Thrombophilia historical perspective

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Asiri Ediriwickrema, M.D., M.H.S. [2] Jaspinder Kaur, MBBS[3]


Hypercoagulability was first discovered by Dr. Rudolf Virchow, a German physician, in the mid-1800s. In 1965, the first descriptions of inherited thrombophilia were published by Dr. Roger O. Egeberg, an American physician.[1][2][3] Later, in the 1990s, the more common mutations associated with primary hypercoagulable states were identified.[4][5]

Historical Perspective

  • 1821-1902: A German physician, Rudolf Virchow, began describing the pathophysiology of hemostasis at age 24.[1]
  • 1856: Rudolf Virchow proposed a hypothesis to explain the etiology of pulmonary emboli, which lead to the understanding of the three primary causes of venous and arterial thrombosis: stasis, injury to the vessel wall and abnormalities in the circulating blood. [6]
  • 1906: Wasserman et al. described the antiphospholipid syndrome. [7]
  • 1965: The first descriptions of inherited thrombophilias were Antithrombin deficiency by Egeberg et al. and dysfibrinogenemia by Beck et al.[2][3]
  • 1981-1984: Dr. John Griffin and Dr. Philip Comp described protein C deficiency and protein S deficiency respectively as a primary hypercoagulable state.[8][9]
  • 1993-1994: Dr. Rogier Bertina and his colleagues identified that activated protein C (APC) resistance was primarily due to a mutation in the factor V gene (guanine to adenine substitution at nucleotide 1691, G1691A) resulting in the Factor V Leiden molecule.[4]
  • 1996: Swibertus R Poort described a prothrombin gene mutation, specificaly the substitution of adenine to guanine at nucleotide 20210 (Prothrombin G20210A), and its association with inherited thrombophilia.[5]


  1. 1.0 1.1 Schafer AI (1994). "Hypercoagulable states: molecular genetics to clinical practice". Lancet. 344 (8939–8940): 1739–42. PMID 7997003.
  2. 2.0 2.1 EGEBERG O (1965). "INHERITED ANTITHROMBIN DEFICIENCY CAUSING THROMBOPHILIA". Thromb Diath Haemorrh. 13: 516–30. PMID 14347873.
  3. 3.0 3.1 Beck EA, Charache P, Jackson DP (1965). "A new inherited coagulation disorder caused by an abnormal fibrinogen ('fibrinogen Baltimore')". Nature. 208 (5006): 143–5. PMID 4956920.
  4. 4.0 4.1 Bertina RM, Koeleman BP, Koster T, Rosendaal FR, Dirven RJ, de Ronde H; et al. (1994). "Mutation in blood coagulation factor V associated with resistance to activated protein C." Nature. 369 (6475): 64–7. doi:10.1038/369064a0. PMID 8164741.
  5. 5.0 5.1 Poort SR, Rosendaal FR, Reitsma PH, Bertina RM (1996). "A common genetic variation in the 3'-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis". Blood. 88 (10): 3698–703. PMID 8916933.
  6. Bagot, Catherine N.; Arya, Roopen (2008). "Virchow and his triad: a question of attribution". British Journal of Haematology. 143 (2): 180–190. doi:10.1111/j.1365-2141.2008.07323.x. ISSN 0007-1048.
  7. Wasserman A, Neisser A, Bruck C. Eine serodiagnostiche Reaction bei Syphilis. Deutsch Med Wöchenschr 1906;32:747
  8. Griffin JH, Evatt B, Zimmerman TS, Kleiss AJ, Wideman C (1981). "Deficiency of protein C in congenital thrombotic disease". J Clin Invest. 68 (5): 1370–3. PMC 370934. PMID 6895379.
  9. Comp PC, Esmon CT (1984). "Recurrent venous thromboembolism in patients with a partial deficiency of protein S." N Engl J Med. 311 (24): 1525–8. doi:10.1056/NEJM198412133112401. PMID 6239102.

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