The thrombin generation assay distinguishes inhibitor from non-inhibitor patients with severe haemophilia A

Abstract

Introduction: 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.

Keywords: F8 mutations; endogenous thrombin potential; inhibitors; severe haemophilia A; thrombin generation assay.