Several different kinds of ‘milestone' in the field of blood coagulation are described from the middle decades of the 20th century. Although viewed from the standpoint of clotting per se, attention is also given to implications for innate immunity. The first milestone considered is the protracted saga of clotting dependence on vitamin K, an adventure that spanned more than five decades beginning in the 1920s. The second has to do with the discovery of a half-dozen ‘new' clotting factors during the period immediately following World War II. A third pursues a narrower focus and examines the once mysterious transformation of fibrinogen into fibrin. Finally, the clinical treatment of classical hemophilia had a remarkable turning point in the 1960s as the result of simple but sensible measures.

Journal Section:
Editor's choice
Keywords:
Vitamin K, Blood clotting factors, Fibrin, Cryoglobulin
1.
Owen CA: A History of Blood Coagulation (Nichols WC, Bowie EJW, eds). Rochester, Mayo Foundation for Medical Education, 2001.
2.
Hougie C: Thrombosis and Bleeding: An Era of Discovery. Vancouver, Trafford, 2004.
3.
Roderick LM: A problem in the coagulation of the blood: sweet clover disease of cattle. Am J Physiol 1931;96:413-425.
4.
Dam H: Cholesterinstoffwechsel in Hühnereiern und Hühnchen. Niochem Z 1929;215:475-492.
5.
Dam H, Schonheyder F: A deficiency disease in chicks resembling scurvy. Biochem J 1934;28:1355-1359.
[PubMed]
https://doi.org/10.1042/bj0281355
6.
Dam H: The antihaemorrhagic vitamin of the chick. Biochem J 1935;29:1273-1285.
[PubMed]
https://doi.org/10.1111/j.1753-4887.1973.tb05050.x
7.
Thayer SA, Maccorquodale DW, Binkley SB, Doisy EA: The isolation of a crystalline compound with vitamin K activity. Science 1938;88:243.
[PubMed]
https://doi.org/10.1126/science.88.2280.243
8.
Campbell HA, Link KP: Studies on the hemorrhagic sweet clover disease. IV. The isolation and crystallization of the hemorrhagic agent. J Biol Chem 1941;138:21-33.
9.
Link KP: The discovery of dicumarol and its sequels. Circulation 1959;19:97-107.
[PubMed]
https://doi.org/10.1161/01.CIR.19.1.97
10.
Nilehn JE, Ganrot P-O: Plasma prothrombin during treatment with dicumarol. I. Immunochemical determination of its concentration in plasma. Scand J Clin Lab Invest 1968;22:17-22.
[PubMed]
https://doi.org/10.3109/00365516809160730
11.
Stenflo J: Dicumarol-induced prothrombin in bovine plasma. Acta Chem Scand 1970;24:3762-3763.
[PubMed]
https://doi.org/10.3891/acta.chem.scand.24-3762
12.
Nelsestuen GL, Suttie JW: The purification and properties of an abnormal prothrombin protein produced by dicoumarol-treated cows: a comparison to normal prothrombin. J Biol Chem 1972;247:8176-8182.
[PubMed]
13.
Shah DV, Suttie JW: Mechanism of action of vitamin K: evidence for the conversion of a precursor protein to prothrombin in the rat. Proc Natl Acad Sci USA 1971;68:1653-1657.
[PubMed]
https://doi.org/10.1073/pnas.68.7.1653
14.
Stenflo J, Fernlund P, Egan W, Roepstorff P: Vitamin K dependent modifications of glutamic acid residues in prothrombin. Proc Natl Acad Sci USA 1974;71:2730-2733.
[PubMed]
https://doi.org/10.1073/pnas.71.7.2730
15.
Nelsestuen GL, Zytkovicz TH, Howard JB: The mode of action of vitamin K: Identification of γ-carboxyglutamic acid as a component of prothrombin. J Biol Chem 1974;249:6347-6350.
[PubMed]
16.
Rost R, Fregin A, Ivaskevevicius V, Conzelmann E, Hortnagel K, Pelz H-J, Lappegard K, Seifried E, Scharrar I, Tuddenham EGD, Muller CR, Strom TM, Oldenburg J: Mutations in VKORC1 cause warfarin resistance and multiple coagulation deficiency type 2. Nature 2004;427:537-541.
[PubMed]
https://doi.org/10.1038/nature02214
17.
Owren PA: Parahaemophilia: hemorrhagic diathesis due to absence of a previously unknown clotting factor. Lancet 1947;249:446-448.
[PubMed]
18.
Quick A: On the constitution of prothrombin. Amer J Physiol 1943;140:212-220.
19.
Owren PA: The fifth coagulation factor (‘factor V'): preparation and properties. Biochem J 1948;43:136-139.
[PubMed]
20.
Owren PA, Bjerklund C: A new, previously unknown clotting factor. Scand J Lab Invest 1949;1:162-163.
https://doi.org/10.3109/00365514909065641
21.
Alexander B, de Vries A, Goldstein R, Landwehr G: A prothrombin conversion accelerator in serum. Science 1949;109:545.
[PubMed]
https://doi.org/10.1126/science.109.2839.545
22.
Loeliger A: Über den Nachweis eines neuen Blutgerinnungsfaktors Faktor VII. Wien Z Inn Med 1952;3:169-180.
[PubMed]
23.
Bergsagel DE, cited in Waaler BA: Simultaneous contribution to the formation of thrombin by the intrinsic and extrinsic blood clotting systems. Scand J Clin Lab Invest 1957;9:322-330.
[PubMed]
https://doi.org/10.3109/00365515709079981
24.
Jaques LB: Nomenclature for blood clotting factors. Canad Med Assoc J 1960;82:1327-1330.
[PubMed]
25.
International Committee on Nomenclature of Blood Clotting Factors: Nomenclature of blood clotting factors. J Amer Med Assoc 1959;170:325-328.
[PubMed]
26.
Rosenthal RL, Dreskin OH, Rosenthal N: Plasma thromboplastin antecedent (PTA) deficiency: clinical, coagulation, therapeutic and hereditary aspects of a new hemophilia-like disease. Blood 1955;10:120-131.
[PubMed]
27.
Ratnoff OD, Colopy JE: A familial hemorrhagic trait associated with a deficiency of a clot-promoting faction of plasma. J Clin Invest 1955;34:602-613.
[PubMed]
https://doi.org/10.1172/JCI103109
28.
Ratnoff OD, Margolius A Jr: Hageman trait: an asymptomatic disorder of blood coagulation. Trans Assoc Am Phys 1955;68:149.
[PubMed]
29.
Wright IS: The nomenclature of blood clotting factors. Thromb Diath Haemorrh 1962;7:381-388.
[PubMed]
30.
Armstrong D, Jepson JB, Keele CA, Stewart JW: Pain-producing substance in human inflammatory exudates and plasma. J Physiol 1957;135:350-370.
[PubMed]
https://doi.org/10.1113/jphysiol.1957.sp005715
31.
Margolis J: Activation of plasma by contact with glass: evidence for release of a common reaction which releases plasma kinin and initiates coagulation. J Physiol 1958;144:1-22.
[PubMed]
https://doi.org/10.1113/jphysiol.1958.sp006082
32.
Blomback B, Yamashina I: On the N-terminal amino acids of fibrinogen and fibrin. Arkiv Kemi 1957;12:299-319.
33.
Eagle H, Harris TN: Studies in blood coagulation. V. The coagulation of blood by proteolytic enzymes (trypsin, papain). J Gen Physiol 1937;20:543-560.
[PubMed]
https://doi.org/10.1085/jgp.20.4.543
34.
Laki K: The polymerization of proteins: the action of thrombin on fibrinogen. Arch Biochem Biophys 1951;32:317-324.
[PubMed]
35.
Mihalyi E: Electrophoretic investigation of fibrin and fibrinogen dissolved in urea solutions. Acta Chem Scand 1950;4:351-358.
36.
Bailey K, Bettelheim FR, Lorand L, Middlebrook RW: Action of thrombin in the clotting of fibrinogen. Nature 1951;167:233-234.
[PubMed]
https://doi.org/10.1038/167233a0
37.
Ferry JD: The mechanism of polymerization of fibrin. Proc Natl Acad Sci USA 1952;38:566-569.
[PubMed]
https://doi.org/10.1073/pnas.38.7.566
38.
Duthie ES: The action of fibrinogen on certain pathogenic cocci. J Gen Microbiol 1955;13:383-393.
[PubMed]
https://doi.org/10.1099/00221287-13-2-383
39.
Kantor FS, Cole RM: A fibrinogen precipitating factor (PFF) of group A streptococci. Proc Soc Exp Biol Med 1959;102:146-150.
[PubMed]
https://doi.org/10.3181/00379727-102-25172
40.
Blomback M: Purification of antihaemophilic globulin. 1. Some studies on the stability of the antihaemophilic globulin activity in fraction I-0 and a method for its partial separation from fibrinogen. Arkiv Kemi 1958;12:367-386.
41.
Pool JG, Robinson J: Observations on plasma banking and transfusion procedures for haemophilic patients using quantitative assay for antihaemophilic globulin. Br J Haematol 1959; 5:24-30.
[PubMed]
https://doi.org/10.1111/j.1365-2141.1959.tb04010.x
42.
Pool JG, Hershgold EJ, Pappenhagen AR: High potency antihaemophilc factor concentrate prepared from cryoglobulin precipitate. Nature 1964;202:312-313.
[PubMed]
https://doi.org/10.1038/203312a0
43.
Pool JG, Shannon AE: Production of high-potency concentrates of antihemophilic globulin in a closed-bag system. New Eng J Med 1965;2731443-1447.
[PubMed]
https://doi.org/10.1056/NEJM196512302732701
© 2015 S. Karger AG, Basel
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
2015
You do not currently have access to this content.