Assessment of Overall Coagulation and Fibrinolytic Activity in Hemophilia A Patients by Using Global Hemostatic Laboratory Methods: Overall Hemostasis Potential, aPTT-waveform Analysis and Endogenous Thrombin Potential

Measurement of FVIII activity allows diagnosis of hemophilia A and categorization of disease severity, but has poor correlation with clinical phenotype. New laboratory methods that assess global hemostasis have been developed, with intention to better diagnose and monitor hemophilia A patients. To assess overall coagulation and fibrinolytic activity in hemophilia A patients using non- standard laboratory methods: overall hemostasis potential (OHP), aPTT-waveform analysis (aPTT- WA) and endogenous thrombin potential (ETP). Total of 63 hemophilia A patients (30 severe and 33 non-severe) and 27 healthy male subjects as control group were tested. OHP method, based on repeated spectrophotometric registration of the fibrin-aggregation in plasma, after addition of small amounts of exogenous thrombin, tissue-type plasminogen activator and calcium, provides besides OHP parameter (area under the fibrin aggregation curve) supplemetary parameters: overall coagulation potential (OCP), overall fibrinolytic potential (OFP) and clot lysis time (CLT). In-house aPTT- WA was performed on BCS with Actin FS (Siemens Healthcare Diagnostics, Germany), obtaining 3 quantitative waveform parameters from 2 different evaluation modes, drifting baseline (DB) and point of inflexion (PI): DELTA (aPTT- PI minus aPTT-DB), RATIO1 (aPTT- PI/aPTT-DB) and RATIO2 (DELTA/aPTT-DB). ETP method, setting C was performed on BCS-XP (Siemens), giving 4 parameters: area under the thrombin generation curve (AUC), peak thrombin concentration (Cmax), time to peak thrombin concentration (t- max) and time to signal beginning (t-lag). Obtained results revealed statistically significant difference (P< ; 0.05) for all parameters between analyzed groups, except for CLT between severe and non-severe group. Global assays can serve as a useful laboratory tool for assessing overall coagulation and fibrinolysis activity, providing at the same time additional information about hemophilia A patients.