Defining Haemostatic Safety Zones for the Practice of Sport in Patients with Severe Haemophilia By Thromboelastography

Introduction: Sport may comprise variable physical activity associated bleeding risk(BRisk) in haemophilia. We aimed to determine value of global thromboelastography (TEG) profile for tailoring prophylaxis in patients younger than 18 years old (YO) with severe haemophilia A (SHA) subjected to activities with different BRisk.

Methods: Patients with SHA, younger than 18 YO and on prophylaxis at least 12 months before inclusion were invited to participate. Patients signed informed consent before inclusion. Samples before prophylactic dosing were collected. Factor VIII (FVIII) and kaolin-activated TEG profile were determined. Physical activity (PhA) and annual joint bleeding rate (AJBR) were recorded retrospectively. BRisk was categorized following the US-National Haemophilia Foundation guidelines (1= safe; 1.5= safe-moderate risk; 2= moderate risk; 2.5= moderate-dangerous risk; 3= dangerous risk of bleeding).

Results: 26 patients, median age (min-max) 10.3 (6.8-14.3) YO were included. Sixty one percent of patients had BRisk= 1.0; 7.7% had BRisk= 2.0 and 2.5; 23,1% had BRisk= 3. In the last 12 months, haemarthrosis were presented in 33% of patients with BRisk=3.0 and 13% in those with BRisk= 1.0. Interesting, patients with BRisk= 2.0 or 2.5 did not present any joint bleeding in the previous year. Median levels of FVIII was 0.5 (0.0-1.9) IU/dl. There were no differences on trough FVIII levels between patients with or without joint bleeds (FVIII= 0.3 [0.0-1.9] and 1.1[0.2-4.4] IU/dl respectively, p=0.515) in the year before. There was no correlation between FVIII trough plasma levels and the AJBR (p=0.416). TEG trough profiles were similar in patients with and without haemarthrosis. However, patients with AJBR=0 presented a clear correlation between trough TEG parameters and BRisk (BRisk vs. k: r=-0,439; p= 0.047 and BRisk vs. alpha angle: r= 0.478; p= 0.025) so that, the higher the exercise-associated BRisk the higher procoagulant state needed to keep a joint-bleeding-free state. This correlation was not found for FVIII.

Conclusions: Kaolin-activated TEG assay may help to define safety zones to minimize bleedings in response to PhA in patients < 18 YO with SHA and may guide prophylaxis tailoring depending on BRisk of PhA.