The incidence rate of SMPP-related ICT remains unreported to date. Currently, only 51 cases (including our cohort of 18 cases) were documented [9,10,11,12,13,14,15,16,17,18,19,20] (Table 3). Our research confirms that the clinical features of SMPP-related ICT lack specificity, with symptom severity varying depending on the size, location, and activity of the thrombus. While mild cases may be asymptomatic or present only with pneumonia-like symptoms, severe cases can lead to cardiopulmonary failure (Case 51 in Table 3), or even sudden death. Thrombus detachment can occur via either the pulmonary or systemic circulation, resulting in embolization to critical organs such as the lungs, brain, kidneys, and spleen. Consequently, the mortality associated with SMPP-related ICT is alarmingly high if not promptly treated.

Our study confirms that the right cardiac chambers are the most common site for ICT, accounting for 84.3% of all cases. According to data from the European Society of Cardiology, the presence of a mobile thrombus in the right cardiac chambers is associated with an unfavorable outcome, with mortality rates ranging from 80 to 100% [21]. However, our study yielded different results. All patients in our cohort had favorable prognoses, and there were no fatalities. The explanation for this discrepancy may lie in the different types of ICT. In our study, SMPP-related ICT cases predominantly exhibited either the chordae tendineae-attached type (61.1%) or the wall-attached type (33.3%), with no instances of the mobile type (as shown in Table 1). This study provides the first evidence that the mechanism underlying ICT related to MPP is not systemic emboli detachment, which typically causes classic ICT. Instead, it appears to involve in situ thrombosis within the heart and major blood vessels.

The pathophysiological mechanisms of SMPP-induced cardiovascular complications remain unclear. These mechanisms can be classified into three categories: direct type (inflammatory cytokines induced by MP lipoproteins causing endocardial injury), indirect type (immune modulation through cross-reaction), and vascular occlusion type (vasculitis and/or thrombosis) [22]. Reports suggest that SMPP-induced vasculitis/thrombosis involves autoimmune reactions and molecular mimicry, promoting the production of antibodies against phospholipids, glycerides, and proteins, resulting in associated vasculitic/thrombotic disorders regardless of a systemic hypercoagulable state [22, 23]. The “pro-thrombotic” effect of anti-phospholipid antibodies is linked to several mechanisms, including cellular activation (direct stimulation of endothelial cell procoagulant activity and enhancement of platelet activation and aggregation), inhibition of endogenous anticoagulants (such as protein C, protein S, anti-thrombin, and annexin A5) [24, 25], impairment of fibrinolysis, and complement activation. Witmer. et al. [26] and Ortel. et al. [27] reported that over 50% of patients with MPP combined with thrombosis tested positive for aCL-IgM, which gradually disappeared during the recovery phase. However, in this study, nine patients were screened for aCL antibodies, and none tested positive.

It’s worth noting that coagulation tests do not definitively indicate a hypercoagulable state. In our study, PT, APTT and fibrinogen levels were all within the normal range. D-dimer levels showed nonspecific results: 44.4% were < 5 µg/mL, and 55.6% were ≥ 5 µg/mL, with a maximum value of 53.25 µg/mL (Case 51 in Table 3). Case 51 experienced extensive pulmonary thrombosis, affecting the right middle and lower lobes, due to partial detachment of a right ventricular thrombus. Additionally, Case 46 had a D-dimer level of 19.6 µg/mL and presented with multi-organ thrombosis, including involvement of the heart, spleen, and kidney. Our findings suggest that while higher D-dimer levels are strongly associated with SMPP-related thrombotic disorders, normal D-dimer levels do not definitively exclude the possibility of thrombotic events.

The diagnosis of SMPP-related ICT primarily relies on echocardiography [28]. This imaging technique reveals the thrombus’s morphology, location, size, activity, as well as cardiac function and blood flow. Echocardiography demonstrates high sensitivity and specificity for diagnosing SMPP-related ICT, making it the preferred non-invasive diagnostic method. However, it’s essential to differentiate SMPP-related ICT from other conditions, such as infective endocarditis or cardiac tumors with associated infections, which can also present with fever, elevated inflammatory markers, and the formation of intracardiac masses or tumors. Infective endocarditis frequently affects the left heart and presents as high fever, cardiac murmur, and peripheral thrombosis [29]. The prevalent pathogen is gram-positive cocci. Blood or vegetation culture and pathological examination can assist in differentiation. Cardiac tumors in children are extremely rare. The use of contrast echocardiography and cardiac magnetic resonance imaging in the assessment of cardiac masses has been shown to be helpful in distinguishing tumors from thrombi [30].

The treatment of ICT lacks standardized guidelines and typically involves anticoagulation, thrombolytic therapy, and surgical thrombectomy. Each approach has its limitations and advantages. Anticoagulation serves as the foundational treatment. Commonly used anticoagulants include low-molecular-weight heparin, vitamin K antagonists, and novel oral anticoagulants such as rivaroxaban and apixaban, which are now being applied in pediatric cases [31, 32]. Thrombolytic therapy is most effective when administered early during thrombus formation. However, the specific time window requires further research. The primary complication associated with thrombolytic therapy is the risk of bleeding, necessitating a thorough assessment of bleeding tendencies before initiating treatment. Recombinant tissue-type plasminogen activator (rt-PA) is the preferred thrombolytic agent. Dong. et al. [18] have reported successful outcomes with thrombolytic therapy in cases of MPP complicated by pulmonary and intracardiac thrombi. However, further research is needed to clarify the indications, administration routes, dosages, and duration of thrombolytic therapy. Currently, surgical thrombectomy remains a topic of ongoing debate regarding timing and necessity. In our cohort, 72.2% underwent combined surgical and anticoagulation therapy, while 27.8% received conservative anticoagulation therapy only. Except for one lost-to-follow-up case, all other patients achieved favorable treatment outcomes, with no recurrence of thrombotic diseases or cardiac-related sequelae. Our patients’ prognosis aligns with reports by Li. et al. [13] and Fu. et al. [20]. Therefore, for pediatric patients with SMPP-related ICT, the indications for thrombectomy remain unclear. Decisions regarding thrombectomy should take into account factors such as thrombus size, location, activity, the possibility of conservative treatment, cardiopulmonary reserve, and comorbidities.