Impaired Hemostatic and Immune Functions of Platelets After Acute Thrombocytopenia.

IF 5.5 2区医学 Q1 HEMATOLOGY

Journal of Thrombosis and Haemostasis Pub Date : 2024-12-13 DOI:10.1016/j.jtha.2024.11.029

Anita Pirabe, Waltraud C Schrottmaier, Dino Mehic, Hubert Hackl, Sabine Frühwirth, Anna Schmuckenschlager, Sarah Beck, Johanna Gebhart, Karoline Gleixner, Wolfgang Sperr, Alice Assinger

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引用次数: 0

Abstract

Background: Platelets are pivotal in maintaining vascular integrity, hemostasis, and immune modulation, with newly generated, immature platelets being the most responsive in fulfilling these tasks. Therefore, the immature platelet fraction provides insights into thrombopoiesis dynamics and clinical prognostication. However, it is currently unclear how immature platelet functions change in settings of acute thrombocytopenia.

Objectives: We aimed to investigate the functional consequences of acute thrombocytopenia on newly generated immature platelets in various mouse models and human subjects.

Methods: To examine platelet functionality after acute thrombocytopenia, we depleted either megakaryocytes using a PF4-specific iDTR transgenic mouse model or platelets via antibody-mediated depletion in mice, and collected blood from acute myeloid leukemia (AML) patients before and after consolidation or induction chemotherapy. Chemotherapy treatment was further repeated in an animal model. We assessed surface receptor expression of activation markers (CD62P, active GPIIb/IIIa, CD40L, CD63, CD107a) and toll-like receptors (TLR2, TLR4, TLR9) on immature and mature platelets following activation. Additionally, we investigated procoagulant platelet formation and platelet-leukocyte interactions in mouse models and AML patients.

Results: In murine models, acute thrombocytopenia led to impaired hemostatic function and altered surface receptor expression in newly generated immature platelets. Similarly, AML patients during regeneration post-chemotherapy exhibited reduced platelet activation and procoagulant function, alongside altered receptor expression and diminished platelet-leukocyte interactions.

Conclusions: After acute thrombocytopenia platelet-mediated hemostasis and immune modulation by newly generated platelets are impaired, underscoring the clinical relevance of understanding platelet function alterations in (post)thrombocytopenic conditions for therapeutic optimization.

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急性血小板减少症后血小板的止血和免疫功能受损。

背景：血小板在维持血管完整性、止血和免疫调节方面起着关键作用，而新生成的未成熟血小板在完成这些任务时反应最为灵敏。因此，未成熟血小板部分有助于了解血栓形成动态和临床预后。然而，目前还不清楚未成熟血小板的功能在急性血小板减少时会发生怎样的变化：我们旨在研究急性血小板减少症对各种小鼠模型和人体中新生成的未成熟血小板功能的影响：为了研究急性血小板减少症后的血小板功能，我们利用PF4特异性iDTR转基因小鼠模型耗竭巨核细胞，或通过抗体介导的小鼠耗竭血小板，并在巩固或诱导化疗前后采集急性髓性白血病（AML）患者的血液。在动物模型中进一步重复化疗治疗。我们评估了活化标志物（CD62P、活性 GPIIb/IIIa、CD40L、CD63、CD107a）的表面受体表达，以及活化后未成熟和成熟血小板上的收费样受体（TLR2、TLR4、TLR9）。此外，我们还研究了小鼠模型和急性髓细胞白血病患者的促凝血血小板形成和血小板-白细胞相互作用：结果：在小鼠模型中，急性血小板减少症导致止血功能受损，新生成的未成熟血小板表面受体表达发生改变。同样，急性髓细胞白血病患者在化疗后再生过程中，血小板活化和促凝功能降低，同时受体表达改变，血小板与白细胞的相互作用减弱：结论：急性血小板减少症后，血小板介导的止血和新生成血小板的免疫调节功能受损，这突出表明了解血小板减少症（后）情况下的血小板功能变化对优化治疗具有临床意义。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Thrombosis and Haemostasis 医学-外周血管病

CiteScore

24.30

自引率

3.80%

发文量

321

审稿时长

1 months

期刊介绍： The Journal of Thrombosis and Haemostasis (JTH) serves as the official journal of the International Society on Thrombosis and Haemostasis. It is dedicated to advancing science related to thrombosis, bleeding disorders, and vascular biology through the dissemination and exchange of information and ideas within the global research community. Types of Publications: The journal publishes a variety of content, including: Original research reports State-of-the-art reviews Brief reports Case reports Invited commentaries on publications in the Journal Forum articles Correspondence Announcements Scope of Contributions: Editors invite contributions from both fundamental and clinical domains. These include: Basic manuscripts on blood coagulation and fibrinolysis Studies on proteins and reactions related to thrombosis and haemostasis Research on blood platelets and their interactions with other biological systems, such as the vessel wall, blood cells, and invading organisms Clinical manuscripts covering various topics including venous thrombosis, arterial disease, hemophilia, bleeding disorders, and platelet diseases Clinical manuscripts may encompass etiology, diagnostics, prognosis, prevention, and treatment strategies.