engleski

Usefulness of global haemostasis assays in haemophilia A patients with discrepant bleeding phenotype

Background/Aims Traditionally used laboratory methods, i.e. one-stage or chromogenic assays for FVIII activity determination do not always and accurately reflect bleeding severity in haemophilia A (HA) patients. As global haemostasis assays provide overall haemostatic status estimation, we investigated the ability of three global assays for identifying bleeding phenotype both in severe and non-severe HA patients, as well as their usefulness in laboratory management of HA patients with discrepant bleeding phenotype. Materials and Methods Overall haemostasis potential (OHP), aPTT-clot waveform analysis (aPTT-CWA), endogenous thrombin potential (ETP) and FVIII activity were measured in 30 severe and 32 non- severe HA patients and 27 male controls. For classification of HA patients regarding bleeding phenotype, we used a scoring method that included three clinical parameters: age at first joint bleed, number of target joints and number of joint/muscle bleeds per year. Bleeding scores ≤4 and ≥5 suggested mild and severe beeding phenotype, respectively. Results All global assays correlated significantly with FVIII activity (P<0.001), enabling clear discrimination between severe, non- severe HA patients and controls. ROC analysis performed for distinguishing patients with severe and mild bleeding phenotype yielded the following AUC values: 0.891 for aPTT-CWA ; 0.769 for OHP ; 0.634 for ETP. Discrepant bleeding phenotype was identified in 11/62 HA patients: 3/30 severe patients presented with mild bleeding phenotype, whereas 8/32 non-severe patients demonstrated severe bleeding phenotype. Global assays allowed detection of all 11 patients with discrepant bleeding phenotype. The best discriminating ability was demonstrated by OHP and DELTA (10/11 and 9/11 discrepant results, respectively) followed by ETP (6/11 discrepant results). Conclusions Global assays are superior bleeding phenotype determinants in a majority of individual HA patients, compared to FVIII alone, and should be included in the diagnostic algorithm at least in patients with discrepant results between FVIII activity and calculated bleeding score.

Hemophilia A ; fibrinolytic system ; overall hemostasis potential (OHP)

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