Department of Internal Medicine, University of Miami, Miami, FL 33136, United States.

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Mycoplasma pneumoniae (M. pneumoniae) is a common bacterial pathogen that causes a wide range of symptoms and infections. It can cause both upper and lower respiratory tracts infections. The most common manifestation is tracheobronchitis, presenting with headache, coryza, and dry or mucopurulent productive cough [1]. This organism is also responsible for approximately 20-40% of community acquired bronchopneumonia in the general population during epidemics, up to 70% in closed populations [2]. Twenty-five percent of patients develop extra-pulmonary complications at variable durations after the onset of or even in the absence of respiratory illness [3].  These extra-pulmonary complications can involve central nervous, cardiovascular, renal, dermatological, and hematological systems [1]. The different mechanisms by which M. pneumoniae causes extra-pulmonary complications are cytokine mediated effects, autoimmunity or immune complexes, and vasculitis or thrombosis, as a result of cytokines and chemokines such as TNF- and IL-8 [4]. Hematological complications involve thrombocytopenia, thrombotic thrombocytopenic purpura, hemophagocytosis, and hemolytic anemia [5]. Hemolytic anemia associated with M. pneumoniae infection has been most commonly attributed to IgM cold agglutinins, whereby IgM autoantibodies attach to the I antigen on red blood cells causing mild hemolysis and rarely severe hemolytic anemia [6]. M. pneumoniae can also cause warm autoimmune hemolytic anemia, characterized by warm-reacting IgM antibodies, however it’s a relatively rare complication with an incidence ranging from 6-13%. [7]. On rare occasions, M. pneumoniae can be complicated by combined IgM cold agglutinins and IgG warm agglutinins hemolytic anemia [8]. Here we report a case of severe cold agglutinin mediated autoimmune hemolytic anemia induced by M. pneumoniae infection in a 72-year-old. We’re reporting this case to emphasize the importance of early clinical recognition of the variable presentations of M. pneumoniae infection.

A 72-year-old male with a medical history of atrial fibrillation, hypertension, hypothyroidism, and a previous diagnosis of bladder cancer treated with pembrolizumab, presented to the emergency department with worsening dyspnea. The patient also had a history of symptomatic bradycardia and underwent pacemaker placement, as well as surgical interventions for atrial septal defect and cleft mitral valve repair. Specifically, the mitral valve cleft was sutured, and the atrial septal defect was closed with a patch at the age of 30. However, the patient still had a residual ostium primum atrial septal defect. He was admitted to the cardiac care unit for management of acute heart failure exacerbation in the setting of congenital heart disease. He was initially treated with diuresis for management of the hypervolemia. His hospital course was complicated by worsening of dyspnea despite diuresis and hemodialysis/ultrafiltration, as well as worsening anemia. Laboratory tests were consistent with hemolysis with an indirect hyperbilirubinemia, elevated LDH level and low haptoglobin levels, as well as a positive coombs test (anti-C3b/d positive but anti-IgG negative). The patient continued to deteriorate hemodynamically with progressive cardiogenic shock in the setting of hemolysis and respiratory failure, eventually with a fatal outcome. Laboratory tests were positive for IgG mycoplasma, consistent with M. pneumoniae infection, and azithromycin was started, but the patient continued to deteriorate and died days later.

Autoimmune hemolytic anemia (AIHA) is a rare condition characterized by the destruction of red blood cells due to autoantibodies targeting the body's own erythrocytes [9]. AIHA can be triggered by various factors, including infections, medications, and systemic diseases. In this case, the patient presented with worsening dyspnea and was found to have severe AIHA in the setting of congenital heart disease and M. pneumoniae infection.

Laboratory findings in this case supported the diagnosis of AIHA. The patient exhibited anemia with a decline in hemoglobin levels compared to baseline, indirect hyperbilirubinemia, elevated lactate dehydrogenase (LDH) levels, and low haptoglobin levels [12]. The positive Coombs test (anti-C3b/d positive but anti-IgG negative) indicated immune-mediated destruction of red blood cells [13]. Additionally, the peripheral blood smear showed the presence of spherocytes, characteristic of hemolytic anemia [14]. M. pneumoniae infection played a significant role in this case. Laboratory tests confirmed the presence of Mycoplasma IgG, indicating a previous or current infection [15]. M. pneumoniae has been implicated in the development of AIHA, particularly through the production of cold agglutinins [16]. Cold agglutinins are autoantibodies that cause red blood cell agglutination and subsequent hemolysis at lower temperatures. The combination of M. pneumoniae infection and the patient's underlying autoimmune susceptibility likely contributed to the development of AIHA. Despite the initiation of appropriate treatment, including antimicrobial therapy, supportive blood transfusions, diuresis, and corticosteroids, the patient's condition continued to deteriorate. The ongoing hemolysis exacerbated his underlying cardiac disease, resulting in progressive cardiogenic shock and respiratory failure. The respiratory failure was presumed to be secondary to M. pneumoniae pneumonia, although respiratory sample polymerase chain reaction (PCR) was not performed.

By reporting this case, we aim to raise awareness among clinicians regarding the potential hematological complications associated with M. pneumoniae infection. Timely recognition of these complications can facilitate early intervention, appropriate treatment, and improved patient outcomes.

Contributors: MAla was directly involved in the patient care of this patient; she obtained consent and collected the data used in this case reports. She also contributed in formulating the discussion and learning points in this article. MAle contributed to the literature review on this topic and writing of the background section, as well as contributing to the discussion and conclusions sections. MAla will act as a study guarantor. Both authors approved the final version of this manuscript and are responsible for all aspects of this study.

Funding: None; Competing interests: None stated.