Overall hemostasis potential and aPTT-clot waveform analysis as powerful laboratory diagnostic tools for identification of hemophilia A patients with unexpected bleeding phenotype.

INTRODUCTION: Traditionally used laboratory methods do not always accurately reflect bleeding severity in hemophilia A (HA) patients. The ability of three global assays for identifying patients with unexpected bleeding phenotype was investigated. METHODS: Overall hemostasis potential (OHP), aPTT-clot waveform analysis (aPTT-CWA), endogenous thrombin potential (ETP), FVIII activities, and prothrombin fragment 1 + 2 concentrations were measured in 62 HA patients (30 severe and 32 non-severe) and 27 male controls. Bleeding phenotype was determined using our proposed scoring system including age at first joint bleed, number of target joints, and number of joint/muscle bleeds per year. Bleeding score ≤ 4 defined patients with mild bleeding phenotype (N = 27); score ≥ 5 defined severe bleeding phenotype (N = 35). RESULTS: The receiver operating characteristic analysis performed for distinguishing patients with severe and mild bleeding phenotype yielded following values of area under the curve: 0.910 (FVIII); 0.891 (aPTT-CWA parameter DELTA); 0.769 (OHP); and 0.634 (ETP). Unexpected bleeding phenotype was identified in 11/62 HA patients: 8/32 (25%) non-severe HA patients had severe, while 3/30 (10%) severe HA patients had mild bleeding phenotype, and global assays enabled the identification of all these patients. OHP and DELTA were revealed as the most reliable parameters for bleeding phenotype determination (10/11 and 9/11 unexpected results, respectively). CONCLUSION: This study emphasizes OHP and aPTT-CWA as a powerful laboratory diagnostic tool in identifying HA patients with unexpected bleeding presentations, with the best results achieved by combining both assays. Global assays should not completely replace FVIII activity measurement but should be a part of the HA diagnostic algorithm.

Two global haemostatic assays as additional tools to monitor treatment in cases of haemophilia A.

Haemophilia A patients with similar levels of factor VIII (FVIII) may have different bleeding phenotypes and responses to treatment with FVIII concentrate. Therefore, a test which determines overall haemostasis may be appropriate for treatment monitoring in some patients. We studied two global haemostatic methods:endogenous thrombin potential (ETP) and overall haemostatic potential(OHP) before and after injection of FVIII concentrate in patients with haemophilia A treated prophylactically and on-demand. A significant correlation between FVIII and both ETP and OHP was observed, while ETP and OHP differed between patients with severe and mild clinical phenotypes. Both ETP and OHP differed significantly between severe, moderate and mild haemophilia A and controls. ETP and OHP increased after intravenous injection of FVIII concentrate in both groups of patients, but in spite of higher pre-treatment values of both ETP and OHP in patients treated prophylactically, and much higher post-treatment FVIII levels in comparison with the values in patients treated on-demand, no difference after treatment was observed for either ETP or OHP. ETP and OHP may be additional alternatives for monitoring (and even for individual tailoring) treatment in patients with haemophilia A.