In this multicenter prospective cohort study, we explored the impact of aPLs on SLE-TP by comparing SLE-TP patients with positive and negative aPLs. We found that SLE-TP patients with aPLs exhibited lower platelet levels, both at baseline and minimum counts, and had a higher relapse rate. Given the increasing recognition of thrombocytopenia’s role in mortality and end-organ damage risk in SLE patients, monitoring and predicting thrombocytopenia efficacy have received increasing attention. The associations discovered in our study suggest that aPLs may serve not only as predictors of thrombocytopenia severity but also as indicators of relapse rates. This suggests that in clinical practice, SLE-TP patients with positive aPLs encounter greater challenges in treatment and should receive more frequent follow-up to prevent recurrence.

Thrombocytopenia is a common manifestation of blood system involvement in SLE patients, with an incidence rate of 7–30% [11]. The pathophysiological mechanisms underlying thrombocytopenia in SLE patients are not fully known, but at least three mechanisms have been identified: impaired production of platelets in the bone marrow, sequestration of platelets in the spleen, or accelerated destruction of platelets in the peripheral circulation [12]. aPLs may play an important role in these processes [13, 14].While it is not officially classified as a criterion, a reduced platelet count is a frequently observed laboratory characteristic in patients with anti-phospholipid syndrome (APS), regardless of whether they have a concurrent diagnosis of SLE. aPLs, which can appear in SLE and APS patients, are a heterogeneous group of autoantibodies reacting against phospholipids, phospholipid-protein complexes, and phospholipid-binding proteins, including lupus anticoagulant (LA), anticardiolipin (aCL) and anti-beta2 glycoprotein I (anti-β2GP1) antibodies [15]. Studies have shown that aPLs may cause thrombocytopenia through various mechanisms: aPLs bind phospholipids on platelet membranes or endothelial cells in a cross reaction, and antibody-opsonized platelets are recognized, phagocytized, and destroyed through Fcγ receptors by macrophages in the spleen, liver and bone marrow [16]. Additionally, aPLs can activate complement through classical pathways, directly mediating platelet destruction [17, 18]. Furthermore, in addition to activating the traditional p38/MAPK (mitogen activated protein kinase, MAPK) signaling pathway [19], recent research has shown that aPLs may also overactivate the mTORC2 (mammalian target of the rapamycin complex 2)/Akt pathway, inducing platelet activation and decreasing platelet count [20]. Our study corroborates the clinical medical perspective on the association between aPLs and SLE-TP.

Despite the increasing attention to the harm caused by severe and recurrent low platelet counts in SLE patients, there is currently no internationally recognized management and effective predictive indicator for SLE-TP. In our study, SLE-TP patients with positive aPLs had lower platelet counts during follow-up, and the relapse rate was higher. Moreover, the severity and relapse rate of thrombocytopenia were positively correlated with the number of types of aPLs, suggesting that aPLs may serve as valuable indicators for disease severity, treatment response and prognosis in SLE-TP patients.

Our study has several limitations. Firstly, due to a relatively small sample size, and the fact that only a subset of patients underwent testing for the types of aPLs, we were unable to investigate the impact of different types of aPLs on platelet reduction. Secondly, a limited number of patients underwent bone marrow aspiration, which hindered our exploration of the effects of aPLs on the platelet production process, such as whether aPLs affect the quantity and maturation of megakaryocytes. Thirdly, comprehensive records of bleeding events in SLE-TP patients were not available, thus preventing a thorough investigation into the influence of aPLs on bleeding occurrences.