Bleeding phenotype of patients with moderate haemophilia A and B assessed by thromboelastometry and thrombin generation

Abstract

Introduction Predicting the bleeding phenotype is crucial for the management of patients with moderate haemophilia. Global coagulation assays evaluate haemostasis more comprehensively than conventional methods. Aim To explore global coagulation assays and the bleeding phenotype of patients with moderate haemophilia A (MHA) and B (MHB). Methods The MoHem study is a cross‐sectional, multicentre study covering Nordic patients with MHA and MHB. Thromboelastometry in whole blood and thrombin generation (TG) in platelet‐poor plasma (1, 2.5 and 5 pM tissue factor (TF)) were compared with joint health (Haemophilia Joint Health Score (HJHS)) and treatment modality. Results We report on 61 patients from Oslo and Helsinki: 24 MHA and 37 MHB. By TG (2.5 pM TF), patients who had been without replacement therapy during the previous 12 months depicted higher endogenous thrombin potential (P = .03). In contrast, those who had low ETP (< median) captured higher HJHS (P = .02). Patients who had undergone orthopaedic surgery generated least thrombin (P = .02). By thromboelastometry, those without the need of factor consumption had short clotting times, and quick times to maximum velocity (< median values) (P = .03). Factor VIII/factor IX activity (FVIII/FIX:C) did not align with the bleeding phenotype, but FIX:C ≤ 3 IU/dL was associated with lower peak thrombin (P = .03). Conclusion TG differentiated patients with moderate haemophilia according to HJHS, annual factor consumption, and whether orthopaedic surgery had been performed. Thromboelastometry differentiated according to factor consumption only. Global coagulation assays may assist predicting the bleeding phenotype in moderate haemophilia.

In patients with hemophilia, a decreased thrombin generation profile is associated with a severe bleeding phenotype

“…Studies using thrombin generation assays (TGAs) found a correlation between TG parameters and the factor activity level [ [3] , [4] , [5] , [6] , [7] , [8] , [9] , [10] ]. In addition, previous studies suggested that the TG profile better determines which hemophilia patients are at increased risk of bleeding [ 3 , 4 , 7 , 8 , [11] , [12] , [13] , [14] , [15] , [16] , [17] ]. A decreased thrombin peak height and thrombin potential were found in patients with a severe clinical bleeding phenotype irrespective of the FVIII or FIX activity level.…”