Effect of plasma levels of factor VIII according to procoagulant phospholipids on the risk of future venous thromboembolism

Background: A high level of plasma coagulation factor (F)VIII is an established and likely causal risk factor for venous thromboembolism (VTE). Procoagulant phospholipids (PPLs) facilitate FVIII activity in coagulation. Objectives: To assess the association between plasma levels of FVIII and risk of...

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Main Authors: Magnus S. Edvardsen, Ellen-Sofie Hansen, Thor Ueland, Nadezhda Latysheva, Pål Aukrust, Omri Snir, Vânia M. Morelli, John-Bjarne Hansen
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:Research and Practice in Thrombosis and Haemostasis
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Online Access:http://www.sciencedirect.com/science/article/pii/S2475037924003315
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author Magnus S. Edvardsen
Ellen-Sofie Hansen
Thor Ueland
Nadezhda Latysheva
Pål Aukrust
Omri Snir
Vânia M. Morelli
John-Bjarne Hansen
author_facet Magnus S. Edvardsen
Ellen-Sofie Hansen
Thor Ueland
Nadezhda Latysheva
Pål Aukrust
Omri Snir
Vânia M. Morelli
John-Bjarne Hansen
author_sort Magnus S. Edvardsen
collection DOAJ
description Background: A high level of plasma coagulation factor (F)VIII is an established and likely causal risk factor for venous thromboembolism (VTE). Procoagulant phospholipids (PPLs) facilitate FVIII activity in coagulation. Objectives: To assess the association between plasma levels of FVIII and risk of future VTE according to PPL clotting time (PPLCT), an inverse surrogate measure of plasma PPL activity. Methods: A population-based nested case-control study comprising 278 incident VTE cases and 593 randomly selected age- and sex-matched controls were derived from the Tromsø cohort. Exposures were determined from data collected at the cohort baseline. Logistic regression was used to estimate odds ratios (ORs) with 95% CIs for VTE across tertiles of FVIII and PPLCT. Results: High (tertile 3) vs low (tertile 1) FVIII antigen levels resulted in an age- and sex-adjusted OR of 1.53 (95% CI, 0.78-3.00) in those with high PPLCT (low PPL activity), while the corresponding OR for those with low PPLCT (high PPL activity) was 1.88 (95% CI, 0.96-3.66). In the biological interaction analysis, participants with both high FVIII and PPL activity had an OR of 1.86 (95% CI, 0.97-3.57) compared with those with low FVIII and PPL activity. In the joint exposure group, 10% (95% CI, −55% to 75%) of VTEs could be attributable to the interaction between FVIII and PPL activity. Results remained similar after further adjustment for body mass index, C-reactive protein, arterial cardiovascular disease, and cancer. Conclusion: The effect of high FVIII levels on VTE risk was particularly augmented in those with high PPL activity, suggesting that the effect of FVIII on VTE risk might be partially dependent on PPL activity.
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spelling doaj-art-d8ce43679752470da77338f24bbd7f5c2024-12-26T08:56:54ZengElsevierResearch and Practice in Thrombosis and Haemostasis2475-03792025-01-0191102636Effect of plasma levels of factor VIII according to procoagulant phospholipids on the risk of future venous thromboembolismMagnus S. Edvardsen0Ellen-Sofie Hansen1Thor Ueland2Nadezhda Latysheva3Pål Aukrust4Omri Snir5Vânia M. Morelli6John-Bjarne Hansen7Thrombosis Research Group, Department of Clinical Medicine, UiT – The Arctic University of Norway, Tromsø, Norway; Division of Internal Medicine, University Hospital of North Norway, Tromsø, NorwayThrombosis Research Group, Department of Clinical Medicine, UiT – The Arctic University of Norway, Tromsø, NorwayThrombosis Research Group, Department of Clinical Medicine, UiT – The Arctic University of Norway, Tromsø, Norway; Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, NorwayThrombosis Research Group, Department of Clinical Medicine, UiT – The Arctic University of Norway, Tromsø, NorwayResearch Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital, Rikshospitalet, Oslo, NorwayThrombosis Research Group, Department of Clinical Medicine, UiT – The Arctic University of Norway, Tromsø, Norway; Department of Medical Biology, UiT – The Arctic University of Norway, Tromsø, NorwayThrombosis Research Group, Department of Clinical Medicine, UiT – The Arctic University of Norway, Tromsø, Norway; Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway; Correspondence Vânia M. Morelli, Thrombosis Research Group, Department of Clinical Medicine, UiT – The Arctic University of Norway, Tromsø N-9037, Norway.Thrombosis Research Group, Department of Clinical Medicine, UiT – The Arctic University of Norway, Tromsø, Norway; Division of Internal Medicine, University Hospital of North Norway, Tromsø, NorwayBackground: A high level of plasma coagulation factor (F)VIII is an established and likely causal risk factor for venous thromboembolism (VTE). Procoagulant phospholipids (PPLs) facilitate FVIII activity in coagulation. Objectives: To assess the association between plasma levels of FVIII and risk of future VTE according to PPL clotting time (PPLCT), an inverse surrogate measure of plasma PPL activity. Methods: A population-based nested case-control study comprising 278 incident VTE cases and 593 randomly selected age- and sex-matched controls were derived from the Tromsø cohort. Exposures were determined from data collected at the cohort baseline. Logistic regression was used to estimate odds ratios (ORs) with 95% CIs for VTE across tertiles of FVIII and PPLCT. Results: High (tertile 3) vs low (tertile 1) FVIII antigen levels resulted in an age- and sex-adjusted OR of 1.53 (95% CI, 0.78-3.00) in those with high PPLCT (low PPL activity), while the corresponding OR for those with low PPLCT (high PPL activity) was 1.88 (95% CI, 0.96-3.66). In the biological interaction analysis, participants with both high FVIII and PPL activity had an OR of 1.86 (95% CI, 0.97-3.57) compared with those with low FVIII and PPL activity. In the joint exposure group, 10% (95% CI, −55% to 75%) of VTEs could be attributable to the interaction between FVIII and PPL activity. Results remained similar after further adjustment for body mass index, C-reactive protein, arterial cardiovascular disease, and cancer. Conclusion: The effect of high FVIII levels on VTE risk was particularly augmented in those with high PPL activity, suggesting that the effect of FVIII on VTE risk might be partially dependent on PPL activity.http://www.sciencedirect.com/science/article/pii/S2475037924003315factor VIIIphosphatidylserinephospholipidsvenous thromboembolismvenous thrombosis
spellingShingle Magnus S. Edvardsen
Ellen-Sofie Hansen
Thor Ueland
Nadezhda Latysheva
Pål Aukrust
Omri Snir
Vânia M. Morelli
John-Bjarne Hansen
Effect of plasma levels of factor VIII according to procoagulant phospholipids on the risk of future venous thromboembolism
Research and Practice in Thrombosis and Haemostasis
factor VIII
phosphatidylserine
phospholipids
venous thromboembolism
venous thrombosis
title Effect of plasma levels of factor VIII according to procoagulant phospholipids on the risk of future venous thromboembolism
title_full Effect of plasma levels of factor VIII according to procoagulant phospholipids on the risk of future venous thromboembolism
title_fullStr Effect of plasma levels of factor VIII according to procoagulant phospholipids on the risk of future venous thromboembolism
title_full_unstemmed Effect of plasma levels of factor VIII according to procoagulant phospholipids on the risk of future venous thromboembolism
title_short Effect of plasma levels of factor VIII according to procoagulant phospholipids on the risk of future venous thromboembolism
title_sort effect of plasma levels of factor viii according to procoagulant phospholipids on the risk of future venous thromboembolism
topic factor VIII
phosphatidylserine
phospholipids
venous thromboembolism
venous thrombosis
url http://www.sciencedirect.com/science/article/pii/S2475037924003315
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