Comparison of People with Hemophilia A and Patients with Nonvalvular Atrial Fibrillation on Oral Anticoagulation by Thrombin Generation.

Recently published guidance on anticoagulation in people with hemophilia (PWH) appraised the literature on whether PWH are naturally anticoagulated: Only two studies compared thrombin generation (TG) in PWH and patients on vitamin K antagonists (VKA), analyzing endogenous thrombin potential (ETP), but were limited by stratifications. We compared TG between PWH A and patients with atrial fibrillation (AF) treated with VKA or direct oral anticoagulants (DOAC). TG was measured by a commercially available assay (Technothrombin), and DOAC levels by mass spectrometry. TG results were compared by equating separate linear regression models, avoiding stratification of the data. We included 565 samples from 110 PWH A, 118 VKA- and 113 DOAC-treated AF patients. TG parameters showed substantial variability among all cohorts, and, accordingly, their relationship with factor (F)VIII, INR, and DOAC levels and ability to differentiate between changes was modest. Importantly, TG curves clustered distinctly between cohorts, and different TG parameters led to varying comparison estimates. FVIII<1 IU/dL in PWH A corresponded to a mean INR-equivalence of 2.3 (95% CI, 2.2-2.5) and 2.0 (1.8-2.2); and a mean DOAC-equivalence of 229.0 (182.1-279.6) and 284.2 (206.2-358.0) ng/mL rivaroxaban, 192.7 (123.0-263.5) and 201.7 (73.8-317.9) ng/mL apixaban, and 313.0 (153.5-448.1) and 242.3 (159.4-328.7) ng/mL dabigatran, using thrombin peak or ETP for estimation, respectively. TG showed substantial variability, differing systematically between PWH A, VKA-treated, and DOAC-treated AF patients. Our data call for caution when using TG to relate the hemostatic potential of PWH A to patients receiving oral anticoagulants and suggest comparisons by individual TG parameters to be overly simplistic.