The antiphospholipid syndrome (APS) is defined by the presence of thrombosis and/or pregnancy morbidity in combination with the persistent presence of circulating antiphospholipid antibodies: lupus ...anticoagulant, anticardiolipin antibodies and/or anti-β2-glycoprotein I antibodies in medium to high titers. The management of thrombosis in patients with APS is a subject of controversy. This set of recommendations is the result of an effort to produce guidelines for therapy within a group of specialist physicians in Cardiology, Neurology, Hematology, Rheumatology and Internal Medicine, with a clinical and research focus on APS.
Determination of lupus anticoagulant (LA), anticardiolipin (aCL) and β2-Glycoprotein 1 (aβ2GP1) antibodies is mandatory to classify patients with antiphospholipid syndrome (APS) into risk categories.
...To measure relevant antibodies, considered to be those of the IgG isotype directed towards β2GP1 and particularly those directed to Domain 1 (Dm1) of the molecule.
In this cross-sectional study we measured IgG aβ2GP1-Dm1 by a chemiluminescent immunoassay in a group of individuals initially positive for IgG aβ2GP1 and classified as triple (LAC+, IgG aCL+, IgG aβ2GP1+, n = 32), double (LAC-, IgG aCL+, IgG aβ2GP1+, n = 23) or single positive (LA-, IgG aCL-, IgG aβ2GP1+, n = 10).
Geometric mean and standard deviation expressed as chemiluminescent units (CU) in triple, double and single positive groups were 273.0 ± 6.2, 18.2 ± 9.6 and 4.4 ± 2.2, respectively. The geometric mean obtained in 40 healthy subjects was 2.0 ± 2.0. Mean CU values were significantly different among groups and with respect to values found in 40 healthy subjects (P < 0.0001). Positive values of IgG aβ2GP1-Dm1 (above 14.2 CU) were found in 45 individuals while 20 individuals (20/65 = 30.8%) positive for IgG aβ2GP1 were negative for IgG aβ2GPI-Dm1. There was a significant association between positive IgG aβ2GP1-Dm1 and thromboembolic events (P = 0.001). Positive and negative values of IgG aβ2GP1-Dm1 were consistently confirmed after 12 weeks, with only three low positive values being negative after 12 weeks. In conclusion, IgG aβ2GP1-Dm1 seems a robust and reproducible test that in association with the classic tests may be useful in clinical practice in identifying individuals at high risk of developing thromboembolic events.
Essentials
Direct oral anticoagulants (DOACs) do not require laboratory monitoring currently.
DOAC specific measurements were performed at trough in patients with atrial fibrillation.
Patients who ...developed thromboembolic events showed lower DOAC plasma levels.
This study supports the concept of measuring DOAC levels at steady state.
Summary
Background
Direct oral anticoagulants (DOACs) are administered at fixed doses without the need for dose adjustment according to laboratory testing. High interindividual variability in drug blood levels has been shown with all DOACs. To evaluate a possible relationship between DOAC C‐trough anticoagulant levels and thromboembolic events, 565 consecutive naive patients with atrial fibrillation (AF) were enrolled in this study performed within the START Laboratory Registry.
Methods
DOAC‐specific measurements (diluted thrombin time or anti‐activated factor II calibrated for dabigatran; anti‐activated FX calibrated for rivaroxaban or apixaban) at C‐trough were performed locally at steady state within 15–25 days after the start of treatment. For each DOAC, the interval of C‐trough levels, from the limit of quantification to the highest value, was subdivided into four equal classes, and results were attributed to these classes; the median values of results were also calculated. Thromboembolic complications occurring during 1 year of follow‐up were recorded.
Results
Thromboembolic events (1.8%) occurred in 10 patients who had baseline C‐trough levels in the lowest class of drug levels. The incidence of thromboembolic events among patients with DOAC C‐trough levels in the lowest level class was 2.4%, and that in the remaining groups was 0%. The patients with thrombotic complications also had a higher mean CHA2DS2‐VASc score than that of the total patient population: 5.3 (95% confidence interval CI 4.3–6.3 versus 3.0 (95% CI 2.9–3.1).
Conclusion
In this study cohort, thrombotic complications occurred only in DOAC‐treated AF patients who had very low C‐trough levels, with a relatively high CHA2DS2‐VASc score. Larger studies are warranted to confirm these preliminary observations.
AIMSWe assessed the cumulative incidence of recurrent stroke, major bleeding and all-cause mortality associated with restarting antithrombotic treatment, in patients experiencing an ...anticoagulation-related event (stroke or major bleeding), occurred during anticoagulation therapy for AF.METHODS AND RESULTSWe performed a retrospective population-based analysis on linked claims data of patients resident in the Veneto Region, treated with DOACs for AF and discharged (2013-2020) from the hospital for stroke, intracranial haemorrhage (ICH), and major bleeding. To adjust for competing risk of death and reduce confounding, we started the follow up after a 120-days blanking period, counting events in patients resuming oral anticoagulation versus those that did not. Risks of all-cause mortality, ischemic stroke (IS)intracranial haemorrhage (ICH), and other major bleeding events (MB) were estimated with multivariable Cox proportional hazard models and propensity score to adjust for differences in baseline characteristics. Overall, 1029 patients (mean age 77 years) were included in the final cohort: 23% experienced an IS, 18% an ICH, and 59% MB. Of these, 77% resumed anticoagulation. The cumulative incidence of events was significantly lower in patients resuming therapy. In the multivariable analysis considering age, sex and propensity score as covariates, resumption of anticoagulation significantly reduced the risk of a cumulative event (HR 0.45, 95%CI 0.35-0.57, p < 0.01). Stratifying for the index event, among patients with IS (92% resumed therapy), we observed a risk reduction of 81%; in patients with ICH (64% resumed therapy), we observed a risk reduction of 64% and for patients with MB (76% resuming therapy), we observed a risk reduction of 49%.CONCLUSIONSIn patients with AF who experienced an anticoagulation-related event, resuming oral anticoagulation was associated with better outcomes for all-cause mortality and subsequent events as compared with patients who did not resume treatment.
. Tripodi A, de Groot PG, Pengo V (IRCCS Cà Granda Ospedale Maggiore Policlinico Foundation and Università degli Studi di Milano, Milan, Italy; Utrecht University Medical Center, Utrecht, the ...Netherlands; Thrombosis Center, University Hospital, Padua, Italy). Antiphospholipid syndrome: laboratory detection, mechanisms of action and treatment (Review). J Intern Med 2011; 270: 110–122.
The antiphospholipid syndrome (APS) identifies a condition at increased risk of vascular occlusion and/or pregnancy complications. Patients are defined as having APS if they have at least one clinical (vascular occlusion and/or pregnancy complications) and one laboratory criterion at the same time. The laboratory criteria that define APS are repeated positivity (confirmed 12 weeks apart) for lupus anticoagulants and/or antibodies targeted against cardiolipin or β2‐glycoprotein I immobilized on solid surfaces. Over the years, APS has attracted the interest of many medical specialties. The aim of this review is to provide an update on (i) the laboratory criteria that determine the presence of APS, (ii) how the antibodies increase the risk of vascular occlusion and foetal loss and (iii) the treatment of the related clinical events.
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