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John FreedmanJohn W SempleAlan H Lazarus Valery LeytinHeyu Ni Margaret L RandVictor S Blanchette HSCCBSSMH.

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Presentation on theme: "John FreedmanJohn W SempleAlan H Lazarus Valery LeytinHeyu Ni Margaret L RandVictor S Blanchette HSCCBSSMH."— Presentation transcript:

1 John FreedmanJohn W SempleAlan H Lazarus Valery LeytinHeyu Ni Margaret L RandVictor S Blanchette HSCCBSSMH

2 ITP Idiopathic thrombocytopenic purpura Immune thrombocytopenic purpura From Hippocrates to Bussel (and a few side-trips in between) immune thrombocytopeni a purpura

3 Greco-Roman: Hippocrates, Galen – life based on four elements: Fire, air, earth, water Blood was one of the four ‘humors’ (air): made in liver, sloshed around through heart where mixed with air Brew of willow tree leaves (salicylates) as analgesic and antipyretic Spleen: source of black bile; “organ full of mystery” Hippocrates 460-377 BCE Galen CE 129-circa 210 [Juliana Anicia Ms, CE 487] Red “eminences”/spots associated with pestilential fevers (plague).

4 Porphyra Gastropod mollusc janthina janthina Purpura πορφυρα

5 C10th: Avicenna (Canon) --- chronic purpura

6 Amatus Lusitanus (Jo n o Rodrigues de Castelo Branco) [1511-1568] Physician, researcher in anatomy, internal medicine, dermatology, mental illness. Peripatetic Converso who fled from Salamanca to Portugal, Ferrara, Ancona, Dubrovnik, Salonika, but was nonetheless physician to several monasteries and to Pope Julius III. Between 1541 and 1561 wrote seven centuriae: each 100 case histories, their treatment, results and pathology, accompanied by learned explanations.



9 1658



12 X 300 1632-1723 Anton van Leeuwenhoek

13 1735 linguist physician composerpoet

14 1775


16 1808




20 The Englishman, William Hewson (1739-1774) was probably the first to observe some platelets.

21 Joseph Lister, Lord 1827-1912 Founder of aseptic surgery Joseph Jackson Lister 1786-1869 Wine merchant 1828

22 1842 + Foucault = daguerrotype Alfred Donne (1801-1878) Child care; breastfeeding

23 1840s to 1860s: Gulliver, Addison: independently made what are probably the first drawings of platelets Zimmerman: ‘elementary bodies’ which came from lymphatics and were precursors of red blood cells; (Hematoblasts) Jones, Beale, Simon, Schultze: platelets were fibrin clots (? derived from leukocytes) Schmidt in Estonia: ? A cell between erythrocyte and leukocyte Addison 1842


25 Brewer DB: Br J Haematol 133:251-258, 2006 Professor of Anatomy, Bonn

26 1874 Aequanimitas Osler “It must still be confessed that we know nothing about the origin or destiny of these corpuscles”

27 1882 “The existence of a constant blood particle, differing from red and white blood cells, has been suspected by several authors for some time”



30 Despite the work’s title (“…et sur son importance dans la trombose et dans la coagulation”), Bizzozero did not focus on the hemostatic or hemorrhagic role of platelets, and appears not to have recognized platelets as a factor in purpura. rbc platelets Georges Hayem (1841-1935): A founder of haematology. Small elements in blood; tendency to clump and to change shape;in 1883, coined term platelet. Hôpital Tenon; St Antoine: several anemias, digestion, stomach, rbc counting, cholera

31 In 1884, Krauss related purpura hemorrhagica to a decrease in circulating platelets 1887

32 1895

33 1890

34 Relation of megakaryocytes to platelets

35 Take off full screen

36 1915: Frank (Breslau) recognized that megakaryocytopoiesis was normal in ITP

37 1915

38 1916MinotFailure of transfusion in ITP 1916MinotPlatelet destruction due to “some reaction” 1916KaznelsonSpleen site of platelet destruction? (Prague)Splenectomy in ITP Other treatments at this time included irradiation by mercury vapor lamps, snake venom, splenic irradiation.

39 1938Troland & Lee ‘Thrombocytopen’ from ITP splenic extracts Platelet count

40 1940WisemanClinical diagnostic criteria for ITP 1946CurtisFailure of splenectomy due to accessory spleen Damashek & Miller, however, continued to argue that ITP was due to a fundamental abnormality of the spleen which ‘exerts an unusual effect on the production of platelets from the megakaryocytes in the marrow’

41 Harrington et al, J Lab Clin Med 38:1, 1951 1951 plasma Passive transfer of ITP with ITP plasma Carl V Moore

42 1951EvansPlasma factor = anti-platelet antibody 1951DamashekDistinction of acute versus chronic ITP 1951WintrobeUse of corticosteroids in ITP Maxwell WintrobeWilliam Damashek

43 1972 --- Sartorius, Am J Ped Hematol Oncol 6:165, 1984 1984: First randomized trial of steroids in ITP

44 Lien 1970s

45 1975Dixon Measurement of PA-IgG 1981Imbach IVIG in ITP 1983Salama Anti-D in ITP 1970s – 1990s Humoral immunity in ITP; antibody specificity New drugs for refractory patients 1990s - Dysregulation of cellular immunity in ITP



48 Literature on history of platelets  Jones HW, Tocantins LM: The history of pupura hemorrhagica. Ann Med Hist 5:349-359, 1933.  Robb-Smith AHT: How the platelets were discovered. Br J Haematol 13:618-639, 1967.  Blanchette M, Freedman J: The history of idiopathic thrombocytopenic purpura (ITP). Transfus Sci 19:231-236, 1998.  Freedman J, Blanchette M: Idiopathic thrombocytopenic purpura (ITP): a historical odyssey. Acta Paediatr Suppl 424:3-6, 1998.  Mustard JF, Kinlough-Rathbone RL, Packham MA: History of platelets. In: Platelets in thrombotic and nonthrombotic disorders: pathophysiology, pharmacology and therapeutics. Gresele P, Page C, Fuster V, Vermylen J, eds. Cambridge University Press, Cambridge, 2002.  Imbach P, Kuhne T, Signer E: Historical aspects and present knowledge of idiopathic thrombocytopenic purpura. Br J Haematol 119:894-900, 2002.  Izaguirre-Avila R: El descubrimiento de las plaquetas. Revista Biomedica Vol 8, 1997.

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