Patient characteristics, according to clusters
| All patients N=253 | Cluster 1 N=101 | Cluster 2 N=67 | P value* | Cluster 3 N=58 | P value† | Cluster 4 N=27 | P value*‡ | |
| Female sex, n (%) | 174 (68.8) | 63 (62.4) | 31 (46.3) | 0.06 | 58 (100.0) | <0.001 | 22 (81.5) | 0.10 |
| Age (years, median, IQR) | 52.0 (38.0–65.0) | 54.0 (41.0–62.0) | 58.0 (43.5– 70.0) | 0.16 | 48.0 (36.0– 62.0) | 0.36 | 41.0 (33.5–54.5) | 0.047 |
| Arterial hypertension, n (%) | 81 (40.9) | 27 (35.1) | 23 (46.0) | 0.30 | 22 (44.0) | 0.41 | 9 (42.9) | 0.69 |
| Dyslipidaemia, n (%) | 49 (25.1) | 16 (1.3) | 15 (30.6) | 0.34 | 12 (24.0) | 0.90 | 6 (28.6) | 0.69 |
| Tobacco, n (%) | 35 (26.5) | 15 (27.3) | 10 (22.7) | 0.78 | 3 (23.1) | 1.00 | 7 (35.0) | 0.72 |
| Diabetes mellitus, n (%) | 22 (15.5) | 8 (13.3) | 6 (13.0) | 1.00 | 6 (40.0) | 0.045 | 2 (9.5) | 0.94 |
| Overweight, n (%) | 52 (31.5) | 14 (22.2) | 12 (28.6) | 0.61 | 16 (39.0) | 0.10 | 10 (52.6) | 0.02 |
| IgG anti-cardiolipin (IU, median, IQR) | 13.0 (4.0–43.0) | 9.7 (3.0–33.9) | 8.6 (4.0–50.0) | 0.23 | 12.0 (5.0–27.2) | 0.41 | 51.5 (22.9– 200.3) | <0.001 |
| IgG anti-cardiolipin medium-high titre positive, n (%) | 64 (28.7) | 19 (20.9) | 21 (32.8) | 0.14 | 10 (22.7) | 0.98 | 14 (58.3) | <0.01 |
| IgG anti-cardiolipin high titre positive, n (%) | 30 (14.0) | 7 (7.9) | 9 (15.3) | 0.25 | 6 (14.0) | 0.43 | 8 (33.3) | <0.01 |
| IgM anti-cardiolipin (IU, median, IQR) | 8.5 (2.0–36.4) | 7.0 (2.0–30.2) | 14.50 (2.6– 46.5) | 0.28 | 7.0 (2.2–20.0) | 0.76 | 45.0 (7.5–82.0) | <0.01 |
| IgM anti-cardiolipin medium-high titre positive, n (%) | 51 (24.1) | 16 (18.0) | 16 (27.6) | 0.24 | 7 (16.7) | 1.00 | 12 (52.2) | <0.01 |
| IgM anti-cardiolipin high titre positive, n (%) | 21 (9.9) | 6 (6.7) | 5 (8.6) | 0.92 | 3 (7.1) | 1.00 | 7 (30.4) | <0.01 |
| IgG anti-β2GP1 (IU, median, IQR) | 3.4 (1.0–25.0) | 2.2 (1.0–10.0) | 3.0 (1.0–19.2) | 0.44 | 6.5 (1.0–24.5) | 0.42 | 68.5 (11.4– 200.3) | <0.001 |
| IgG anti-β2GP1 medium-high titre positive, n (%) | 70 (31.4) | 21 (23.6) | 15 (24.6) | 1.00 | 18 (39.1) | 0.09 | 16 (59.3) | 0.001 |
| IgG anti-β2GP1 high titre positive, n (%) | 32 (15.0) | 8 (9.0) | 6 (10.2) | 1.00 | 6 (14.3) | 0.54 | 12 (50.0) | <0.001 |
| IgM anti-β2GP1 (IU, median, IQR) | 3.00 (1.00– 24.00) | 4.0 (1.0–20.3) | 2.5 (1.0–28.7) | 0.91 | 2.0 (1.0–7.9) | 0.07 | 29.0 (2.0–77.4) | 0.001 |
| IgM anti-β2GP1 medium-high titre positive, n (%) | 66 (29.7) | 24 (27.0) | 18 (29.5) | 0.88 | 8 (17.4) | 0.31 | 16 (61.5) | <0.01 |
| IgM anti-β2GP1 high titre positive, n (%) | 13 (6.1) | 3 (3.4) | 2 (3.4) | 1.00 | 2 (4.8) | 1.00 | 6 (26.1) | <0.01 |
| LA, n (%) | 102 (65.0) | 38 (62.3) | 19 (50.0) | 0.32 | 26 (76.5) | 0.24 | 19 (79.2) | 0.22 |
| Triple positivity, n (%) | 47 (19.3) | 10 (10.2) | 7 (11.1) | 1.00 | 7 (12.5) | 0.87 | 23 (85.2) | <0.001 |
| Antinuclear antibodies, n (%) | 58 (30.7) | 15 (19.0) | 5 (12.8) | 0.56 | 18 (39.1) | 0.03 | 20 (80.0) | <0.001 |
| Anti-dsDNA antibodies, n (%) | 16 (12.4) | 6 (10.3) | 2 (6.9) | 0.90 | 0 (0.0) | 0.382 | 8 (32.0) | 0.04 |
| aPL carrier, n (%) | 107 (42.3) | 100 (99.0) | 0 (0.0) | <0.001 | 7 (12.1) | <0.001 | 0 (0.0) | <0.001 |
| Thrombotic phenotype, n (%) | 125 (49.4) | 1 (1.0) | 67 (100.0) | <0.001 | 31 (53.4) | <0.001 | 26 (96.3) | <0.001 |
| Arterial thrombosis, n (%) | 53 (22.1) | 1 (1.0) | 19 (28.4) | <0.001 | 19 (38.8) | <0.001 | 15 (55.6) | <0.001 |
| Stroke, n (%) | 33 (15.8) | 1 (1.1) | 17 (27.9) | <0.001 | 6 (15.4) | <0.01 | 9 (40.9) | <0.001 |
| Transient ischaemic attack, n (%) | 3 (1.4) | 0 (0.0) | 1 (1.6) | 0.86 | 1 (2.6) | 0.68 | 1 (4.5) | 0.46 |
| Myocardial infarction, n (%) | 12 (5.7) | 0 (0.0) | 4 (6.6) | 0.06 | 4 (10.3) | 0.01 | 4 (18.2) | 0.001 |
| Pulmonary embolism, n (%) | 32 (13.6) | 1 (1.0) | 22 (34.4) | <0.001 | 5 (10.0) | 0.03 | 4 (16.0) | <0.01 |
| Deep vein thrombosis, n (%) | 60 (25.1) | 0 (0.0) | 33 (50.0) | <0.001 | 14 (28.0) | <0.001 | 13 (48.1) | <0.001 |
| Obstetrical phenotype, n (%) | 56 (24.2) | 0 (0.0) | 0 (0.0) | NA | 47 (94.0) | <0.001 | 9 (33.3) | <0.001 |
| No of obstetrical adverse events, n (%) | NA | <0.001 | <0.001 | |||||
| 0 | 174 (75.7) | 87 (100.0) | 66 (100.0) | 3 (6.0) | 18 (66.7) | |||
| 1 | 33 (14.3) | 0 (0.0) | 0 (0.0) | 29 (58.0) | 4 (14.8) | |||
| 2 | 4 (1.7) | 0 (0.0) | 0 (0.0) | 3 (6.0) | 1 (3.7) | |||
| ≥3 | 19 (8.3) | 0 (0.0) | 0 (0.0) | 15 (30.0) | 4 (14.8) | |||
| One or more unexplained deaths at or beyond the 10th week of gestation, n (%) | 11 (5.3) | 0 (0.0) | 0 (0.0) | NA | 8 (25.8) | <0.001 | 3 (11.1) | 0.01 |
| Three or more unexplained consecutive spontaneous miscarriage before the 10th week, n (%) | 15 (7.1) | 0 (0.0) | 0 (0.0) | NA | 13 (39.4) | <0.001 | 2 (7.4) | 0.09 |
| Premature births before the 34th week, n (%) | 7 (3.3) | 0 (0.0) | 0 (0.0) | NA | 5 (15.2) | 0.001 | 2 (7.4) | 0.09 |
| Preeclampsia, HELLP syndrome or placental abruption, n (%) | 16 (7.6) | 1 (1.2) | 0 (0.0) | 1.000 | 10 (29.4) | <0.001 | 5 (18.5) | <0.01 |
| Non-criteria manifestations, n (%) | 71 (28.2) | 31 (30.7) | 10 (15.2) | 0.04 | 12 (20.7) | 0.24 | 18 (66.7) | 0.001 |
| Autoimmune cytopenia, n (%) | 26 (10.4) | 13 (12.9) | 0 (0.0) | <0.01 | 4 (7.0) | 0.38 | 9 (33.3) | 0.03 |
| Neurological manifestations, n (%) | 22 (8.8) | 9 (9.0) | 5 (7.6) | 0.97 | 4 (7.0) | 0.90 | 4 (14.8) | 0.60 |
| APS nephropathy, n (%) | 4 (1.6) | 2 (2.0) | 0 (0.0) | 0.67 | 0 (0.0) | 0.74 | 2 (7.4) | 0.42 |
| Libman Sachs endocarditis, n (%) | 3 (1.2) | 0 (0.0) | 0 (0.0) | NA | 1 (1.8) | 0.78 | 2 (7.4) | 0.06 |
| Livedo reticularis, n (%) | 7 (2.8) | 4 (4.0) | 0 (0.0) | 0.26 | 3 (5.3) | 1.00 | 0 (0.0) | 0.66 |
| Thrombotic microangiopathy, n (%) | 8 (3.2) | 4 (4.0) | 2 (3.0) | 1.00 | 0 (0.0) | 0.32 | 2 (7.4) | 0.82 |
| Catastrophic APS, n (%) | 2 (0.8) | 0 (0.0) | 0 (0.0) | NA | 0 (0.0) | NA | 2 (7.4) | 0.07 |
| Anticoagulant treatment, n (%) | 115 (48.5) | 8 (8.2) | 50 (80.6) | <0.001 | 34 (64.2) | <0.001 | 23 (95.8) | <0.001 |
| Antiplatelet therapy, n (%) | 80 (33.9) | 15 (15.5) | 26 (40.0) | 0.001 | 27 (51.9) | <0.001 | 12 (54.5) | <0.001 |
| Hydroxychloroquine, n (%) | 32 (13.3) | 8 (8.2) | 4 (6.1) | 0.84 | 10 (19.2) | 0.09 | 10 (40.0) | <0.001 |
| Steroids, n (%) | 33 (14.2) | 14 (14.7) | 4 (6.1) | 0.14 | 7 (14.3) | 1.000 | 8 (34.8) | 0.06 |
| Death, n (%) | 21 (8.3) | 3 (3.0) | 12 (17.9) | < 0.01 | 3 (5.2) | 0.79 | 3 (11.1) | 0.21 |
| Relapse, n (%) | 44 (17.4) | 0 (0.0) | 16 (23.9) | <0.001 | 15 (25.9) | <0.001 | 13 (48.1) | <0.001 |
| Follow-up duration (months, median, IQR) | 38.4 (11.5– 106.3) | 120.0 (120.0– 120.0) | 24.0 (5.0–84.8) | 0.16 | 36.0 (11.4– 48.0) | 0.15 | 48.0 (24.0– 115.0) | 0.21 |
Qualitative variables and quantitative variables were compared between clusters using Fisher and Kruskal-Wallis tests, respectively.
*Comparison between cluster 1 and cluster 2.
†Comparison between cluster 1 and cluster 3.
‡Comparison between cluster 1 and cluster 4.
aPL, antiphospholipid; APS, antiphospholipid syndrome; dsDNA, double-stranded DNA; HELLP, haemolysis, elevated liver enzymes and low platelet count; LA, lupus anticoagulant; β2GP1, beta-2 glycoprotein 1.