Diffuse alveolar hemorrhage in antiphospholipid syndrome: a French series of 26 patients

Vincent Grobost; Mélanie Ramos; Cécile Yelnik; Marie De Antonio; Nathalie Morel; Jean-François Viallard; Eric Hachulla; Marc André; Anne-Marie Milesi Lecat; Sébastien Trouillier; Maxime Samson; Christian Lavigne; Aurelien Lebreton; Marc Lambert; Marc Ruivard; Nathalie Costedoat-Chalumeau

doi:10.1093/rheumatology/keaf658

Diffuse alveolar hemorrhage in antiphospholipid syndrome: a French series of 26 patients

Rheumatology (Oxford). 2025 Dec 14:keaf658. doi: 10.1093/rheumatology/keaf658. Online ahead of print.

Authors

Vincent Grobost^{1

2}, Mélanie Ramos², Cécile Yelnik³, Marie De Antonio⁴, Nathalie Morel^{5

6}, Jean-François Viallard⁷, Eric Hachulla³, Marc André⁸, Anne-Marie Milesi Lecat⁹, Sébastien Trouillier¹⁰, Maxime Samson¹¹, Christian Lavigne¹², Aurelien Lebreton¹³, Marc Lambert³, Marc Ruivard¹, Nathalie Costedoat-Chalumeau⁶

Affiliations

¹ Service de médecine Interne, Clermont-Ferrand University Hospital, CHU Estaing, 1 Place Lucie et Raymond Aubrac, CLERMONT-FERRAND, 63100, France.
² Service de Pneumologie, Clermont-Ferrand University Hospital, CHU Gabriel Montpied, 58 Av. Montalembert, CLERMONT-FERRAND, 63003, France.
³ Univ. Lille, CHU Lille, Département de Médecine Interne et d'Immunologie Clinique, Centre de référence des Maladies Auto-Immunes et Auto-inflammatoires Systémiques rares de l'Adulte du Nord, Nord-Ouest, Méditerranée et Guadeloupe (CeRAINOM), European Reference Network on Rare Connective Tissue and Musculoskeletal Diseases Network (ReCONNECT), Lille, F-59000, France.
⁴ Biostatistics Unit, Clermont-Ferrand University Hospital, CLERMONT-FERRAND, 63000, France.
⁵ Service de Rhumatologie, Hôpital Pellegrin, Centre de référence des maladies auto-immunes et auto-inflammatoires systémiques rares RESO, CHU de Bordeaux, Bordeaux, France.
⁶ Service de Médecine Interne, Centre de référence des maladies auto-immunes et auto-inflammatoires systémiques rares d'Ile-de-France, de l'Est et de l'Ouest, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris (AP-HP) - Université Paris Cité, Paris, France.
⁷ Internal Medicine and Infectious diseases, Hôpital Haut-Lévêque, CHU de Bordeaux, 5, avenue de Magellan, 33604, Pessac, ; Université de Bordeaux, Bordeaux, France.
⁸ Department of Internal Medicine, CHU Gabriel Montpied, 58 Av. Montalembert, - 63003, -CLERMONT-FERRAND, France. Université Clermont Auvergne Inserm U1071, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), USC-INRA 2018, Clermont-Ferrand, ; Centre de référence constitutif des maladies auto-immunes et auto-inflammatoires systémiques rares d'Auvergne, France.
⁹ Service de médecine Interne, Jacques Lacarin Hospital, Bd Denière, VICHY, 03200, France.
¹⁰ Service de médecine Interne, Henri Mondor Hospital, 50 Av. de la République, AURILLAC, 15000, France.
¹¹ Department of Internal Medicine and Clinical Immunology, Referral Center for Rare Systemic Autoimmune and Autoinflammatory Diseases (MAIS), Dijon Bourgogne University Hospital, Dijon, France.
¹² Service de Médecine Interne et Immunologie Clinique, Centre de référence des maladies autoimmunes systémiques rares du Nord, Nord-Ouest, Méditerranée, Guadeloupe (CeRAINOM-Angers), CHU Angers, Angers, France.
¹³ Department of Haemostasis Laboratory, Clermont-Ferrand University Hospital, CHU Gabriel Montpied, 58 Av. Montalembert, CLERMONT-FERRAND, 63003, France.

PMID: 41390974
DOI: 10.1093/rheumatology/keaf658

Abstract

Objectives: Diffuse alveolar hemorrhage (DAH) is a rare and poorly understood manifestation of antiphospholipid (AP) syndrome (APS). This study describes the clinical presentation, treatment, and prognosis of DAH in APS with or without CAPS.

Methods: Retrospective multicentre French study includes all APS patients diagnosed according to the Sydney criteria with a history of definite DAH.

Results: Of the 26 patients included, 15 (58%) were female (median age, 45.5 years; 95%CI, 35-58.1); 23 (88%) patients had a history of thrombotic events (6 arterial), and 13 (50%) of CAPS. Twenty (77%) were triple-positive for APL antibodies, 5 (19%) had systemic lupus erythematosus, and DAH was inaugural for 7 (27%) patients. Twenty-two patients (85%) were treated with anticoagulants, 22 (85%) with steroids, and 8 (31%) with immunosuppressive therapy. Complete remission was achieved in 18 (69%) cases. DAH relapses occurred in 14 patients (54%) after a median of 1.8 (95% CI 1.1-3.6) years. Risk factors for DAH relapse were histories of arterial thrombosis (HR 4.6, 95%CI 1.2-17), TIA or stroke (HR 7.8, 95%CI 2.2-28), mechanical ventilation during DAH episode (HR 6.1, 95%CI 0.99-37) and triple APL positivity. Multivariate analysis showed a higher risk of DAH relapse in patients without (vs with) CAPS (HR 6.8, 95%CI 1.0-45.3; p = 0.048). Overall mortality was higher in patients with CAPS (7.7% at 1 year and 37.1% at 5 years); no patients without CAPS died.

Conclusion: The immediate prognosis of DAH, mainly treated with anticoagulants and steroids, was good. Patients with CAPS had a higher mortality rate in the long-term follow-up. Triple-positive and/or arterial phenotype patients more frequently experienced DAH relapses even when treated with anticoagulants.

Keywords: Antiphospholipid syndrome; Catastrophic antiphospholipid syndrome; Diffuse alveolar hemorrhage.

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