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The thrombin generation assay distinguishes inhibitor from non‐inhibitor patients with severe haemophilia A
Author(s) -
Mancuso M. E.,
Chantarangkul V.,
Clerici M.,
Fasulo M. R.,
Padovan L.,
Scalambrino E.,
Peyvandi F.,
Tripodi A.,
Santagostino E.
Publication year - 2016
Publication title -
haemophilia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.213
H-Index - 92
eISSN - 1365-2516
pISSN - 1351-8216
DOI - 10.1111/hae.12927
Subject(s) - medicine , haemophilia , coagulation , haemophilia a , mutation , protease inhibitor (pharmacology) , gastroenterology , thrombin , thrombin generation , pharmacology , immunology , surgery , genetics , gene , virus , biology , platelet , antiretroviral therapy , viral load
Patients with haemophilia A (HA) have impaired thrombin generation (TG) capacity and TG assay (TGA) values are linearly related to plasma factor VIII (FVIII) levels. Aim This study carried out in patients with unmeasurable FVIII (<1 IU dL −1 ) was aimed at unravelling any difference in TG capacity in patients with or without inhibitors. Methods Blood samples were collected from patients in a non‐bleeding state, after a 5‐day wash‐out period from last treatment. Results TGA was performed in 102 patients with severe HA (15% with high‐responding inhibitors; 51% with null F8 mutations, that as expected were more prevalent in inhibitor than in non‐inhibitor patients). TG capacity was significantly lower in inhibitor than non‐inhibitor patients and in those with null mutations than in those with non‐null mutations. When the TG capacity was evaluated only in patients with null mutations with and without inhibitors it was lower in the presence of inhibitors. Conclusions This study shows a greater TG impairment in inhibitor patients irrespective of FVIII levels, inhibitor titre and F8 mutation type, suggesting a role for the TGA in unravelling functional interferences of anti‐FVIII inhibitors on coagulation system activation.