Emmanuel J Favaloro1,2, Susan Oliver1, Soma Mohammed1, Ronny Vong1. 1. Haematology, Institute of Clinical Pathology and Medical Research (ICPMR), NSW Health Pathology, Westmead Hospital, Westmead, NSW, Australia. 2. Sydney Centres for Thrombosis and Haemostasis, Westmead Hospital, Westmead, NSW, Australia.
Abstract
INTRODUCTION: Diagnosis of von Willebrand disease (VWD) is challenging due to heterogeneity of VWD and test limitations. Many von Willebrand factor (VWF) assays are utilized, including antigen (Ag), activity and multimer analysis. Activity assays include ristocetin cofactor using platelets (VWF:RCo) or other particles incorporating recombinant glycoprotein I ('VWF:GPIbR'), or other GPI binding assays using gain-of-function mutations ('VWF:GPIbM'), or collagen binding (VWF:CB). AIM: To comparatively evaluate modern contemporary VWF activity assays vs VWF multimer analysis using modern contemporary methods. MATERIALS AND METHODS: Several VWF activity assays (VWF:RCo, VWF:GPIbR, VWF:GPIbM, VWF:CB) assessed (typically as a ratio against VWF:Ag) against a new semi-automated procedure for different types of VWD (1, 3, 2A, 2B, 2M), plus control material (n = 580). The evaluation also focussed on relative loss of high and very high molecular weight multimers (HMWM and VHMWM) by densitometric scanning. RESULTS: All evaluated VWF activity/Ag ratios showed high correlation to the presence/absence of HMWM and VHMWM, although VWF:CB/Ag and VWF:GPIbR/Ag ratios using an automated chemiluminescence method yielded highest correlation coefficients (r = .909 and .874, respectively, for HMWM). Use of the investigative procedure (VHMWM) identified fewer false positives for 'loss' in type 1 VWD. CONCLUSIONS: This comparative investigation identified that new automated chemiluminescence VWF activity assays best identified relative loss or presence of HMWM and VHMWM according to activity to Ag ratios and an alternative investigative method for identifying VHMWM in multimer testing for a new commercial multimer method may lead to fewer false identifications of HMW loss in type 1 VWD.
INTRODUCTION: Diagnosis of von Willebrand disease (VWD) is challenging due to heterogeneity of VWD and test limitations. Many von Willebrand factor (VWF) assays are utilized, including antigen (Ag), activity and multimer analysis. Activity assays include ristocetin cofactor using platelets (VWF:RCo) or other particles incorporating recombinant glycoprotein I ('VWF:GPIbR'), or other GPI binding assays using gain-of-function mutations ('VWF:GPIbM'), or collagen binding (VWF:CB). AIM: To comparatively evaluate modern contemporary VWF activity assays vs VWF multimer analysis using modern contemporary methods. MATERIALS AND METHODS: Several VWF activity assays (VWF:RCo, VWF:GPIbR, VWF:GPIbM, VWF:CB) assessed (typically as a ratio against VWF:Ag) against a new semi-automated procedure for different types of VWD (1, 3, 2A, 2B, 2M), plus control material (n = 580). The evaluation also focussed on relative loss of high and very high molecular weight multimers (HMWM and VHMWM) by densitometric scanning. RESULTS: All evaluated VWF activity/Ag ratios showed high correlation to the presence/absence of HMWM and VHMWM, although VWF:CB/Ag and VWF:GPIbR/Ag ratios using an automated chemiluminescence method yielded highest correlation coefficients (r = .909 and .874, respectively, for HMWM). Use of the investigative procedure (VHMWM) identified fewer false positives for 'loss' in type 1 VWD. CONCLUSIONS: This comparative investigation identified that new automated chemiluminescence VWF activity assays best identified relative loss or presence of HMWM and VHMWM according to activity to Ag ratios and an alternative investigative method for identifying VHMWM in multimer testing for a new commercial multimer method may lead to fewer false identifications of HMW loss in type 1 VWD.
Authors: Ferdows Atiq; Esmee Wuijster; Moniek P M de Maat; Marieke J H A Kruip; Marjon H Cnossen; Frank W G Leebeek Journal: J Thromb Haemost Date: 2021-01-24 Impact factor: 5.824
Authors: Johan Boender; Ferdows Atiq; Marjon H Cnossen; Johanna G van der Bom; Karin Fijnvandraat; Joke de Meris; Moniek P M de Maat; Karin P M van Galen; Britta A P Laros-van Gorkom; Karina Meijer; Jeroen Eikenboom; Frank W G Leebeek Journal: Hemasphere Date: 2021-02-17