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The recent RAPS trial demonstrated that APS patients treated with rivaroxaban had a significant twofold-increased thrombin potential, suggesting a higher thrombotic risk, in comparison with warfarin users. Furthermore, several reports of APS patients treated with DOACs have raised safety issues. Our systematic review identified 122 published APS patients treated with DOACs; among them, 19 experienced a recurrent thrombosis while on DOACs. Of note, triple positivity (positivity of all three laboratory criteria for APS) was associated with a 3.5-fold increased risk for recurrent thrombosis. In conclusion, DOACs should be used with caution in APS patients and randomized control trials with clinical primary endpoints assessing clinical efficacy and safety are awaited to establish whether the prescription of DOACs could be a safe alternative to warfarin.

Background Antibodies binding to domain I of β2-glycoprotein I (aDI) and activated protein C (APC) resistance are associated with an increased risk of thrombosis in cross-sectional studies. The objective of this study was to assess their predictive value for future thromboembolic events in patients with antiphospholipid antibodies (aPL) or antiphospholipid syndrome. Methods This prospective multicenter cohort study included consecutive patients with aPL or systemic lupus erythematosus. We followed 137 patients (43.5 ± 15.4 year old; 107 women) for a mean duration of 43.1 ± 20.7 months. Results We detected aDI IgG antibodies by ELISA in 21 patients. An APC sensitivity ratio (APCsr) was determined using a thrombin generation–based test. The APCsr was higher in patients with anti–domain I antibodies demonstrating APC resistance (0.75 ± 0.13 vs 0.48 ± 0.20, P < 0.0001). In univariate analysis, the hazard ratio (HR) for thrombosis over time was higher in patients with aDI IgG (3.31 [95% CI, 1.15–9.52]; P = 0.03) and patients with higher APC resistance (APCsr >95th percentile; HR, 6.07 [95% CI, 1.69–21.87]; P = 0.006). A sensitivity analysis showed an increased risk of higher aDI IgG levels up to HR 5.61 (95% CI, 1.93–16.31; P = 0.01). In multivariate analysis, aDI IgG (HR, 3.90 [95% CI, 1.33–11.46]; P = 0.01) and APC resistance (HR, 4.98 [95% CI, 1.36–18.28]; P = 0.02) remained significant predictors of thrombosis over time. Conclusions Our study shows that novel tests for antibodies recognizing domain I of β2-glycoprotein I and functional tests identifying APC resistance are significant predictors of thrombosis over time and may be useful for risk stratification.

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Recently, it has been demonstrated that endothelial proliferation in kidneys can be explained by the activation of the mammalian target of rapamycin complex (mTORC) pathway by antiphospholipid antibodies (aPL). These data support the existence of an APS-related vasculopathy in different locations which can explain-in part-the different manifestations of APS. This review focuses on the various manifestations of APS as a result of APS-related vasculopathy, as well as pathophysiology, current screening, and treatment options for clinicians to be aware of.

Chorea may occur in systemic lupus erythematosus (SLE) and primary antiphospholipid antibody syndrome (PAPS). Vascular lesions and immune-mediated excitatory mechanisms have been proposed as the underlying pathophysiology.1,2 Accordingly, immunosuppressive therapy has been employed in antiphospholipid antibody (aPL)-associated chorea. [3][4][5] We report the correlation between clinical symptoms, laboratory activity of aPL, and striatal hypermetabolism in 18 F-fluorodeoxyglucose (FDG) PET in a patient with aPL-associated hemichorea. This patient was successfully treated with low-dose methotrexate.Case report. A 41-year-old right-handed woman developed involuntary movements of the left hand in June 1999. Within 2 weeks, the symptoms progressed to uncontrollable jerks of the left arm and leg, with clumsiness of finger movements, twitching of the left face with squeezing of the eye, and speech difficulties due to clumsiness of the tongue. She was unable to continue working. Her medical history included moderate hypertension treated with losartan 50 mg per day, hysterectomy, and cigarette smoking (12 pack-years). Family history of movement disorders was negative.A cranial MRI revealed no ischemic lesion. CSF, EEG, intraand extracranial DCI, and ophthalmologic examination results were normal. Tests for lupus anticoagulant (LA) were positive, with increased activated partial thromboplastin time (aPTT) (38.7 s; normal, 21.0 to 36.0 s) and dilute Russell viper venom time ratio (dRVVT-ratio) (2.2; normal, Ͻ1.2); the anticardiolipin antibody titer (IgG) (aCL-IgG) was elevated (86.0 U/mL; normal, Ͻ18 U/mL). All other laboratory results including platelet count, complement factor 3 and 4, anti-ds-DNA antibodies, antinuclear antibodies, HIV antibodies, treponema pallidum hemagglutination assay (serum and CSF), acanthocytes, serum copper and ceruloplasmin, and thyroid function were normal. A preliminary diagnosis of aPL-associated chorea was made.Six weeks after the first manifestation of chorea, treatment was initiated with low-dose methotrexate, 20 mg orally once per week, which led to a rapid improvement. After 4 weeks of continuous medication, choreatic movements were no longer detectable and the laboratory follow-up showed an improved result for aCLIgG (55.7 U/mL) and a downward trend of LA (aPTT 34.5 s; dRVVT-ratio 1.7).Methotrexate treatment was discontinued after 9 weeks. Eight days after the last intake, the patient again noticed involuntary movements of the left hand and foot. Neurologic examination 12 days after the last methotrexate intake confirmed a mild to moderate relapse of left-sided hemichorea. Laboratory results showed increased LA (aPTT 39.5 s; dRVVT-ratio 1.9) and aCL-IgG (75.2 U/mL). An FDG PET performed to study striatal hypermetabolism revealed an increase of FDG uptake in the right caudate nucleus as compared with the left side (6.36 Ϯ 1.5%; p Ͻ 0.05) (figure).Medication was started again at 20 mg methotrexate per week. After 2 weeks, choreatic movements were no longer detectable. After 6 weeks of co...

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