Studies evaluating the risk of thrombotic events in lupus patients with positive aPLs
| Authors and year . | Study design . | No. of pts with SLE . | aPLs analysed . | Significant results . | Detailed data . |
|---|---|---|---|---|---|
| Mehrani et al. 2011 [30] | P | 796 | IgA/IgG/IgM aCL, IgA/IgG/IgM aβ2GPI | IgA aβ2GPI is significantly associated with DVT, total VT and stroke | − IgA aβ2GPI OR (95% CI) for DVT: 2.08 (1.31–3.30) |
| − IgA aβ2GPI OR (95% CI) for total VT (superficial, DVT and other venous): 1.70 (1.12–2.59) | |||||
| − IgA aβ2GPI OR (95% CI) for stroke: 1.79 (1.01–3.15) | |||||
| − IgA aβ2GPI OR (95% CI) for myocardial infarction: 0.43 (0.10–1.87) | |||||
| Domingues et al. 2016 [23] | P | 1390 | IgA/IgG/IgM aCL | IgG aCL is significantly associated with any thrombotic events and VT | − IgM aCL RR (95% CI) for any thrombotic event: 1.2 (0.8–2.0), P = 0.40 |
| − IgM aCL RR (95% CI) for ATa: 1.5 (0.8–2.6), P = 0.22 | |||||
| − IgM aCL RR (95% CI) for VT: 1.3 (0.7–2.4), P = 0.36 | |||||
| − IgG aCL RR (95% CI) for any thrombotic event: 1.8 (1.2–2.7), P = 0.0052 | |||||
| − IgG aCL RR (95% CI) for ATa: 1.6 (0.9–2.8), P = 0.097 | |||||
| − IgG aCL RR (95% CI) for VT: 1.9 (1.1–3.2), P = 0.015 | |||||
| − IgA aCL RR (95% CI) for any thrombotic event: 1.7 (0.7–4.2), P = 0.23 | |||||
| − IgA aCL RR (95% CI) for ATa: 2.4 (0.9–6.4), P = 0.088 | |||||
| − IgG aCL RR (95% CI) for VT: 1.7 (0.5–5.3), P = 0.37 | |||||
| Petri et al. 2020 [35] | P | 785 | LA | Persistent LA positivity is significantly associated with thrombotic events regardless of the method used to define it | − Persistent positivity defined by the first two LA assessments: • Rate of thromboses per 100 person-years: 4.3 • Adjusted RR (95% CI) for thrombosis: 3.42 (1.76–6.65), P = 0.0003 |
| The authors did not distinguish between VT and AT | − Persistent positivity based on annual assessments: • Rate of thromboses per 100 person-years: 4.2 • Adjusted RR (95% CI) for thrombosis: 3.08 (1.83–5.19), P < 0.0001 | ||||
| − Persistent positivity based on the first 16 assessments: • Rate of thromboses per 100 person-years: 3.8 • Adjusted RR (95% CI) for thrombosis: 2.75 (1.71–4.42), P < 0.0001 | |||||
| Demir et al. 2021 [24] | P | 821 | LA, IgA/IgG/IgM aCL, IgA/IgG/IgM aβ2GPI | IgA aβ2GPI is significantly associated with any thrombosis and VT after adjusting for LA | − LA: age-adjusted RR (95% CI) for any thrombosis: 3.56 (2.01–6.30), P < 0.0001 |
| − LA: age-adjusted RR (95% CI) for VT: 4.89 (2.25–10.64), P < 0.0001 | |||||
| − LA: age-adjusted RR (95% CI) for ATa: 3.14 (1.41–6.97), P = 0.005 | |||||
| − IgA aβ2GPI age-adjusted RR (95% CI) for any thrombosis after adjusting for LA: 1.73 (1.04–2.88), P = 0.0362 | |||||
| − IgA aβ2GPI age-adjusted RR (95% CI) for ATa after adjusting for LA: 1.33 (0.64–2.78), P = 0.4469 | |||||
| − IgA aβ2GPI age-adjusted RR (95% CI) for VT after adjusting for LA: 2.27 (1.13–4.59), P = 0.0218 | |||||
| Age-adjusted RR (95% CI) for any thrombosis: | |||||
| − LA + IgG aCL: 0.76 (0.21–2.74), P = 0.6715 | |||||
| − LA + IgM aCL: 0.63 (0.14–2.85), P = 0.5537 | |||||
| − LA + IgA aCL: 1.42 (0.18–11), P = 0.7352 | |||||
| − LA + IgG aβ2GPI: 0.96 (0.27–3.46), P = 0.9481 | |||||
| − LA + IgM aβ2GPI: 0.73 (0.2–2.64), P = 0.6333 | |||||
| − LA + IgA aβ2GPI: 0.58 (0.23–1.45), P = 0.2438 | |||||
| Akhter et al. 2013 [38] | CS | 326 | LA, IgA/IgG/IgM aCL, IgA/IgG/IgM aβ2GPI, IgA/IgG/IgM anti-DI β2GPI, IgA/IgG/IgM anti-D4/D5 β2GPI, IgG/IgM aPS-PT | IgA aCL was significantly associated with all thrombosis and VT | − IgA aCL OR (95% CI) for all thrombosis: 9.5 (1.2–75.8), P = 0.034 |
| − IgA aCL OR (95% CI) for VT: 4.3 (1.2–14.8), P = 0.023 | |||||
| − IgA aCL OR (95% CI) for stroke: 2.0 (0.6–7.4), P = 0.28 | |||||
| Samarkos et al. 2006 [21] | R | 130 | IgA/IgG/IgM aCL, IgA/IgG/IgM aβ2GPI | IgM aCL was significantly associated with VT | OR not provided (P = 0.001) |
| Swadźba et al. 2007 [20] | R | 235 | LA, IgG/IgM aCL, IgG/IgM aβ2GPI | IgM/IgG aCL and IgG aβ2GPI were significantly associated with ATa | IgM aCL OR for AT: 2.25 (P < 0.05) |
| IgG aCL OR for AT: 5.67 (P < 0.05) | |||||
| IgG aβ2GPI OR for AT: 4.69 (P < 0.05) | |||||
| Sciascia et al. 2012 [55] | R | 230 | LA, IgG/IgM aCL, IgG/IgM aβ2GPI, IgG/IgM aPS-PT, IgG/IgM aPT, IgG/IgM aPE | Among 23 combinations of aPLs, the triple positivity of LA, aβ2GPI and aPS-PT was the strongest predictor for thrombosisa and/or APOs | OR (95% CI) for thrombosis: |
| − LA + aPS-PT + aβ2GPI: 23.2 (2.57–46.12) | |||||
| − LA + aβ2GPI: 13.78 (2.04–16.33) | |||||
| − LA + aPS-PT: 10.47 (2.21–26.97) | |||||
| − aPS-PT + aβ2GPI: 9.13 (2.17–15.62) | |||||
| Murthy et al. 2013 [36] | R | 773 | IgA/IgG/IgM aCL, IgA/IgG/IgM aβ2GPI | IgA aβ2GPI was significantly associated with all thrombosis, VT and ATa | − Isolated IgA aβ2GPI adjusted OR (95% CI) for all thrombosis: 5.1 (2.2–12.4), P = 0.0003 |
| − Isolated IgA aβ2GPI adjusted OR (95% CI) for AT: 5.8 (2.3–15.2), P = 0.0003 | |||||
| − Isolated IgA aβ2GPI adjusted OR (95% CI) for VT: 2.3 (1.0–5.4, P = 0.061) | |||||
| Pericleous et al. 2016 [37] | R | 145 | IgA/IgG/IgM aCL, IgA/IgG/IgM aβ2GPI, IgA/IgG/IgM anti-DI β2GPI | IgA aCL, aβ2GPI and anti-DI aβ2GPI were all significantly associated with APS The association of any aCL and/or aβ2GPI isotype with anti-DI antibodies was associated with a 3- to 5-fold increase in the risk of APS compared with the double positivity of aCL and aβ2GPI | HR (95% CI) for APS − IgA aCL: 1.3 (0.9–1.9) − IgA aβ2GPI: 5.3 (2.1–13.3) − IgA anti-DI β2GPI: 2.2 (1.3–3.7) − IgG anti-DI β2GPI: 3.5 (1.8–6.8) − IgM anti-DI β2GPI: 2.8 (1.5–4.9) − IgG aPLs: • aCL/aβ2GPI + anti-DI β2GPI: 36.9 (17.7–76.9) • double or single positivity aCL/aβ2GPI: 11.5 (6.3–21.0) − IgM aPLs: • aCL/aβ2GPI + anti-DI β2GPI: 21.3 (9.1–50.4) • double or single positivity aCL/aβ2GPI: 7.3 (3.0–17.5) − IgA aPLs: • aCL/aβ2GPI + anti-DI β2GPI: 24.8 (12.3–49.9) • double or single positivity aCL/aβ2GPI: 5.0 (2.7–9.2) |
| Tkachenko et al. 2020 [56] | R | 107 | LA, IgG/IgM aCL, IgG/IgM aβ2GPI, aPch, aPe, aPg, aPi, aPs, aAnV and aPt | The presence of >4 IgG aPLs was an independent risk factor for thrombosis | >4 aPL IgG OR (95% CI) for thrombosis: 10.87 (1.16–101.54) |
| Elbagir et al. 2021 [43] | R | 91 Sudanese + 332 Swedish | IgA/IgG/IgM aPS-PT, IgA/IgG/IgM aCL, IgA/IgG/IgM aβ2GPI | At univariate analysis, all the isotypes of aPS-PT were independent risk factors for VT, while only IgA aPS-PT was an independent risk factor for AT aPS-PT was not associated with MI IgA aPS-PT was associated with cerebrovascular events At multivariate analysis, IgA aPS-PT was independently associated with cerebrovascular events and IgM/IgG aPS-PT was independently associated with VT | Univariate analysis: − IgA aPS-PT OR (95% CI) for AT: 3.9 (1.3–10.6) − aPS-PT was not associated with MI − IgA aPS-PT was associated with cerebrovascular events − IgM aPS-PT OR (95% CI) for VT: 7.4 (3.1–18.1) Multivariate analysis: − IgA aPS-PT OR (95% CI) for cerebrovascular events: 5.1 (1.3–16.8) − IgM and IgG aPS-PT OR for VT: exact data not provided OR (95% CI) for VT: − IgG/M aβ2GPI + aPS-PT: 6.3 (2.8–13.9) − IgA/IgG/IgM aβ2GPI + aPS-PT: 6.8 (3.1–14.5) − IgG/IgM aβ2GPI + aCL + LA: 5.2 (2.5–10.7) − IgA/IgG/IgM aβ2GPI + aPS-PT + LA: 8.1 (3.7–17.8) |
| Farina et al. 2023 [51] | R | 501 | IgG aCL, IgG aβ2GPI, IgG anti-DI β2GPI | ORs for VT/ATa not provided | Comparison of single positive vs double/triple positive vs negative Kaplan–Meier curves for cardiovascular events: P = 0.0057 |
| Authors and year . | Study design . | No. of pts with SLE . | aPLs analysed . | Significant results . | Detailed data . |
|---|---|---|---|---|---|
| Mehrani et al. 2011 [30] | P | 796 | IgA/IgG/IgM aCL, IgA/IgG/IgM aβ2GPI | IgA aβ2GPI is significantly associated with DVT, total VT and stroke | − IgA aβ2GPI OR (95% CI) for DVT: 2.08 (1.31–3.30) |
| − IgA aβ2GPI OR (95% CI) for total VT (superficial, DVT and other venous): 1.70 (1.12–2.59) | |||||
| − IgA aβ2GPI OR (95% CI) for stroke: 1.79 (1.01–3.15) | |||||
| − IgA aβ2GPI OR (95% CI) for myocardial infarction: 0.43 (0.10–1.87) | |||||
| Domingues et al. 2016 [23] | P | 1390 | IgA/IgG/IgM aCL | IgG aCL is significantly associated with any thrombotic events and VT | − IgM aCL RR (95% CI) for any thrombotic event: 1.2 (0.8–2.0), P = 0.40 |
| − IgM aCL RR (95% CI) for ATa: 1.5 (0.8–2.6), P = 0.22 | |||||
| − IgM aCL RR (95% CI) for VT: 1.3 (0.7–2.4), P = 0.36 | |||||
| − IgG aCL RR (95% CI) for any thrombotic event: 1.8 (1.2–2.7), P = 0.0052 | |||||
| − IgG aCL RR (95% CI) for ATa: 1.6 (0.9–2.8), P = 0.097 | |||||
| − IgG aCL RR (95% CI) for VT: 1.9 (1.1–3.2), P = 0.015 | |||||
| − IgA aCL RR (95% CI) for any thrombotic event: 1.7 (0.7–4.2), P = 0.23 | |||||
| − IgA aCL RR (95% CI) for ATa: 2.4 (0.9–6.4), P = 0.088 | |||||
| − IgG aCL RR (95% CI) for VT: 1.7 (0.5–5.3), P = 0.37 | |||||
| Petri et al. 2020 [35] | P | 785 | LA | Persistent LA positivity is significantly associated with thrombotic events regardless of the method used to define it | − Persistent positivity defined by the first two LA assessments: • Rate of thromboses per 100 person-years: 4.3 • Adjusted RR (95% CI) for thrombosis: 3.42 (1.76–6.65), P = 0.0003 |
| The authors did not distinguish between VT and AT | − Persistent positivity based on annual assessments: • Rate of thromboses per 100 person-years: 4.2 • Adjusted RR (95% CI) for thrombosis: 3.08 (1.83–5.19), P < 0.0001 | ||||
| − Persistent positivity based on the first 16 assessments: • Rate of thromboses per 100 person-years: 3.8 • Adjusted RR (95% CI) for thrombosis: 2.75 (1.71–4.42), P < 0.0001 | |||||
| Demir et al. 2021 [24] | P | 821 | LA, IgA/IgG/IgM aCL, IgA/IgG/IgM aβ2GPI | IgA aβ2GPI is significantly associated with any thrombosis and VT after adjusting for LA | − LA: age-adjusted RR (95% CI) for any thrombosis: 3.56 (2.01–6.30), P < 0.0001 |
| − LA: age-adjusted RR (95% CI) for VT: 4.89 (2.25–10.64), P < 0.0001 | |||||
| − LA: age-adjusted RR (95% CI) for ATa: 3.14 (1.41–6.97), P = 0.005 | |||||
| − IgA aβ2GPI age-adjusted RR (95% CI) for any thrombosis after adjusting for LA: 1.73 (1.04–2.88), P = 0.0362 | |||||
| − IgA aβ2GPI age-adjusted RR (95% CI) for ATa after adjusting for LA: 1.33 (0.64–2.78), P = 0.4469 | |||||
| − IgA aβ2GPI age-adjusted RR (95% CI) for VT after adjusting for LA: 2.27 (1.13–4.59), P = 0.0218 | |||||
| Age-adjusted RR (95% CI) for any thrombosis: | |||||
| − LA + IgG aCL: 0.76 (0.21–2.74), P = 0.6715 | |||||
| − LA + IgM aCL: 0.63 (0.14–2.85), P = 0.5537 | |||||
| − LA + IgA aCL: 1.42 (0.18–11), P = 0.7352 | |||||
| − LA + IgG aβ2GPI: 0.96 (0.27–3.46), P = 0.9481 | |||||
| − LA + IgM aβ2GPI: 0.73 (0.2–2.64), P = 0.6333 | |||||
| − LA + IgA aβ2GPI: 0.58 (0.23–1.45), P = 0.2438 | |||||
| Akhter et al. 2013 [38] | CS | 326 | LA, IgA/IgG/IgM aCL, IgA/IgG/IgM aβ2GPI, IgA/IgG/IgM anti-DI β2GPI, IgA/IgG/IgM anti-D4/D5 β2GPI, IgG/IgM aPS-PT | IgA aCL was significantly associated with all thrombosis and VT | − IgA aCL OR (95% CI) for all thrombosis: 9.5 (1.2–75.8), P = 0.034 |
| − IgA aCL OR (95% CI) for VT: 4.3 (1.2–14.8), P = 0.023 | |||||
| − IgA aCL OR (95% CI) for stroke: 2.0 (0.6–7.4), P = 0.28 | |||||
| Samarkos et al. 2006 [21] | R | 130 | IgA/IgG/IgM aCL, IgA/IgG/IgM aβ2GPI | IgM aCL was significantly associated with VT | OR not provided (P = 0.001) |
| Swadźba et al. 2007 [20] | R | 235 | LA, IgG/IgM aCL, IgG/IgM aβ2GPI | IgM/IgG aCL and IgG aβ2GPI were significantly associated with ATa | IgM aCL OR for AT: 2.25 (P < 0.05) |
| IgG aCL OR for AT: 5.67 (P < 0.05) | |||||
| IgG aβ2GPI OR for AT: 4.69 (P < 0.05) | |||||
| Sciascia et al. 2012 [55] | R | 230 | LA, IgG/IgM aCL, IgG/IgM aβ2GPI, IgG/IgM aPS-PT, IgG/IgM aPT, IgG/IgM aPE | Among 23 combinations of aPLs, the triple positivity of LA, aβ2GPI and aPS-PT was the strongest predictor for thrombosisa and/or APOs | OR (95% CI) for thrombosis: |
| − LA + aPS-PT + aβ2GPI: 23.2 (2.57–46.12) | |||||
| − LA + aβ2GPI: 13.78 (2.04–16.33) | |||||
| − LA + aPS-PT: 10.47 (2.21–26.97) | |||||
| − aPS-PT + aβ2GPI: 9.13 (2.17–15.62) | |||||
| Murthy et al. 2013 [36] | R | 773 | IgA/IgG/IgM aCL, IgA/IgG/IgM aβ2GPI | IgA aβ2GPI was significantly associated with all thrombosis, VT and ATa | − Isolated IgA aβ2GPI adjusted OR (95% CI) for all thrombosis: 5.1 (2.2–12.4), P = 0.0003 |
| − Isolated IgA aβ2GPI adjusted OR (95% CI) for AT: 5.8 (2.3–15.2), P = 0.0003 | |||||
| − Isolated IgA aβ2GPI adjusted OR (95% CI) for VT: 2.3 (1.0–5.4, P = 0.061) | |||||
| Pericleous et al. 2016 [37] | R | 145 | IgA/IgG/IgM aCL, IgA/IgG/IgM aβ2GPI, IgA/IgG/IgM anti-DI β2GPI | IgA aCL, aβ2GPI and anti-DI aβ2GPI were all significantly associated with APS The association of any aCL and/or aβ2GPI isotype with anti-DI antibodies was associated with a 3- to 5-fold increase in the risk of APS compared with the double positivity of aCL and aβ2GPI | HR (95% CI) for APS − IgA aCL: 1.3 (0.9–1.9) − IgA aβ2GPI: 5.3 (2.1–13.3) − IgA anti-DI β2GPI: 2.2 (1.3–3.7) − IgG anti-DI β2GPI: 3.5 (1.8–6.8) − IgM anti-DI β2GPI: 2.8 (1.5–4.9) − IgG aPLs: • aCL/aβ2GPI + anti-DI β2GPI: 36.9 (17.7–76.9) • double or single positivity aCL/aβ2GPI: 11.5 (6.3–21.0) − IgM aPLs: • aCL/aβ2GPI + anti-DI β2GPI: 21.3 (9.1–50.4) • double or single positivity aCL/aβ2GPI: 7.3 (3.0–17.5) − IgA aPLs: • aCL/aβ2GPI + anti-DI β2GPI: 24.8 (12.3–49.9) • double or single positivity aCL/aβ2GPI: 5.0 (2.7–9.2) |
| Tkachenko et al. 2020 [56] | R | 107 | LA, IgG/IgM aCL, IgG/IgM aβ2GPI, aPch, aPe, aPg, aPi, aPs, aAnV and aPt | The presence of >4 IgG aPLs was an independent risk factor for thrombosis | >4 aPL IgG OR (95% CI) for thrombosis: 10.87 (1.16–101.54) |
| Elbagir et al. 2021 [43] | R | 91 Sudanese + 332 Swedish | IgA/IgG/IgM aPS-PT, IgA/IgG/IgM aCL, IgA/IgG/IgM aβ2GPI | At univariate analysis, all the isotypes of aPS-PT were independent risk factors for VT, while only IgA aPS-PT was an independent risk factor for AT aPS-PT was not associated with MI IgA aPS-PT was associated with cerebrovascular events At multivariate analysis, IgA aPS-PT was independently associated with cerebrovascular events and IgM/IgG aPS-PT was independently associated with VT | Univariate analysis: − IgA aPS-PT OR (95% CI) for AT: 3.9 (1.3–10.6) − aPS-PT was not associated with MI − IgA aPS-PT was associated with cerebrovascular events − IgM aPS-PT OR (95% CI) for VT: 7.4 (3.1–18.1) Multivariate analysis: − IgA aPS-PT OR (95% CI) for cerebrovascular events: 5.1 (1.3–16.8) − IgM and IgG aPS-PT OR for VT: exact data not provided OR (95% CI) for VT: − IgG/M aβ2GPI + aPS-PT: 6.3 (2.8–13.9) − IgA/IgG/IgM aβ2GPI + aPS-PT: 6.8 (3.1–14.5) − IgG/IgM aβ2GPI + aCL + LA: 5.2 (2.5–10.7) − IgA/IgG/IgM aβ2GPI + aPS-PT + LA: 8.1 (3.7–17.8) |
| Farina et al. 2023 [51] | R | 501 | IgG aCL, IgG aβ2GPI, IgG anti-DI β2GPI | ORs for VT/ATa not provided | Comparison of single positive vs double/triple positive vs negative Kaplan–Meier curves for cardiovascular events: P = 0.0057 |
The authors did not provide the OR/RR for cardiovascular and cerebrovascular events separately.
aAnV: anti-annexin V antibodies; aβ2GPI: anti-β2-glycoprotein I antibodies; anti-DI aβ2GPI: anti-domain I β2-glycoprotein I antibodies; anti-D4/D5 aβ2GPI: anti-domain 4/5 β2-glycoprotein I antibodies; aPch: anti-phosphatidylcholine antibodies; aPE: anti-phosphatidylethanolamine antibodies; aPg: anti-phosphatidylglycerol antibodies; aPi: anti-phosphatidylinositol antibodies; aPT: antiprothrombin; AT: arterial thrombosis; CS: cross-sectional; DVT: deep venous thrombosis; HR: hazard ratio; MI: myocardial infarction; OR: odds ratio; P: prospective; pts: patients; R: retrospective; RR: risk ratio; VT: venous thrombosis.
Studies evaluating the risk of thrombotic events in lupus patients with positive aPLs
| Authors and year . | Study design . | No. of pts with SLE . | aPLs analysed . | Significant results . | Detailed data . |
|---|---|---|---|---|---|
| Mehrani et al. 2011 [30] | P | 796 | IgA/IgG/IgM aCL, IgA/IgG/IgM aβ2GPI | IgA aβ2GPI is significantly associated with DVT, total VT and stroke | − IgA aβ2GPI OR (95% CI) for DVT: 2.08 (1.31–3.30) |
| − IgA aβ2GPI OR (95% CI) for total VT (superficial, DVT and other venous): 1.70 (1.12–2.59) | |||||
| − IgA aβ2GPI OR (95% CI) for stroke: 1.79 (1.01–3.15) | |||||
| − IgA aβ2GPI OR (95% CI) for myocardial infarction: 0.43 (0.10–1.87) | |||||
| Domingues et al. 2016 [23] | P | 1390 | IgA/IgG/IgM aCL | IgG aCL is significantly associated with any thrombotic events and VT | − IgM aCL RR (95% CI) for any thrombotic event: 1.2 (0.8–2.0), P = 0.40 |
| − IgM aCL RR (95% CI) for ATa: 1.5 (0.8–2.6), P = 0.22 | |||||
| − IgM aCL RR (95% CI) for VT: 1.3 (0.7–2.4), P = 0.36 | |||||
| − IgG aCL RR (95% CI) for any thrombotic event: 1.8 (1.2–2.7), P = 0.0052 | |||||
| − IgG aCL RR (95% CI) for ATa: 1.6 (0.9–2.8), P = 0.097 | |||||
| − IgG aCL RR (95% CI) for VT: 1.9 (1.1–3.2), P = 0.015 | |||||
| − IgA aCL RR (95% CI) for any thrombotic event: 1.7 (0.7–4.2), P = 0.23 | |||||
| − IgA aCL RR (95% CI) for ATa: 2.4 (0.9–6.4), P = 0.088 | |||||
| − IgG aCL RR (95% CI) for VT: 1.7 (0.5–5.3), P = 0.37 | |||||
| Petri et al. 2020 [35] | P | 785 | LA | Persistent LA positivity is significantly associated with thrombotic events regardless of the method used to define it | − Persistent positivity defined by the first two LA assessments: • Rate of thromboses per 100 person-years: 4.3 • Adjusted RR (95% CI) for thrombosis: 3.42 (1.76–6.65), P = 0.0003 |
| The authors did not distinguish between VT and AT | − Persistent positivity based on annual assessments: • Rate of thromboses per 100 person-years: 4.2 • Adjusted RR (95% CI) for thrombosis: 3.08 (1.83–5.19), P < 0.0001 | ||||
| − Persistent positivity based on the first 16 assessments: • Rate of thromboses per 100 person-years: 3.8 • Adjusted RR (95% CI) for thrombosis: 2.75 (1.71–4.42), P < 0.0001 | |||||
| Demir et al. 2021 [24] | P | 821 | LA, IgA/IgG/IgM aCL, IgA/IgG/IgM aβ2GPI | IgA aβ2GPI is significantly associated with any thrombosis and VT after adjusting for LA | − LA: age-adjusted RR (95% CI) for any thrombosis: 3.56 (2.01–6.30), P < 0.0001 |
| − LA: age-adjusted RR (95% CI) for VT: 4.89 (2.25–10.64), P < 0.0001 | |||||
| − LA: age-adjusted RR (95% CI) for ATa: 3.14 (1.41–6.97), P = 0.005 | |||||
| − IgA aβ2GPI age-adjusted RR (95% CI) for any thrombosis after adjusting for LA: 1.73 (1.04–2.88), P = 0.0362 | |||||
| − IgA aβ2GPI age-adjusted RR (95% CI) for ATa after adjusting for LA: 1.33 (0.64–2.78), P = 0.4469 | |||||
| − IgA aβ2GPI age-adjusted RR (95% CI) for VT after adjusting for LA: 2.27 (1.13–4.59), P = 0.0218 | |||||
| Age-adjusted RR (95% CI) for any thrombosis: | |||||
| − LA + IgG aCL: 0.76 (0.21–2.74), P = 0.6715 | |||||
| − LA + IgM aCL: 0.63 (0.14–2.85), P = 0.5537 | |||||
| − LA + IgA aCL: 1.42 (0.18–11), P = 0.7352 | |||||
| − LA + IgG aβ2GPI: 0.96 (0.27–3.46), P = 0.9481 | |||||
| − LA + IgM aβ2GPI: 0.73 (0.2–2.64), P = 0.6333 | |||||
| − LA + IgA aβ2GPI: 0.58 (0.23–1.45), P = 0.2438 | |||||
| Akhter et al. 2013 [38] | CS | 326 | LA, IgA/IgG/IgM aCL, IgA/IgG/IgM aβ2GPI, IgA/IgG/IgM anti-DI β2GPI, IgA/IgG/IgM anti-D4/D5 β2GPI, IgG/IgM aPS-PT | IgA aCL was significantly associated with all thrombosis and VT | − IgA aCL OR (95% CI) for all thrombosis: 9.5 (1.2–75.8), P = 0.034 |
| − IgA aCL OR (95% CI) for VT: 4.3 (1.2–14.8), P = 0.023 | |||||
| − IgA aCL OR (95% CI) for stroke: 2.0 (0.6–7.4), P = 0.28 | |||||
| Samarkos et al. 2006 [21] | R | 130 | IgA/IgG/IgM aCL, IgA/IgG/IgM aβ2GPI | IgM aCL was significantly associated with VT | OR not provided (P = 0.001) |
| Swadźba et al. 2007 [20] | R | 235 | LA, IgG/IgM aCL, IgG/IgM aβ2GPI | IgM/IgG aCL and IgG aβ2GPI were significantly associated with ATa | IgM aCL OR for AT: 2.25 (P < 0.05) |
| IgG aCL OR for AT: 5.67 (P < 0.05) | |||||
| IgG aβ2GPI OR for AT: 4.69 (P < 0.05) | |||||
| Sciascia et al. 2012 [55] | R | 230 | LA, IgG/IgM aCL, IgG/IgM aβ2GPI, IgG/IgM aPS-PT, IgG/IgM aPT, IgG/IgM aPE | Among 23 combinations of aPLs, the triple positivity of LA, aβ2GPI and aPS-PT was the strongest predictor for thrombosisa and/or APOs | OR (95% CI) for thrombosis: |
| − LA + aPS-PT + aβ2GPI: 23.2 (2.57–46.12) | |||||
| − LA + aβ2GPI: 13.78 (2.04–16.33) | |||||
| − LA + aPS-PT: 10.47 (2.21–26.97) | |||||
| − aPS-PT + aβ2GPI: 9.13 (2.17–15.62) | |||||
| Murthy et al. 2013 [36] | R | 773 | IgA/IgG/IgM aCL, IgA/IgG/IgM aβ2GPI | IgA aβ2GPI was significantly associated with all thrombosis, VT and ATa | − Isolated IgA aβ2GPI adjusted OR (95% CI) for all thrombosis: 5.1 (2.2–12.4), P = 0.0003 |
| − Isolated IgA aβ2GPI adjusted OR (95% CI) for AT: 5.8 (2.3–15.2), P = 0.0003 | |||||
| − Isolated IgA aβ2GPI adjusted OR (95% CI) for VT: 2.3 (1.0–5.4, P = 0.061) | |||||
| Pericleous et al. 2016 [37] | R | 145 | IgA/IgG/IgM aCL, IgA/IgG/IgM aβ2GPI, IgA/IgG/IgM anti-DI β2GPI | IgA aCL, aβ2GPI and anti-DI aβ2GPI were all significantly associated with APS The association of any aCL and/or aβ2GPI isotype with anti-DI antibodies was associated with a 3- to 5-fold increase in the risk of APS compared with the double positivity of aCL and aβ2GPI | HR (95% CI) for APS − IgA aCL: 1.3 (0.9–1.9) − IgA aβ2GPI: 5.3 (2.1–13.3) − IgA anti-DI β2GPI: 2.2 (1.3–3.7) − IgG anti-DI β2GPI: 3.5 (1.8–6.8) − IgM anti-DI β2GPI: 2.8 (1.5–4.9) − IgG aPLs: • aCL/aβ2GPI + anti-DI β2GPI: 36.9 (17.7–76.9) • double or single positivity aCL/aβ2GPI: 11.5 (6.3–21.0) − IgM aPLs: • aCL/aβ2GPI + anti-DI β2GPI: 21.3 (9.1–50.4) • double or single positivity aCL/aβ2GPI: 7.3 (3.0–17.5) − IgA aPLs: • aCL/aβ2GPI + anti-DI β2GPI: 24.8 (12.3–49.9) • double or single positivity aCL/aβ2GPI: 5.0 (2.7–9.2) |
| Tkachenko et al. 2020 [56] | R | 107 | LA, IgG/IgM aCL, IgG/IgM aβ2GPI, aPch, aPe, aPg, aPi, aPs, aAnV and aPt | The presence of >4 IgG aPLs was an independent risk factor for thrombosis | >4 aPL IgG OR (95% CI) for thrombosis: 10.87 (1.16–101.54) |
| Elbagir et al. 2021 [43] | R | 91 Sudanese + 332 Swedish | IgA/IgG/IgM aPS-PT, IgA/IgG/IgM aCL, IgA/IgG/IgM aβ2GPI | At univariate analysis, all the isotypes of aPS-PT were independent risk factors for VT, while only IgA aPS-PT was an independent risk factor for AT aPS-PT was not associated with MI IgA aPS-PT was associated with cerebrovascular events At multivariate analysis, IgA aPS-PT was independently associated with cerebrovascular events and IgM/IgG aPS-PT was independently associated with VT | Univariate analysis: − IgA aPS-PT OR (95% CI) for AT: 3.9 (1.3–10.6) − aPS-PT was not associated with MI − IgA aPS-PT was associated with cerebrovascular events − IgM aPS-PT OR (95% CI) for VT: 7.4 (3.1–18.1) Multivariate analysis: − IgA aPS-PT OR (95% CI) for cerebrovascular events: 5.1 (1.3–16.8) − IgM and IgG aPS-PT OR for VT: exact data not provided OR (95% CI) for VT: − IgG/M aβ2GPI + aPS-PT: 6.3 (2.8–13.9) − IgA/IgG/IgM aβ2GPI + aPS-PT: 6.8 (3.1–14.5) − IgG/IgM aβ2GPI + aCL + LA: 5.2 (2.5–10.7) − IgA/IgG/IgM aβ2GPI + aPS-PT + LA: 8.1 (3.7–17.8) |
| Farina et al. 2023 [51] | R | 501 | IgG aCL, IgG aβ2GPI, IgG anti-DI β2GPI | ORs for VT/ATa not provided | Comparison of single positive vs double/triple positive vs negative Kaplan–Meier curves for cardiovascular events: P = 0.0057 |
| Authors and year . | Study design . | No. of pts with SLE . | aPLs analysed . | Significant results . | Detailed data . |
|---|---|---|---|---|---|
| Mehrani et al. 2011 [30] | P | 796 | IgA/IgG/IgM aCL, IgA/IgG/IgM aβ2GPI | IgA aβ2GPI is significantly associated with DVT, total VT and stroke | − IgA aβ2GPI OR (95% CI) for DVT: 2.08 (1.31–3.30) |
| − IgA aβ2GPI OR (95% CI) for total VT (superficial, DVT and other venous): 1.70 (1.12–2.59) | |||||
| − IgA aβ2GPI OR (95% CI) for stroke: 1.79 (1.01–3.15) | |||||
| − IgA aβ2GPI OR (95% CI) for myocardial infarction: 0.43 (0.10–1.87) | |||||
| Domingues et al. 2016 [23] | P | 1390 | IgA/IgG/IgM aCL | IgG aCL is significantly associated with any thrombotic events and VT | − IgM aCL RR (95% CI) for any thrombotic event: 1.2 (0.8–2.0), P = 0.40 |
| − IgM aCL RR (95% CI) for ATa: 1.5 (0.8–2.6), P = 0.22 | |||||
| − IgM aCL RR (95% CI) for VT: 1.3 (0.7–2.4), P = 0.36 | |||||
| − IgG aCL RR (95% CI) for any thrombotic event: 1.8 (1.2–2.7), P = 0.0052 | |||||
| − IgG aCL RR (95% CI) for ATa: 1.6 (0.9–2.8), P = 0.097 | |||||
| − IgG aCL RR (95% CI) for VT: 1.9 (1.1–3.2), P = 0.015 | |||||
| − IgA aCL RR (95% CI) for any thrombotic event: 1.7 (0.7–4.2), P = 0.23 | |||||
| − IgA aCL RR (95% CI) for ATa: 2.4 (0.9–6.4), P = 0.088 | |||||
| − IgG aCL RR (95% CI) for VT: 1.7 (0.5–5.3), P = 0.37 | |||||
| Petri et al. 2020 [35] | P | 785 | LA | Persistent LA positivity is significantly associated with thrombotic events regardless of the method used to define it | − Persistent positivity defined by the first two LA assessments: • Rate of thromboses per 100 person-years: 4.3 • Adjusted RR (95% CI) for thrombosis: 3.42 (1.76–6.65), P = 0.0003 |
| The authors did not distinguish between VT and AT | − Persistent positivity based on annual assessments: • Rate of thromboses per 100 person-years: 4.2 • Adjusted RR (95% CI) for thrombosis: 3.08 (1.83–5.19), P < 0.0001 | ||||
| − Persistent positivity based on the first 16 assessments: • Rate of thromboses per 100 person-years: 3.8 • Adjusted RR (95% CI) for thrombosis: 2.75 (1.71–4.42), P < 0.0001 | |||||
| Demir et al. 2021 [24] | P | 821 | LA, IgA/IgG/IgM aCL, IgA/IgG/IgM aβ2GPI | IgA aβ2GPI is significantly associated with any thrombosis and VT after adjusting for LA | − LA: age-adjusted RR (95% CI) for any thrombosis: 3.56 (2.01–6.30), P < 0.0001 |
| − LA: age-adjusted RR (95% CI) for VT: 4.89 (2.25–10.64), P < 0.0001 | |||||
| − LA: age-adjusted RR (95% CI) for ATa: 3.14 (1.41–6.97), P = 0.005 | |||||
| − IgA aβ2GPI age-adjusted RR (95% CI) for any thrombosis after adjusting for LA: 1.73 (1.04–2.88), P = 0.0362 | |||||
| − IgA aβ2GPI age-adjusted RR (95% CI) for ATa after adjusting for LA: 1.33 (0.64–2.78), P = 0.4469 | |||||
| − IgA aβ2GPI age-adjusted RR (95% CI) for VT after adjusting for LA: 2.27 (1.13–4.59), P = 0.0218 | |||||
| Age-adjusted RR (95% CI) for any thrombosis: | |||||
| − LA + IgG aCL: 0.76 (0.21–2.74), P = 0.6715 | |||||
| − LA + IgM aCL: 0.63 (0.14–2.85), P = 0.5537 | |||||
| − LA + IgA aCL: 1.42 (0.18–11), P = 0.7352 | |||||
| − LA + IgG aβ2GPI: 0.96 (0.27–3.46), P = 0.9481 | |||||
| − LA + IgM aβ2GPI: 0.73 (0.2–2.64), P = 0.6333 | |||||
| − LA + IgA aβ2GPI: 0.58 (0.23–1.45), P = 0.2438 | |||||
| Akhter et al. 2013 [38] | CS | 326 | LA, IgA/IgG/IgM aCL, IgA/IgG/IgM aβ2GPI, IgA/IgG/IgM anti-DI β2GPI, IgA/IgG/IgM anti-D4/D5 β2GPI, IgG/IgM aPS-PT | IgA aCL was significantly associated with all thrombosis and VT | − IgA aCL OR (95% CI) for all thrombosis: 9.5 (1.2–75.8), P = 0.034 |
| − IgA aCL OR (95% CI) for VT: 4.3 (1.2–14.8), P = 0.023 | |||||
| − IgA aCL OR (95% CI) for stroke: 2.0 (0.6–7.4), P = 0.28 | |||||
| Samarkos et al. 2006 [21] | R | 130 | IgA/IgG/IgM aCL, IgA/IgG/IgM aβ2GPI | IgM aCL was significantly associated with VT | OR not provided (P = 0.001) |
| Swadźba et al. 2007 [20] | R | 235 | LA, IgG/IgM aCL, IgG/IgM aβ2GPI | IgM/IgG aCL and IgG aβ2GPI were significantly associated with ATa | IgM aCL OR for AT: 2.25 (P < 0.05) |
| IgG aCL OR for AT: 5.67 (P < 0.05) | |||||
| IgG aβ2GPI OR for AT: 4.69 (P < 0.05) | |||||
| Sciascia et al. 2012 [55] | R | 230 | LA, IgG/IgM aCL, IgG/IgM aβ2GPI, IgG/IgM aPS-PT, IgG/IgM aPT, IgG/IgM aPE | Among 23 combinations of aPLs, the triple positivity of LA, aβ2GPI and aPS-PT was the strongest predictor for thrombosisa and/or APOs | OR (95% CI) for thrombosis: |
| − LA + aPS-PT + aβ2GPI: 23.2 (2.57–46.12) | |||||
| − LA + aβ2GPI: 13.78 (2.04–16.33) | |||||
| − LA + aPS-PT: 10.47 (2.21–26.97) | |||||
| − aPS-PT + aβ2GPI: 9.13 (2.17–15.62) | |||||
| Murthy et al. 2013 [36] | R | 773 | IgA/IgG/IgM aCL, IgA/IgG/IgM aβ2GPI | IgA aβ2GPI was significantly associated with all thrombosis, VT and ATa | − Isolated IgA aβ2GPI adjusted OR (95% CI) for all thrombosis: 5.1 (2.2–12.4), P = 0.0003 |
| − Isolated IgA aβ2GPI adjusted OR (95% CI) for AT: 5.8 (2.3–15.2), P = 0.0003 | |||||
| − Isolated IgA aβ2GPI adjusted OR (95% CI) for VT: 2.3 (1.0–5.4, P = 0.061) | |||||
| Pericleous et al. 2016 [37] | R | 145 | IgA/IgG/IgM aCL, IgA/IgG/IgM aβ2GPI, IgA/IgG/IgM anti-DI β2GPI | IgA aCL, aβ2GPI and anti-DI aβ2GPI were all significantly associated with APS The association of any aCL and/or aβ2GPI isotype with anti-DI antibodies was associated with a 3- to 5-fold increase in the risk of APS compared with the double positivity of aCL and aβ2GPI | HR (95% CI) for APS − IgA aCL: 1.3 (0.9–1.9) − IgA aβ2GPI: 5.3 (2.1–13.3) − IgA anti-DI β2GPI: 2.2 (1.3–3.7) − IgG anti-DI β2GPI: 3.5 (1.8–6.8) − IgM anti-DI β2GPI: 2.8 (1.5–4.9) − IgG aPLs: • aCL/aβ2GPI + anti-DI β2GPI: 36.9 (17.7–76.9) • double or single positivity aCL/aβ2GPI: 11.5 (6.3–21.0) − IgM aPLs: • aCL/aβ2GPI + anti-DI β2GPI: 21.3 (9.1–50.4) • double or single positivity aCL/aβ2GPI: 7.3 (3.0–17.5) − IgA aPLs: • aCL/aβ2GPI + anti-DI β2GPI: 24.8 (12.3–49.9) • double or single positivity aCL/aβ2GPI: 5.0 (2.7–9.2) |
| Tkachenko et al. 2020 [56] | R | 107 | LA, IgG/IgM aCL, IgG/IgM aβ2GPI, aPch, aPe, aPg, aPi, aPs, aAnV and aPt | The presence of >4 IgG aPLs was an independent risk factor for thrombosis | >4 aPL IgG OR (95% CI) for thrombosis: 10.87 (1.16–101.54) |
| Elbagir et al. 2021 [43] | R | 91 Sudanese + 332 Swedish | IgA/IgG/IgM aPS-PT, IgA/IgG/IgM aCL, IgA/IgG/IgM aβ2GPI | At univariate analysis, all the isotypes of aPS-PT were independent risk factors for VT, while only IgA aPS-PT was an independent risk factor for AT aPS-PT was not associated with MI IgA aPS-PT was associated with cerebrovascular events At multivariate analysis, IgA aPS-PT was independently associated with cerebrovascular events and IgM/IgG aPS-PT was independently associated with VT | Univariate analysis: − IgA aPS-PT OR (95% CI) for AT: 3.9 (1.3–10.6) − aPS-PT was not associated with MI − IgA aPS-PT was associated with cerebrovascular events − IgM aPS-PT OR (95% CI) for VT: 7.4 (3.1–18.1) Multivariate analysis: − IgA aPS-PT OR (95% CI) for cerebrovascular events: 5.1 (1.3–16.8) − IgM and IgG aPS-PT OR for VT: exact data not provided OR (95% CI) for VT: − IgG/M aβ2GPI + aPS-PT: 6.3 (2.8–13.9) − IgA/IgG/IgM aβ2GPI + aPS-PT: 6.8 (3.1–14.5) − IgG/IgM aβ2GPI + aCL + LA: 5.2 (2.5–10.7) − IgA/IgG/IgM aβ2GPI + aPS-PT + LA: 8.1 (3.7–17.8) |
| Farina et al. 2023 [51] | R | 501 | IgG aCL, IgG aβ2GPI, IgG anti-DI β2GPI | ORs for VT/ATa not provided | Comparison of single positive vs double/triple positive vs negative Kaplan–Meier curves for cardiovascular events: P = 0.0057 |
The authors did not provide the OR/RR for cardiovascular and cerebrovascular events separately.
aAnV: anti-annexin V antibodies; aβ2GPI: anti-β2-glycoprotein I antibodies; anti-DI aβ2GPI: anti-domain I β2-glycoprotein I antibodies; anti-D4/D5 aβ2GPI: anti-domain 4/5 β2-glycoprotein I antibodies; aPch: anti-phosphatidylcholine antibodies; aPE: anti-phosphatidylethanolamine antibodies; aPg: anti-phosphatidylglycerol antibodies; aPi: anti-phosphatidylinositol antibodies; aPT: antiprothrombin; AT: arterial thrombosis; CS: cross-sectional; DVT: deep venous thrombosis; HR: hazard ratio; MI: myocardial infarction; OR: odds ratio; P: prospective; pts: patients; R: retrospective; RR: risk ratio; VT: venous thrombosis.
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