Predictors of experiencing a negative LA test (n = 164)
| Variables . | Univariable . | Adjusted for VKA at baseline . |
|---|---|---|
| Demographic characteristics | Subdistribution hazard ratio (95% CI, P) | |
| Age at study inclusion (per 5 y increase) | 0.95 (0.88-1.03, P = .244) | 0.97 (0.90-1.06, P = .540) |
| Female gender | 0.73 (0.35-1.52, P = .399) | 0.77 (0.37-1.61, P = .486) |
| Clinical history | ||
| Prior history of thrombosis | 3.15 (1.54-6.44, P = .002) | 2.82 (1.27-9.25, P = .011) |
| Arterial | 1.62 (0.77-4.30, P = .200) | 1.52 (0.71-3.27, P = .290) |
| Venous | 2.39 (1.28-4.45, P = .006) | 2.02 (0.98-4.17, P = .057) |
| Both | 2.20 (0.73-6.60, P = .178) | 1.61 (0.45-5.77, P = .460) |
| History of pregnancy complications* | 1.48 (0.68-3.24, P = .330) | 1.34 (0.61-2.94, P = .470) |
| Comorbidities at baseline | ||
| Autoimmune rheumatic diseases† | 1.23 (0.67-2.26, P = .507) | 1.23 (0.68-2.24, P = .496) |
| SLE | 1.60 (0.79-3.23, P = .191) | 1.52 (0.76-3.01, P = .235) |
| LLD | 0.63 (0.25-1.62, P = .342) | 0.67 (0.26-1.71, P = .403) |
| Active smoker at baseline | 0.52 (0.25-1.07, P = .074) | 0.55 (0.27-1.14, P = .109) |
| Hypertension | 0.98 (0.52-1.87, P = .962) | 0.94 (0.49-1.80, P = .851) |
| Diabetes | 0.81 (0.25-2.61, P = .730) | 0.77 (0.24-2.48, P = .660) |
| Anticoagulation at baseline | ||
| VKA | 2.03 (1.13-3.64, P = .018) | N/A |
| LMWH | 1.19 (0.52-2.74, P = .681) | 1.31 (0.58-2.94, P = .520) |
| LDA | 1.04 (0.56-1.95, P = .894) | 1.13 (0.61-2.09, P = .691) |
| None | 0.44 (0.22-0.91, P = .028) | 0.58 (0.25-1.35, P = .207) |
| Disease-related biomarkers | ||
| aPTT-LA (per 10 s increase) | 0.93 (0.85-1.02, P = .110) | 0.90 (0.82-0.99, P = .029) |
| LA positivity only | 0.50 (0.21-1.16, P = .106) | 0.52 (0.22-1.23, P = .138) |
| IgM aCL–positive‡ | 1.41 (0.65-3.04, P = .390) | 2.00 (0.85-4.71, P = .110) |
| IgG aCL–positive‡ | 1.61 (0.88-2.95, P = .120) | 1.41 (0.76-2.61, P = .280) |
| aCL IgM (per doubling) | 0.99 (0.83-1.18, P = .921) | 1.04 (0.85-1.28, P = .673) |
| aCL IgG (per doubling) | 1.12 (1.00-1.26, P = .055) | 1.08 (0.96-1.22, P = .176) |
| aCL+ (IgM and/or IgG)‡ | 1.68 (0.93-3.05, P = .086) | 1.58 (0.87-2.87, P = .133) |
| IgM aβ2GPI–positive‡ | 0.99 (0.53-1.87, P = .980) | 1.06 (0.57-1.99, P = .860) |
| IgG aβ2GPI–positive‡ | 2.83 (1.42-5.61, P = .003) | 2.55 (1.27-5.09, P = .008) |
| aβ2GPI IgM (per doubling) | 0.98 (0.83-1.17, P = .860) | 1.03 (0.86-1.24, P = .732) |
| aβ2GPI IgG (per doubling) | 1.14 (1.03-1.26, P = .009) | 1.09 (0.98-1.22, P = .098) |
| aβ2GPI+ (IgM and/or IgG)‡ | 2.26 (0.96-5.30, P = .061) | 2.12 (0.90-5.02, P = .086) |
| “Triple positivity”‡ | 1.55 (0.84-2.86, P = .158) | 1.48 (0.86-2.73, P = .206) |
| Antiprothrombin IgM (per doubling) | 0.72 (0.56-0.93, P = .011) | 0.75 (0.79-0.99, P = .040) |
| Antiprothrombin IgG (per doubling) | 0.91 (0.78-1.05, P = .199) | 0.87 (0.76-0.99, P = .037) |
| Antiprothrombin IgM–positive§ | 0.73 (0.33-1.63, P = .438) | 0.86 (0.37-2.00, P = .730) |
| Antiprothrombin+ IgG§ | 0.89 (0.44-1.78, P = .738) | 0.65 (0.31-1.35, P = .251) |
| Antiprothrombin+ (IgM and/or IgG)§ | 0.68 (0.35-1.31, P = .247) | 0.60 (0.31-1.16, P = .131) |
| Variables . | Univariable . | Adjusted for VKA at baseline . |
|---|---|---|
| Demographic characteristics | Subdistribution hazard ratio (95% CI, P) | |
| Age at study inclusion (per 5 y increase) | 0.95 (0.88-1.03, P = .244) | 0.97 (0.90-1.06, P = .540) |
| Female gender | 0.73 (0.35-1.52, P = .399) | 0.77 (0.37-1.61, P = .486) |
| Clinical history | ||
| Prior history of thrombosis | 3.15 (1.54-6.44, P = .002) | 2.82 (1.27-9.25, P = .011) |
| Arterial | 1.62 (0.77-4.30, P = .200) | 1.52 (0.71-3.27, P = .290) |
| Venous | 2.39 (1.28-4.45, P = .006) | 2.02 (0.98-4.17, P = .057) |
| Both | 2.20 (0.73-6.60, P = .178) | 1.61 (0.45-5.77, P = .460) |
| History of pregnancy complications* | 1.48 (0.68-3.24, P = .330) | 1.34 (0.61-2.94, P = .470) |
| Comorbidities at baseline | ||
| Autoimmune rheumatic diseases† | 1.23 (0.67-2.26, P = .507) | 1.23 (0.68-2.24, P = .496) |
| SLE | 1.60 (0.79-3.23, P = .191) | 1.52 (0.76-3.01, P = .235) |
| LLD | 0.63 (0.25-1.62, P = .342) | 0.67 (0.26-1.71, P = .403) |
| Active smoker at baseline | 0.52 (0.25-1.07, P = .074) | 0.55 (0.27-1.14, P = .109) |
| Hypertension | 0.98 (0.52-1.87, P = .962) | 0.94 (0.49-1.80, P = .851) |
| Diabetes | 0.81 (0.25-2.61, P = .730) | 0.77 (0.24-2.48, P = .660) |
| Anticoagulation at baseline | ||
| VKA | 2.03 (1.13-3.64, P = .018) | N/A |
| LMWH | 1.19 (0.52-2.74, P = .681) | 1.31 (0.58-2.94, P = .520) |
| LDA | 1.04 (0.56-1.95, P = .894) | 1.13 (0.61-2.09, P = .691) |
| None | 0.44 (0.22-0.91, P = .028) | 0.58 (0.25-1.35, P = .207) |
| Disease-related biomarkers | ||
| aPTT-LA (per 10 s increase) | 0.93 (0.85-1.02, P = .110) | 0.90 (0.82-0.99, P = .029) |
| LA positivity only | 0.50 (0.21-1.16, P = .106) | 0.52 (0.22-1.23, P = .138) |
| IgM aCL–positive‡ | 1.41 (0.65-3.04, P = .390) | 2.00 (0.85-4.71, P = .110) |
| IgG aCL–positive‡ | 1.61 (0.88-2.95, P = .120) | 1.41 (0.76-2.61, P = .280) |
| aCL IgM (per doubling) | 0.99 (0.83-1.18, P = .921) | 1.04 (0.85-1.28, P = .673) |
| aCL IgG (per doubling) | 1.12 (1.00-1.26, P = .055) | 1.08 (0.96-1.22, P = .176) |
| aCL+ (IgM and/or IgG)‡ | 1.68 (0.93-3.05, P = .086) | 1.58 (0.87-2.87, P = .133) |
| IgM aβ2GPI–positive‡ | 0.99 (0.53-1.87, P = .980) | 1.06 (0.57-1.99, P = .860) |
| IgG aβ2GPI–positive‡ | 2.83 (1.42-5.61, P = .003) | 2.55 (1.27-5.09, P = .008) |
| aβ2GPI IgM (per doubling) | 0.98 (0.83-1.17, P = .860) | 1.03 (0.86-1.24, P = .732) |
| aβ2GPI IgG (per doubling) | 1.14 (1.03-1.26, P = .009) | 1.09 (0.98-1.22, P = .098) |
| aβ2GPI+ (IgM and/or IgG)‡ | 2.26 (0.96-5.30, P = .061) | 2.12 (0.90-5.02, P = .086) |
| “Triple positivity”‡ | 1.55 (0.84-2.86, P = .158) | 1.48 (0.86-2.73, P = .206) |
| Antiprothrombin IgM (per doubling) | 0.72 (0.56-0.93, P = .011) | 0.75 (0.79-0.99, P = .040) |
| Antiprothrombin IgG (per doubling) | 0.91 (0.78-1.05, P = .199) | 0.87 (0.76-0.99, P = .037) |
| Antiprothrombin IgM–positive§ | 0.73 (0.33-1.63, P = .438) | 0.86 (0.37-2.00, P = .730) |
| Antiprothrombin+ IgG§ | 0.89 (0.44-1.78, P = .738) | 0.65 (0.31-1.35, P = .251) |
| Antiprothrombin+ (IgM and/or IgG)§ | 0.68 (0.35-1.31, P = .247) | 0.60 (0.31-1.16, P = .131) |
Reported results are subdistribution hazard ratios for time to first negative LA test. Subdistribution hazard ratios >1 indicate a higher risk of a change and ratios <1 a lower risk. Presented data are from univariable models (left column) and from multivariable models adjusted for VKA use at baseline (right column). Results “per doubling” were obtained by using a log2(+1)-transformation of the underlying variable. LDA, low-dose aspirin.
Pregnancy complications were defined according to Sapporo criteria in the subgroup of 117 females who had at least 1 documented pregnancy.
Autoimmune rheumatic diseases were defined as a composite of systemic lupus erythematosus and lupus-like disease according to a local panel of rheumatology experts.
Cutoffs were defined as follows according to ISTH/Sapporo criteria cutoffs: aCL >40 GPL/MPL U/mL, aβ2GPI >8 GPL/MPL U/mL. Triple-positivity was defined as being positive for LA and at least one class of immunoglobulins (IgM or IgG) for aCL and aβ2GPI.
Cutoffs were defined by the 90th percentile in 33 healthy volunteers without history of thrombosis, antiprothrombin IgM ≥11.54 U/mL, antiprothrombin IgG ≥8.68 U/mL.