Autoimmune hemolytic anemia (AIHA) is a rare immune-mediated disorder caused by autoantibodies directed against red blood cell antigens. Mixed-type AIHA, characterized by the coexistence of warm-reactive IgG and cold-reactive complement-fixing antibodies, is uncommon and often diagnostically challenging due to overlapping serologic features and transfusion incompatibility. We report the case of a 40-year-old woman who presented with an acute onset of breathlessness, palpitations, and severe fatigability. She was found to have severe anemia (hemoglobin 2.7 g/dL), reticulocytosis, indirect hyperbilirubinemia, and red cell agglutination on peripheral smear. Both direct and indirect Coombs tests were strongly positive, while antibody screening demonstrated panreactivity with positive autocontrol. The monospecific direct antiglobulin test confirmed positivity for IgG and C3d, establishing the diagnosis of mixed-type AIHA. In view of hemodynamic instability, transfusion with the least-incompatible packed red cells was performed under warming precautions, alongside high-dose intravenous corticosteroids. The patient improved symptomatically, with hemoglobin rising to 8.8 g/dL. Autoimmune workup revealed high-titer antinuclear antibody and anti-SSA positivity, suggesting an evolving systemic autoimmune disorder. Mixed-type AIHA accounts for less than 10% of cases but is associated with significant morbidity due to combined extravascular and complement-mediated hemolysis, often necessitating cautious transfusion of least-incompatible blood in life-threatening anemia and escalation to rituximab or other immunosuppressive agents. This case highlights the diagnostic complexity, therapeutic challenges, and need for long-term autoimmune surveillance in patients with mixed-type AIHA.

The study aimed to find out the correlation of positive direct antiglobulin test (DAT) with features of autoimmune hemolysis in patients presenting to a tertiary care center in Northern India. Patient history, lab findings, and immune-hematological findings which can influence the management of patients with auto-immune hemolytic anemia were studied. DAT helps to differentiate immune hemolysis from non-immune hemolysis in patients with hemolytic anemia. A prospective study over 18 months was performed on DAT-positive samples of patients showing features of auto-immune hemolysis. The laboratory markers of hemolysis were correlated with immune-hematological studies like elution-adsorption, antibody specificity, and titer. Out of 1371 requests received for Immuno-hematological workup of patients with hemolysis, 92 (6.71%) met the inclusion criteria. Thirty (32.6%) patients were diagnosed with primary (Idiopathic) Auto-immune Hemolytic Anemia (AIHA), and the remaining 62(67.3%) patients had secondary AIHA. The gender distribution in primary AIHA was male: female as 1:2.7, while in secondary AIHA it was observed as male: female to be 1:1.3.The median age for primary AIHA was found to be 23.7 years (range 1 year to 48 years), and for secondary AIHA it was found to be 44.6 years (range 2 to 85 years). Of all AIHA patients tested, 85.8% showed the presence of warm autoantibodies in their sera while 7.6% had mixed-type AIHA and the remaining 6.5% had cold autoantibodies. The study highlights a strong association between higher strength of DAT positivity, multiple antibodies/immunoglobulins with complements coating red cells, and a higher titer of IgG and IgG1 & IgG3 subclass with the severity of hemolysis.

Cold agglutinin disease (CAD) is a rare autoimmune hemolytic anemia that can lead to significant complications due to hemolysis during aortic surgery, requiring hypothermic circulatory arrest. Sutimlimab, a humanized monoclonal IgG4 antibody that binds to and inactivates the complement protein C1s, is a complement inhibitor used for the treatment of CAD. However, there are no reports of its use in aortic surgery that required hypothermic circulatory arrest. We describe the case of an 80-year-old female with acute type A aortic dissection and a 55-mm ascending aortic aneurysm. The patient was scheduled to undergo urgent surgery for type A aortic dissection and aortic aneurysm; however, CAD was detected. Under consultation with hematologists, sutimlimab was initiated three days before surgery for CAD. Partial arch replacement was performed by using the elephant trunk technique under mild hypothermic circulatory arrest with cerebral perfusion and cold cardioplegia. The postoperative course was uneventful. On postoperative day 18, the patient was discharged without any hemolysis-related deficits. Herein, we report a case of partial arch replacement with mild hypothermic circulatory arrest for type A aortic dissection and an aortic aneurysm with CAD after sutimlimab treatment. There are no established methods for the perioperative management of patients with preexisting cold agglutination disease undergoing cardiovascular surgery requiring hypothermic circulatory arrest. Sutimlimab, an anti-complement (C1s) monoclonal antibody, is relatively easy to administer and may help avoid postoperative hemolytic complications.

Autoimmune hemolytic anemia (AIHA) is uncommon in the pediatric population, particularly when it manifests as severe anemia. AIHA is characterized by a positive direct antiglobulin test (DAT) and immune-mediated red blood cell (RBC) destruction. AIHA is subclassified on the basis of the thermal characteristics of autoantibody into warm, cold, and mixed. Mixed AIHA shows both the common types and characteristics of warm and cold types. A 14-year-old male, born of nonconsanguineous marriage, admitted with complaints of dizziness and hematuria. It was not associated with decreased urine output and abdominal pain. The child had a similar type of history 2 years back for that, he was treated with a 3-unit-packed RBC transfusion. On examination marked pallor, icterus and mild splenomegaly were present. Diagnosis of mixed AIHA was done on the basis of a DAT and was 4+ positive against Ig G and C3d. In cold, an agglutination test was done which was > 1:64 in titer. In peripheral blood smear, at below 37°C, it denoted the clumping of RBC with polychromasia, which is not reversed at room temperature. The child was treated with broad spectrum antibiotics, multiple-packed RBC transfusion, and injection methyl prednisolone. In follow-up, the child's clinically improved but DAT for immunoglobulin G remained positive and prednisolone was tapered to a maintenance dose of 0.5 mg/kg on alternate days. Mixed AIHA in pediatrics is an extremely rare disease, especially when presenting with severe anemia. It is very difficult to diagnose and treat. Hence, detailed clinical and extensive laboratory workup is required to diagnose the case. Clinical presentation of mixed AIHA, other than acute hemolysis, may manifest as blood group cross-match incompatibility, which is challenging for pathologists and awareness of this occurrence is essential for clinicians. A case of mixed AIHA should be treated with steroids immediately along with supportive care of packed RBC transfusion with the least incompatibility and long-term follow-up is required to improve outcome. RésuméL’anémie hémolytique auto-immune (AHAI) est rare chez les enfants, en particulier lorsqu’elle se manifeste par une anémie sévère. L’AHAI se caractérise par un test direct à l’antiglobuline (TDA) positif et une destruction des globules rouges (GR) à médiation immunitaire. L’AHAI est classée selon les caractéristiques thermiques des auto-anticorps : chaude, froide et mixte. L’AHAI mixte présente les types courants et les caractéristiques des types chaud et froid. Un garçon de 14 ans, né d’un mariage non consanguin, a été admis pour des vertiges et une hématurie. Ces symptômes n’étaient pas associés à une diminution du débit urinaire ni à des douleurs abdominales. L’enfant avait présenté des antécédents similaires deux ans auparavant, et avait donc été traité par une transfusion de 3 unités de GR. À l’examen, une pâleur marquée, un ictère et une légère splénomégalie étaient présents. Le diagnostic d’AHAI mixte a été posé sur la base d’un TDA et la positivité était de 4+ pour les Ig G et C3d. À froid, un test d’agglutination a été réalisé, dont le titre était supérieur à 1:64. Un frottis sanguin périphérique, à moins de 37 °C, a révélé une agglutination des globules rouges avec polychromasie, irréversible à température ambiante. L’enfant a été traité par antibiotiques à large spectre, transfusion de globules rouges concentrés et injection de méthylprednisolone. Lors du suivi, l’état clinique de l’enfant s’est amélioré, mais le test d’immunoglobuline G (TDA) est resté positif et la prednisolone a été réduite progressivement à une dose d’entretien de 0,5 mg/kg un jour sur deux. L’AHAI mixte en pédiatrie est une maladie extrêmement rare, surtout en cas d’anémie sévère. Son diagnostic et son traitement sont très difficiles. Par conséquent, un bilan clinique détaillé et des analyses de laboratoire approfondies sont nécessaires pour diagnostiquer ce cas. Le tableau clinique d’une AHAI mixte, autre qu’une hémolyse aiguë, peut se manifester par une incompatibilité de groupe sanguin, ce qui représente un défi pour les pathologistes et la connaissance de cette éventualité est essentielle pour les cliniciens. Un cas d’AIHA mixte doit être traité immédiatement avec des stéroïdes, accompagné de soins de soutien par transfusion de globules rouges concentrés, avec la moindre incompatibilité et un suivi à long terme est nécessaire pour améliorer le résultat.

In patients with autoimmune hemolytic anaemia (AIHA), numerous factors can influence disease severity, and thrombotic complications are associated with increased morbidity and mortality. Reports of autoimmune hemolytic anemia complicated by acute cerebral infarction are relatively rare. We report a case of an 82-year-old female patient with hypertension who developed mixed-type AIHA complicated by acute cerebral infarction following intravenous infusion of ceftriaxone after erysipelas in which the patient's previous hemoglobin (Hb) level was maintained at approximately 108 g/L. After developing erysipelas and treatment with ceftriaxone, the patient experienced a continuous decline in Hb, hematocrit (HT), and red blood cell (RBC) counts. Direct antiglobulin test (DAT) was positive for IgG and C3d, and both the reticulocyte count and proportion were elevated. The treatment regimen included methylprednisolone, enoxaparin for anticoagulation, and clopidogrel for antiplatelet aggregation. Following targeted treatment, the patient's condition improved. Clinicians should be aware of the potential contributing factors in patients with mixed-type AIHA who develop neurological deficits due to severe anemia. This case report aims to emphasize the laboratory aspects of mixed-type AIHA and the necessity for clinicians to recognize the potentially fatal consequences of acute thromboembolism in mixed-type AIHA.