Abstract
Whole blood coagulation tests such as thromboelastography and platelet function analyser (PFA-100) are increasingly used for the investigation of haemostatic disorders. These global tests offer the advantages of a simple use and fast results. Although PFA-100 using the ADP cartridge has been validated as a useful tool to assess primary haemostatic disturbancies and has a high sensitivity to detect Von Willebrand disease (VWD), this test is neither specific for, nor predicitve of, any particular disorder of primary haemostasis. On the other hand, the potential usefulness of thromboelastography for the evaluation of VWD has so far not been investigated.
The present study was undertaken in order to determine alterations of the thromboelastogram tracing in patients with VWD and evaluate its usefulness in adjunction to PFA-100 for the diagnosis and characterisation of VWD.
Thromboelastographic analysis (Pentafarm RoTEM® ) was performed, as previously described by Sorensen et al. (J Thromb Haemost. 2003 Mar;1(3):551–8), over a 36 months period on all consecutive patients referred for bleeding work-up to the Haemostasis and Thrombosis Unit of the Cliniques universitaires Saint-Luc, Brussels, Belgium. Ninety-three patients fulfilling the diagnosis criteria of VWD were analysed (38 ± 18 year, 29 males-64 females). The distribution of VWD types was as follows: type 1 (59), type 2 (31) with subtypes 2A (12), 2M (17), 2B (2) and type 3 (3). The control population included 43 healthy individuals (24 females, 19 males, mean age: 38 ± 10 yr). For each patient, the following tests were performed: closure time measured by PFA-100 using the ADP cartridge, Von Willlebrand factor antigen (VWF:Ag) and activity (VWF:Ac) (collagen binding assay), factor VIII level (one-stage assay) and RoTEM®. The following parameters of the RoTEM® tracing were analysed: clotting time (CT), clot formation time (CFT), maximum clot firmness (MCF), alpha angle and maximum clot lysis (ML).
VWD was associated with a significant prolongation of the CT and the CFT. By contrast, the MCF, the alpha angle and the ML were not significantly different between patients and controls. By multiple regression analysis, the CT and CFT prolongation was found to be influenced only by the reduction of the factor VIII levels. The most important prolongations of the CT and the CFT were found in type 3 VWD reflecting the severe factor VIII deficiency. No significant differences of the RoTEM® parameters were found between type 1, subtypes 2A and 2M, which altogether represent the majority (94%) of the VWD population. CT and CFT prolongation was not correlated with other parameters (closure time, VWF:Ag and VWF:Ac). As expected, the closure time was determined by the level of VWF activity.
In conclusion, although we observed a significant prolongation of the CT and the CFT in patients with VWD, RoTEM® appears to be of limited value for the diagnosis and characterization of VWD. Nevertheless, RoTEM® could be used as a screening tool to identify factor VIII deficiency present in a subset of patients with VWD.
Congenital Factor Deficiencies in Children: A Report of a Single-Center Experience