Thrombocytopenia and thrombocytosis caused by viral or bacterial infections are commonly observed in patients with ITP. For most ITP children, infections pose a significant challenge to the daily management of ITP, as they can add to the immune burden by upsetting the already established balance of platelet production and destruction. According to China’s National Health Commission, there has been an increase in respiratory infections caused by M. pneumoniae in northern China since August 2023. This increase has primarily affected children and adolescents, leading to a rise in cases of M. pneumoniae pneumonia (MPP) and severe MPP. [1, 2, 10]
M. pneumoniae infection can cause direct and indirect lung damage. MPP leads to various and different severity levels of extra-respiratory manifestations, including dermatological symptoms and neurological complications, while thromboembolism is an uncommon yet severe complication. [11]
Pulmonary arteriovenous thromboembolism is the most common form of thromboembolism in MPP. Cerebral artery embolism and cardiac thrombosis are also common in cases of extrapulmonary thromboembolism. Thromboembolism is relatively rare in children and is mainly associated with infection, especially in cases of MPP. MPP has been proven to be a significant risk factor for thromboembolism. [12]
In our observation, M. pneumoniae infections have a dual effect on platelet count in pediatric patients with ITP who continue TPO-RAs, but thrombocytopenia remains predominant. After seven days of MP infection, there was a ‘transient change’ in platelet count contrary to the initial trend at the onset of the infection. In most patients, the platelet count comes back to the baseline around 21 days after the infection. Platelets play a crucial role in hemostasis and coagulation and are extensively involved in various pathophysiological mechanisms, such as inflammatory responses and immunomodulation[13]. There is increasing evidence that megakaryocytes in the lungs, in addition to bone marrow, are one of the main drivers of platelet production. Lefrançais E et al. showed that megakaryocytes originating from the bone marrow and other extrapulmonary sites migrate to the lungs to release platelets and dynamically circulate through the lungs[14]. When respiratory pathogens infect the lung, heavily aggregated platelets in the pulmonary are involved in the immunity war. This disrupts the previously established balance between platelet production and destruction in ITP patients, resulting in fluctuations in platelet count.
The increasing large-scale, population-based studies have shown increased rates of both venous thromboembolism (VTE) and arterial thromboembolism (ATE) in patients with ITP compared with individuals without ITP[15, 16]. Some studies also showed that TPO-RA is an independent risk factor for developing thrombosis and remained significant with multivariate analysis together with age and secondary ITP diagnosis. Thrombosis is a common and challenging issue in chronic ITP patients undergoing TPO-RAs therapy.[17] So, the MPP pandemic has introduced new challenges for managing patients with ITP, especially for chronic cases with TPO-RAs. In this study, although we observed polarized platelet fluctuations and encountered one case of venous sinus, further research is needed to confirm the relationship among MPP, TPO-RAs, and thrombotic events.
The main limitation of this study was that it was an observational cohort study, and the level of evidence of experimental results needs to be improved. The small number of patients in the non-TRA group makes it difficult to conduct head-to-head comparisons. In addition, the short observation period and lack of data collection on symptoms and related immunological tests during MP infection will be supplemented in future studies.