Abstract
Objectives
This study sought to evaluate the clinical implications of thrombocytopenia in pediatric patients diagnosed with systemic lupus erythematosus (SLE) and to explore its relationship with various disease features. Furthermore, the research aimed to identify risk factors that affect the occurrence of SLE-associated thrombocytopenia.
Methods
A single-center retrospective study was conducted involving 236 pediatric patients diagnosed with SLE at Children’s Hospital of Fudan University from January 2020 and December 2025. Clinical information and laboratory parameters, such as complement levels, autoantibody profiles, and platelet counts, were systematically collected. Participants were divided into two groups and those without, based on their platelet counts at the time they were diagnosed with SLE. The presence of thrombocytopenia was determined at diagnosis, and further subgroup analyses were carried out based on the severity of the condition. All statistical analyses, such as logistic regression and one-way ANOVA, were conducted using SPSS version 26.0.
Results
Thrombocytopenia was observed in 19.5% (46 out of 236) of the patients. In comparison to the cohort without thrombocytopenia, the thrombocytopenia group demonstrated significantly increased incidences of leukopenia, leukocyte reduction, and positivity for antiphospholipid antibody IgM, anti-β2-glycoprotein-1 antibody, and lupus anticoagulant (P < 0.05). Furthermore, severe thrombocytopenia (defined as a platelet count below 50 × 10⁹/L) was correlated with a markedly higher prevalence of lupus anticoagulant positivity relative to the mild-to-moderate thrombocytopenia subgroup. Logistic regression analysis revealed that leukopenia, elevated erythrocyte sedimentation rate (ESR), positivity for Anti-β2 glycoprotein 1 antibodies, high lupus anticoagulant, and neuropsychiatric manifestations were significantly associated with the presence of thrombocytopenia.
Conclusion
Thrombocytopenia frequently occurs in pediatric patients with SLE and demonstrates a significant correlation with leukopenia, the presence of antiphospholipid antibodies, and involvement of major organs. Additionally, further multicenter prospective investigations are necessary to clarify the contribution of platelets to the pathogenesis of SLE. In clinical practice, when thrombocytopenia is identified in pediatric SLE patients, thorough evaluation for antiphospholipid antibodies and neuropsychiatric systemic lupus erythematosus (NPSLE) is warranted.
Keywords: Systemic lupus erythematosus, Platelet count, Thrombocytopenia, Clinical features, Pediatrics
Introduction
Systemic lupus erythematosus (SLE) is an autoimmune disorder marked by the presence of pathogenic autoantibodies and the deposition of immune complexes, which result in damage to multiple organ systems [1, 2]. The clinical presentation of SLE is notable heterogeneous [3, 4]. Immune thrombocytopenia (ITP) represents a frequent hematologic manifestation within SLE and may, in some cases, constitute the initial clinical presentation [5, 6]. This condition is closely linked to an unfavorable prognosis and functions as an independent risk factor for disease progression [5, 7].
In addition to their established function in hemostasis, platelets are increasingly acknowledged as active participants in the immune system, playing a significant role in the pathophysiology of immune‑mediated inflammatory diseases [8, 9]. Nevertheless, clinical investigations focusing explicitly on platelet involvement in SLE remain scarce. The present study aims to examine the association between platelet counts and both clinical and serological characteristics in pediatric SLE patients, with the objective of elucidating the role of platelets in the pathogenesis of SLE. Furthermore, this study aims to concentrate solely on assessing the clinical importance, correlations, and predictors of thrombocytopenia at the time of diagnosis in children with SLE.
Patients and methods
Study design and participants
This retrospective study, conducted at a single-center, encompassed pediatric patients diagnosed with SLE at the Children’s Hospital of Fudan University from January 2020 to December 2025. Attention was given to patients presenting with thrombocytopenia at the time of diagnosis. The diagnosis of SLE was established according to the classification criteria set forth by the 1997 American College of Rheumatology (ACR), the 2012 Systemic Lupus International Collaborating Clinics (SLICC), or the 2019 European Alliance of Associations for Rheumatology (EULAR)/ACR guidelines [10, 11]. Immune thrombocytopenia was defined as a platelet count below 100 × 10⁹/L in the absence of alternative identifiable etiologies at the time of diagnosis [12, 13]. Exclusion criteria comprised: (1) thrombotic microangiopathy; (2) hepatosplenic conditions such as portal hypertension, cirrhosis, or splenomegaly; (3) hematologic disorders including leukemia, myelodysplastic syndrome, and hemophagocytic lymphohistiocytosis); (4) drug-induced thrombocytopenia; and (5) severe active infections. Ethical approval for the study was obtained from the Fudan University Ethics Review Committee (approval number 2025 [344]), and the research was conducted in accordance with the principles outlined in the Declaration of Helsinki.
Data collection
Data obtained from electronic medical records encompassed patient demographics, disease duration, clinical presentations [14], completed blood counts parameters (including white blood cells, neutrophils, lymphocytes, hemoglobin and platelets), inflammatory markers such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), complement system components (C3, C4, CH50), and autoantibody profiles comprising antinuclear antibodies, anti-double-stranded DNA (anti-dsDNA), anti-Smith, anti-U1RNP, anti-Ro60, anti-Ro52, anti-SSB, anti-nucleosome, anti-histone, anticardiolipin antibodies (IgM, IgG, IgA and anti-β2-glycoprotein-1), and lupus anticoagulant. Additionally, results from the direct Coombs test results and the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDIA-2 K) score were recorded [15, 16].
Statistical analysis
Data analysis was conducted utilizing SPSS version 26.0. Continuous variables are reported as mean ± standard deviation (SD) or median with interquartile range, depending on data distribution, whereas categorical variables are presented as frequencies and percentages. Group differences were assessed using one-way analysis of variance (ANOVA) or logistic regression models, as appropriate. Logistic proportional hazards regression was employed to identify risk factors associated with thrombocytopenia. Statistical significance was defined by a two-tailed p-value less than 0.05.
Results
Baseline characteristics
The study population consisted of 236 pediatric patients diagnosed with SLE, with a mean age of 11.1 ± 2.7 years and a predominance of females (78.8%). The average duration of disease duration was 4.9 ± 10.3 months. Disease activity was notably elevated, as indicated by a mean SLEDAI-2 K score of 14.4 ± 8.7. The most frequently observed clinical features included rash (63.6%), fever (48.3%), vasculitis (26.7%), arthritis (24.2%), oral ulcers (13.6%), and alopecia (7.6%). Organ involvement was primarily characterized by lupus nephritis (57.2%), followed by pulmonary manifestations (21.2%), neuropsychiatric lupus (15.7%), cardiac complications (8.5%) and thrombotic events (5.1%). Hematological abnormalities were prevalent, with thrombocytopenia observed in 19.5%, leukopenia in 40.3%, and anemia in 67.8% of the cohort. Among those who had a kidney biopsy (45.3% of the group), the renal pathology was classified as class Ⅱ (12.7%), class Ⅲ (5.9%), class Ⅳ (19.9%), and class Ⅴ (6.8%). Complement system activation was frequently evidenced by decreased levels of C3, C4, and CH50 in 63.1%, 65.3%, and 73.3% of patients, respectively. Autoantibody profiling reveled positivity rates of 100% for ANA 100%, 70.8% for anti-dsDNA, 43.2% for anti-Smith, and 45.3% for anti-U1RNP antibodies. Additionally, antiphospholipid antibodies were detected with positivity rates of 54.7% for anti-β2-glycoprotein-1, 49.6% for lupus anticoagulant, and 68.6% for a positive direct Coombs test. Elevated fibrin degradation products (FDP) were seen in 40.3% of patients, increased D-dimer levels in 72.9% (Table 1).
Table 1.
Baseline characteristics of patients with SLE (n = 236)
| Variable | Value |
|---|---|
| Female, n (%) | 186 (78.8%) |
| Age (years), median | 11.1 ± 2.7 |
| Disease duration (months), median | 4.9 ± 10.3 |
| Leukocyte count (109/L), median | 5.7 ± 3.8 |
| Leukopenia, n (%) | 95 (40.3%) |
| Anemia, n (%) | 160 (67.8%) |
| Platelet count (109/L), median | 190.7 ± 98.3 |
| Thrombocytopenia, n (%) | 46 (19.5%) |
| CRP (mg/L), median | 6.7 ± 19.4 |
| ESR (mm/h), median | 45.8 ± 33.2 |
| ANA positivity, n (%) | 236 (100%) |
| Anti-dsDNA positivity, n (%) | 167 (70.8%) |
| Anti-Smith positivity, n (%) | 102 (43.2%) |
| Anti-U1RNP positivity, n (%) | 107 (45.3%) |
| Anti-Ro60 positivity, n (%) | 49 (20.8%) |
| Anti-Ro52 positivity, n (%) | 45 (19.1%) |
| Anti-SSB positivity, n (%) | 34 (14.4%) |
| Antinucleosome antibody positivity, n (%) | 74 (31.4%) |
| Antihistone antibodies positivity, n (%) | 84 (35.6%) |
| Antiphospholipid antibodies IGG positivity, n (%) | 40 (16.9%) |
| Antiphospholipid antibodies IGA positivity, n (%) | 7 (3.0%) |
| Antiphospholipid antibodies IGM positivity, n (%) | 29 (12.3%) |
| Anti-β2 glycoprotein 1 antibody positivity, n (%) | 129 (54.7%) |
| Elevated lupus anticoagulant, n (%) | 117 (49.6%) |
| Elevated FDP, n (%) | 95 (40.3%) |
| Elevated D-dimer, n (%) | 172 (72.9%) |
| Direct Coombs’ test, n (%) | 162 (68.6%) |
| C3 (g/L), median | 0.6 ± 0.4 |
| Low C3, n (%) | 149 (63.1%) |
| C4 (g/L), median | 0.1 ± 0.1 |
| Low C4, n (%) | 154 (65.3%) |
| CH50 | 19.1 ± 14.5 |
| Low CH50, n (%) | 173 (73.3%) |
| Fever, n (%) | 114 (48.3%) |
| Rash, n (%) | 150 (63.6%) |
| Alopecia, n (%) | 18 (7.6%) |
| Oral ulcers, n (%) | 32 (13.6%) |
| Arthritis, n (%) | 57 (24.2%) |
| Myositis, n (%) | 12 (5.1%) |
| Vasculitis, n (%) | 63 (26.7%) |
| Pericarditis, n (%) | 20 (8.5%) |
| Lupus nephritis, n (%) | 135 (57.2%) |
| Albuminuria | 93 (39.4%) |
| Cylindruria | 70 (29.7%) |
| Hematuria | 85 (36.0%) |
| Leukocyturia | 59 (25.0%) |
| Renal pathological type, n (%) | 107 (45.3%) |
| Ⅱ | 30 (12.7%) |
| Ⅲ | 14 (5.9%) |
| Ⅳ | 47 (19.9%) |
| Ⅴ | 16 (6.8%) |
| Neuropsychiatric lupus, n (%) | 37 (15.7%) |
| Thrombus, n (%) | 12 (5.1%) |
| Cardiac complications, n (%) | 5 (2.1%) |
| Pulmonary manifestations, n (%) | 50 (21.2%) |
| SLEDAI 2 K score, median | 14.4 ± 8.7 |
Abbreviations: SLE, Systemic Lupus Erythematosus; CRP, C-Reactive Protein; ESR, Erythrocyte Sedimentation Rate; ANA, Antinuclear Antibody; Anti-dsDNA, Anti-double-stranded DNA antibody; Anti-U1RNP, Anti-U1 Ribonucleoprotein antibody; Anti-Ro60, Anti-Ro/SSA 60kD antibody; Anti-Ro52, Anti-Ro/SSA 52kD antibody; Anti-SSB, Anti-Sjogren Syndrome type B (anti-La) antibody; IgG, Immunoglobulin G; IgA, Immunoglobulin A; IgM, Immunoglobulin M; aPL, Antiphospholipid antibodies; Anti-β2-GPI, Anti-β2-glycoprotein I antibody; LA, Lupus Anticoagulant; FDP, Fibrinogen/Fibrin Degradation Products; C3, Complement component 3; C4, Complement component 4; CH50, 50% Hemolytic Complement activity; SLEDAI-2 K, Systemic Lupus Erythematosus Disease Activity Index 2000; cSLE, Childhood-onset Systemic Lupus Erythematosus; SD, Standard Deviation
Comparison between thrombocytopenia and non-thrombocytopenia groups
No statistically significant differences were identified between the thrombocytopenia group (n = 46) and the non-thrombocytopenia group (n = 190) with respect to gender, age, disease duration, most autoantibodies, complement levels, FDP and D-DI, clinical manifestations, or organ involvement (P > 0.05). Nevertheless, the thrombocytopenia cohort exhibited a significantly greater prevalence of leukopenia (44.7% vs. 35.8%, P < 0.01), whereas the erythrocyte sedimentation rate (ESR) was elevated in the non-thrombocytopenia group (48.5 ± 34.4 compared to 34.5 ± 25.0, P = 0.01). Additionally, the thrombocytopenia group demonstrated significantly higher positivity rates for antiphospholipid antibody IgM (21.7% vs. 10.0%, P < 0.01), anti‑β2‑glycoprotein‑1 antibody (70.0% vs. 51.1%, P = 0.024), and lupus anticoagulant (65.2% vs. 45.8%, P = 0.018) (Table 2).
Table 2.
Comparison between thrombocytopenia and non-thrombocytopenia groups
| Variable | Thrombocytopenia (N = 46) | Non-thrombocytopenia (N = 190) | P value |
|---|---|---|---|
| Female, n (%) | 36 (78.3%) | 150 (78.9%) | 0.919 |
| Age (years), median | 11.0 ± 2.7 | 11.1 ± 2.7 | 0.887 |
| Disease duration (months), median | 5.8 ± 10.4 | 4.7 ± 10.3 | 0.514 |
| Leukocyte count (109/L), median | 4.2 ± 2.2 | 6.1 ± 4.0 | < 0.01 |
| Leukopenia, n (%) | 27 (44.7%) | 68 (35.8%) | < 0.01 |
| Anemia, n (%) | 33 (71.7%) | 127 (66.8%) | 0.524 |
| Platelet count (109/L), median | 55.5 ± 25.1 | 223.4 ± 79.7 | < 0.01 |
| CRP (mg/L), median | 5.7 ± 18.7 | 6.9 ± 19.6 | 0.697 |
| ESR (mm/H), median | 34.5 ± 25.0 | 48.5 ± 34.4 | 0.010 |
| ANA positivity, n (%) | 46 (100%) | 190 (100%) | / |
| Anti-dsDNA positivity, n (%) | 33 (71.7%) | 134 (70.6%) | 0.871 |
| Anti-Smith positivity, n (%) | 15 (32.6%) | 87 (45.8%) | 0.105 |
| Anti-U1RNP positivity, n (%) | 17 (37.0%) | 90 (47.4%) | 0.203 |
| Anti-Ro60 positivity, n (%) | 5 (10.9%) | 44 (23.1%) | 0.065 |
| Anti-Ro52 positivity, n (%) | 5 (10.9%) | 40 (21.1%) | 0.115 |
| Anti-SSB positivity, n (%) | 5 (10.9%) | 29 (15.3%) | 0.446 |
| Antinucleosome antibody positivity, n (%) | 16 (34.8%) | 58 (30.5%) | 0.577 |
| Antihistone antibodies positivity, n (%) | 14 (30.4%) | 70 (36.8%) | 0.415 |
| Antiphospholipid antibodies IGG positivity, n (%) | 5 (10.9%) | 35 (18.4%) | 0.221 |
| Antiphospholipid antibodies IGA positivity, n (%) | 0 (0%) | 7 (3.7%) | 0.186 |
| Antiphospholipid antibodies IGM positivity, n (%) | 10 (21.7%) | 19 (10.0%) | 0.030 |
| Anti-β2 glycoprotein 1 antibody positivity, n (%) | 32 (70.0%) | 97 (51.1%) | 0.024 |
| Elevated lupus anticoagulant, n (%) | 30 (65.2%) | 87 (45.8%) | 0.018 |
| Elevated FDP, n (%) | 18 (39.1%) | 77 (40.5%) | 0.862 |
| Elevated D-dimer, n (%) | 31 (67.4%) | 141 (74.2%) | 0.351 |
| Direct Coombs’ test, n (%) | 32 (69.6%) | 130 (68.4%) | 0.881 |
| C3 (g/L), median | 0.57 ± 0.40 | 0.59 ± 0.34 | 0.695 |
| Low C3, n (%) | 29 (63.0%) | 120 (63.2%) | 0.988 |
| C4 (g/L), median | 0.10 ± 0.10 | 0.12 ± 0.13 | 0.294 |
| Low C4, n (%) | 29 (63.0%) | 125 (65.8%) | 0.726 |
| CH50 | 18.6 ± 13.4 | 19.2 ± 14.9 | 0.816 |
| Low CH50, n (%) | 35 (76.1%) | 138 (72.6%) | 0.635 |
| Fever, n (%) | 20 (43.5%) | 94 (49.5%) | 0.465 |
| Rash, n (%) | 25 (54.3%) | 125 (65.8%) | 0.148 |
| Alopecia, n (%) | 3 (6.5%) | 15 (7.9%) | 0.753 |
| Oral ulcers, n (%) | 8 (17.4%) | 24 (12.6%) | 0.398 |
| Arthritis, n (%) | 9 (19.6%) | 48 (25.3%) | 0.418 |
| Myositis, n (%) | 0 (0%) | 12 (6.3%) | 0.080 |
| Vasculitis, n (%) | 9 (19.6%) | 54 (28.4%) | 0.223 |
| Pericarditis, n (%) | 5 (10.9%) | 15 (7.9%) | 0.516 |
| Lupus nephritis, n (%) | 23 (50.0%) | 112 (58.9%) | 0.271 |
| Albuminuria | 17 (37.0%) | 76 (40.0%) | 0.705 |
| Cylindruria | 14 (30.4%) | 56 (29.5%) | 0.898 |
| Hematuria | 17 (37.0%%) | 68 (35.8%) | 0.882 |
| Leukocyturia | 10 (21.7%) | 49 (25.8%) | 0.569 |
| Renal pathological type, n (%) | 18 (39.1%) | 89 (46.8%) | |
| Ⅱ | 3 (6.5%) | 27 (14.2%) | 0.160 |
| Ⅲ | 3 (6.5%) | 11 (5.8%) | 0.850 |
| Ⅳ | 9 (19.6%) | 38 (20.0%) | 0.947 |
| Ⅴ | 3 (6.5%) | 13 (6.8%) | 0.938 |
| Neurologic involvement, n (%) | 3 (6.5%) | 34 (17.9%) | 0.057 |
| Thrombus, n (%) | 4 (8.7%) | 8 (4.2%) | 0.214 |
| Cardiac involvement, n (%) | 1 (2.2%) | 4 (2.1%) | 0.977 |
| Pulmonary involvement, n (%) | 10 (21.7%) | 40 (21.1%) | 0.919 |
| SLEDAI 2 K score, median | 14.1 ± 10.0 | 14.5 ± 8.4 | 0.785 |
Abbreviations: SLE, Systemic Lupus Erythematosus; CRP, C-Reactive Protein; ESR, Erythrocyte Sedimentation Rate; ANA, Antinuclear Antibody; Anti-dsDNA, Anti-double-stranded DNA antibody; Anti-U1RNP, Anti-U1 Ribonucleoprotein antibody; Anti-Ro60, Anti-Ro/SSA 60kD antibody; Anti-Ro52, Anti-Ro/SSA 52kD antibody; Anti-SSB, Anti-Sjogren Syndrome type B (anti-La) antibody; IgG, Immunoglobulin G; IgA, Immunoglobulin A; IgM, Immunoglobulin M; aPL, Antiphospholipid antibodies; Anti-β2-GPI, Anti-β2-glycoprotein I antibody; LA, Lupus Anticoagulant; FDP, Fibrinogen/Fibrin Degradation Products; C3, Complement component 3; C4, Complement component 4; CH50, 50% Hemolytic Complement activity; SLEDAI-2 K, Systemic Lupus Erythematosus Disease Activity Index 2000; SD, Standard Deviation
Severity stratification and risk factor analysis
Patients diagnosed with thrombocytopenia were stratified into two subgroups according to platelet counts: severe thrombocytopenia (< 50 × 10⁹/L, n = 20) and mild‑to‑moderate (50～100 × 10⁹/L, n = 26). The severe thrombocytopenia subgroup exhibited a significantly higher frequency of lupus anticoagulant positivity compared to the mild-to-moderate subgroup (90.0% vs. 46.2%, P < 0.01). Conversely, the incidence of positive direct Coombs test results was significantly lower in the severe group relative to the mild-to-moderate group (50.0% vs. 84.6%, P = 0.011). No statistically significant differences were identified between the two severity groups concerning age, disease duration, presence of other autoantibodies, complement levels, FDP and D-DI, or organ involvement (Table 3).
Table 3.
A comparative analysis of the clinical features of patients with systemic lupus erythematosus (SLE) presenting with mild to moderate thrombocytopenia (platelet count between 50 and less than 100 × 10^9/L) versus those exhibiting severe thrombocytopenia (platelet count below 50 × 10^9/L)
| Variable | PLT < 50 (N = 20) | 50 ≤ PLT < 100 (N = 26) | P value |
|---|---|---|---|
| Female, n (%) | 13 (65.0%) | 23 (88.4%) | 0.056 |
| Age (years), median | 11.4 ± 2.8 | 10.7 ± 2.6 | 0.445 |
| Disease duration (months), median | 8.5 ± 14.5 | 3.7 ± 4.9 | 0.118 |
| Leukocyte count (109/L), median | 4.3 ± 2.8 | 4.0 ± 1.7 | 0.655 |
| Leukopenia, n (%) | 11 (55.0%) | 16 (61.5%) | 0.655 |
| Anemia, n (%) | 13 (65.05) | 20 (76.9%) | 0.373 |
| Platelet count (109/L), median | 33.6 ± 15.0 | 72.4 ± 16.8 | < 0.01 |
| CRP (mg/L), median | 10.1 ± 28.0 | 2.3 ± 3.2 | 0.170 |
| ESR (mm/H), median | 40.3 ± 28.1 | 30.0 ± 21.9 | 0.167 |
| ANA positivity, n (%) | 20 (100.0%) | 26 (100.0%) | / |
| Anti-dsDNA positivity, n (%) | 15 (75%) | 18 (69.2%) | 0.667 |
| Anti-Smith positivity, n (%) | 7 (35.0%) | 8 (30.8%) | 0.851 |
| Anti-U1RNP positivity, n (%) | 11 (55.0%) | 7 (26.9%) | 0.053 |
| Anti-Ro60 positivity, n (%) | 1 (5%) | 4 (15.4%) | 0.262 |
| Anti-Ro52 positivity, n (%) | 1 (5%) | 4 (15.4%) | 0.262 |
| Anti-SSB positivity, n (%) | 2 (10%) | 3 (11.5%) | 0.868 |
| Antinucleosome antibody positivity, n (%) | 7 (35.0%) | 9 (34.6%) | 0.927 |
| Antihistone antibodies positivity, n (%) | 6 (30.0%) | 8 (30.8%) | 0.955 |
| Antiphospholipid antibodies IGG positivity, n (%) | 3 (15.0%) | 2 (7.7%) | 0.430 |
| Antiphospholipid antibodies IGA positivity, n (%) | 0 (0%) | 0 (0%) | / |
| Antiphospholipid antibodies IGM positivity, n (%) | 5 (25.0%) | 5 (19.2%) | 0.638 |
| Anti-β2 glycoprotein 1 antibody positivity, n (%) | 16 (80.0%) | 18 (69.2%) | 0.410 |
| Elevated lupus anticoagulant, n (%) | 18 (90.0%) | 12 (46.2%) | < 0.01 |
| Elevated FDP, n (%) | 9 (45.0%) | 9 (34.6%) | 0.474 |
| Elevated D-dimer, n (%) | 12 (60.0%) | 19 (73.1%) | 0.348 |
| Direct Coombs’ test, n (%) | 10 (50.0%) | 22 (84.6%) | 0.011 |
| C3 (g/L), median | 0.6 ± 0.4 | 0.5 ± 0.4 | 0.635 |
| Low C3, n (%) | 13 (65.0%) | 16 (61.5%) | 0.809 |
| C4 (g/L), median | 0.1 ± 0.1 | 0.09 ± 0.07 | 0.464 |
| Low C4, n (%) | 12 (60.0%) | 17 (65.4%) | 0.708 |
| CH50 | 17.3 ± 12.3 | 19.7 ± 14.3 | 0.545 |
| Low CH50, n (%) | 17 (85.0%) | 18 (69.2%) | 0.214 |
| Fever, n (%) | 10 (50.0%) | 10 (38.5%) | 0.434 |
| Rash, n (%) | 11 (55.0%) | 14 (53.8%) | 0.938 |
| Alopecia, n (%) | 2 (10.0%) | 1 (3.8%) | 0.402 |
| Oral ulcers, n (%) | 4 (20.0%) | 4 (15.4%) | 0.682 |
| Arthritis, n (%) | 4 (20.0%) | 5 (19.2%) | 0.948 |
| Myositis, n (%) | 0 | 0 | / |
| Vasculitis, n (%) | 4 (20.0%) | 5 (19.2%) | 0.948 |
| Pericarditis, n (%) | 1 (5.0%) | 4 (15.4%) | 0.262 |
| Lupus nephritis, n (%) | 9 (45.0%) | 14 (53.8%) | 0.552 |
| Albuminuria, n (%) | 6 (30.0%) | 11 (42.3%) | 0.391 |
| Cylindruria, n (%) | 4 (20.0%) | 10 (38.5%) | 0.177 |
| Hematuria, n (%) | 5 (25.0%) | 12 (46.2%) | 0.141 |
| Leukocyturia, n (%) | 3 (15.0%) | 7 (26.9%) | 0.331 |
| Renal pathological type, n (%) | |||
| Ⅱ | 1 (5.0%) | 2 (7.7%) | 0.714 |
| Ⅲ | 1 (5.0%) | 2 (7.7%) | 0.714 |
| Ⅳ | 3 (15.0%) | 6 (23.1%) | 0.494 |
| Ⅴ | 1 (5.0%) | 2 (7.7%) | 0.714 |
| Neurologic involvement, n (%) | 1 (5.0%) | 2 (7.7%) | 0.714 |
| Thrombus, n (%) | 1 (5.0%) | 3 (11.5%) | 0.435 |
| Cardiac involvement, n (%) | 1 (5.0%) | 0 | 0.249 |
| Pulmonary involvement, n (%) | 4 (20.0%) | 6 (23.1%) | 0.802 |
| SLEDAI 2 K score, median | 13.2 ± 8.7 | 14.8 ± 10.9 | 0.573 |
Abbreviations: SLE, Systemic Lupus Erythematosus; ESR, Erythrocyte Sedimentation Rate; ANA, Antinuclear Antibody; Anti-dsDNA, Anti-double-stranded DNA antibody; Anti-U1RNP, Anti-U1 Ribonucleoprotein antibody; Anti-Ro60, Anti-Ro/SSA 60kD antibody; Anti-Ro52, Anti-Ro/SSA 52kD antibody; Anti-SSB, Anti-Sjogren Syndrome type B (anti-La) antibody; IgG, Immunoglobulin G; IgM, Immunoglobulin M; aPL, Antiphospholipid antibodies; Anti-β2-GPI, Anti-β2-glycoprotein I antibody; LA, Lupus Anticoagulant; FDP, Fibrinogen/Fibrin Degradation Products; C3, Complement component 3; C4, Complement component 4; CH50, 50% Hemolytic Complement activity; SLEDAI-2 K, Systemic Lupus Erythematosus Disease Activity Index 2000; PLT, Platelet count; SD, Standard Deviation
Among the variables examined, leukopenia (Exp (B) = 0.265, 95% confidence interval (CI), P < 0.01), positivity for anti-β2 glycoprotein 1 antibody (Exp (B) = 3.005, 95% CI, P = 0.025), elevated ESR (Exp (B) = 0.980, 95% CI, P = 0.025), high lupus anticoagulant (Exp (B) = 3.088, 95% CI 1.184 to 8.056, P = 0.021) and neuropsychiatric manifestations (Exp (B) = 0.090, 95% CI 0.014–0.576, P = 0.011)were significantly correlated with an elevated risk of thrombocytopenia in SLE patients. Other immunological markers, complement component levels, and the SLEDAI 2 K score did not exhibit statistically significant associations in this univariate analysis (Table 4).
Table 4.
Logistic regression analysis of risk factors for thrombocytopenia in patients with SLE
| Variable | Exp (B) | 95% CI | P |
|---|---|---|---|
| Leukopenia | 0.265 | 0.109～0.644 | < 0.01 |
| ESR (mm/H) | 0.980 | 0.963～0.998 | 0.025 |
| Anti-β2 glycoprotein 1 antibody | 3.005 | 1.145～7.882 | 0.025 |
| High lupus anticoagulant | 3.088 | 1.184～8.056 | 0.021 |
| Neurologic involvement | 0.090 | 0.014～0.576 | 0.011 |
Abbreviations: SLE, Systemic Lupus Erythematosus; ESR, Erythrocyte Sedimentation Rate; Anti-β2-GPI, Anti-β2-glycoprotein I antibody; LA, Lupus Anticoagulant; CI, Confidence Interval; Exp(B), Exponentiated regression coefficient (Odds Ratio)
Discussion
This retrospective analysis examined the clinical characteristics of 236 pediatric patients diagnosed with cSLE, with an emphasis on individuals presenting with thrombocytopenia. The results indicate that cSLE accompanied by thrombocytopenia, notably in its severe manifestation, displays distinct serological patterns and clinical correlations. These results are important for assessing risk [17]. The observed prevalence of thrombocytopenia, recorded at 19.5%, is consistent with previously documented findings in cases of cSLE [18, 19].
The multivariate logistic regression analysis identified several independent factors associated with thrombocytopenia in this cohort of patients with childhood-onset SLE. Notably, the presence of anti-β2 glycoprotein 1 antibody and a high titer of lupus anticoagulant emerged as significant positive risk factors. These findings robustly support the role of antiphospholipid antibodies in the pathogenesis of thrombocytopenia in SLE, likely through immune-mediated platelet destruction or activation [20]. Conversely, leukopenia and neuropsychiatric involvement were identified as negative predictors, suggesting a protective effect.
The pathogenesis of thrombocytopenia in SLE is multifactorial, involving both immune-mediated peripheral platelet destruction and impaired platelet production. Antiphospholipid antibodies, particularly anti-β2-glycoprotein I and lupus anticoagulant, may directly bind to platelet membranes, promoting platelet activation, aggregation, and subsequent clearance by the reticuloendothelial system. Additionally, immune complexes and anti-platelet glycoprotein antibodies (e.g., anti-GPIIb/IIIa and anti-GPIb/IX) contribute to antibody-mediated platelet destruction via Fcγ receptor-mediated phagocytosis [21]. Although anti-platelet antibodies were not systematically measured in the present cohort, their role in SLE-associated thrombocytopenia is well documented, and future studies should incorporate platelet autoantibody profiling to further elucidate this mechanism [22].
Regarding the correlation between thrombocytopenia and lupus nephritis (LN), our data showed no significant difference in the overall prevalence of LN or in the distribution of LN histological classes (Classes II-V) between patients with and without thrombocytopenia (Table 2). This suggests that thrombocytopenia in pediatric SLE is not primarily driven by renal involvement but rather reflects a distinct autoimmune profile. The absence of significant differences in plasma fibrinogen degradation products (FDP) and D-dimer levels between the two groups argues against subclinical disseminated intravascular coagulation as a major contributor to thrombocytopenia in this cohort. Similarly, although thrombotic events were numerically more frequent in the thrombocytopenia group (8.7% vs. 4.2%), this difference did not reach statistical significance, possibly due to the low overall incidence of thrombosis in pediatric SLE.
Limitations
This study has several limitations. Its single-center retrospective design limits generalizability, and the sample size, particularly of the thrombocytopenia subgroup, constrains statistical power. The lack of functional platelet assays or activation markers precludes mechanistic insights. Future multicenter prospective studies incorporating detailed platelet phenotyping are needed to clarify the pathogenic role of platelets in SLE.
Conclusion
Thrombocytopenia is a frequent and clinically significant manifestation in pediatric SLE, closely associated with leukopenia, antiphospholipid antibodies, and major organ involvement. When thrombocytopenia is present in pediatric SLE patients, a comprehensive assessment for antiphospholipid antibodies and neuropsychiatric involvement should be performed, as these factors carry important prognostic and therapeutic implications [23].
Acknowledgements
The authors have no acknowledgments to declare.
Author contributions
Y.F. and Y.S. conceptualized the study. C.S. developed the methodology and performed validation. Y.F. conducted formal analysis and contributed to the investigation. C.S. handled data curation and project administration. Y.F. wrote the original draft. C.S., H.W., and Y.S. reviewed and edited the manuscript. H.W. and Y.S. supervised the study and acquired funding. All authors read and approved of the final manuscript.
Funding
This study was supported by Shanghai Municipal Hospital Development Center (Grant No. SHDC12024623) and Shanghai Hospital Association (Grant No.MZ2024008). These different funding sources had no role in study design, collection, analysis, interpretation of data, writing of the report, or the decision to submit the paper for publication.
Data availability
The datasets used and/or analyzed during the current study are available from the supplementary material submitted online.
Declarations
Ethics approval and consent to participate
The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Institutional Review Board at Children’s Hospital of Fudan University (Approval No. 2025 − 344). As a retrospective analysis of anonymized data from the Hospital Information System, the requirement for informed consent was waived by the Institutional Review Board. For participants under the age of 16, written informed consent for inclusion in the registry and research use of anonymized data was obtained from their parents or legal guardians during their admission for hospital.
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Yang Fu and Tianxing Feng share the first author and contribute equally to this manuscript.
Contributor Information
Hongsheng Wang, Email: honswang@hotmail.com.
Yu Shi, Email: shiyu_821008@163.com.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The datasets used and/or analyzed during the current study are available from the supplementary material submitted online.