Sukati Suriyan, Kotepui Kwuntida Uthaisar, Masangkay Frederick Ramirez, Tseng Ching-Ping, Mahittikorn Aongart, Anabire Nsoh Godwin, Wilairatana Polrat, Wangdi Kinley, Majima Hideyuki J, Suwannatrai Apiporn Thinkhamrop, Klangbud Wiyada Kwanhian, Mala Wanida, Rattanatham Rujikorn, Kotepui Manas
Medical Technology, School of Allied Health Sciences, Walailak University, Tha Sala, Nakhon Si Thammarat, Thailand.
Hematology and Transfusion Science Research Center, Walailak University, Tha Sala, Nakhon Si Thammarat, Thailand.
Sci Rep. 2025 Jan 5;15(1):858. doi: 10.1038/s41598-024-84907-x.
D-dimer, a byproduct of cross-linked fibrin degradation, arises during the fibrinolysis process, breaking down blood clots in circulation. This systematic review and meta-analysis aimed to synthesize evidence of D-dimer alteration in people with malaria, including variations in disease severity. The systematic review was registered in PROSPERO with registration number CRD42024528245. Searches were performed in EMBASE, Scopus, MEDLINE, PubMed, Nursing & Allied Health Premium, and Journals@Ovid on March 25, 2024, to identify original studies that reported D-dimer in patients with Plasmodium infections. The methodological quality of the included studies was assessed using the Joanna Briggs Institute critical appraisal tools. Thematic synthesis and meta-analysis were carried out to synthesize the findings of the included studies. A total of 24 studies were included in the review out of 1,115 records identified. According to the evaluated studies, patients with Plasmodium infections had higher D-dimer levels. A meta-analytic evaluation of D-dimer levels between patients with and without Plasmodium infections revealed a significant elevation of D-dimer in patients with infection, with high heterogeneity (SMD = 2.11, 95% CI = 0.59; 3.64, P = 0.007, I² = 98%, 6 studies, 1,418 participants, random-effects model). However, no significant alterations in D-dimer levels were observed following the comparison between patients with severe and uncomplicated malaria, also with high heterogeneity (SMD = 2.54, 95% CI = -1.60; 6.68, P = 0.23, I² = 99%, 3 studies, 595 participants). The findings suggested that malaria patients have significantly higher D-dimer levels compared to non-malarial individuals. However, there was no significant difference in D-dimer levels between severe and uncomplicated malaria cases. These results highlight the potential of D-dimer as a biomarker for Plasmodium infections, but its clinical utility requires further validation. Future studies should prioritize standardizing D-dimer measurement methods, including assay types, threshold values, and sample types, to ensure consistent and reliable application in clinical settings. Additionally, large, multicentric cohorts are needed to establish robust guidelines for incorporating D-dimer into malaria management practices. Further research should also explore the role of D-dimer in the pathogenesis of Plasmodium infections to deepen our understanding of their clinical significance.
D - 二聚体是交联纤维蛋白降解的副产物，在纤维蛋白溶解过程中产生，可分解循环中的血凝块。本系统评价和荟萃分析旨在综合疟疾患者D - 二聚体变化的证据，包括疾病严重程度的差异。该系统评价已在国际前瞻性系统评价注册库（PROSPERO）注册，注册号为CRD42024528245。2024年3月25日，在EMBASE、Scopus、MEDLINE、PubMed、护理与联合健康高级数据库以及Ovid期刊数据库中进行检索，以识别报告疟原虫感染患者D - 二聚体情况的原始研究。使用乔安娜·布里格斯研究所的批判性评价工具评估纳入研究的方法学质量。进行主题综合和荟萃分析以综合纳入研究的结果。在识别出的1115条记录中，共有24项研究被纳入该评价。根据评估研究，疟原虫感染患者的D - 二聚体水平较高。对有和无疟原虫感染患者的D - 二聚体水平进行的荟萃分析评估显示，感染患者的D - 二聚体显著升高，异质性较高（标准化均数差[SMD] = 2.11，95%置信区间[CI] = 0.59；3.64，P = 0.007，I² = 98%，6项研究，1418名参与者，随机效应模型）。然而，在比较重症疟疾和非重症疟疾患者后，未观察到D - 二聚体水平有显著变化，异质性也较高（SMD = 2.54，95% CI = -1.60；6.68，P = 0.23，I² = 99%，3项研究，595名参与者）。研究结果表明，与非疟疾个体相比，疟疾患者的D - 二聚体水平显著更高。然而，重症疟疾和非重症疟疾病例之间的D - 二聚体水平没有显著差异。这些结果凸显了D - 二聚体作为疟原虫感染生物标志物的潜力，但其临床实用性需要进一步验证。未来的研究应优先标准化D - 二聚体测量方法，包括检测类型、阈值和样本类型，以确保在临床环境中一致且可靠地应用。此外，需要大型多中心队列来建立将D - 二聚体纳入疟疾管理实践的强有力指南。进一步的研究还应探索D - 二聚体在疟原虫感染发病机制中的作用，以加深我们对其临床意义的理解。
