ABO Discrepancy Revealing Cold Agglutinin Syndrome in Pancreatic Neoplasm: Literature Review Regarding a Case Volume 62- Issue 5

Isabela de Lima Santos¹, Michelle de Menezes Rocha¹, Fernando Antônio Sellos Ribeiro¹ and Angela Cristina Estalote²*

• ¹Ministério da Saúde/ Blood Bank of the Hospital Federal Cardoso Fontes, Brazil
• ²Avenida Guilherme de Almeida 670/205, Brazil

Received: August 06, 2025; Published: August 13, 2025

*Corresponding author: Angela Cristina Estalote, Avenida Guilherme de Almeida 670/205, CEP: 22790-100 Rio de Janeiro, RJ, Brazil

DOI: 10.26717/BJSTR.2025.62.009820

Abstract PDF

Paraneoplastic syndromes (PNS) are rare in patients with solid tumours. This paper describes a case involving the rare occurrence of cold agglutinin syndrome (CAS) in conjunction with pancreatic head neoplasia (Santos IL, et al. [1]).

Abbreviations: PRBC: Packed Red Blood Cells; PNS: Paraneoplastic Syndromes; CAS: Cold Agglutinin Syndrome; AIHA: Autoimmune Haemolytic Anaemia; DAT: Direct Antiglobulin Test; IAS: Irregular Antibody Screening

CAS is characterized by spontaneous erythrocyte agglutination associated with accelerated destruction of red blood cells by the immune system. CAS is generally associated with autoimmune diseases and lymphoproliferative neoplasms and is very rare in solid tumors. The diagnosis of autoimmune haemolytic anaemia (AIHA) is based on clinical or laboratory evidence of hemolytic anemia and the detection of autoantibodies, specifically IgM, with a positive C3 direct antiglobulin test (DAT) and the presence of circulating cold agglutinins in the serum. Due to the excess of circulating free antibodies, an ABO blood group discrepancy may be observed.

Clinical Case

A 64-year-old woman was admitted for surgery due to a pancreatic neoplasia. Reserve of packed red blood cells (PRBC) was requested. Blood samples were tested by the Sephadex® gel column agglutination method (Johnson ST, et al. [2]).

Results/ Observations

The initial sample at room temperature showed discrepancies in the ABO blood group classification (Figure 1). The irregular antibody screening (IAS) and autologous control were positive (Figure 2). The identification of the irregular antibody with a standard cell panel and autologous RBC determined its reactivity with all the red blood cells tested. The agglutinin titer was 1024 (data not shown). The DAT screening was positive for anti-IgM, -C3c, and -C3d (Figure 3). Despite the laboratory findings, the patient did not present any clinical manifestations of CAS. Preheating a new sample and further testing at 37°C revealed blood group A RhD positive (Figure 4). IAS was negative, and DAT was reactive only with anti-C3d (Figure 5). Using the same heating method at 37°C, compatible RBCs were found (Figure 6). The tumor was considered inoperable. The patient progressed without treatment and specific clinical symptoms of CAS, despite worsening anemia (Hb=6.8g/dL) and of the immunohematological profile. He died 7 months after diagnosis.

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PNS is a rare phenomenon in patients with solid tumors, defined as clinical or laboratory alterations not directly related to tumor growth, but rather to the ectopic production of biological substances or immune reactions associated with the neoplasm. Ovarian dermoid cysts (benign) and lymphomas are directly associated with AIHA. In a literature review (1945-2009), Puthenparambil J, et al. [3] (Puthenparambil J, Lechner K & Kornek G) observed 53 cases of AIHA associated with non-hematological solid neoplasms, and among them, only one case was associated with pancreatic neoplasm. The majority of AIHA occurred 6 months before or after cancer diagnosis. There was no association between the type of AIHA and the site of the neoplasm, and complete remission was achieved by treating the underlying neoplasm. It is noteworthy that none of the patients with cold antibodies (1/3 of them) presented any symptoms related to CAS. The present case is noteworthy due to the rarity in the relevant literature of the association of CAS and pancreatic neoplasia.

1. Santos IL, Rocha MM, Sellos Ribeiro FA, Estalote AC (2023) Discrepância ABO revelando Síndrome por Aglutinina Fria em neoplasia de pâ Revisão da literatura a proposto de um caso. Hematol Transfus Cell Ther 45(S4): S734.
2. Johnson ST, Judd WJ, Storry JR (2021) Judd´s methods in immunohematology. (4^th )., AABB.
3. Puthenparambil J, Lechner K, Kornek G (2010) Autoimmune hemolytic anemia as a paraneoplastic phenomenon in solid tumors: A critical analysis of 52 cases reported in the literature. Wien Klin Wochenschr 122: 229-236.