Efficacy of dipyridamole plus IVIG and aspirin on anti-platelet aggregation factors and inflammatory factors in children with Kawasaki disease.

Am J Transl Res 2025;17(1):330-337 www.ajtr.org /ISSN:1943-8141/AJTR0161347 Original Article Efficacy of dipyridamole plus IVIG and aspirin on anti-platelet aggregation factors and inflammatory factors in children with Kawasaki disease Lijiang Du*, Quan Gan*, Wei Ma, Chuanfu Qiao, Yunjiao Luo Department of Infection, Kunming Children’s Hospital, Kunmin 650200, Yunnan, PR China. *Equal contributors. Received October 21, 2024; Accepted December 9, 2024; Epub January 15, 2025; Published January 30, 2025 Abstract: Background: While standard therapeutic regimens for Kawasaki disease (KD) in children have exhibited some efficacy, they remain far from ideal. Thus, the pursuit of alternative or improved treatment modalities remis clinically critical. Objective: This study primarily aimed to assess the effect of dipyridamole (DIP) plus human intravenous immunoglobulin (IVIG) and aspirin (ASP) as to efficacy, antiplatelet aggregation factors, and inflammatory markers in children with KD. Methods: A total of 95 pediatric KD patients were selected from February 2021 to July 2024, with 44 cases in the control group treated with IVIG + ASP and 51 cases in the research group given DIP in addition to IVIG + ASP. The efficacy, symptom resolution time (defervescence, limb swelling, mucosal congestion, and cervical lymphadenopathy), coronary artery injury, coagulation function (thrombin time [TT], prothrombin time [PT], and activated partial thromboplastin time [APTT]), antiplatelet aggregation factors (erythrocyte sedimentation rate [ESR], white blood cell count [WBC], and platelet count [PLT]), and inflammatory factors (C-reactive protein [CRP], and tumor necrosis factor-α [TNF-α], interleukin-6 [IL-6]) levels were compared between the two groups. Results: The research group exhibited a higher overall treatment efficacy rate, shorter symptom resolution times, and a significantly lower incidence of coronary artery injury compared to the control group. No significant differences were observed between the two groups or before and after treatment within the same group in coagulation function indices. Markedly reduced levels of anti-platelet aggregation factors and inflammatory markers were observed in the research group versus those in the control group. Conclusion: DIP in combination with IVIG and ASP significantly enhances treatment efficacy and improves levels of antiplatelet aggregation factors and inflammatory markers in children with KD. Keywords: Dipyridamole, IVIG, aspirin, Kawasaki disease in children, efficacy Introduction Kawasaki disease (KD) is the leading cause of acquired heart disease in children in developed countries and is a self-limiting, systemic vasculitis in pediatric patients [1]. KD manifests through a series of characteristic clinical signs, including persistent febrile episodes lasting over five consecutive days, rashes, lymph node enlargement, and limb lesions [2]. Epidemiological data show the highest annual incidence of KD in Asian countries, with a seasonal peak in early spring [3, 4]. The etiology of KD is complex and not fully elucidated, though it is generally believed to be related to coronary artery involvement triggered by an infectious agent, such as a viral infection [5]. The pathologic mechanisms of KD also involve severe inflammation and reactive thrombocytosis caused by immune complexes and the molecular signals they produce, which lead to organ damage [6, 7]. Standard treatment for KD includes intravenous human immunoglobulin (IVIG) and aspirin (ASP), which reduces the risk of coronary artery aneurysms in affected children from 25% to 5% [8]. However, 10% to 38% of patients fail to respond to this treatment or experience recurrent fever [9], possibly due to the development of IVIG resistance, indicating the need for additional intervention to suppress the inflammatory response [10]. Dipyridamole (DIP) is a tetrasubstituted pyrimidine-pyrimidine derivative that acts as an anti- https://doi.org/10.62347/XIDS4307 Kawasaki disease treatment in children platelet agent by inhibiting platelet aggregation. It works primarily by increasing adenosine concentration, inhibiting phosphodiesterase activity, and lowering thromboxane A2 (TXA2) levels [11]. In addition to its antiplatelet effects, DIP also exhibits antiviral, anti-inflammatory, and antioxidant properties, making it useful in treating ischemic cerebrovascular disease. When used alongside aspirin (ASP), DIP enhances antiplatelet effects and can increase circulating monocyte-platelet complexes in the body over time [12, 13]. Furthermore, DIP has been shown to reduce the risk of liver cancer in patients with type 2 diabetes [14]. While DIP monotherapy has demonstrated limited efficacy in children with KD, with a platelet suppression rate of only 47% [15], it is often used in combination with other drugs. Research on DIP plus IVIG and ASP in the treatment of KD in children remains scarce, and there is also some controversy regarding the effectiveness of antiplatelet therapy regimens. For instance, the systematic review by Tanoshima et al. [16] noted insufficient evidence to support the clinical effectiveness of antiplatelet agents such as DIP and ASP in treating KD. This study attempts to verify the clinical efficacy of combining DIP, IVIG, and ASP in pediatric KD patients. Patients and methods General data This retrospective study included 95 children with KD admitted to the hospital from February 2021 to July 2024. The patients were divided into a control group of 44 patients treated with IVIG and aspirin (ASP) and a research group of 51 patients who received additional dipyridamole (DIP) alongside IVIG + ASP. No significant differences in general data were observed between the two groups (P>0.05). This study was approved by the Ethics Committee of Kunming Children’s Hospital. swelling of the lips and oral mucosa; skin rashes and erythema; non-suppurative enlargement of cervical lymph nodes; initial treatment. Exclusion criteria: Use of IVIG or ASP before admission; congenital heart disease or hematopoietic system diseases; severe infection or secondary bacterial infection; abnormal mental state or malnutrition. Treatment methods Both groups of children received routine antipyretic treatment upon admission. The control group was treated with IVIG and ASP: Within 10 days of onset, the child was given IVIG (specification: 2.5 g (50 mL)/bottle; Ningbo Puli Pharmacy Co., Ltd., 1003) at a dose of 1 g/kg each time, completed within 4-6 hours, for 2 days. Additionally, ASP tablets (specification: 0.5 g/tablet; Beijing Kangruina Biotechnology Co., Ltd., A1189) were administered orally at a dose of 30-50 mg/(kg·d), divided into three doses taken in the morning, noon, and evening. After the fever subsided, the dosage was gradually reduced to 3-5 mg/(kg·d). The treatment continued for a total of 2 months. The research group received additional treatment with DIP (Beijing Biolab Science and Technology Co (...truncated)