Ina Isabella Høiland1, Robin Amanda Liang2, Kristian Hindberg2, Nadezhda Latysheva3, Ole-Lars Brekke4, Tom Eirik Mollnes5, John-Bjarne Hansen3. 1. K. G. Jebsen - Thrombosis Research and Expertise Center (TREC), Department of Clinical Medicine, UiT - The Arctic University of Norway, Tromsø, Norway. Electronic address: ina.i.hoiland@uit.no. 2. K. G. Jebsen - Thrombosis Research and Expertise Center (TREC), Department of Clinical Medicine, UiT - The Arctic University of Norway, Tromsø, Norway. 3. K. G. Jebsen - Thrombosis Research and Expertise Center (TREC), Department of Clinical Medicine, UiT - The Arctic University of Norway, Tromsø, Norway; Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway. 4. K. G. Jebsen - Thrombosis Research and Expertise Center (TREC), Department of Clinical Medicine, UiT - The Arctic University of Norway, Tromsø, Norway; Research Laboratory, Nordland Hospital, Bodø, Norway. 5. K. G. Jebsen - Thrombosis Research and Expertise Center (TREC), Department of Clinical Medicine, UiT - The Arctic University of Norway, Tromsø, Norway; Department of Immunology, Oslo University Hospital, University of Oslo, Norway; Research Laboratory, Nordland Hospital, Bodø, Norway.
Abstract
INTRODUCTION: Deep vein thrombosis (DVT) originates in the valvular sinuses of large veins in a local milieu characterized by stasis and severe hypoxia. This may induce complement- and coagulation activation, which potentially increases the risk of venous thromboembolism (VTE). The aim of the present study was to investigate whether the activity of the complement pathways, the level of mannose-binding lectin (MBL) and tissue-factor (TF) induced thrombin generation were associated with risk of unprovoked VTE. METHODS: A case-control study was performed in patients with unprovoked VTE (n = 24) and age- and sex-matched healthy controls (n = 24). Serum complement pathway activity was measured by the total complement screen assay (Wieslab®). MBL was quantified by ELISA. Plasma TF-induced thrombin generation was measured using the CAT-assay. RESULTS: Activity in the highest quintile of the classical pathway was associated with increased odds of unprovoked VTE (OR 4.5, 95% CI; 0.8-24.7). Moreover, MBL deficiency (≤100 ng/ml) was associated with unprovoked VTE (OR 3.5, 95% Cl; 0.8-15.3). VTE patients had shortened TF-induced lag-time (4.8 ± 0.6 min vs. 5.8 ± 2.1 min, p < 0.001) and a higher endogenous thrombin potential (ETP) (1383 ± 267 nM∗h vs. 1265 ± 247 nM∗h, p = 0.07) than controls. No association between the classical complement pathway activity or MBL deficiency, and parameters of TF-induced thrombin generation was observed. CONCLUSION: Our findings suggest that high activity of the classical complement pathway, and MBL deficiency, might be associated with an increased odds of unprovoked VTE, independent of activation of TF-induced coagulation.
INTRODUCTION:Deep vein thrombosis (DVT) originates in the valvular sinuses of large veins in a local milieu characterized by stasis and severe hypoxia. This may induce complement- and coagulation activation, which potentially increases the risk of venous thromboembolism (VTE). The aim of the present study was to investigate whether the activity of the complement pathways, the level of mannose-binding lectin (MBL) and tissue-factor (TF) induced thrombin generation were associated with risk of unprovoked VTE. METHODS: A case-control study was performed in patients with unprovoked VTE (n = 24) and age- and sex-matched healthy controls (n = 24). Serum complement pathway activity was measured by the total complement screen assay (Wieslab®). MBL was quantified by ELISA. Plasma TF-induced thrombin generation was measured using the CAT-assay. RESULTS: Activity in the highest quintile of the classical pathway was associated with increased odds of unprovoked VTE (OR 4.5, 95% CI; 0.8-24.7). Moreover, MBL deficiency (≤100 ng/ml) was associated with unprovoked VTE (OR 3.5, 95% Cl; 0.8-15.3). VTEpatients had shortened TF-induced lag-time (4.8 ± 0.6 min vs. 5.8 ± 2.1 min, p < 0.001) and a higher endogenous thrombin potential (ETP) (1383 ± 267 nM∗h vs. 1265 ± 247 nM∗h, p = 0.07) than controls. No association between the classical complement pathway activity or MBL deficiency, and parameters of TF-induced thrombin generation was observed. CONCLUSION: Our findings suggest that high activity of the classical complement pathway, and MBL deficiency, might be associated with an increased odds of unprovoked VTE, independent of activation of TF-induced coagulation.
Authors: Inge A M van Erp; Iliana Michailidou; Thomas A van Essen; Mathieu van der Jagt; Wouter Moojen; Wilco C Peul; Frank Baas; Kees Fluiter Journal: Neurotherapeutics Date: 2022-10-12 Impact factor: 6.088
Authors: Khanh T Do; Laura Quan Man Chow; Karen Reckamp; Rachel E Sanborn; Howard Burris; Francisco Robert; D Ross Camidge; Conor E Steuer; John H Strickler; Amy Weise; Jennifer M Specht; Martin Gutierrez; Peter Haughney; Shawna Hengel; Christina Louise Derleth; Timothy A Yap Journal: Oncologist Date: 2021-09-22