Antiphospholipid syndrome (APS) is an autoimmune prothrombotic disorder characterized by persistent antiphospholipid antibodies (aPLs). Diffuse alveolar hemorrhage (DAH) is a rare but severe microvascular manifestation of APS associated with high morbidity and mortality.

We retrospectively analyzed six consecutive patients with primary APS complicated by DAH who had been followed at our institution between 2018 and 2025. Clinical presentation, laboratory and radiological findings, treatment strategies, and outcomes were evaluated.

Median age was 37.5 years (female:male 4:2). DAH was confirmed by bronchoscopy in all patients; triple aPL positivity was present in all. Most patients required hospitalization for severe respiratory failure, and recurrent DAH was frequent. Two patients died: one from uncontrolled DAH complicated by invasive fungal infection, and the other from pulmonary embolism. Two patients had a milder chronic course with fluctuating HRCT infiltrates but no severe hypoxemia. All patients received high-dose glucocorticoids followed by maintenance immunosuppression with rituximab, usually combined with mycophenolate. Adjunctive therapies included plasma exchange, intravenous immunoglobulin, and eculizumab. Antibody titers remained persistently positive in all cases.

APS-associated DAH is a life-threatening complication with frequent relapses and poor prognosis, particularly in patients with triple positivity and recurrent DAH. None of the patients achieved long-term remission, and all experienced disease progression despite aggressive immunosuppressive therapy. Early recognition, aggressive immunosuppression, and close monitoring are crucial, while novel therapeutic options are urgently needed.