Screening for von Willebrand Disease With a New Analyzer Using High Shear Stress: A Study of 60 Cases

Abstract

We have evaluated the performance of a new analyzer using high shear stress, the PFA-100 (Platelet Function Analyzer, Dade International, Massy, France), for screening of patients with von Willebrand disease (vWD). Whole citrated blood is aspirated through a capillary to the central aperture of a membrane coated with collagen and with a platelet agonist (either epinephrine or adenosine diphosphate [ADP]). The time required to obtain occlusion of the aperture by a platelet plug is defined as the closure time (CT). We studied 60 patients with different types of vWD and 96 normal subjects. Fourteen subjects with hemophilia and 15 patients with a platelet disorder were also analyzed. When omitting results from two patients with type 2N, the 58 other patients with type 1, type 2A, type 2B, type 3, or acquired vWD all exhibited an abnormal occlusion with collagen-ADP (sensitivity, 100%) and 56 of 58 had an abnormal CT with collagen-epinephrine (sensitivity, 96.5%). Only two patients with mild type 1 were not detected with collagen-epinephrine. In comparison, the bleeding time (BT) was normal in 20 patients: 17 with type 1, two with type 2A, and one with acquired vWD (sensitivity, 65.5%). The specificity of the PFA-100 was over 95% with both types of cartridges. Thus, the analyzer is well adapted to routine testing, as it has the advantages of simplicity and ease of execution, and demonstrates a high sensitivity, clearly superior to that of BT, for the screening of patients with vWD.

Variables influencing Platelet Function Analyzer‐100TM closure times in healthy individuals

“…A direct comparison between our blood group O and non-O individuals revealed significantly greater CEPI and CADP-CT and lower VWF:CBA values in subjects with blood group O, whereas BT and PA was not significantly different between both groups. We confirmed a significant linear correlation between PFA-100 TM results and VWF and between CEPI-CT and CADP-CT (Fressinaud et al, 1998;Cattaneo et al, 1999;Jilma-Stohlawetz et al, 2001;Favarolo, 2002;Wuillemin et al, 2002;Chakroun et al, 2004; Table IV). The BT correlated significantly with ADPPA and AAPA and the PA values correlated significantly with each other.…”

“…This resulted in substantially differing references ranges between study groups (Jilma, 2001). As the upper limits of respective reference ranges are the cutoff levels required to calculate sensitivity, specificity and predictive values in clinical studies, it is not surprising that many (Fressinaud et al, 1998;Cattaneo et al, 1999;Dean et al, 2000;Schlammadinger et al, 2000;Cariappa et al, 2003;Posan et al, 2003) but not all (Wuillemin et al, 2002;Quiroga et al, 2004) trials found the PFA-100 TM system to be sufficiently sensitive and superior to the bleeding time (BT) in detecting VWD.…”

“…Comparison between our blood group O and non-O individuals and regression analysis supported previous conclusions that PFA-100 TM CT more significantly reflect VWF activity than platelet function. Most clinical studies in patients with VWD and platelet disorders had proven the good sensitivity of the PFA-100 TM system to detect VWD (Fressinaud et al, 1998;Cattaneo et al, 1999;Dean et al, 2000;Schlammadinger et al, 2000;Jilma, 2001;Favarolo, 2002;Cariappa et al, 2003;Posan et al, 2003) but a lower diagnostic performance for diagnosing mild platelet dysfunction (Favarolo, 2002;Wuillemin et al, 2002;Posan et al, 2003;Quiroga et al, 2004). A direct comparison between our blood group O and non-O individuals revealed significantly greater CEPI and CADP-CT and lower VWF:CBA values in subjects with blood group O, whereas BT and PA was not significantly different between both groups.…”

Disease progression and defects in primary hemostasis as major cause of bleeding in multiple myeloma

“…For As far as the diagnosis of VWD is concerned, the PFA100 undoubtedly performs excellently. 20,28,29 P < .001, Figure 3). Interestingly, patients with more than one bleeding episode showed a considerably shortened overall survival too.…”

The diagnosis of von Willebrand disease: a guideline from the UK Haemophilia Centre Doctors’ Organization

“…The closure time in the PFA-100 has recently been proposed as superior to the bleeding time as it is reproducible, simple and predictive; detecting VWD with a sensitivity of >95% compared with 50% for the bleeding time [54]. Like the bleeding time it is not specific for VWD and it may be prolonged by other defects of primary haemostasis except collagen disorders.…”