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3840 Cold Autoimmune Hemolytic Anemia Secondary to Mycoplasma Pneumoniae Infection in Adults: Results from a Large French Observational Study (MYCOLD study)

Program: Oral and Poster Abstracts
Session: 101. Red Cells and Erythropoiesis, Excluding Iron: Poster III
Hematology Disease Topics & Pathways:
Research, Bacterial, Epidemiology, Autoimmune hemolytic anemia, Clinical Research, Diseases, Immune Disorders, Infectious Diseases, Real-world evidence
Monday, December 9, 2024, 6:00 PM-8:00 PM

Kevin Chevalier1*, Matthieu Holub2*, Romain Palich2*, Karine Blanckaert3*, Louis Terriou, M.D4*, Bérangère Arnould5*, Samuel Deshayes6*, Julie Merindol7*, Simon Rolland8*, Simon Valentin9*, Rishma Amarsy10*, Sylvain Audia11*, Virginie Baltes12*, Amaury Barret13*, Dorothée Chopin14*, Mélissa Clément15*, Marine Coeffier16*, Thibault Comont17*, Soline De Monteynard18*, Charles Declerck19*, Corinne Haioun, MD, PhD20, Pauline Durand21*, Mikael Ebbo22*, Amélie Godot23*, Sarra Hamrouni24*, Charlotte Kaueffer25*, Jean-Emmanuel Kahn26*, Ludovic Lassel27*, Sophie Leautez28*, Anne-Lise Lecapitaine29*, Gwenael Lemoal30*, David Luque Paz31*, Martin Martinot32*, Natacha Mrozek33*, Valentine Pagis10*, Thomas Perpoint34*, Jean-Francois Viallard, MD PhD35*, Clément Viguier36*, Matthieu Mahevas, MD, PhD37*, Bertrand Godeau37*, Etienne Crickx, MD, PhD37* and Marc Michel, MD38*

1Internal Medicine, CHU Henri Mondor, Le Kremlin-Bicêtre, AL, France
2Pitié Salpétrière, Paris, France
3CHU Lille, Lille, France
4CHU Lille, Université de Lille, Lille, France
5CHU Rouen, Rouen, France
6Caen University Hospital, Caen, France
7University Hospital of Nice, Nice, France
8CHU Brest, Brest, France
9CHU Nancy, Nancy, France
10CHU Lariboisière, Paris, France
11CHU Dijon Bourgogne - Hopital Francois Mitterrand, Dijon, France
12CHU Bicêtre, Paris, FRA
13Centre hospitalier d'Arcachon, Arcachon, France
14CHU Saint-Antoine, PARIS (75012), FRA
15Centre hospitalier d'Aurillac, Aurillac, France
16Centre hospitalier d'Abbeville, Abbeville, France
17Internal Medicine and Immune Diseases, University Hospital Toulouse - Cancer Institute, Toulouse, France
18CHU Avicenne, Bobigny, France
19CHU Angers, Angers, France
20Lymphoid Malignancies Department, Henri Mondor University Hospital, AP-HP, Créteil, France
21Centre hospitalier de Libourne, Libourne, France
22Hôpital De La Timone, Aix-Marseille Université, Marseille, France
23Centre hospitalier de Dole, Dole, France
24Centre hospitalier de Melun, Melun, France
25Nouvel Hopital Civil, Hopitaux Universitaires De, Strasbourg, FRA
26CHU Ambroise Paré, Boulogne Billancourt, FRA
27Assistancepublique-hôPitaux De Paris, HôPital Tenon, Paris, FRA
28CHD vendée, La-Roche-sur-Yon, France
29Centre hospitalier Compiègne Noyon, Compiègne, France
30CHU Poitiers, Poitiers, France
31CHU Rennes, Rennes, France
32Colmar Hospital, Colmar, FRA
33CHU Clermont Ferrand, Clermont Ferrand, France
34Hospices Civils of Lyon, Lyon, France
35Department of Internal Medicine, Bordeaux University Hospital, Pessac, France
36IUCT-Oncopole, CHU Toulouse, Toulouse, France
37Internal medicine department, Henri Mondor Hospital, APHP, Créteil, France
38Henri-Mondor University Hospital, Assistance Publique-Hôpitaux de Paris, UPEC, Creteil, France

Introduction

Mycoplasma pneumoniae (MP) is mostly responsible for infections of the lower respiratory tract but can also be associated with extrapulmonary manifestations, including cold antibody autoimmune hemolytic anemia (cAIHA). While the detection of cold agglutinins (CA) is relatively common in MP infection, symptomatic and/or severe forms of cAIHA are rare in this context. This association is poorly described in the literature as no large series of patients have been reported so far. The outbreak of MP infections that occurred in Northern Europe and France during last fall and winter gave rise to an unusual number of MP-associated cAIHAs. The aim of this study were to better describe the characteristics, the management and outcome of patients diagnosed with MP-associated cAIHA. and to assess the usefulness of glucocorticoids (GC) in this setting.

Patients and Methods

We conducted an ambispective (retrospective and prospective), observational, multicenter, national study. Patients were recruited by i) call for observations throughout the network of the French national society of internal medicine (SNFMI) and the French reference center for autoimmune cytopenias (CERECAI) and ii) identification of cases included in the MYCADO study (a large national multicenter observational study of MP infections). To be included, patients had to be 18 years of age or older, have a confirmed MP infection requiring hospitalization associated with cAIHA, with a nadir hemoglobin (Hb) level < 10 g/dL and a positive direct antiglobulin test with a C3d pattern.

Results

In total, 50 patients (50% of females, with a median age [IQR] of 47 [38.5-63.5] years) at diagnosis were included. Of these, 24 (48%) had risk factors for respiratory infection (active smoking in 16 (32%) patients, asthma in 6 (12%) others), 21 (42%) had cardiovascular risk factors (hypertension, diabetes, dyslipidemia, or obesity), 4 (8%) had a history of malignant hemopathy, and 4 (8%) patients were immunocompromised. Forty-eight (96%) patients had respiratory signs related to MP infection, 20 (40%) had gastrointestinal manifestations (31.3%), 14/40 (35%) had “dark” urine and 1 (2%) had acrocyanosis. Eight (16%) patients had venous thromboembolism (including pulmonary embolism in 7 (14%)) and 22 (44%) had to be admitted in intensive care unit.

The median Hb level at cAIHA diagnosis was 7 [5.9-9.8] g/dL, with a median reticulocytes count of 90 [60-144] x 109/L, and median LDH, haptoglobin, and undirect bilirubin levels of respectively 676 [470-1358] IU/L, 0 [0-0.38] g/L and 16 [7.7-51] μmol/L. Thirty-nine (78%) patients required red blood cell (RBC) transfusions, with a mean of 3 packed RBC/patient. Nineteen (38%) patients received one or more treatments "specifically" for AIHA, including GC in 14 (25%) cases and erythropoietin in 4 (8%). All patients received antibiotics, mostly macrolides (92% of the patients) for treating MP infection

MP infection resolved completely without sequelae in 43/50 (86%) cases. After a mean follow-up of 54 [27-80] days after cAIHA onset, 39/47 (83%) patients were in complete remission (defined by a stable Hb level beyond 10 g/dL off therapy), 6 (12.7%) in partial remission (defined by an increase of at least 2 g/dL of the Hb level from baseline but below 10 g/dL) and 2 (4%) patients died (one from septic shock secondary and one from pulmonary embolism).

When we compared patients who did not receive any “specific” treatment for AIHA other than antibiotic ± transfusion (n=31, 62%) with those treated with GC alone (n=14, 28%), we found that patients with GC had more severe cAIHA with a lower Hb nadir (6.4 [5.9-7.4] vs. 5 [5.7-5.9] g/dl, p=0.001), a greater number of packed RBC transfused (2 [0-2] vs. 1.25 [3.5-4.75], p=0.03), and a lower rate of complete remission of cAIHA (4/14 (28.6%) vs. (26/28 (92.9%), p=0.02). However, GC did not appear to improve neither the outcome nor the time to Hb normalization in patients with MP –associated cAIHA.

Conclusion

These data show that cAIHA associated with MP infection is not exceptional; and that although being often initially severe, with a high rate of venous thrombotic events, it has a good prognosis and recovers (either spontaneously or after transfusion) within few weeks in parallel with the bacterial infection. Based on our study, there is no evidence suggesting that GC, which were used for the management of the most severe cases, are helpful in this setting for reducing the duration of cAIHA.

Disclosures: Terriou: Novartis: Consultancy, Honoraria; Alexion Pharma: Consultancy, Honoraria; Sobi: Consultancy, Honoraria; Roche: Consultancy, Honoraria. Audia: Amgen: Honoraria; Novartis: Honoraria; Argenx: Honoraria; Sanofi: Honoraria. Michel: Novartis: Honoraria, Speakers Bureau; Sanofi: Honoraria, Speakers Bureau; Sobi: Honoraria, Speakers Bureau; Alexion: Honoraria, Speakers Bureau; Argenx: Honoraria; Grifols: Speakers Bureau.

*signifies non-member of ASH