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A dysfibrinogenemia leading to resistance to bovine thrombin

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Depoorter, Maxime [UCL] Eeckhoudt, Stéphane [UCL]

Introduction: A 26-year-old woman presented to our institute for a routine check-up. Nothing was abnormal excepted a prolonged Thrombin Time and a low fibrinogen concentration determined by the Clauss method. Fibrinogen concentration was then measured by PT-derived method, and revealed normal levels. This was therefore suggestive for a dysfibrinogenemia. The patient had no history of haemostatic problems and was under no medication. Her family history revealed nothing relevant, but death of her father from a cerebrovascular accident. Methods and results: Complementary tests were performed: Platelet Function Assay, Factor VIII coagulant activity, von Willebrand antigen quantification, Ristocetin Cofactor activity, thromboelastogram and euglobulin lysis time were all within normal ranges. Finally, thrombin time and Clauss fibrinogen using a human thrombin instead of a bovine thrombine revealed normal results. DNA was then extracted for sequencing the genes coding for fibrinogen. This revealed the presence of a substitution Arg.Cys in position 275 of the c-chain of the fibrinogen. Discussion: This mutation has already been reported in the literature with four cases of thrombosis, three cases of haemorrhage and eight had no clinical signs. The gamma chain is implicated in several crucial interactions such as the primary polymerization 'a', the binding to calcium, the factor XIIIa-induced crosslinking, the binding to plasminogen and to tissue plasminogen activator. Results of the literature show that this mutation has several impacts on in vitro tests, and we proved that those can be corrected by the use of human thrombin.

Document type Article de périodique (Journal article) – Article de recherche
Publication date 2014
Language Anglais
Journal information "Acta Clinica Belgica (Multilingual Edition)" - Vol. 69, no. 6, p. 451-453 (2014)
Peer reviewed yes
Publisher Maney ((United Kingdom) London)
issn 0001-5512
e-issn 2295-3337
Publication status Publié
Affiliations UCL - SSS/IREC - Institut de recherche expérimentale et clinique
UCL - (SLuc) Service de biologie hématologique
Links
  1. Côté HC, Blood., 92, 2195 (1998)
  2. Schmelzer Charles H., Ebert Ray F., Bell William R., Fibrinogen baltimore iv: congenital dysfibrinogenemia with a γ275 (ARG → CYS) substitution, 10.1016/0049-3848(89)90172-2
  3. Flood V, Thromb Haemost., 99, 985 (2008)
  4. Yoshida N, Blood., 71, 480 (1988)
  5. Imafuku Yuji, Tanaka Kyoko, Takahashi Kiyoaki, Ogawa Kazuei, Sanpei Minoru, Yamada Hidekazu, Sato Akira, Yoshida Hiroshi, Identification of a dysfibrinogenemia of γR275C (Fibrinogen Fukushima), 10.1016/s0009-8981(02)00293-0
  6. Terukina S, J Biol Chem., 263, 13579 (1988)
  7. Steinmann C, Blood Coagul Fibrinolysis., 5, 463 (1994)
  8. Siebenlist KR, Blood Coagul Fibrinolysis., 11, 293 (2000)
  9. Rein Chantelle M, Anderson Brian L, Ballard Morgan M, Domes Christopher M, Johnston Joshua M, Madsen Russell Jared, Wolper Kathryn KM, Terker Andrew S, Strother John M, Deloughery Thomas G, Farrell David H, Severe bleeding in a woman heterozygous for the fibrinogen γR275C mutation : , 10.1097/mbc.0b013e3283393c7c
  10. Matsuda M, Baba M, Morimoto K, Nakamikawa C, "Fibrinogen Tokyo II". An abnormal fibrinogen with an impaired polymerization site on the aligned DD domain of fibrin molecules., 10.1172/jci111027
  11. Mosesson M W, Siebenlist K R, DiOrio J P, Matsuda M, Hainfeld J F, Wall J S, The role of fibrinogen D domain intermolecular association sites in the polymerization of fibrin and fibrinogen Tokyo II (gamma 275 Arg-->Cys)., 10.1172/jci118091
  12. Linenberger M.L., Kindelan J., Bennett R.L., Reiner A.P., C�t� H.C.F., Fibrinogen Bellingham: A ?-chain R275C substitution and a ?-promoter polymorphism in a thrombotic member of an asymptomatic family, 10.1002/1096-8652(200008)64:4<242::aid-ajh2>3.0.co;2-o
  13. Kamijyo Y, Jpn J Clin Pathol., 57, 651 (2009)
  14. Terasawa F, Thromb Haemost., 81, 763 (1999)
  15. Borrell M., Gar?? M., Coll I., Vallv?? C., Tirado I., Soria J. M., Sala N., Mu??oz C., Oliver A., Garc??a A., Fontcuberta J., Abnormal polymerization and normal binding of plasminogen and t-PA in three new dysfibrinogenaemias : Barcelona III and IV (??Arg 275???His) and Villajoyosa (??Arg 275???Cys), 10.1097/00001721-199505000-00002
  16. Ebert Ray F., Bell William R., Fibrinogen baltimore IV: Congenital dysfibrinogenemia with delayed fibrin monomer polymerization, 10.1016/0049-3848(85)90054-4
  17. Barthels Monika, Sandvo� Gerd, ?Fibrinogen Hannover?, ein weiteres atypisches Fibrinogen, 10.1007/bf00999856
  18. Human variant fibrinogen database. Available from: http://www.geht.org
  19. http://www.omim.org/entry/134850#reference44
Bibliographic reference Depoorter, Maxime ; Eeckhoudt, Stéphane. A dysfibrinogenemia leading to resistance to bovine thrombin. In: Acta Clinica Belgica (Multilingual Edition), Vol. 69, no. 6, p. 451-453 (2014)
Permanent URL http://hdl.handle.net/2078.1/164191