title: A dysfibrinogenemia leading to resistance to bovine thrombin.
abstract: BACKGROUND
  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.
  
  
  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 γ-chain of the fibrinogen.
  
  
  CONCLUSIONS
  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 cross-linking, 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.
authors.forename: M
authors.initials: M
authors.lastname: Depoorter
authors.forename: S
authors.initials: S
authors.lastname: Eeckhoudt
mesh_terms: D000328:Adult; D000347:Afibrinogenemia / Q000175:diagnosis* / Q000235:genetics*; D000818:Animals; D001780:Blood Coagulation Tests; D002417:Cattle; D005260:Female; D005340:Fibrinogen / Q000235:genetics*; D006801:Humans; D009154:Mutation / Q000235:genetics*
chemical_list: D005340:Fibrinogen
keywords: Bovine thrombin,; Clauss method; Coagulation,; Dysfibrinogenemia,; Fibrinogen gamma chain,; Fibrinogen,; Human thrombin,; Thrombin time,