title: Optimal monitoring of bypass therapy in hemophilia A patients with inhibitors by the use of clot waveform analysis.
abstract: BACKGROUND
  Assays to determine the optimal hemostatic effects of bypass therapy in hemophilia A (HA) patients with inhibitors are difficult to compare. Clot waveform analysis (CWA), based on the continuous monitoring of routine coagulation parameters (prothrombin time/activated partial thromboplastin time), offers a useful method for assessing global clotting function.
  
  
  OBJECTIVE
  To investigate the technique of CWA for the hemostatic monitoring of bypass therapy in HA patients with inhibitors.
  
  
  RESULTS
  Ellagic acid (Elg), tissue factor (TF) or both (Elg/TF) were used as trigger reagents in CWA. The standard parameters - clot time (CT), maximum coagulation velocity (|min1|), and acceleration (|min2|) - were recorded. Optimal monitoring was defined as: (i) a significant difference in these parameters between plasma from HA patients with inhibitors and normal plasmas; and (ii) a significant improvement in these indices in HA patients with inhibitors after bypass therapy. Experiments in vitro demonstrated that there were significant differences between plasma from HA patients with inhibitors and normal plasma with various triggers, in the order Elg > Elg/TF >> TF. Addition of therapeutically achievable concentrations of bypassing agents, however, showed significant improvements in the different parameters only with Elg/TF, suggesting that this reagent provided the most appropriate assay. A total of 20 plasmas from HA patients with inhibitors in which bypassing agents were infused were evaluated ex vivo by Elg/TF CWA. The postinfusion parameters CT and |min2| reflected clinical effects, and were close to normal levels. Furthermore, Elg/TF CWA facilitated quantitative evaluation of perioperative hemostatic management of bypass therapy in HA patients with inhibitors.
  
  
  CONCLUSIONS
  CWA is a promising method for the quantitative monitoring of bypass therapy during routine automated clotting assays with a modified trigger reagent comprising a well-balanced mixture of Elg and TF.
authors.affiliation: Department of Pediatrics, Nara Medical University, Kashihara, Nara, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Haku
authors.forename: K
authors.initials: K
authors.lastname: Nogami
authors.forename: T
authors.initials: T
authors.lastname: Matsumoto
authors.forename: K
authors.initials: K
authors.lastname: Ogiwara
authors.forename: M
authors.initials: M
authors.lastname: Shima
mesh_terms: D000293:Adolescent; D000328:Adult; D001777:Blood Coagulation; D001779:Blood Coagulation Factors / Q000737:chemistry*; D001780:Blood Coagulation Tests / Q000379:methods; D002648:Child; D005169:Factor VIII / Q000737:chemistry; D006467:Hemophilia A / Q000097:blood*; D006487:Hemostasis; D006801:Humans; D008875:Middle Aged; D010314:Partial Thromboplastin Time; D011517:Prothrombin Time; D013925:Thromboplastin / Q000737:chemistry; D055815:Young Adult
chemical_list: D001779:Blood Coagulation Factors; C078147:F8 protein, human; D005169:Factor VIII; D013925:Thromboplastin
keywords: blood coagulation factor inhibitors; clinical laboratory techniques; factor VIII; hemophilia A; hemostatic techniques