自己免疫性溶血性貧血

A 22-year-old woman developed palpitations, fatigue, and right leg pain 18 days after suffering from Mycoplasma pneumoniae (MP) pneumonia. Laboratory tests revealed severe hemolytic anemia with elevated lactate dehydrogenase levels, a C3b/C3d-positive direct antiglobulin test, and high cold agglutinin titers, confirming cold autoimmune hemolytic anemia. Thyroid studies showed asymptomatic thyrotoxicosis without tenderness, which was consistent with painless thyroiditis. Venous ultrasonography revealed deep vein thrombosis in the right popliteal and soleal veins. She improved with cold avoidance and apixaban treatment. This case underscores that multi-organ immune complications can emerge during the subacute phase of an MP infection.

BACKGROUND: Cold agglutinin disease (CAD) is a rare autoimmune hemolytic anemia characterized by clonal immunoglobulin M (IgM) autoantibodies that activate complement at low temperatures, leading to hemolysis. Diagnostic practices remain inconsistent, with considerable interlaboratory variability and no established guidelines. Objective - To develop a consensus-based diagnostic framework for CAD through a structured Delphi methodology, with the goal of harmonizing laboratory practices across medical centers. MATERIALS AND METHODS: A total of 30 experts in classic hematology and transfusion medicine were invited to participate in a two-round, web-based modified Delphi survey; 27 (90%) completed both rounds. A scientific board developed 37 diagnostic statements covering five domains: CAD definition, clinical evaluation, immunohematological testing, and pre-analytical and analytical procedures. Statements were rated on a 5-point Likert scale, with consensus defined a priori as a score of 4 or 5 by ≥80% of respondents. RESULTS: All 37 statements achieved consensus, with 36 (97.3%) doing so in Round 1 and the remaining one in Round 2 after re-evaluation. The panel provided recommendations on when to suspect CAD and specified necessary diagnostic tests, including C3d positivity on direct antiglobulin test (DAT) with monospecific antisera and the detection of cold agglutinins in serum. They heavily emphasized the importance of sample handling at 37°C, alongside issuing recommendations on cold agglutinin titration, transfusion management, and immune-hematologic follow-up. DISCUSSION: This expert consensus provides a standardized diagnostic approach for CAD, addressing current gaps in clinical and laboratory evaluation. Implementing these recommendations is expected to improve diagnostic accuracy and consistency, facilitating better patient outcomes and national harmonization of practices.

Both atypical hemolytic uremic syndrome (aHUS) and malignant hypertension (MHT) are causes of thrombotic microangiopathy (TMA), and their coexistence has been reported. We describe a 22-year-old man who exhibited severe hypertension, pulmonary hemorrhage, and acute kidney injury. Laboratory evaluation revealed thrombocytopenia, microangiopathic hemolytic anemia, and severe kidney dysfunction, without evidence of retinal hemorrhage or renal artery stenosis. Given suspicion for MHT-related thrombotic microangiopathy or immune-mediated pulmonary-renal syndrome, antihypertensive therapy, continuous hemodiafiltration, corticosteroids, and plasma exchange were initiated. However, autoimmune serologic testing was negative, von Willebrand factor protease (ADAMTS13) activity was preserved without inhibitor, and stool cultures were negative, leading to discontinuation of plasma exchange and tapering of corticosteroids. Thereafter, hematologic abnormalities transiently improved, but kidney dysfunction persisted, and pulmonary hemorrhage and cytopenia recurred with a marked reduction in complement C3 despite stabilized blood pressure reduction. Plasma exchange was resumed, and ravulizumab was initiated. Kidney biopsy demonstrated ischemic glomerular changes without immune deposits and marked narrowing of the interlobar arteries. Although genetic analysis identified variants in complement-related genes, definitive causative abnormalities remained undetermined. The patient was discharged with recovered kidney function, normalization of complement proteins, and sustained hematologic remission. Collectively, this clinical course is compatible with aHUS. We consider that MHT might trigger overt aHUS with pulmonary-renal syndrome-like features.

INTRODUCTION: Hemolysis is a physiologic condition that results from the lysis of red blood cells and the release of their contents into the plasma. This condition may occur in the setting of a genetic, infectious, mechanical, or immune-mediated process. Classically, hemolysis results in a primarily indirect hyperbilirubinemia as free hemoglobin is metabolized to bilirubin, which is then conjugated and excreted; however, in rare instances, severe and chronic hemolysis may saturate the biliary excretion system and result in a direct hyperbilirubinemia. METHODS: In this report, we present a 73-year-old man who presented with severe jaundice and was found to have warm autoimmune hemolytic anemia. RESULTS: The patient's total bilirubin level was 72.4 mg/dL, with a direct bilirubin level of 43.6 mg/dL and elevated liver enzymes. Imaging was consistent with an obstructive process, and hilar thickening on magnetic resonance cholangiopancreatography raised concern for a superimposed cholangiocarcinoma. Endoscopic retrograde cholangiopancreatography, however, removed several black pigment stones, known to be associated with chronic hemolysis, and cytology brushings were negative for malignancy. DISCUSSION: This case is an excellent illustration of how sustained extravascular hemolysis can overwhelm hepatic excretory capacity and produce secondary cholestasis that mimics malignancy.

OBJECTIVE: To characterize the long-term clinical course of children with hematologic non-criteria manifestations and persistent antiphospholipid antibodies (aPL), and to identify predictors of progression to antiphospholipid syndrome (APS) and/or systemic lupus erythematosus (SLE). METHODS: We conducted a prospective cohort study of children (<18 years) with persistent aPL positivity and hematologic involvement (thrombocytopenia, autoimmune hemolytic anemia [AIHA], or Evans syndrome) followed at a tertiary pediatric rheumatology center between 1995 and 2024, with follow-up extending into adulthood. Progression to clinically classifiable APS and/or SLE was the primary endpoint. Kaplan-Meier and Cox proportional hazards models evaluated predictors at presentation and in complementary time-dependent analyses. RESULTS: Among 42 enrolled children, 40 were evaluable, of whom 11 (27.5%) progressed to APS and/or SLE. Evans syndrome at presentation was associated with the highest hazard of progression compared with isolated thrombocytopenia (HR 6.21, 95% CI 1.46-26.41). In time-dependent analyses, Evans syndrome emerging during follow-up remained associated with progression. Isolated thrombocytopenia showed the lowest risk, whereas AIHA represented an intermediate state that did not independently predict progression. Lupus anticoagulant was nearly universal, and broader high-risk aPL profiles were more common among progressors but were not statistically significant. CONCLUSION: In children with persistent aPL positivity, Evans syndrome was the hematologic phenotype most strongly associated with progression to APS and/or SLE, whereas isolated thrombocytopenia followed a largely indolent course. Evolving hematologic phenotypes may improve risk stratification and inform long-term monitoring strategies within the APS-SLE spectrum.