title: An in-vitro assessment of tranexamic acid as an adjunct to rFVIII or rFVIIa treatment in haemophilia A.
abstract: Haemophilia is characterised by defective thrombin generation, reduced clot stability and spontaneous bleeding. Treatment with factor VIII (FVIII) concentrate or bypassing agents (e.g. recombinant factor VIIa (rFVIIa)) is generally effective. Occasionally, haemostasis is not achieved, which may reflect a failure of factor concentrate to normalise clot stability. Tranexamic acid (TXA) is often used to aid haemostasis in surgery (e.g. joint replacements and dental procedures). Used routinely as an adjunct, it may enhance clot stability and allow effective, reliable, and cost-effective treatment at lower doses of factor concentrate. This study hypothesised that clot stabilising adjunct TXA is required in addition to factor substitution to normalise clot stability in whole blood from patients with severe haemophilia A. The in vitro effect of varying concentrations of recombinant FVIII or recombinant FVIIa and adjunct TXA on whole blood clot stability was measured by thromboelastometry. Coagulation was triggered by tissue factor and clots were challenged with tissue plasminogen activator. The area under the elasticity curve was the primary endpoint. High concentrations of FVIII and rFVIIa increased clot stability to levels that were not significantly different from controls (Mean ± SD: control 112,694 ± 84,115; FVIII 78,662 ± 74,126; rFVIIa 95,918 ± 88,492). However, the response was highly variable between individuals and demonstrates why some patients show clinical resistance to treatment. Addition of TXA resulted in normalised clot stability in all individuals, even when combined with the lowest doses of factor concentrate. The results support the concept that a more efficient, reliable and cost effective treatment may be obtained if TXA is combined with factor concentrates to treat individuals with haemophilia.
authors.affiliation: Centre for Haemophilia and Thrombosis, Guy's and St Thomas' NHS Foundation Trust, Westminster Bridge Road, London, SE1 7EH, UK, catherinerea@doctors.org.uk.
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Rea
authors.forename: Jonathan H
authors.initials: JH
authors.lastname: Foley
authors.forename: David H
authors.initials: DH
authors.lastname: Bevan
authors.forename: Benny
authors.initials: B
authors.lastname: Sørensen
mesh_terms: D000293:Adolescent; D000328:Adult; D000933:Antifibrinolytic Agents / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D005169:Factor VIII / Q000008:administration & dosage*; D015942:Factor VIIa / Q000008:administration & dosage*; D006467:Hemophilia A / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage; D014148:Tranexamic Acid / Q000008:administration & dosage* / Q000097:blood; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000933:Antifibrinolytic Agents; D011994:Recombinant Proteins; D014148:Tranexamic Acid; D005169:Factor VIII; C103587:recombinant FVIIa; D015942:Factor VIIa