Medizinische Klinik und Poliklinik I, Klinikum der Universität München, Ludwig-Maximilians-Universität, Munich, Germany.
German Center for Cardiovascular Research (DZHK), partner site Munich Heart Alliance, Munich, Germany.
Thromb Haemost. 2024 Nov;124(11):1027-1039. doi: 10.1055/s-0043-1775965. Epub 2023 Oct 16.
Deep vein thrombosis (DVT) is a common condition associated with significant mortality due to pulmonary embolism. Despite advanced prevention and anticoagulation therapy, the incidence of venous thromboembolism remains unchanged. Individuals with elevated hematocrit and/or excessively high erythropoietin (EPO) serum levels are particularly susceptible to DVT formation. We investigated the influence of short-term EPO administration compared to chronic EPO overproduction on DVT development. Additionally, we examined the role of the spleen in this context and assessed its impact on thrombus composition.
We induced ligation of the caudal vena cava (VCC) in EPO-overproducing Tg(EPO) mice as well as wildtype mice treated with EPO for two weeks, both with and without splenectomy. The effect on platelet circulation time was evaluated through FACS analysis, and thrombus composition was analyzed using immunohistology.
We present evidence for an elevated thrombogenic phenotype resulting from chronic EPO overproduction, achieved by combining an EPO-overexpressing mouse model with experimental DVT induction. This increased thrombotic state is largely independent of traditional contributors to DVT, such as neutrophils and platelets. Notably, the pronounced prothrombotic effect of red blood cells (RBCs) only manifests during chronic EPO overproduction and is not influenced by splenic RBC clearance, as demonstrated by splenectomy. In contrast, short-term EPO treatment does not induce thrombogenesis in mice. Consequently, our findings support the existence of a differential thrombogenic effect between chronic enhanced erythropoiesis and exogenous EPO administration.
Chronic EPO overproduction significantly increases the risk of DVT, while short-term EPO treatment does not. These findings underscore the importance of considering EPO-related factors in DVT risk assessment and potential therapeutic strategies.
深静脉血栓形成（DVT）是一种常见病症，可导致肺栓塞而引起高死亡率。尽管有先进的预防和抗凝治疗，静脉血栓栓塞的发生率仍未改变。血细胞比容和/或红细胞生成素（EPO）血清水平过高的个体特别容易形成 DVT。我们研究了短期 EPO 给药与慢性 EPO 过度产生对 DVT 发展的影响。此外，我们研究了脾脏在这方面的作用，并评估了其对血栓组成的影响。
我们通过 EPO 过表达 Tg(EPO)小鼠和野生型小鼠的尾静脉结扎（VCC）诱导，以及 EPO 治疗两周的野生型小鼠，包括脾切除术和不脾切除术，来研究 EPO 对血小板循环时间的影响，并通过免疫组化分析血栓组成。
我们提出了一种由慢性 EPO 过度产生引起的升高的血栓形成表型的证据，该表型通过结合 EPO 过表达小鼠模型和实验性 DVT 诱导来实现。这种增加的血栓形成状态在很大程度上独立于传统的 DVT 贡献因素，如中性粒细胞和血小板。值得注意的是，只有在慢性 EPO 过度产生的情况下，红细胞（RBC）的明显促血栓形成作用才会显现，并且脾切除术不会影响 RBC 的清除。相比之下，短期 EPO 治疗不会在小鼠中引起血栓形成。因此，我们的研究结果支持慢性增强的红细胞生成和外源性 EPO 给药之间存在不同的促血栓形成作用。
慢性 EPO 过度产生会显著增加 DVT 的风险，而短期 EPO 治疗则不会。这些发现强调了在 DVT 风险评估和潜在治疗策略中考虑 EPO 相关因素的重要性。
