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非重度甲型血友病患者关节状况的真实世界证据:一项多中心研究。

Real-World Evidence on Joint Condition in Non-Severe Hemophilia A Patients: A Multicenter Study.

作者信息

Marco-Rico Ana, Calvo-Villas José Manuel, López-Jaime Francisco-José, Canaro Hirnyk Mariana, Nieto Hernández Maria Del Mar, Herrero Martín Sonia, Entrena-Ureña Laura, Marcellini-Antonio Shally, Díaz-Jordán Bolívar L, Jurado-Herrera Sergio, Pérez-González Noelia Florencia, García-Díaz Covadonga, García-Candel Faustino, Fernández-Bello Ihosvany, Marco-Vera Pascual

机构信息

Hematology Department, Hospital General Universitario Dr. Balmis-ISABIAL, Alicante, Spain.

Hematology Department, Hospital Universitario Miguel Servet, Zaragoza, Spain.

出版信息

J Blood Med. 2025 May 19;16:251-258. doi: 10.2147/JBM.S517596. eCollection 2025.


DOI:10.2147/JBM.S517596
PMID:40417706
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12101468/
Abstract

PURPOSE: Patients with non-severe hemophilia A (PwnSHA) may be at risk for joint damage (JD), yet data remain scarce. Our aim was to evaluate the joint condition in PwnSHA in a real-world setting. PATIENTS AND METHODS: A nationwide, multicenter, cross-sectional study was conducted. To mitigate the impact of discrepancies between factor VIII (FVIII) assays, baseline FVIII levels were determined using chromogenic and one-step clotting assays. Mutation in F8 gene, baseline FVIII levels, thrombin generation and age were assessed. The joint condition was described using the HEAD-US score by trained specialists at each participating hospital. RESULTS: One hundred and twenty-four patients were recruited, 84 of them with an available HEAD-US evaluation, who were finally included in our analysis. The median age was 38.4 years (18.3-48.5). Twenty percent (16/84) had moderate hemophilia (MoH) with FVIII levels of 4.0 IU/dL (2.6-4.6), and 80% (68/84) had mild hemophilia (MiH) with FVIII levels of 14.8 IU/dL (10.4-19.9), (p< 0.001). JD (HEAD-US>0) was observed in 50% (8/16) of MoH patients (HEAD-US= 6.5 [5.5-8.5]) and in 40% (27/68) of those with MiH (HEAD-US= 3.0 [2.0-6.5]), p=0.198. In the moderate group, JD was primarily observed in ankles (44%), while in the MiH group, knees were the most affected (31%). MoH patients reported a hypocoagulable thrombin generation profile compared to MiH patients (p<0.05). CONCLUSION: Near half of PwnSHA had JD. A worse joint health and a lower thrombin generation was observed in MoH population. These patients can benefit from an early prophylaxis and prevent further joint deterioration. Future research should explore additional variables that might influence joint condition.

摘要

目的:非重度甲型血友病患者(PwnSHA)可能存在关节损伤(JD)风险,但相关数据仍然匮乏。我们的目的是在真实世界环境中评估PwnSHA患者的关节状况。 患者与方法:开展了一项全国性、多中心横断面研究。为减轻凝血因子VIII(FVIII)检测方法差异的影响,采用发色底物法和一步凝血法测定基线FVIII水平。评估F8基因突变、基线FVIII水平、凝血酶生成情况和年龄。由各参与医院的专业人员使用HEAD-US评分描述关节状况。 结果:共招募了124例患者,其中84例有可用的HEAD-US评估结果,最终纳入我们的分析。中位年龄为38.4岁(18.3 - 48.5岁)。20%(16/84)为中度血友病(MoH),FVIII水平为4.0 IU/dL(2.6 - 4.6),80%(68/84)为轻度血友病(MiH),FVIII水平为14.8 IU/dL(10.4 - 19.9),(p<0.001)。50%(8/16)的MoH患者出现JD(HEAD-US>0)(HEAD-US = 6.5 [5.5 - 8.5]),40%(27/68)的MiH患者出现JD(HEAD-US = 3.0 [2.0 - 6.5]),p = 0.198。在中度组中,JD主要出现在踝关节(44%),而在MiH组中,膝关节受影响最大(31%)。与MiH患者相比,MoH患者的凝血酶生成呈低凝状态(p<0.05)。 结论:近一半的PwnSHA患者存在JD。在MoH人群中观察到更差的关节健康状况和更低的凝血酶生成。这些患者可从早期预防中获益,防止关节进一步恶化。未来的研究应探索可能影响关节状况的其他变量。

相似文献

[1]
Real-World Evidence on Joint Condition in Non-Severe Hemophilia A Patients: A Multicenter Study.

J Blood Med. 2025-5-19

[2]
Prolonged α-thrombin-related activation and delayed active protein C-associated degradation confer mild phenotype in a patient with severe hemophilia A with F8 p.H118R.

Int J Hematol. 2022-10

[3]
[HEAD-US-C quantitative ultrasound assessment scale in evaluation of joint damage in patients with moderate or severe hemophilia A received on-demand versus prophylaxis replacement therapy].

Zhonghua Xue Ye Xue Za Zhi. 2018-10-14

[4]
Variation in baseline factor VIII concentration in a retrospective cohort of mild/moderate hemophilia A patients carrying identical F8 mutations.

J Thromb Haemost. 2017-2-3

[5]
Pharmacodynamic monitoring of factor VIII replacement therapy in hemophilia A: Combining thrombin and plasmin generation.

J Thromb Haemost. 2020-12

[6]
Minimum factor VIII levels to prevent joint bleeding in mild hemophilia A.

Blood Adv. 2023-12-12

[7]
Moderate- to vigorous-intensity physical activities for hemophilia A patients during low-dose pharmacokinetic-guided extended half-life factor VIII prophylaxis.

Orphanet J Rare Dis. 2024-3-26

[8]
Discrepancy between one-stage clotting and chromogenic factor VIII activity in women with hemophilia A and hemophilia A carriers: a retrospective clinical study.

J Thromb Haemost. 2025-6

[9]
Correlation between Hemophilia Early Arthropathy Detection with Ultrasound (HEAD-US) score and Hemophilia Joint Health Score (HJHS) in patients with hemophilic arthropathy.

PLoS One. 2021

[10]
The factor VIII treatment history of non-severe hemophilia A.

J Thromb Haemost. 2020-12

本文引用的文献

[1]
HGVS Nomenclature 2024: improvements to community engagement, usability, and computability.

Genome Med. 2024-12-20

[2]
Utilizing artificial intelligence for the detection of hemarthrosis in hemophilia using point-of-care ultrasonography.

Res Pract Thromb Haemost. 2024-10-23

[3]
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Haemophilia. 2024-3

[4]
Minimum factor VIII levels to prevent joint bleeding in mild hemophilia A.

Blood Adv. 2023-12-12

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Obesity-Related Knee Osteoarthritis-Current Concepts.

Life (Basel). 2023-7-28

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Thrombin generation and implications for hemophilia therapies: A narrative review.

Res Pract Thromb Haemost. 2022-12-21

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J Thromb Haemost. 2021-9

[8]
Asymptomatic Joint Bleeding and Joint Health in Hemophilia: A Review of Variables, Methods, and Biomarkers.

J Blood Med. 2021-4-1

[9]
The factor VIII treatment history of non-severe hemophilia A.

J Thromb Haemost. 2020-12

[10]
Hemophilia without prophylaxis: Assessment of joint range of motion and factor activity.

Res Pract Thromb Haemost. 2020-7-6

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