Systemic Lupus Erythematosus Related Thrombotic Microangiopathy: A Retrospective Study Based on Chinese SLE Treatment and Research Group (CSTAR) Registry

Thrombotic microangiopathy (TMA) is a rare but severe hematological complication in systemic lupus erythematosus (SLE) patients, characterized by microvascular thrombosis, thrombocytopenia, and microangiopathic hemolytic anemia. This study retrospectively analyzed 138 SLE-TMA cases from the Chinese SLE Treatment and Research Group (CSTAR) registry to delineate clinical characteristics, treatment outcomes, and prognostic risk factors.

Study Design and Patient Selection

The multicenter retrospective analysis included patients from seven tertiary hospitals in China between March 2012 and April 2022. TMA diagnosis required two major criteria—microangiopathic hemolytic anemia (evidenced by schistocytes and elevated lactate dehydrogenase [LDH]) and thrombocytopenia (<100 × 10⁹/L)—plus at least one minor criterion: neuropsychiatric involvement, renal dysfunction (hematuria, proteinuria, or reduced glomerular filtration rate), or other organ damage. Renal TMA confirmation necessitated biopsy findings of endothelial swelling, narrowed capillaries, or intracapillary thrombi. Thrombotic thrombocytopenic purpura (TTP) was defined by ADAMTS13 activity <10% with inhibitor presence. Exclusion criteria included TMA secondary to drugs, infections, malignancies, or non-SLE autoimmune diseases.

Demographic and Clinical Characteristics

The cohort comprised 138 patients (88.4% female) with a mean age of 34.1 ± 13.8 years at TMA onset. Notably, 33.3% (46/138) presented with TMA as their initial SLE manifestation. Median SLE duration before TMA diagnosis was 8.5 months (range: 1.0–74.8 months). All patients exhibited hemolytic anemia and thrombocytopenia, while neuropsychiatric symptoms (e.g., seizures, altered consciousness) occurred in 64.5% (89/138) and renal involvement in 81.9% (113/138). Renal biopsies confirmed TMA in 29/41 cases.

Laboratory Findings

Key laboratory abnormalities included severe thrombocytopenia (median platelet count: 26.5 × 10⁹/L), anemia (mean hemoglobin: 69.2 g/L), elevated LDH (median: 647.5 U/L), and hyperbilirubinemia (median total bilirubin: 18.45 µmol/L). Reduced estimated glomerular filtration rate (eGFR; median: 40 mL·min⁻¹·1.73 m⁻²) highlighted renal impairment. Complement consumption (low C3: 0.56 g/L; low C4: 0.10 g/L) and autoantibody positivity (anti-dsDNA: 60.1%; anti-Smith: 36.3%) were common. ADAMTS13 activity <10% occurred in 54.1% (46/85 tested), with inhibitors detected in 57.5% (46/80).

Treatment Strategies

Immunosuppressive therapy included high-dose glucocorticoids (median prednisone: 140.6 mg/day) in 65.9% (91/138), with 68.8% (95/138) undergoing plasma exchange. Hydroxychloroquine (93.5%) and additional immunosuppressants (90.6%) like cyclophosphamide, mycophenolate mofetil, or rituximab were widely used. Nearly half (44.2%) received combined glucocorticoid pulses and plasma exchange.

Mortality and Risk Factors

The mortality rate was 12.3% (17/138), with median survival time post-TMA onset of 43 days. Leading causes of death included severe infections (52.9%, 9/17), hemorrhagic complications (41.2%, 7/17), and cardiogenic shock (5.9%, 1/17). Deceased patients exhibited distinct profiles: lower leukocyte counts (median: 3.93 × 10⁹/L vs. 6.79 × 10⁹/L; P = 0.018), higher lymphopenia prevalence (76.5% vs. 37.4%; P = 0.005), elevated D-dimer (median: 3.85 µg/mL vs. 2.45 µg/mL; P = 0.042), and reduced eGFR (median: 22 vs. 43 mL·min⁻¹·1.73 m⁻²; P = 0.044). Severe infections occurred in 56% (65/116) of the cohort, with 88.2% (15/17) of fatalities linked to infectious complications.

Organ Damage Accrual

Among survivors, 49.6% (60/121) experienced new or worsened organ damage (∆Systemic Lupus International Collaborating Clinics Damage Index [SDI] ≥1) within one year. Multivariate analysis identified baseline SDI ≥1 (odds ratio [OR]: 5.58; 95% CI: 1.21–40.8; P = 0.045) and eGFR <30 mL·min⁻¹·1.73 m⁻² (OR: 9.90; 95% CI: 3.98–27.10; P <0.001) as independent risk factors for damage progression.

SLE-TTP vs. SLE-Non-TTP Subgroups

Patients with ADAMTS13 activity 22.2 µmol/L; OR: 4.09; P = 0.031) and preserved renal function (eGFR >60 mL·min⁻¹·1.73 m⁻²; OR: 7.73; P = 0.013). Mortality did not differ between subgroups, but SLE-non-TTP patients had higher rates of renal function decline (median eGFR: 34 vs. 89 mL·min⁻¹·1.73 m⁻²; P = 0.001).

Discussion and Implications

This study underscores the high morbidity and mortality of SLE-TMA, particularly in patients with leukopenia, lymphopenia, or renal dysfunction. The association between severe infections and mortality highlights the need for vigilant monitoring and prophylactic measures in high-risk patients. Baseline organ damage and renal impairment (eGFR <30 mL·min⁻¹·1.73 m⁻²) emerged as critical predictors of poor outcomes, emphasizing the importance of early renal protection strategies.

The distinction between SLE-TTP and SLE-non-TTP subgroups has therapeutic implications. While ADAMTS13-deficient patients may benefit from plasma exchange and immunosuppression targeting antibody-mediated pathology, SLE-non-TTP cases (likely representing atypical hemolytic uremic syndrome [HUS] or renal-limited TMA) may require complement inhibition or renal-focused therapies.

Limitations and Future Directions

The retrospective design and limited ADAMTS13 testing (61.6% of cohort) constrain causal inferences. Prospective studies with standardized ADAMTS13 assessments and larger sample sizes are needed to validate risk factors and refine treatment protocols.

Conclusion

SLE-TMA remains a life-threatening complication with heterogeneous presentations. Early recognition of risk factors—leukopenia, renal dysfunction, and pre-existing organ damage—can guide aggressive interventions to reduce mortality and long-term morbidity. Multidisciplinary management integrating rheumatology, nephrology, and hematology expertise is essential for optimizing outcomes.

doi.org/10.1097/CM9.0000000000003388

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