title: Investigation of the phenotype heterogeneity in severe hemophilia A using thromboelastography, thrombin generation, and thrombodynamics.
abstract: BACKGROUND
  Hemophilia A (HA) patients with similar factor VIII levels can demonstrate varying bleeding tendencies. In particular, 10-15% of all severe HA patients (FVIII:C<1IUdL(-1)) do not require regular replacement therapy. Modern global coagulation assays can help to detect and study this "mild" bleeding phenotype. Here, we investigated the coagulation status of different bleeding phenotypes using various types of global coagulation assays.
  
  
  METHODS
  Ten HA patients with severe phenotype and eleven patients with mild phenotypes were included in the study. For each patient, thromboelastography (TE), thrombodynamics (TD), and kaolin- or tissue factor-induced thrombin generation (TG) were measured. TG in platelet-rich plasma (PRP) was investigated using our original modification when the thrombin generation curve showed two peaks, previously shown to depend on platelet activity. We also utilized TG and TD with the addition of thrombomodulin.
  
  
  RESULTS
  The second peak amplitude and ETP of PRP TG were the only parameters that were significantly higher in mild bleeders (peak 41.6 ± 3.5 nM, ETP 1966 ± 169 nM*min) than in patients with severe bleeding (peak 28.3 ± 3.3 nM, ETP 1359 ± 130 nM*min).
  
  
  CONCLUSIONS
  Our results suggest that severe and mild HA phenotypes could be distiguished by TG assay in PRP suggesting that difference in platelet activity can be involved in the phenotype formation. According to our previous results we can suppose that the mechanism of the phenotypic heterogeneity is linked with TG mediated by PS-expressing platelets.
authors.affiliation: The Center for Theoretical Problems of Physicochemical Pharmacology, Kosygina Street 4, Moscow 119991, Russia. taran_@list.ru
authors.forename: Ivan D
authors.initials: ID
authors.lastname: Tarandovskiy
authors.forename: Anna N
authors.initials: AN
authors.lastname: Balandina
authors.forename: Konstantine G
authors.initials: KG
authors.lastname: Kopylov
authors.forename: Nadezhda I
authors.initials: NI
authors.lastname: Konyashina
authors.forename: Maria A
authors.initials: MA
authors.lastname: Kumskova
authors.forename: Mikhail A
authors.initials: MA
authors.lastname: Panteleev
authors.forename: Fazoil I
authors.initials: FI
authors.lastname: Ataullakhanov
mesh_terms: D000328:Adult; D000368:Aged; D001780:Blood Coagulation Tests; D006467:Hemophilia A / Q000097:blood* / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007616:Kaolin / Q000378:metabolism; D008875:Middle Aged; D053657:Platelet-Rich Plasma / Q000378:metabolism; D013916:Thrombelastography; D013917:Thrombin / Q000378:metabolism; D013925:Thromboplastin / Q000378:metabolism; D055815:Young Adult
chemical_list: D007616:Kaolin; D013925:Thromboplastin; D013917:Thrombin