Anna Vikerfors1, Elisabet Svenungsson2, Anna Ågren3, Fariborz Mobarrez4, Katarina Bremme5, Margareta Holmström3, Anna Eelde3, Maria Bruzelius3, Graciela Elgue4, Håkan Wallén4, Aleksandra Antovic6. 1. Karolinska Institutet, Department of Medicine Solna, Unit of Rheumatology, Karolinska University Hospital, Stockholm, Sweden. Electronic address: anna.vikerfors@karolinska.se. 2. Karolinska Institutet, Department of Medicine Solna, Unit of Rheumatology, Karolinska University Hospital, Stockholm, Sweden. 3. Coagulation Unit, Haematology Centre, Karolinska University Hospital and Department of Medicine, Karolinska Institutet, Stockholm, Sweden. 4. Karolinska Institutet, Department of Clinical Sciences, Danderyds Hospital, Division of Cardiovascular Medicine, Stockholm, Sweden. 5. Karolinska Institutet, Department of Women's and Children's Health, Division of Obstetrics and Gynaecology, Karolinska University Hospital, Stockholm, Sweden. 6. Karolinska Institutet, Department of Medicine Solna, Unit of Rheumatology, Karolinska University Hospital, Stockholm, Sweden; Karolinska Institutet, Department of Clinical Sciences, Danderyds Hospital, Division of Cardiovascular Medicine, Stockholm, Sweden.
Abstract
OBJECTIVE: The antiphospholipid syndrome (APS) is defined by persistent antiphospholipid antibodies together with thrombosis and/or pregnancy morbidity. We investigated the tightness of fibrin clot and fibrinolytic function in plasma samples from APS patients compared with two control groups. MATERIAL AND METHODS: APS patients (n=49), healthy controls (HC) (n=19) and warfarin-treated nonAPS thrombosis controls (nonAPS-TC) (n=39) were investigated. Fibrin permeability was assessed as the permeability coefficient (Ks) by a flow measurement technique. Additionally, clot density and fibrinolytic function was analysed by a turbidimetric clotting and lysis assay. Fibrin structure was visualised using scanning electron microscopy. Finally, the number of cell-derived microparticles (MPs) in the samples were correlated to fibrin permeability RESULTS AND CONCLUSIONS: The Ks value was lower in samples from APS-patients compared to HC and nonAPS-TC (p<0.0001 for both) indicating a less permeable fibrin clot in APS patients. Scanning electron microscopy images confirmed compact fibrin with smaller intrinsic pores and thinner fibers in samples from APS patients as compared to HC. Prolonged fibrinolysis (clot lysis) times were present in the subgroup of APS patients with previous arterial thrombosis (n=15) as compared to HC and to nonAPS-TC (all p-values<0.05). In conclusion, tighter fibrin clots were formed in plasma from APS patients compared with healthy controls and warfarin treated patients with thrombosis of "nonAPS origin". This new observation presents a possible mechanism contributing to the thrombotic predisposition of APS patients. Impaired fibrinolysis, selectively present among APS patients with previous arterial thrombosis, may further aggravate the pro-thrombotic state in this APS subgroup.
OBJECTIVE: The antiphospholipid syndrome (APS) is defined by persistent antiphospholipid antibodies together with thrombosis and/or pregnancy morbidity. We investigated the tightness of fibrin clot and fibrinolytic function in plasma samples from APSpatients compared with two control groups. MATERIAL AND METHODS:APSpatients (n=49), healthy controls (HC) (n=19) and warfarin-treated nonAPS thrombosis controls (nonAPS-TC) (n=39) were investigated. Fibrin permeability was assessed as the permeability coefficient (Ks) by a flow measurement technique. Additionally, clot density and fibrinolytic function was analysed by a turbidimetric clotting and lysis assay. Fibrin structure was visualised using scanning electron microscopy. Finally, the number of cell-derived microparticles (MPs) in the samples were correlated to fibrin permeability RESULTS AND CONCLUSIONS: The Ks value was lower in samples from APS-patients compared to HC and nonAPS-TC (p<0.0001 for both) indicating a less permeable fibrin clot in APSpatients. Scanning electron microscopy images confirmed compact fibrin with smaller intrinsic pores and thinner fibers in samples from APSpatients as compared to HC. Prolonged fibrinolysis (clot lysis) times were present in the subgroup of APSpatients with previous arterial thrombosis (n=15) as compared to HC and to nonAPS-TC (all p-values<0.05). In conclusion, tighter fibrin clots were formed in plasma from APSpatients compared with healthy controls and warfarin treated patients with thrombosis of "nonAPS origin". This new observation presents a possible mechanism contributing to the thrombotic predisposition of APSpatients. Impaired fibrinolysis, selectively present among APSpatients with previous arterial thrombosis, may further aggravate the pro-thrombotic state in this APS subgroup.
Authors: Piotr Mazur; Bogusław Gawęda; Joanna Natorska; Michał Ząbczyk; Anetta Undas; Jerzy Sadowski; Grzegorz Kopeć; Marcin Waligóra; Piotr Podolec; Bogusław Kapelak Journal: J Thromb Thrombolysis Date: 2016-08 Impact factor: 2.300