Thrombosis Research Group, Department of Clinical Medicine, UiT-the Arctic University of Norway, Tromsø, Norway.
Thrombosis Research Group, Department of Clinical Medicine, UiT-the Arctic University of Norway, Tromsø, Norway.
J Thromb Haemost. 2023 Oct;21(10):2844-2853. doi: 10.1016/j.jtha.2023.06.022. Epub 2023 Jun 29.
High factor VIII (FVIII) levels and large platelets, as reflected by a high mean platelet volume (MPV), are separately associated with increased risk of venous thromboembolism (VTE). Whether the combination of high FVIII levels and large platelets has a supra-additive effect on VTE risk is unknown.
We aimed to investigate the joint effect of high FVIII levels and large platelets, as reflected by high MPV, on the risk of future incident VTE.
A population-based nested case-control study with 365 incident VTE cases and 710 controls was derived from the Tromsø study. FVIII antigen levels and MPV were measured in blood samples drawn at baseline. Odds ratios with 95% CIs were estimated across FVIII tertiles (<85%, 85%-108%, and ≥108%) and within predefined MPV strata (<8.5, 8.5-9.5, and ≥9.5 fL).
VTE risk increased linearly across FVIII tertiles (P < .001) in models adjusted for age, sex, body mass index, and C-reactive protein. In the combined analysis, participants with FVIII levels in the highest tertile and an MPV of ≥9.5 fL (ie, joint exposure) had an odds ratio for VTE of 2.71 (95% CI, 1.44-5.11) compared with those with FVIII levels in the lowest tertile and an MPV of <8.5 fL (reference). In the joint exposure group, 52% (95% CI, 17%-88%) of VTEs were attributable to the biological interaction between FVIII and MPV.
Our results suggest that large platelets, as reflected by high MPV, might play a role in the mechanism by which high FVIII level increases the risk of incident VTE.
高因子 VIII（FVIII）水平和大血小板，反映在高平均血小板体积（MPV）上，分别与静脉血栓栓塞（VTE）风险增加相关。高 FVIII 水平和大血小板的组合是否对 VTE 风险有超加性影响尚不清楚。
我们旨在研究高 FVIII 水平和大血小板（反映在高 MPV 上）联合对未来发生 VTE 的风险的影响。
这项基于人群的嵌套病例对照研究，来源于特罗姆瑟研究，共纳入 365 例 VTE 病例和 710 例对照。在基线时采集血样，检测 FVIII 抗原水平和 MPV。采用多元逻辑回归模型计算 FVIII 三分位（<85%、85%-108%和≥108%）和 MPV 预设分层内（<8.5、8.5-9.5 和≥9.5 fL）的比值比（OR）及其 95%置信区间（CI）。
在调整年龄、性别、体重指数和 C 反应蛋白后，VTE 风险随 FVIII 三分位呈线性增加（P<0.001）。在联合分析中，FVIII 水平处于最高三分位且 MPV≥9.5 fL（即联合暴露）的患者发生 VTE 的 OR 为 2.71（95%CI，1.44-5.11），而 FVIII 水平处于最低三分位且 MPV<8.5 fL（参考）的患者发生 VTE 的 OR 为 1.00。在联合暴露组中，52%（95%CI，17%-88%）的 VTE 归因于 FVIII 和 MPV 之间的生物学相互作用。
我们的研究结果表明，大血小板（反映在高 MPV 上）可能在高 FVIII 水平增加发生 VTE 的风险的机制中发挥作用。
