Background: APS is an autoimmune disease characterized by persistent antiphospholipid antibodies (aPLs) positivity, with a wide manifestation spectrum ranging from asymptomatic aPLs positivity, “non-criteria manifestations” (i.e. thrombocytopenia and aPL-related nephropathy), thrombosis, obstetric morbidity, to life-threatening catastrophic APS. A risk stratification is needed for management guidance and prognosis assessment.

Aims: To identify phenotypes among aPL-positive patients and assess the prognosis of each phenotype.

Methods: This is a single-center, prospective cohort study of aPL-positive patients who presented to Peking Union Medical College Hospital from 2004 to 2020. Demographic characteristics, aPL-related manifestations, cardiovascular risk factors and antibodies profiles were recorded. The primary end point was defined as a combination of newly onset thrombosis, major bleeding events, non-criteria manifestations and all-cause death. Hierarchical cluster analysis was applied to identify clusters and Kaplan-Meier survival analysis was performed among clusters, using R software.

Results: Four clusters among 383 patients (70.2% female; mean age 37.7 years) were identified (Figure 1). Cluster 1 (n=138): female patients with SLE, non-criteria manifestations, triple aPLs positivity. Cluster 2 (n=112): male patients with obesity, smoking history, hypertension, hyperhomocysteinemia, triple aPLs positivity and the highest thrombosis rate. Cluster 3 (n=83): female patients with obstetric morbidity. Cluster 4 (n=50): 62% male patients with isolated LA positivity. Four clusters of variables were also identified (Figure 1). From Kaplan-Meier survival analysis, 1-, 5- and 10-year event-free survival rates were 92.6%, 79.8% and 66.8%, respectively (Figure 2A). Cluster 3 showed the lowest incidence of primary endpoint, while the other three clusters shared similar prognosis (Figure 2B).

Hierarchical cluster analysis of 383 aPL-positive patients (x axis) and 15 variables (y axis) with the Euclidean distance and the Ward method. Four clusters of patients (Cluster 1, 2, 3, 4) and four clusters of variables (Cluster A, B, C, D) were identified separately. Non-criteria manifestations included thrombocytopenia, hemolytic anemia, heart valve disease, aPL-related nephropathy, livedo reticularis, skin ulcer, cognitive impairment, seizure and chorea. HPN, hypertension; BMI, body mass index; SLE, systemic lupus erythematosus; aCL: anticardiolipin antibodies; LA: lupus anticoagulant.A) Cumulative event-free survival curves in 383 aPL-positive patients: 1-, 5- and 10-year event-free survival rates were 92.6%, 79.8% and 66.8%, respectively. B) Cumulative event-free survival curves of four clusters: the 5-year event-free survival rates in clusters 1, 2, 3 and 4 were 79.4%, 71.0%, 94.3% and 79.4%, respectively; the 10-year event-free survival rates in clusters 1, 2, 3 and 4 were 71.8%, 47.3%, 70.7% and 79.4%, respectively. Cluster 1: secondary APS; Cluster 2: male patients with multiple cardiovascular risk factors; Cluster 3: obstetric morbidity; Cluster 4: isolated LA positivity.

Conclusions: We identified 4 clinical phenotypes of aPL-positive patients. Non-criteria manifestations may indicate underlying SLE, for which immunosuppressive therapy besides anticoagulation may be necessary. Patients with isolated LA positivity suffered similar risks with secondary APS and male patients. Attention should be paid to male patients, and the screening of cardiovascular risk factors should never be ignored.

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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/clinical-characteristics-and-prognosis-of-antiphospholipid-syndrome-patients-based-on-cluster-analysis-a-10-year-cohort-study/