严重 A 型血友病基因突变与产生抑制剂风险之间的关系：大型单中心研究

IF 1.4 4区医学 Q4 HEMATOLOGY

Transfusion and Apheresis Science Pub Date : 2024-09-08 DOI:10.1016/j.transci.2024.104002

Arash Ahmadfard Moghadam , Amir Reza Manafzadeh , MR Nikoonia , Seyedeh Somayeh Moazezi , Khadijeh Dajliry Nekoei , Farahnaz Ramezan , Davood Bashash , Mohsen Hamidpour , Shadi Tabibian

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引用次数: 0

摘要

背景严重甲型血友病（HA）患者的主要问题之一是产生针对第八因子的中和抗体。本研究旨在分析重症甲型血友病患者的分子和临床特征，并确定某些基因变异是否会导致这些患者产生抑制剂。方法在 2000 年 3 月 20 日至 2023 年 6 月 31 日期间对重症甲型血友病患者进行了一项单中心研究。研究收集了患者的人口统计学数据和实验室结果。结果共有 480 例重症 HA 患者（408 例未服用抑制剂，72 例服用抑制剂）参与了这项研究。患者确诊时的中位年龄为 6 个月（IQR：3 个月至 18 个月）。199例（41.5%）患者出现了Inv-22。在出现抑制的患者中，53 例（73.6%）被归类为高滴度，19 例（26.4%）被归类为低滴度。Inv-22、抑制剂形成的阳性家族史和高强度注射史与抑制剂形成的风险有显著的统计学关联。这将使我们能够对患者进行分层，从而产生重要的临床影响，尤其是在患者的管理和预后方面。

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Relationship between mutations in severe hemophilia A and risk of inhibitor development: A large single-center study

Background

One of the major problems for patients with severe hemophilia A (HA) is the development of neutralizing antibodies against factor VIII. This study aimed to analyze the molecular and clinical profiles of patients with severe HA and to determine if certain genetic variants predispose to inhibitor development in these patients.

Methods

A single-center study was conducted among patients with severe HA between March 20, 2000, and June 31, 2023. Demographic data and laboratory results of patients were collected. The inverse-shifting PCR (IS-PCR) technique was initially used to screen patients for intron 22 and 1 inversions (Inv-22 and Inv-1).

Results

A total of 480 patients with severe HA (408 without inhibitors and 72 with inhibitors) were enrolled in this study. The median age of the patients at the time of diagnosis was 6 months (IQR: 3 months to 18 months). Inv-22 was observed in 199 (41.5 %) of the cases. Among those patients who developed inhibitors, 53 (73.6 %) were classified as high-titer and 19 (26.4 %) as low-titer. Inv-22, positive family history of inhibitor formation, and history of intense injections revealed a statistically significant association with the risk of inhibitor development.

Conclusion

The results of this study confirm the important role of different genetic variants, family history of inhibitor formation, and history of intense injections for the formation of inhibitors in patients with severe HA. This would allow us to stratify the patients which can have important clinical implications, especially in terms of their management and outcome.

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来源期刊

Transfusion and Apheresis Science 医学-血液学

CiteScore

3.60

自引率

5.30%

发文量

181

审稿时长

42 days

期刊介绍： Transfusion and Apheresis Science brings comprehensive and up-to-date information to physicians and health care professionals involved in the rapidly changing fields of transfusion medicine, hemostasis and apheresis. The journal presents original articles relating to scientific and clinical studies in the areas of immunohematology, transfusion practice, bleeding and thrombotic disorders and both therapeutic and donor apheresis including hematopoietic stem cells. Topics covered include the collection and processing of blood, compatibility testing and guidelines for the use of blood products, as well as screening for and transmission of blood-borne diseases. All areas of apheresis - therapeutic and collection - are also addressed. We would like to specifically encourage allied health professionals in this area to submit manuscripts that relate to improved patient and donor care, technical aspects and educational issues. Transfusion and Apheresis Science features a "Theme" section which includes, in each issue, a group of papers designed to review a specific topic of current importance in transfusion and hemostasis for the discussion of topical issues specific to apheresis and focuses on the operators'' viewpoint. Another section is "What''s Happening" which provides informal reporting of activities in the field. In addition, brief case reports and Letters to the Editor, as well as reviews of meetings and events of general interest, and a listing of recent patents make the journal a complete source of information for practitioners of transfusion, hemostasis and apheresis science. Immediate dissemination of important information is ensured by the commitment of Transfusion and Apheresis Science to rapid publication of both symposia and submitted papers.