Pregnancy outcomes and risk factors for thrombocytopenia in pregnant patients with systemic lupus erythematosus

Abstract

Background

To compare pregnancy outcomes between systemic lupus erythematosus (SLE) patients with thrombocytopenia and those without, and to develop a nomogram for assessing the risk of developing SLE-related thrombocytopenia during pregnancy.

Methods

Clinical data from 178 pregnant patients with SLE were analyzed. Patients were classified into thrombocytopenia and normal platelet groups using a platelet count cutoff of < 100 × 10^9/L. Pregnancy outcomes were compared between these groups. A nomogram was developed to identify factors associated with thrombocytopenia based on univariate and multivariable logistic regression analyses. The performance of the nomogram was assessed through receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA).

Results

Among the 178 patients, 34 were in the thrombocytopenia group and 144 in the normal platelet group. SLE patients with thrombocytopenia had a significantly higher rate of active disease (55.9% vs. 5.6%, P < 0.001) and a higher SLE-Pregnancy Disease Activity Index (SLEPDAI) (4.71 ± 3.04 vs. 2.29 ± 1.88, P < 0.001). When comparing patients with thrombocytopenia (categorized by platelet counts < 50 × 10^9/L and > 50 × 10^9/L) to the control group, the incidence of severe preeclampsia (20.00% vs. 15.79% vs. 4.86%, P = 0.027) and postpartum hemorrhage (26.32% vs. 6.67% vs. 3.47%, P = 0.007) was also significantly higher in the thrombocytopenia group. This group exhibited elevated rates of pregnancy loss (73.33% vs. 31.58% vs. 4.17%, P < 0.001) and stillbirth (20.00% vs. 15.79% vs. 0.69%, P < 0.001). Active disease, previous abortion, and anti-β2GPI antibodies positivity were identified as independent factors of developing SLE-related thrombocytopenia during pregnancy. The area under the curve for the nomogram was 0.833 (95% CI: 0.753–0.913). Both the calibration curve and DCA indicated that the model performed well.

Conclusion

Thrombocytopenia in pregnant patients with SLE is associated with increased disease activity and a higher incidence of adverse outcomes, including pregnancy loss and stillbirth. The nomogram for developing thrombocytopenia during pregnancy may help clinicians improve the management of this group of patients.

Clinical trial number

not applicable.

Background

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder that affects multiple organs and is characterized by widespread inflammation. The global prevalence of SLE is approximately 78.73 per 100,000 individuals, with around 3.04 million women affected [1]. The condition most commonly affects women of childbearing age and is associated with adverse pregnancy outcomes, including complications for both the mother and the fetus [2]. Women with SLE are at an increased risk for both fetal complications, including intrauterine growth restriction (IUGR), preterm birth, pregnancy loss, and stillbirth, as well as maternal complications such as pre-eclampsia, postpartum hemorrhage, and disease flare during pregnancy [3].

Thrombocytopenia develops in 5–10% of pregnancies and can arise from a variety of causes, including autoimmune conditions like SLE, immune thrombocytopenic purpura (ITP), and antiphospholipid syndrome (APS), as well as pregnancy-specific conditions such as gestational thrombocytopenia (GT), preeclampsia, and HELLP syndrome [4]. ITP during pregnancy is caused by autoantibodies against platelet glycoproteins, leading to platelet destruction. This condition often presents with isolated thrombocytopenia without other systemic manifestations, although it can sometimes result in bleeding complications. In contrast, APS is characterized by the presence of antiphospholipid antibodies, which increase the risk of thrombosis and recurrent pregnancy loss [5]. Thrombocytopenia in APS is typically related to a hypercoagulable state and may occur alongside thrombotic events, distinguishing it from SLE-related thrombocytopenia, which is driven by immune-mediated platelet destruction. HELLP syndrome, typically presenting in the second or third trimester, is characterized by a triad of hemolysis, elevated liver enzymes, and thrombocytopenia. It is associated with hypertension and multisystem complications, often requiring urgent delivery. GT is a relatively benign condition, typically presenting with mild platelet reduction, which resolves postpartum without significant maternal or fetal complications [6].

SLE-related thrombocytopenia develops secondary to platelet destruction caused by antiplatelet antibodies, circulating immune complexes, or other related mechanisms. It is often linked to active disease, and pregnant women with thrombocytopenia are at higher risk for adverse pregnancy outcomes, including pregnancy loss, preterm birth, and fetal growth restriction. Thrombocytopenia is also a recognized hematological criterion in the American College of Rheumatology’s classification criteria for SLE [7, 8]. Research indicates that thrombocytopenia is associated with severe clinical manifestations and poor prognosis in SLE patients [9]. It has also been identified as an independent predictor of mortality in some studies, although specific data on pregnant patients are limited [10, 11]. However, there is a notable gap in the literature regarding the impact of thrombocytopenia during pregnancy in SLE patients. The potential overlap with other conditions such as APS further complicates the understanding of thrombocytopenia in pregnant women with SLE.

In this study, we aim to compare pregnancy outcomes between SLE patients with thrombocytopenia and those without, with a specific focus on maternal and fetal health. Additionally, we have developed a nomogram to assess the risk of thrombocytopenia in pregnant SLE patients. This tool is designed to help clinicians identify patients at higher risk for thrombocytopenia-related complications, improving early detection and management, and ultimately contributing to better pregnancy outcomes for women with SLE.

Patients and methods

Patients

A retrospective study was conducted on 178 pregnant patients with SLE admitted to the First Affiliated Hospital of Sun Yat-sen University between February 2012 and October 2023. All patients met the 1997 ACR classification criteria for SLE [12]. Patients were categorized into two groups based on their platelet count: those with thrombocytopenia and those without, in accordance with the ACR criteria for thrombocytopenia in SLE [13]. Thrombocytopenia was considered related to SLE if it occurred in the context of active disease or was consistent with immune-mediated mechanisms. Platelet levels were measured at the time of admission and subsequently throughout the pregnancy, with additional measurements taken more frequently if clinically indicated (e.g., during disease flares). The platelet count at the time of admission was used as the baseline. Only persistent thrombocytopenia, defined as a platelet count consistently below 100 × 10^9/L throughout the pregnancy, was considered for inclusion. Transient drops in platelet count that recovered during the same admission or trimester were excluded. Patients with thrombocytopenia due to gestational thrombocytopenia, HELLP syndrome, acute fatty liver of pregnancy, thrombotic thrombocytopenic purpura, hemolytic-uremic syndrome, infections, or heparin-induced thrombocytopenia (HIT) were excluded. Patients with APS were excluded; only those with positive antiphospholipid (aPL) antibodies but without clinical symptoms of thrombotic or obstetric complications were included in the analysis. Additionally, patients lacking regular follow-up or complete records were excluded. The study was approved by the Ethics Committee of the First Affiliated Hospital of Sun Yat-sen University. Given the retrospective nature of the research, the Ethics Committee waived the requirement for informed consent, in accordance with the Declaration of Helsinki.

Clinical data

Maternal baseline information included age, gestational age, disease duration, and obstetric history. Previous abortion included both spontaneous abortion (miscarriage) and therapeutic abortion (elective termination). Laboratory data comprised albumin levels, hemoglobin levels, complement levels (C3 and C4), anti-double-stranded DNA (anti-dsDNA) antibodies, anti-Ro/SSA and anti-La/SSB antibodies, anti-RNP antibodies, anti-cardiolipin (aCL) antibodies, anti-β2-glycoprotein I (anti-β2GPI) antibodies, and lupus anticoagulants (LAC). Disease activity in pregnancy was assessed using the SLE-Pregnancy Disease Activity Index (SLEPDAI) [14], with the highest score used for statistical analysis. Active at conception was defined as an SLEPDAI or SLEDAI score of ≥ 4, or the daily use of more than 10 mg of prednisone [15]. We gathered information on the patients’ pregnancy medication history, which included glucocorticoids, hydroxychloroquine (HCQ), immunosuppressants, aspirin and low molecular weight heparin (LMWH). Immunosuppressants included cyclosporine A, tacrolimus and azathioprine.

Definition of maternal and fetal outcomes

Adverse maternal outcomes included: [1] Gestational diabetes mellitus (GDM), defined as any degree of glucose intolerance or diabetes first identified during pregnancy [2]. Hypertensive disorders of pregnancy, classified into four categories [16], chronic hypertension, gestational hypertension, preeclampsia-eclampsia, and chronic hypertension with preeclampsia. Gestational hypertension: blood pressure ≥ 140/90 mmHg at least twice after 20 weeks of gestation with ≥ 6 h between readings. Preeclampsia: hypertension with proteinuria > 0.3 g/L/day or sudden onset of hypertension and proteinuria after 20 weeks of gestation. Eclampsia requires seizures. Severe preeclampsia: systolic blood pressure ≥ 160 or diastolic blood pressure ≥ 110 mmHg after 20 weeks of gestation with multi-organ involvement; [3] Antepartum hemorrhage, defined as vaginal bleeding occurring after 28 weeks of gestation; [4] Postpartum hemorrhage, defined as blood loss exceeding 500 mL within 24 h after delivery.

Live birth was defined as the delivery of a live infant at ≥ 20 weeks of gestation, with the newborn surviving for at least 6 days. The primary outcome of pregnancy loss was defined as any pregnancy that did not result in a live birth. This includes spontaneous abortion (loss of pregnancy before 20 weeks of gestation), therapeutic abortion (induced termination due to lupus or other life-threatening obstetric complications), and stillbirth (intrauterine fetal death after 20 weeks of gestation). Adverse fetal outcomes included preterm birth (< 37 weeks of gestation), fetal distress (pathological conditions due to hypoxia or acidosis that compromise fetal well-being), premature rupture of membranes (PROM) (spontaneous rupture of membranes before the onset of labor), IUGR (defined as a fetus with an estimated fetal weight (EFW) below the 10th percentile for gestational age, accompanied by at least one additional indicator of compromised growth, such as abnormal Doppler findings or reduced amniotic fluid), small for gestational age (SGA) (birth weight below the 10th percentile for gestational age and sex, regardless of whether the fetus had a history of growth restriction), admission to the neonatal intensive care unit (NICU), neonatal asphyxia, low birth weight (< 2500 g), and extremely low birth weight (< 1500 g).

Feature selection and model establishment

Univariate and multivariate logistic regression analyses were conducted to identify risk factors associated with thrombocytopenia in pregnant women with SLE. Variables with a p-value less than 0.05 in univariate analysis were included in the multivariate logistic regression model. Stepwise forward selection was applied to identify the most clinically relevant factors associated with thrombocytopenia. To create a clinically applicable and easy-to-use tool, a nomogram was developed based on the results of the multivariate regression analysis [17]. The points for each factor were calculated by mapping the regression coefficients onto a scale, and the total score for each patient was obtained by summing the points for all three variables. The total score corresponds to the probability of thrombocytopenia in pregnant SLE patients. The model’s performance was evaluated using the receiver operating characteristic (ROC) curve, with the area under the curve (AUC) serving as the primary measure of the model’s discrimination ability. An AUC closer to 1.0 indicates excellent discrimination, while values near 0.5 suggest no predictive value. The calibration curve was plotted to assess the accuracy of the nomogram’s predictions, with a closer alignment of predicted and observed probabilities indicating better accuracy. Additionally, decision curve analysis (DCA) was performed to evaluate the clinical utility of the model by quantifying its net benefit, considering both true and false positives at various threshold probabilities.

Statistical analysis

To evaluate the impact of isolated aPL positivity, we performed a sensitivity analysis by excluding 28 patients with isolated aPL positivity (defined as LAC positivity, aCL IgG/IgM > 40 U, or anti-β2GPI antibodies positivity, without APS clinical criteria). The remaining cohort (n = 150 vs. original n = 178) was re-analyzed using the same statistical approaches. Continuous data are reported as mean ± standard deviation (SD) and compared using t-tests, with Mann-Whitney U tests for non-normally distributed data. Categorical data are described as frequencies and percentages, and compared using chi-square tests. A p-value < 0.05 was considered statistically significant. Data analysis was conducted using R software (version 4.3.2) and SPSS (version 26.0).

Results

Demographics

This study included 178 pregnant women with SLE, categorized into two groups based on the presence of thrombocytopenia: the control group (N = 144) and the thrombocytopenia group (N = 34). The average platelet count in the thrombocytopenia group was 50.71 ± 32.37 × 10^9/L, with 15 patients having a platelet count ≤ 50 × 10^9/L. The mean (SD) age of these patients was 30.47 ± 5.37 years, and the mean (SD) disease duration was 5.18 ± 4.24 years. There were no significant differences in age, disease duration, or renal involvement between the thrombocytopenia and control groups. However, patients with thrombocytopenia demonstrated significantly higher active disease during pregnancy (55.9% vs. 5.6%, P < 0.001) and elevated SLEPDAI scores (4.71 ± 3.04 vs. 2.29 ± 1.88, P < 0.001) compared to those without thrombocytopenia. In terms of pregnancy features, the previous abortion rate (67.7% vs. 46.5%, P = 0.027) and number of pregnancies (2.47 ± 1.21 vs. 2.02 ± 1.10, P = 0.037) were significantly higher in the thrombocytopenia group compared to the control group. No significant differences were observed between the two groups regarding previous preterm birth rates or the use of assisted reproductive technologies (Table 1).

Table 1 Comparison between SLE patients with and without thrombocytopenia

In terms of treatment, most stable lupus patients received daily prednisone at a dose of 5–10 mg. The glucocorticoid dosage in the thrombocytopenia group was higher than in the control group. Five patients with thrombocytopenia were treated with intravenous steroid pulse therapy. Four of these patients had platelet counts below 50, and one exhibited multi-organ involvement, affecting the nervous system, kidneys, and hematologic system. Given the elevated disease activity and critically low platelet levels, intravenous steroid pulse therapy was initiated post-induction. Among thrombocytopenic patients, 24 individuals (70.6%) were treated with HCQ at a daily dose of 0.2–0.4 g. The frequency of HCQ use was lower in thrombocytopenic patients compared to those without thrombocytopenia (70.6% vs. 86.1%, P = 0.03). A few patients used immunosuppressants during pregnancy. In the thrombocytopenia group, 9 patients received cyclosporine, 1 received azathioprine, and 1 received tacrolimus. There were no statistically significant differences between the two groups regarding the use of aspirin and LMWH.

Maternal and fetal outcomes

Among 34 SLE patients with thrombocytopenia, 26 were primiparous, 8 were multiparous, and 15 had severe thrombocytopenia (platelet count < 50 × 10^9/L). A total of 17 live births were reported (50%, 17/34), with 11 deliveries by cesarean section and 6 by vaginal birth. When comparing patients with thrombocytopenia (categorized by platelet counts < 50 × 10^9/L and > 50 × 10^9/L) to the control group, patients with thrombocytopenia exhibited a significantly higher incidence of severe preeclampsia (20.00% vs. 15.79% vs. 4.86%, P = 0.027) and postpartum hemorrhage (6.67% vs. 26.32% vs. 3.47%, P = 0.007). No significant differences were observed between the groups in the rates of gestational diabetes, gestational hypertension, or preeclampsia (Table 2).

Table 2 Adverse pregnancy outcomes in patients with SLE SLE, systemic lupus erythematosus; GDM, gestational diabetes mellitus; SGA, small for gestational age infant; BW, birth weight; IUGR, intrauterine growth retardation; PROM, premature rupture of membranes

Pregnancies with thrombocytopenia showed significantly higher rates of pregnancy loss (73.33% vs. 31.58% vs. 4.17%, P < 0.001) and stillbirth (20.00% vs. 15.79% vs. 0.69%, P < 0.001) compared to controls. Causes of pregnancy loss included lupus flare-induced induction (10/17, 58.8%), stillbirth (6/17, 35.3%), and spontaneous miscarriage (1/17, 5.9%). Additionally, 6 cases (18.2%) involved preterm birth, with 3 infants (8.82%) born before 34 weeks of gestation. While preterm birth rates did not differ significantly between groups, the gestational age at delivery was notably lower in the thrombocytopenia group (29.29 ± 9.74 vs. 33.19 ± 7.45 vs. 37.14 ± 2.20, P < 0.001). There were no significant differences in PROM, birth weight, fetal growth restriction, neonatal asphyxia, or fetal distress between the groups.

After excluding aPL-positive patients, thrombocytopenia remained significantly associated with severe preeclampsia, postpartum hemorrhage, pregnancy loss, and stillbirth (Table S1). The minimal changes in effect sizes suggest that isolated aPL positivity did not substantially confound the observed associations.

Univariate and multivariate analysis

Univariate analysis reveals that SLE patients with concomitant thrombocytopenia exhibit significantly higher frequencies of elevated SLEPDAI scores, active disease, a greater number of pregnancies, previous abortions, hypocomplementemia, low serum C4 levels, and positive anti-β2GPI antibodies (P < 0.05). Additionally, the odds ratio (OR) for HCQ usage in the thrombocytopenia group was 0.39 (95% confidence interval [CI]: 0.16–0.93), indicating that HCQ usage was less likely in the thrombocytopenia group, which may suggest a potential protective effect in the control group. Multivariate analysis identified active disease (OR 15.06 [CI: 3.92–57.84], P < 0.001), previous abortion (OR 4.82 [CI: 1.11–20.86], P = 0.035), and anti-β2GPI antibodies positivity (OR 5.04 [CI: 1.18–21.51], P = 0.029) as independent risk factors (Table 3).

Table 3 Univariate and multivariate analysis of factors predicting thrombocytopenia in the training cohort of pregnant SLE patients

Development of the nomogram

To create a clinically applicable tool for assessing thrombocytopenia in pregnant SLE patients, we developed a nomogram (Fig. 1A) based on the results of the multivariate analysis. The nomogram demonstrated strong performance, with an AUC of 0.833 (95% CI: 0.753–0.913) (Fig. 1B), indicating robust sensitivity and specificity. The calibration curve (Fig. 1C) confirmed the model’s excellent discriminatory power, showing a close correspondence between predicted and observed probabilities. This indicates that the nomogram can reliably predict thrombocytopenia risk in pregnant SLE patients. Furthermore, the DCA demonstrated that the nomogram provides a net benefit across a wide range of threshold probabilities (Fig. 1D).

Fig. 1

Developing and validating a nomogram for thrombocytopenia in pregnant SLE patients. (A) Nomogram incorporating three independent predictors: active disease, previous abortion, and anti-β2GPI positivity. (B) Receiver operating characteristic (ROC) curve for model discrimination (AUC = 0.833). (C) Calibration curve assessing agreement between predicted and observed probabilities. (D) Decision curve analysis (DCA) evaluating clinical net benefit across threshold probabilities

Discussion

Thrombocytopenia is a prevalent hematologic manifestation of SLE. Thrombocytopenia in pregnant SLE patients has been linked to adverse maternal and fetal outcomes. Consequently, early detection and prompt management of thrombocytopenia are essential for improving patient prognosis [18]. Currently, there is a lack of research on the early assessment and identification of pregnancy-related thrombocytopenia in SLE. In our study, we developed a nomogram based on clinically accessible disease characteristics of pregnant SLE patients with thrombocytopenia.

Studies on non-pregnant SLE patients have indicated that thrombocytopenia is associated with higher disease activity, increased likelihood of end-organ damage, and higher mortality rates. Fernandez et al. demonstrated that early thrombocytopenia is associated with severe and active SLE, while severe thrombocytopenia is significantly correlated with organ damage [10]. A large cohort study conducted in China found that patients with thrombocytopenia in SLE experience reduced long-term survival rates [19]. In a multi-ethnic cohort study in the United States, Jallouli et al. included 182 SLE patients and discovered that thrombocytopenia is linked to more severe disease. Additionally, their multivariable logistic regression analysis revealed that thrombocytopenia increases the risk of both organ damage and mortality [20]. In this study, we observed that, consistent with findings in non-pregnant SLE patients, pregnant patients with thrombocytopenia experience a higher overall incidence of active disease. Moreover, these patients have higher SLEPDAI scores compared to those without thrombocytopenia, which indirectly reflects greater disease activity and a poorer prognosis during pregnancy. Given the increased risk of adverse outcomes associated with thrombocytopenia, we recommend routine screening for thrombocytopenia in all pregnant women with SLE, particularly those with a history of disease flares, previous pregnancy losses, or elevated SLE disease activity. Early identification can help guide timely interventions, such as more frequent monitoring of platelet counts and appropriate adjustments in immunosuppressive therapy. Additionally, our study highlights that disease activity, particularly as reflected in SLEPDAI scores, is a key factor influencing the risk of thrombocytopenia and adverse pregnancy outcomes. In clinical practice, close monitoring of disease activity in pregnant SLE patients is crucial.

Research on the association between thrombocytopenia during pregnancy and pregnancy outcomes remains limited. Our study reveals that, in comparison to the control group, thrombocytopenia in SLE patients during pregnancy is linked to higher rates of pregnancy loss and stillbirth. A study involving 115 patients with antiphospholipid syndrome found that thrombocytopenia was associated with SGA (12.12% vs. 31.25%, p = 0.043), preterm birth before 37 weeks (16.16% vs. 43.75%, p = 0.010), and fetal intrauterine death (2.02% vs. 12.50%, p = 0.033) [21]. However, SLE-related thrombocytopenia differs from other causes, such as GT, APS, and ITP. APS, driven by aPL, complicates pregnancy through thrombotic events and recurrent pregnancy loss, whereas GT is generally benign and resolves postpartum. ITP may also elevate the risk for stillbirth, fetal loss, and premature delivery [22]. We excluded APS patients to avoid confounding by aPL, which can independently affect thrombocytopenia and pregnancy outcomes. This allowed us to focus on SLE as the primary cause of thrombocytopenia in pregnancy. We included SLE patients with isolated aPL positivity because aPL are common in SLE and may reflect disease activity. The association between anti-β2GP-I positivity and thrombocytopenia, rather than lupus anticoagulant, aligns with previous studies showing that anti-β2GPI antibodies are more directly linked to thrombocytopenia in SLE, whereas lupus anticoagulant is primarily associated with thrombotic events [23]. Our study suggests that anti-β2GPI antibodies contribute to immune-mediated thrombocytopenia in SLE, independent of APS-related thrombosis. These findings, combined with our results, underscore the importance of distinguishing between thrombocytopenia caused by SLE and other conditions, such as APS, to guide appropriate clinical management.

We also observed a high rate of previous abortions in both groups. SLE itself increases the risk of pregnancy loss due to disease-related factors, including immune dysregulation, disease activity, and vascular abnormalities [24]. In addition, some pregnancies may have been unintended, and patients may have continued medications that are contraindicated during pregnancy, which could have further increased the risk of pregnancy loss. Furthermore, the use of medications like cyclophosphamide, which are necessary to control disease activity but have adverse effects on pregnancy outcomes, may also contribute to miscarriage [25].

In this study, only a small proportion of patients with moderate or severe thrombocytopenia received immunosuppressive therapy. This reflects the clinical challenge of balancing effective disease management with the safety of both the mother and the fetus. Upon analyzing patient histories, we identified several factors that contributed to the limited use of immunosuppressants in this cohort. Firstly, concerns regarding the potential teratogenic effects and other adverse outcomes associated with immunosuppressive therapy during pregnancy were prominent. Many patients were understandably hesitant to use these medications due to the possible risks to fetal development. Secondly, some patients had previously been treated with cyclosporine or tacrolimus, but their intolerance to side effects and limited efficacy led to reluctance in continuing these therapies. These patients had experienced inadequate disease control, which compounded their hesitation in using these agents during pregnancy. As a result, a more cautious approach was adopted, prioritizing the use of corticosteroids and hydroxychloroquine to control disease activity while minimizing fetal risks [26, 27]. The decision to use immunosuppressants was made on a case-by-case basis, closely monitoring the patient’s condition and weighing the risks and benefits of each treatment option. This highlights the complex and individualized decision-making process in managing thrombocytopenia during pregnancy, where maternal safety, disease control, and fetal well-being are all critical factors to consider.

The recognized mechanism of thrombocytopenia in SLE patients involves the destruction of platelets by anti-platelet autoantibodies. Platelets contribute to immune dysregulation by inducing interferon production in immune cells, providing CD40L to support B lymphocyte function, and serving as a source of autoantigens [28]. Additionally, patients may have antiphospholipid antibodies. The pathogenesis of thrombocytopenia in SLE is further complicated by the intricate interactions between antiphospholipid antibodies and platelet antigen antibodies [29]. Treatment strategies for thrombocytopenia vary significantly depending on the underlying cause. Thrombocytopenia in APS is generally managed with anticoagulation therapy to prevent thromboembolic events, whereas ITP in pregnancy is typically managed with oral corticosteroids to suppress platelet destruction. In contrast, SLE-related thrombocytopenia is treated by controlling disease activity through immunosuppressive therapies, as it is driven by immune dysregulation rather than clotting abnormalities. Pregnancy-related complications, such as HELLP syndrome, require urgent delivery and management of maternal complications, highlighting the complexity of managing thrombocytopenia in high-risk pregnancies. HELLP syndrome presents distinct challenges compared to SLE and APS, necessitating a rapid and aggressive clinical approach to prevent serious maternal and fetal morbidity [30]. Thus, while thrombocytopenia in SLE and other autoimmune conditions shares certain features, such as platelet destruction, the underlying pathophysiology and management strategies differ significantly. This underscores the importance of individualized treatment approaches that consider the unique pathophysiological mechanisms of each condition to optimize both maternal and fetal health.

This study has several limitations. First, as a retrospective study, it lacks complete information on all SLE patients. Second, the inclusion of patients with isolated aPL positivity may have introduced some degree of bias, as the effects of aPL on thrombocytopenia in SLE patients may not be fully distinguishable from those of APS. Third, the sample size of the thrombocytopenia group was relatively small, which limits the ability to perform more robust stratified analyses and may affect the generalizability of the findings. Larger studies with more patients are necessary to confirm and refine our conclusions. Finally, the nomogram has not been externally validated, limiting its generalizability. While internal validation through ROC, calibration, and decision curve analyses supports its predictive accuracy, external validation in independent cohorts is needed to confirm its applicability. Therefore, we recommend conducting larger, prospective cohort studies with external validation to confirm the model’s robustness.

In summary, our findings indicate that thrombocytopenia in pregnant SLE patients is associated with higher disease activity, increased rates of pregnancy loss, and stillbirth. Further research is essential to elucidate the mechanisms underlying these complications and to develop more targeted and precise therapies. Early detection of thrombocytopenia during pregnancy, timely diagnosis of unexplained thrombocytopenia, and appropriate treatment are crucial for reducing adverse pregnancy outcomes and enhancing the chances of a successful pregnancy.

Conclusions

Thrombocytopenia in pregnant patients with SLE is significantly associated with heightened disease activity and an elevated risk of adverse pregnancy outcomes, such as pregnancy loss and stillbirth. These findings highlight the critical need for meticulous monitoring and proactive management in this high-risk population. The nomogram developed in this study offers a practical tool for clinicians to assess risk and guide individualized treatment strategies, potentially improving maternal and fetal outcomes in patients with SLE-related thrombocytopenia.