OC 63.3 - Combined effect of high factor VIII levels and high mean platelet volume on the risk of future venous thromboembolism

Tuesday, June 27, 2023

15:15 – 15:30 ET

Room: 520

Session Available As: On-Demand

Co-Author(s)

EH

Ellen-Sofie Hansen

PhD student
Thrombosis Research Group (TREC), Department of Clinical Medicine, UiT – The Arctic University of Norway, Tromsø, Norway
Tromsø, Troms, Norway
ME

Magnus S. Edvardsen

PhD student
Thrombosis Research Group (TREC), Department of Clinical Medicine, UiT – The Arctic University of Norway, Tromsø, Norway
Tromsø, Troms, Norway
NL

Nadezhda Latysheva

Researcher
Thrombosis Research Group (TREC), Department of Clinical Medicine, UiT – The Arctic University of Norway, Tromsø, Norway
Tromsø, Troms, Norway
PA

Pål Aukrust

Professor
Faculty of Medicine, University of Oslo, Oslo, Norway
Oslo, Oslo, Norway
TU

Thor Ueland

Professor
Faculty of Medicine, University of Oslo, Oslo, Norway
Oslo, Oslo, Norway
JH

John-Bjarne Hansen, MD, PhD

Professor
Thrombosis Research Center (TREC), Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway
Tromsø, Troms, Norway
Sigrid K. Brækkan, PhD (she/her/hers)

Professor
Thrombosis Research Center (TREC), Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway
Tromsø, Troms, Norway

Presenting Author(s)

Vânia M. Morelli, MD PhD

Researcher
Thrombosis Research Group (TREC), Department of Clinical Medicine, UiT – The Arctic University of Norway, Tromsø, Norway
Tromsø, Troms, Norway

Background: The association between high factor VIII (FVIII) levels and venous thromboembolism (VTE) is well-established but the mechanisms underlying this association are not fully understood. Large platelets, as reflected by a high mean platelet volume (MPV), are prone to expose phosphatidylserine on their membrane and associated with increased VTE risk. As thrombin generation is facilitated by a complex of activated FVIII and FIX formed on platelet membrane, we hypothesize that high FVIII combined with large platelets has supra-additive effect on VTE risk due to biological interaction.

Aims: To investigate the joint effect of high FVIII plasma levels and high MPV on the risk of future VTE.

Methods: A population-based nested case-control study with 365 incident VTE-cases and 710 controls was derived from the Tromsø Study cohort. FVIII and MPV were determined at baseline. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated across combined categories of FVIII tertiles ( < 85%, 85-108%, ≥108%) and predefined MPV strata ( < 8.5, 8.5-9.5, ≥9.5fL) in models adjusted for age, sex, body mass index, C-reactive protein and platelet count. Ethical approval and informed consent were obtained.

Results: In each MPV stratum, the VTE risk increased linearly across FVIII tertiles, and the highest risk estimates were observed among participants with MPV≥9.5 fL (Table 1). Participants with FVIII levels in the highest tertile and MPV≥9.5 fL (i.e., joint exposure) had an OR for VTE of 2.71 (95% CI 1.44-5.10) compared with those with FVIII in the lowest tertile and MPV < 8.5 fL (reference). In the joint exposure group, 52% (95% CI 13%-89%) of VTEs were attributable to the biological interaction between FVIII and MPV.

Conclusion(s): The combination of high FVIII levels and large platelets had a supra-additive effect on VTE risk. Our findings might suggest that FVIII would contribute to the VTE risk by interacting biologically with large platelets.

Learning Objectives:

Upon completion, participant will be able to describe the rationale for studying the interaction between high factor VIII levels and high mean platelet volume in relation to the VTE risk
Upon completion, participant will be able to debate the combined effect of high factor VIII levels and high mean platelet volume on the risk of future venous thromboembolism
Upon completion, participant will be able to reflect about the potential implications of the interaction between high factor VIII and high mean platelet volume in VTE pathogenesis