自己免疫性溶血性貧血

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Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare, life-threatening thrombotic microangiopathy caused by severe ADAMTS13 deficiency due to anti-ADAMTS13 autoantibodies. The resulting persistence of ultra-large von Willebrand factor (VWF) multimers promotes uncontrolled platelet adhesion and aggregation in the microcirculation, leading to thrombocytopenia, microangiopathic hemolytic anemia, and ischemic organ injury. Therapeutic plasma exchange (TPE) has transformed the prognosis of iTTP by removing circulating autoantibodies and replenishing functional ADAMTS13, and it remains a life-saving intervention in acute disease. However, TPE is invasive, resource-intensive, dependent on central venous access and plasma availability, and associated with catheter-related, hemodynamic, metabolic, infectious, and plasma-related adverse events. The therapeutic landscape has changed substantially with the incorporation of immunosuppression and the anti-VWF nanobody caplacizumab. Caplacizumab rapidly blocks VWF-platelet interactions at the effector level, whereas corticosteroids and B-cell-directed therapy target the autoimmune basis of iTTP. Triple therapy with TPE, immunosuppression, and caplacizumab accelerates platelet recovery and reduces unfavorable outcomes. At the same time, accumulating observational evidence and early prospective data suggest that selected patients may achieve remission with caplacizumab plus immunosuppression without routine first-line TPE. This perspective review critically re-evaluates the role of TPE in contemporary iTTP management. We propose that TPE should no longer be viewed exclusively as an obligatory universal first-line intervention, but rather as a contextualized component of individualized, response-adapted care. TPE remains indispensable for severe, unstable, or refractory disease and must be immediately available when TPE-free treatment is attempted. Safe implementation of TPE-free strategies requires experienced centers, rapid ADAMTS13 testing, immediate access to caplacizumab and immunosuppression, careful patient selection, and close clinical and laboratory monitoring. Defining which patients can be treated safely without TPE is a central challenge for future trials and guideline development.

BACKGROUND: Atypical autoimmune hemolytic anemias (AIHA) include DAT-negative forms and those driven by IgA autoantibodies. IgA-mediated AIHA is rare, with limited evidence on clinical severity and management beyond first-line steroids. We revised our series of IgA-mediated AIHA and reviewed the literature. MATERIALS AND METHODS: We retrospectively evaluated patients with IgA-positive AIHA followed at a tertiary hematologic center in Milan since May 1978. Published reports from 2010 to January 28, 2025 were also reviewed. RESULTS: Thirteen patients with IgA-mediated AIHA were identified among 409 AIHA cases. Median age was 60 years, and 69.2% were female. Fatigue was the most common symptom; mean hemoglobin was 7.9 g/dL. Dual IgA/IgG positivity occurred in 69.2%, while triple IgA/IgG/IgM positivity occurred in 7.7%. All but one patient received corticosteroids, 33% rituximab, 16.6% IVIg, and 23.1% transfusions. One patient received bortezomib followed by mycophenolate mofetil and plasma exchange. During a median follow-up of 36 months, 63.6% relapsed. Infections and thrombotic events occurred in 16.7% each, with no deaths. The literature review included 35 patients from 19 studies. Most were female (62%), aged 3 months to 77 years. Tachycardia and dyspnea were the most common symptoms; mean hemoglobin was 5.6 g/dL. DAT showed dual IgA/IgG or IgA/IgM positivity in 54.3%. Corticosteroids were administered to all reported patients, IVIg and rituximab to 14% and 23%, respectively. Splenectomy was performed in 6%, and 93% received transfusions. Infections occurred in 14%, thrombotic events in 7.1%, and one patient was refractory and died. DISCUSSION: IgA-mediated AIHA is a rare, heterogeneous subtype characterized by frequent dual antibody positivity, suboptimal corticosteroid response, and substantial risks of relapse and complications, requiring careful monitoring and individualized management. These findings highlight the need for improved recognition of IgA-mediated disease and prospective studies to define optimal second-line therapies and outcomes in affected patients.

BACKGROUND: Real-world evidence on therapeutic plasma exchange (TPE) from low- and middle-income countries remains limited. Egyptian data across multiple organ systems are scarce. This study aimed to evaluate the indications, safety, efficacy, and predictors of outcomes in patients undergoing TPE at a tertiary center in Egypt over 7 years. METHODS AND FINDINGS: This retrospective cohort study included 221 consecutive patients who underwent TPE (2016-2022) at Zagazig University Hospitals, Egypt. Patients were stratified into renal, neurologic, hematologic, and metabolic groups. Primary outcomes were clinical response and all-cause mortality. Multivariate logistic regression, Cox proportional hazards models, and Kaplan-Meier survival analysis were performed. Among 221 patients (57.9% male; mean age 36.0 years), the most frequent indications were Guillain-Barré syndrome, thrombotic thrombocytopenic purpura, and myasthenia gravis crisis. ASFA category I indications constituted 77.8% of procedures, with response rates decreasing significantly across categories (p = 0.03). Overall response rate was 77.9% (complete remission in 93.0% of responders), with mortality 14.5%. Response rates exceeded 85% in autoimmune hemolytic anemia, hyperviscosity syndrome, and TTP. Neurologic indications achieved 81.6% response; renal indications showed lower response (73.2%) and highest mortality (21.3%). Adverse events occurred in 37.2% of patients, all mild-to-moderate with no session terminations. Independent mortality predictors included mechanical ventilation, creatinine >2.5 mg/dL, renal indication, hemoglobin <8 g/dL, while ASFA category I was protective (all aORs 2.67-5.22). In exploratory analyses, PLASMIC score ≥6 and time to TPE ≤ 2 days were associated with complete remission in TTP, while Hughes score ≥4 and time to TPE > 7 days were associated with poor functional outcome in GBS. These findings require external validation before clinical application. Diffuse alveolar hemorrhage (n = 9) demonstrated 100% mortality despite intervention, whereas SLE patients (n = 23) had 52.2% mortality, with 47.8% achieving complete remission or clinical improvement. A three-tier risk model stratified patients into high, intermediate, and low mortality risk groups. Independent predictors of clinical response included neurologic, hematologic, and metabolic indications compared to renal, ASFA category I, and ≥5 TPE sessions, while hemoglobin <8 g/dL and creatinine >2.5 mg/dL predicted poorer response. CONCLUSIONS: This single-center Egyptian TPE cohort demonstrates high efficacy and safety when aligned with ASFA guidelines. Neurologic and hematologic indications achieve optimal outcomes; renal indications and critical illness markers predict poorer prognosis. The PLASMIC score, treatment urgency in TTP and GBS, and the proposed three-tier model represent exploratory findings that, if prospectively validated, could become actionable prognostic tools. These findings suggest that evidence-based TPE expansion in resource-limited settings may be feasible, though multicenter validation is required.

INTRODUCTION: Acute hepatitis A (AHA) is typically self-limited, with complications occurring in only 0.1% of patients. Autoimmune hemolytic anemia (AIHA) following AHA is exceedingly rare; only four adult cases have been reported. We present the first documented pediatric case of DAT-negative AIHA following severe AHA. CASE PRESENTATION: A 13-year-old Middle Eastern female presented with worsening jaundice, dark urine, and breathlessness 4 weeks after a confirmed AHA diagnosis. Laboratory evaluation revealed hemolysis: hemoglobin 8.1 g/dL, LDH 560 U/L, haptoglobin 0.14 g/L, reticulocyte count 7.28%, and indirect bilirubin 19.3 mg/dL. The direct antiglobulin test (DAT) was negative on three occasions. Extensive testing excluded Glucose-6-phosphate dehydrogenase deficiency, thalassemias, hereditary spherocytosis, malignancies, and other autoimmune diseases. Immunoglobulin studies showed elevated IgA (596.2 mg/dL) with normal IgG and IgM. CLINICAL DISCUSSION: Diagnosis of DAT-negative AIHA was established through the exclusion of hereditary causes and confirmed by a rapid response to prednisolone 1 mg/kg/day (hemoglobin rose from 8.1 to 10.4 g/dL within 1 week). This case highlights that 3-11% of AIHA cases are DAT-negative due to IgA or IgM antibodies or low-affinity IgG. CONCLUSION: DAT-negative AIHA should be suspected in unexplained post-viral hemolysis despite a negative DAT. Early empiric corticosteroids can be both diagnostic and therapeutic. Key clinical lessons: (1) DAT-negative AIHA accounts for 3-11% of cases and may be IgA-mediated; (2) Systematic exclusion of hereditary hemolytic anemias is essential in high-prevalence populations; (3) Rapid response to corticosteroids supports immune-mediated etiology and justifies continued treatment.