoplastic Thrombocytopenia. Brit. med. J 02: 692 1956;
• 98 Shaw S, Oliver R. M. A. Congenital Hypoplastic Thrombocytopenia with Skeletal Deformities in Siblings. Blood 14: 374 1959;
• 99 Fanconi G. Familiäre infantile perniziosaartige Anämie. Jb. Kinderheilk 117: 257 1927;
• 100 Bloom G. E, Warner S, Gerald P. S, Diamond L. K. Chromosome Abnormalities in Constitutional Aplastic Anemia. New Engl. J. Med 274: 8 1966;
• 101 Wiskott A. Familiärer angeborener Morbus Werlhoff? Mschr. Kinderheilk 68: 212 1937;
• 102 Aldrich R. A, Steinberg A. G, Campbell D. G. Pedigree Demonstrating Sex-Linked Recessive Condition Characterised by Draining Ears, Eczematoid Dermatitis and Bloody Diarrhea. Pediatrics 13: 133 1954;
• 103 Krivit W, Good R. A. Aldrich’s Syndrome (Thrombocytopenia, Eczema, and Infection in Infants) : Studies of Defense Mechanisms. J. Dis. Child 97: 137 1959;
• 104 Motulsky A. G. Mutations and Sex-Linked Thrombocytopenia. Lancet II: 1449 1960;
• 105 Wolff J. A. Wiskott-Aldrich Syndrome - Clinical, Immunologic, and Pathologic Observations. J. Pediat 70: 221 1967;
• 106 Gröttum K. A, Hovig T, Holmsen H, Abrahamsen A, Jeremic M, Seip M. Wiskott-Aldrich Syndrome: Qualitative Platelet Defects and Short Platelet Survival. Brit. J. Haemat 17: 373 1969;
• 107 Kuramoto A, Steiner M, Baldini M. G. Lack of Platelet Response to Stimulation in the Wiskott-Aldrich Syndrome. New Engl. J. Med 282: 475 1970;
• 108 Gondsmit A. M, Leeuwen V, James J. Döhle Bodies and Acute Myeloblastic Leukaemia in One Family. A New Familial Disorder ? Brit. J. Haemat 20: 557 1971;
• 109 Eeaston J. A, Fessas C. The Incidence of Döhle Bodies in Various Diseases and their Association with Thrombocytopenia. Brit. J. Haemat 12: 54 1966;
• 110 Scheurlen P. G, Schneider W, Klemm D, Gross R. Monoklonale (L-Ketten) Gammopathie mit Riesenplättchen-Thrombocytopathie. Klin. Wschr 48: 699 1970;
• 111 Bussi L, Jean G, Le Coultre L. Ultrastructural Aspects of Platelets and Megakaryocytes in a Case of ‘Primary’ Thrombocythaemia. Acta haemat. (Basel) 35: 113 1966;
• 112 Simar L. J, Hughes J. Ultrastructure des plaquettes dans deux cas de thrombocythemie. Actahaemat. (Basel) 41: 33 1969;
• 113 Schulz H, Pottel A. Elektronenmikroskopische Untersuchungen der Megakaryozyten und Thrombozyten eines Falles von primär hämorrhagischer Thrombozythämie. Blut 19: 208 1969;
• 114 Harker L. A, Finch C. A. Thrombokinetics in Man. J. clin. Invest 48: 963 1969;
• 115 Frick P. G. Primary Thrombocythemia. Clinical, hematological and chromosomal studies of 13 patients. Helv. med. Acta 35: 20 1969;
• 116 Najean Y, Ardaillou N, Dresch C. Platelet Lifespan. Ann. Rev. Med 20: 47 1969;
• 117 Madison F. W. The Role of Allergy in the Pathogenesis of Purpura and Thrombocytopenia. Blood 03: 1083 1948;