Manal Ibrahim-Kosta1, Pascal Bailly2, Monique Silvy2, Noemie Saut3, Pierre Suchon1, Pierre-Emmanuel Morange4, Jacques Chiaroni2, David-Alexandre Trégouët5, Louisa Goumidi6. 1. Aix Marseille Univ, INSERM, INRAE, C2VN, Marseille, France; Hematology Laboratory, La Timone University Hospital of Marseille, Marseille, France. 2. Etablissement Français du Sang PACA-Corse "Biologie des Groupes Sanguins", Marseille, France; Aix Marseille Univ, EFS, CNRS, ADES, "Biologie des Groupes Sanguins", Marseille, France. 3. Aix Marseille Univ, INSERM, INRAE, C2VN, Marseille, France; Hematology Laboratory, La Timone University Hospital of Marseille, Marseille, France; CRB Assistance Publique - Hôpitaux de Marseille, HemoVasc (CRB AP-HM HemoVasc), Marseille, France. 4. Aix Marseille Univ, INSERM, INRAE, C2VN, Marseille, France; Hematology Laboratory, La Timone University Hospital of Marseille, Marseille, France; CRB Assistance Publique - Hôpitaux de Marseille, HemoVasc (CRB AP-HM HemoVasc), Marseille, France. Electronic address: pierre.morange@ap-hm.fr. 5. INSERM UMR_S 1219, Bordeaux Population Health Research Center, University of Bordeaux, France. 6. Aix Marseille Univ, INSERM, INRAE, C2VN, Marseille, France.
Abstract
INTRODUCTION: ABO blood group influence the risk of venous thromboembolism (VTE) by modifying A and B glycosyltransferases (AGT and BGT) activities that further modulates Factor VIII (FVIII) and von Willebrand Factor (VWF) plasma levels. The aim of this work was to evaluate the association of plasma GTs activities with VWF/FVIII plasma levels and VTE risk in a case-control study. MATERIALS AND METHODS: 420 cases were matched with 420 controls for age and ABO blood group. GT activities in plasma were measured using the quantitative transfer of tritiated N-acetylgalactosamine or galactose to the 2'-fucosyl-lactose and expressed in disintegration per minute/30 μL of plasma and 2 h of reaction (dpm/30 μL/2H). FVIII and VWF plasma levels were respectively measured using human FVIII-deficient plasma in a 1-stage factor assay and STA LIATEST VWF (Diagnostica Stago). RESULTS: A and B GT activities were significantly lower in cases than in controls (8119 ± 4027 vs 9682 ± 4177 dpm/30 μL/2H, p = 2.03 × 10-5, and 4931 ± 2305 vs 5524 ± 2096 dpm/30 μL/2H, p=0.043 respectively). This association was observed whatever the ABO blood groups. The ABO A1 blood group was found to explain~80% of AGT activity. After adjusting for ABO blood groups, AGT activity was not correlated to VWF/FVIII plasma levels. Conversely, there was a moderate correlation (ρ ~ 0.30) between BGT activity and VWF/ FVIII plasma levels in B blood group carriers. CONCLUSION: Work showed, for the first time, that GT activities were decreased in VTE patients in comparison to controls with the same ABO blood group. The biological mechanisms responsible for this association remained to be determined.
INTRODUCTION:ABO blood group influence the risk of venous thromboembolism (VTE) by modifying A and B glycosyltransferases (AGT and BGT) activities that further modulates Factor VIII (FVIII) and von Willebrand Factor (VWF) plasma levels. The aim of this work was to evaluate the association of plasma GTs activities with VWF/FVIII plasma levels and VTE risk in a case-control study. MATERIALS AND METHODS: 420 cases were matched with 420 controls for age and ABO blood group. GT activities in plasma were measured using the quantitative transfer of tritiated N-acetylgalactosamine or galactose to the 2'-fucosyl-lactose and expressed in disintegration per minute/30 μL of plasma and 2 h of reaction (dpm/30 μL/2H). FVIII and VWF plasma levels were respectively measured using humanFVIII-deficient plasma in a 1-stage factor assay and STA LIATEST VWF (Diagnostica Stago). RESULTS: A and B GT activities were significantly lower in cases than in controls (8119 ± 4027 vs 9682 ± 4177 dpm/30 μL/2H, p = 2.03 × 10-5, and 4931 ± 2305 vs 5524 ± 2096 dpm/30 μL/2H, p=0.043 respectively). This association was observed whatever the ABO blood groups. The ABO A1 blood group was found to explain~80% of AGT activity. After adjusting for ABO blood groups, AGT activity was not correlated to VWF/FVIII plasma levels. Conversely, there was a moderate correlation (ρ ~ 0.30) between BGT activity and VWF/ FVIII plasma levels in B blood group carriers. CONCLUSION: Work showed, for the first time, that GT activities were decreased in VTEpatients in comparison to controls with the same ABO blood group. The biological mechanisms responsible for this association remained to be determined.
Authors: Louisa Goumidi; Florian Thibord; Kerri L Wiggins; Ruifang Li-Gao; Mickael R Brown; Astrid van Hylckama Vlieg; Joan-Carles Souto; José-Manuel Soria; Manal Ibrahim-Kosta; Noémie Saut; Delphine Daian; Robert Olaso; Philippe Amouyel; Stéphanie Debette; Anne Boland; Pascal Bailly; Alanna C Morrison; Denis O Mook-Kanamori; Jean-François Deleuze; Andrew Johnson; Paul S de Vries; Maria Sabater-Lleal; Jacques Chiaroni; Nicholas L Smith; Frits R Rosendaal; Daniel I Chasman; David-Alexandre Trégouët; Pierre-Emmanuel Morange Journal: Blood Date: 2021-04-29 Impact factor: 25.476
Authors: Ruchika Goel; Evan M Bloch; France Pirenne; Arwa Z Al-Riyami; Elizabeth Crowe; Laetitia Dau; Kevin Land; Mary Townsend; Thachil Jecko; Naomi Rahimi-Levene; Gopal Patidar; Cassandra D Josephson; Satyam Arora; Marion Vermeulen; Hans Vrielink; Celina Montemayor; Adaeze Oreh; Salwa Hindawi; Karin van den Berg; Katherine Serrano; Cynthia So-Osman; Erica Wood; Dana V Devine; Steven L Spitalnik Journal: Vox Sang Date: 2021-02-12 Impact factor: 2.996