2026-08-06 | Reversal of refractory systemic lupus erythematosus-associated immune thrombotic thrombocytopenic purpura and cerebritis via optimized lymphoplasmapheresis: a case report and literature review.
Systemic lupus erythematosus (SLE) complicated by immune thrombotic thrombocytopenic purpura (iTTP) and lupus cerebritis is a severe clinical event. Standard therapeutic plasma exchange (TPE) frequently fails in this context due to a "rebound effect", as it clears circulating antibodies but spares the intravascular reservoir of autoreactive lymphocytes. A 30-year-old male presented with refractory SLE, severe iTTP (platelet count: 5.00 × 10^9/L; ADAMTS13 activity: 1.49%), and imaging-confirmed lupus cerebritis. The patient underwent a unique "A-B-A" treatment trajectory. While five sessions of standard TPE at an outside facility did not fully halt the hyper-regenerative hemolysis and CNS progression, the implementation of an optimized lymphoplasmapheresis (LPE) regimen at our center induced rapid hematological remission, progressive radiological resolution of brain lesions, and the alleviation of immune-mediated renal injury, culminating in restored renal function and decreased proteinuria. The optimized LPE protocol utilized a novel dual-parameter modulation (synchronizing blood drawing speed and hematocrit) to precisely extract the pathogenic lymphocyte-rich buffy coat without exacerbating anemia. Paired quantitative analysis of the patient's peripheral blood and LPE effluent provided direct evidence of substantial cytokine (e.g., IL-10, IL-8, TNF-α) clearance. This facilitated the rapid seroconversion of antinuclear and anti-dsDNA antibodies. Furthermore, this targeted cellular depletion reduced the required allogeneic replacement plasma volume by up to 50% compared with standard TPE, conserving blood bank resources. Optimized LPE may interrupt the autoimmune cascade by simultaneously reducing circulating humoral mediators and lymphocyte-rich cellular components. This single-case observation supports its potential as a resource-sparing rescue strategy for refractory autoimmune microangiopathy, although further validation is required.
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2026-08-05 | Favorable Outcome With Eculizumab in Hemolytic Uremic Syndrome Presenting With Severe Neurological Complications: A Case Report.
Thrombotic microangiopathies (TMAs) are a group of rare, life-threatening disorders characterized by a classic triad of MAHA, severe thrombocytopenia, and ischemic tissue injury. Thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) are the main types of TMAs. Based on the cause, HUS can be classified as typical or atypical. We present the case of a 4-year-old child referred to King Fahad Medical City in Riyadh, Saudi Arabia, with complaints of bloody diarrhea, vomiting, and fever. The condition progressed to altered consciousness, seizures, and quadriparesis. Upon admission, the patient received plasma infusion and underwent peritoneal dialysis. Eculizumab therapy was initiated 1 week after the presentation. Hematological and renal parameters improved rapidly, but neurological recovery was gradual, with significant progress observed over 6 years of follow-up. This case highlights that severe neurological manifestations can be an initial feature of HUS, not just TTP. Eculizumab was effective and life-saving in pediatric patients with TMA and severe neurological involvement, though CNS recovery may take years.
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2026-08-03 | Caplacizumab-Enabled Treatment of Immune-Mediated Thrombotic Thrombocytopenic Purpura Without Plasma Exchange: Evidence, Patient Selection, and Practical Considerations.
BackgroundImmune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare, life-threatening autoimmune condition driven by severe ADAMTS13 deficiency. Therapeutic plasma exchange (TPE) is the traditional cornerstone of acute therapy, as it clears autoantibodies and replenishes functional ADAMTS13. However, caplacizumab-an anti-von Willebrand factor nanobody that rapidly blocks platelet-von Willebrand factor interactions-has raised the possibility of safely omitting TPE in carefully selected patients.ObjectiveTo review the biological rationale, current clinical evidence, patient-selection criteria, safety profile, and practical implementation of utilizing caplacizumab for iTTP treatment without relying on plasma exchange.MethodsA comprehensive narrative review was conducted. It analyzed published case reports, case series, registry data, comparative cohort studies, and guideline-relevant literature focusing on TPE-free or TPE-sparing caplacizumab-based regimens for iTTP.ResultsEvidence has evolved from isolated, necessity-driven cases to robust multicenter comparative data. Caplacizumab-based, TPE-free treatment combined with immunosuppression consistently drives rapid platelet recovery, typically within three to five days. Large comparative cohorts demonstrate that clinical response, exacerbation rates, refractoriness, and mortality are similar to conventional TPE-based therapies. Furthermore, the TPE-free approach offers the benefits of shorter hospital stays and reduced intensive care utilization. However, a subset of patients with inadequate initial platelet responses or complex comorbidities still required rescue TPE.ConclusionTPE-free caplacizumab therapy is a promising, highly targeted strategy, though it should not replace standard therapy outside experienced centers. Safe implementation demands confirmed iTTP, clinical stability, immediate caplacizumab availability, rigorous ADAMTS13 monitoring, adequate immunosuppression, and predefined thresholds for rescue TPE.
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2026-08-02 | Comparison of Clinical Characteristics and Outcomes of Systemic Lupus Erythematosus-associated Thrombotic Thrombocytopenic Purpura and Idiopathic Thrombotic Thrombocytopenic Purpura: A Single Centre Study from Eastern India
Objective: To investigate the clinical characteristics and outcomes of thrombotic thrombocytopenic purpura (TTP) in patients with systemic lupus erythematosus (SLE) compared to idiopathic TTP (I-TTP). Methods: This retrospective cohort study included adult patients with SLE-TTP ( n = 9) and I-TTP ( n = 7) treated at a tertiary care centre in East India from January 2019 to July 2024. Patients with SLE-TTP fulfilled the 2019 American College of Rheumatology criteria for SLE, and TTP was defined if microangiopathic haemolytic anaemia and thrombocytopenia (platelet count <100,000 cells/µl) were present with an intermediate-to-high-risk PLASMIC score. Clinical characteristics, treatment details and outcomes were extracted from medical records. Treatment response was assessed using complete remission criteria and survival analysis. Results: The SLE-TTP group consisted of all female patients with a median age of 27 years, significantly younger compared to the I-TTP cohort (median age of 55 years, P = .01). Haematological parameters were comparable between groups. Complete response rate was achieved in eight out of nine patients (89%) in SLE-TTP and five out of seven patients (71%) in the I-TTP group ( P = .4). The median time to complete response was 27 and 45 days for SLE-TTP and I-TTP groups, respectively ( P = .31). Conclusion: SLE-TTP patients were younger at diagnosis compared to I-TTP. The findings are exploratory, and further research with a larger sample size and additional biomarkers is warranted to enhance understanding and management of SLE-TTP and I-TTP.
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2026-07-31 | Aberrant neutrophil and complement activation in thrombotic microangiopathies in pregnancy - Is there a missing link?
Pregnancy-related acute kidney injury is a major global health burden associated with increased maternal and fetal morbidity and mortality. Thrombotic microangiopathies (TMA) occurring in pregnancy or postpartum include severe preeclampsia/Hemolysis Elevated Liver Enzymes Low Platelets (HELLP) syndrome, atypical Hemolytic Uremic Syndrome (aHUS) and Thrombotic Thrombocytopenic Purpura (TTP). Severe acute kidney injury and progression to chronic kidney disease are particularly associated with complement-mediated thrombotic microangiopathy/atypical hemolytic uremic syndrome and may also complicate severe preeclampsia/HELLP syndrome, while renal involvement is usually less prominent in TTP. Interestingly, preeclampsia, HELLP syndrome, aHUS, TTP, lupus nephritis and antiphospholipid syndrome share common autoimmune pathogenic mechanisms, as both are characterized by exaggerated neutrophil activation and increased neutrophil extracellular traps (NETs) release, as well as complement activation. In an era of targeted therapies, the lack of treatment of preeclampsia and HELLP results from the limited understanding of the underlying pathogenetic mechanisms. Eculizumab, a C5 inhibitor that targets the complement, significantly reduced the risk of ESKD in women with pregnancy-associated aHUS, supporting the therapeutic relevance of complement modulation. In this review, we performed a narrative synthesis of established and emerging experimental, translational and clinical data on pregnancy-associated TMAs, summarizing current evidence on the interaction between neutrophil dysregulation, NET formation, complement activation and endothelial injury in pregnancy-associated thrombotic microangiopathies. A better understanding of the neutrophil-NET-complement axis may help refine diagnostic distinctions among overlapping pregnancy-associated thrombotic microangiopathies and facilitate the development of more targeted therapeutic strategies.
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