Thrombocytopenia in antiphospholipid syndrome: predictors, prognostic implications, and thrombotic risk in a large cohort study

BACKGROUND: Antiphospholipid syndrome (APS) is a multifaceted autoimmune disorder associated with thrombosis and pregnancy morbidity. Thrombocytopenia, a frequent manifestation of APS, presents unique clinical challenges due to its dual association with thrombotic and hemorrhagic risks. This study investigates the incidence, characteristics, and predictors of thrombocytopenia in a large cohort of antiphospholipid antibodies (aPL)-positive patients and its association with other clinical manifestations. METHODS: We conducted a multicenter retrospective cohort study from 2014 to 2024 involving 211 aPL-positive patients at San Giovanni Bosco and San Luigi Gonzaga Hospital, Turin, Italy. Data on demographic, laboratory, and clinical features were collected every six months or at the occurrence of new clinical events. Thrombocytopenia definitions excluded other etiologies. Laboratory and clinical evaluations included thrombosis risk factors, autoantibody profiles, and treatment regimens. RESULTS: Thrombocytopenia occurred in 42 patients (20 %), with varying severity: mild (33 %), moderate (38 %), and severe (29 %). Severe cases primarily exhibited platelet counts below 20 × 10^9/L. Patients with thrombocytopenia demonstrated higher rates of thrombotic events, venous recurrences, deep vein thrombosis, pulmonary embolism, and catastrophic APS (CAPS). Renal involvement was more frequent, while inflammatory manifestations (pericarditis, pleuritis, and arthralgia) were less common. Patients with thrombocytopenia showed higher frequency of anti-β2 glycoprotein I antibodies IgG positivity and leukopenia. Therapeutic interventions included increased use of steroids, intravenous immunoglobulins, mycophenolate, and rituximab. Thrombocytopenia was more prevalent in systemic APS diagnoses (21 % vs. 3 %). CONCLUSION: Thrombocytopenia in APS patients, particularly in severe cases, correlates with heightened thrombotic risk and systemic manifestations. These findings highlight the importance of customized strategies that balance thrombosis prevention with bleeding risk, especially in complex cases.