Identification of Phenotypes in Thrombotic Primary Antiphospholipid Syndrome Using Cluster Analysis: A step Towards Personalized Medicine.

IF 5.5 2区医学 Q1 HEMATOLOGY

Journal of Thrombosis and Haemostasis Pub Date : 2025-06-13 DOI:10.1016/j.jtha.2025.06.010

Gabrielle M Santos, Paula David, Or Hen, Juan Luis Ontiveros-Austria, Rotem Liran, Sergio Rodriguez-Rodriguez, Julia Cerchiari de Godói, Yonatan Shneor Patt, Shaked Beladev, Erica Okazaki, Marina Collela, Bianca Stefanello, Gabriela G Yamaguti-Hayakawa, Cynthia Rothschild, Joyce Annichino-Bizzachi, Angel Vargas-Ruiz, Paula Prestes, Vanderson Rocha, Erich V de Paula, Omer Gendelman, Ophira Salomon, Roberta Demichelis-Gomez, Ana Barrera-Vargas, Howard Amital, Paula Villaça, Yehuda Shoenfeld, Fernanda A Orsi

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引用次数: 0

Abstract

Background: Thrombotic risk in primary antiphospholipid syndrome (APS) is a result of complex, yet undefined, interactions among multiple factors. While long-term anticoagulation reduces thrombotic complications, its efficacy varies, with thrombosis recurrence rates ranging from 5-20% within two years. Emerging therapies may benefit specific APS subgroups, although identifying and stratifying these groups remains a significant challenge.

Objective: To identify specific phenotypic subgroups of thrombotic primary APS based on clinical and laboratory characteristics to provide insight for both personalized diagnostic and therapeutic strategies.

Patients/methods: Multicenter retrospective cohort study including 663 patients with thrombotic primary APS who were followed in Brazil, Israel, and Mexico (2018-2023). Hierarchical cluster analysis categorized patients based on demographics, thrombotic characteristics, comorbidities, and laboratory data.

Results: Cluster analysis identified three distinct phenotypes. Cluster 1 (n=348) included older patients (median age 43 years) with high cardiovascular risk factors (hypertension, diabetes, and dyslipidemia) and predominantly arterial thrombosis (53%, p<0.001). Cluster 2 (n=119) included younger patients (median age 35 years) with high recurrence rates (71%, p<0.001) of venous thromboembolism (80%, p<0.001) and higher anticardiolipin prevalence (29%, p<0.001). Cluster 3 (n=196) featured the youngest patients (median age 29 years), predominantly triple aPL positive (98.5%, p<0.001), with complement consumption (C3: 17%, p=0.003), thrombocytopenia (12%, p=0.05), and venous thrombosis (73%, p<0.001).

Conclusion: This study identified three distinct phenotypes of thrombotic primary APS, each characterized by the predominance of cardiovascular risk factors, hypercoagulability, or immunological derangements. The findings provide a basis for developing personalized management strategies to improve patient outcomes.

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利用聚类分析鉴定血栓性原发性抗磷脂综合征的表型：迈向个性化医疗的一步。

背景：原发性抗磷脂综合征（APS）的血栓形成风险是多种因素之间复杂但尚未确定的相互作用的结果。虽然长期抗凝可以减少血栓并发症，但其疗效不一，两年内血栓复发率在5-20%之间。新兴疗法可能有利于特定的APS亚组，尽管识别和分层这些组仍然是一个重大挑战。目的：根据临床和实验室特征确定血栓性原发性APS的特定表型亚群，为个性化诊断和治疗策略提供见解。患者/方法：多中心回顾性队列研究，包括巴西、以色列和墨西哥的663例血栓性原发性APS患者（2018-2023）。分层聚类分析根据人口统计学、血栓形成特征、合并症和实验室数据对患者进行分类。结果：聚类分析鉴定出三种不同的表型。第1组（n=348）包括具有高心血管危险因素（高血压、糖尿病和血脂异常）和主要动脉血栓形成（53%）的老年患者（中位年龄43岁）。结论：本研究确定了血栓性原发性APS的三种不同表型，每一种表型都以心血管危险因素、高凝性或免疫紊乱为主要特征。研究结果为制定个性化管理策略以改善患者预后提供了基础。

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.