See also Galli M. The antiphospholipid triangle. This issue, pp 234–6.
Summary. Background: The characteristics and the clinical course of antiphospholipid syndrome (APS) in high‐risk patients that ...are positive for all three recommended tests that detect the presence of antiphospholipid (aPL) antibodies have not been described. Methods: This retrospective analysis of prospectively collected data examined patients referred to Italian Thrombosis Centers that were diagnosed with definite APS and tested positive for aPL lupus anticoagulant (LA), anti‐cardiolipin (aCL), and anti‐β2‐glycoprotein I (β2GPI) antibodies. Laboratory data were confirmed in a central reference laboratory. Results: One hundred and sixty patients were enrolled in this cohort study. The qualifying events at diagnosis were venous thromboembolism (76 cases; 47.5%), arterial thromboembolism (69 cases; 43.1%) and pregnancy morbidity (11 cases; 9.7%). The remaining four patients (2.5%) suffered from catastrophic APS. The cumulative incidence of thromboembolic events in the follow‐up period was 12.2% (95%CI, 9.6–14.8) after 1 year, 26.1% (95%CI, 22.3–29.9) after 5 years and 44.2% (95%CI, 38.6–49.8) after 10 years. This was significantly higher in those patients not taking oral anticoagulants as compared with those on treatment (HR=2.4 95%CI 1.3–4.1; P < 0.003). Major bleeding associated with oral anticoagulant therapy was low (0.8% patient/years). Ten patients died (seven were cardiovascular deaths). Conclusions: Patients with APS and triple positivity for aPL are at high risk of developing future thromboembolic events. Recurrence remains frequent despite the use of oral anticoagulants, which significantly reduces the risk of thromboembolism.
Summary
Background
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.
Objectives
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.
Patients/methods
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).
Results and conclusion
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.
Background
New oral anticoagulants may simplify long-term therapy in conditions requiring anticoagulation. Rivaroxaban is a direct factor Xa inhibitor that has been extensively studied and is now ...approved for the prevention and therapy of a number of thromboembolic conditions.
Objective and methods
This is a multicentre, randomized, open-label, study that will evaluate if Rivaroxaban 20 mg od (or 15 mg od in patients with moderate renal insufficiency) is non-inferior to warfarin (INR target 2.5), for the prevention of thromboembolic events, major bleeding and death in high risk (triple positive) patients with antiphospholipid syndrome. Secondary endpoints will assess the incidence of any individual component of the composite end point. An external adjudication committee will evaluate all suspected outcome events. This will be a unique trial, as it will enrol the biggest homogenous cohort of high risk APS individuals.
Conclusion
The methods and the study design should be appropriate to achieve study results that are both scientifically valid and relevant to clinical practice.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Summary
Background
The revised classification criteria for the antiphospholipid syndrome state that antiphospholipid (aPL) antibodies (lupus anticoagulant LAC and/or anticardiolipin aCL and/or ...anti‐β2‐glycoprotein I aβ2GPI antibodies) should be detected on two or more occasions at least 12 weeks apart. Consequently, classification of patient risk and adequacy of treatment may be deferred by 3 months.
Objectives
In order to early classify patient risk, we evaluated whether aPL positivity confirmation is related to aPL antibody profiles.
Patients and Methods
Consecutive patients referred to our center who were initially positive in one or more tests exploring the presence of aPL were tested after 3 months. During a 4‐year period, 225 patients were initially positive in one or more tests, and 161 were available for confirmation after 3 months. Patients were classified as triple‐positive (n = 54: LAC+, aCL+, aβ2GPI+, same isotype), double‐positive (n = 50: LAC–, aCL+, aβ2GPI+, same isotype) and single‐positive (n = 53: LAC or aCL or aβ2GPI antibodies as the sole positive test).
Results
Among subjects with triple positivity at initial testing, 98% (53 of 54) had their aPL profile confirmed after 12 weeks. The double‐positive and single‐positive groups had data confirmed in 42 of 50 (84%) and 23 of 57 (40%) subjects, respectively.
Conclusions
Our results show that high‐risk subjects with triple‐positive aPL profiles are identified early, at the time of the initial screening tests.
Abstract Diagnosis of antiphospholipid syndrome (APS) is essentially based on the detection of circulating antiphospholipid (aPL) antibodies. Progress have been made on the standardization of tests ...exploring the presence of aPL as guidelines on coagulation and immunological tests were recently published in the literature. Clinical relevance of aPL profile has come from prospective cohort studies in populations with a homogeneous antibody profile supporting the view that triple positivity is a high risk pattern in patients and carriers. In addition to the classic ones, several other tests have been proposed for the diagnosis of APS. The detection of antibodies directed to domain 1 and 4/5 of β2-Glycoprotein I (β2GP1) were found to be particularly sound. Several issues remain to be addressed. We do not yet know what is the physiological function of β2GP1 and the pathophysiology of thrombosis and pregnancy loss in these patients. Moreover, treatment is poorly defined especially in the case of feared catastrophic APS.
Non–vitamin K antagonist oral anticoagulants (NOACs) do not need routine laboratory monitoring but measurement of drug concentration is important in emergency conditions. Specific laboratory tests ...are not readily available or not implemented in every hospital. Point-of-Care Tests (POCT) may bridge this gap and be used as a bedside solution.
Feasibility of POCT to assess plasma levels of dabigatran, rivaroxaban and apixaban.
Activated Coagulation Time-Low Range (ACT - LR) using a portable Hemochron Signature Elite for dabigatran and prothrombin time (expressed as INR) by Coaguchek XS Pro for rivaroxaban and apixaban were obtained at trough and peak in 136 consecutive patients taking NOACs (70 on dabigatran, 45 on rivaroxaban and 20 on apixaban). Using a paired study design, drug concentrations were concurrently determined by functional specific tests.
The correlation between NOACs concentration and the values obtained using the POCTs was high for dabigatran and rivaroxaban (r = 0.80 and r = 0.82, respectively) and low for apixaban (r = 0.21). ACT-LR ≤ 188 s better detected dabigatran levels ≤ 50 ng/ml, with a sensitivity of 87.5% and a specificity of 84.1%. ACT-LR values > 217 s better discriminated value of dabigatran > 200 ng/ml, with a sensitivity of 86.7% and a specificity of 81.4%. INR Coaguchek values ≤ 1.2 better identified patients with rivaroxaban values < 100 ng/ml, with sensitivity of 90%, specificity of 88.5%. This analysis was not possible for apixaban.
In emergency situations POCT use may provide useful immediate information on dabigatran and rivaroxaban concentration.
•In certain clinical situations NOACs monitoring may be of value.•Peak and trough POCT and plasma concentration levels of NOACs were assessed.•There was a good correlation between POCT and plasma levels of dabigatran and rivaroxaban.•POCT might be a feasible tool to guide decisions certain situations in NOACs receiving patients.
Abstract Triple positivity (positive Lupus Anticoagulant, anticardiolipin and anti β2-glycoptrotein I antibodies) identifies the pathogenic autoantibody (anti Domain I of β2-glycoptroteinI) that is ...present in patients with definite Antiphospholipid Syndrome (APS). This is supported by the fact that aβ2GPI antibodies obtained by affinity purification in these patients possess LA activity. Moreover, patients and carriers of this profile carry a much higher risk of thrombosis and pregnancy loss than APS patients with positivity for only one of the tests. Thus, very different risk categories exist among patients with APS as well as among carriers of aPL. Clinical studies and interventional trials should first take these high risk subjects into consideration.
Abstract Objective Anti-prothrombin (aPT) antibodies have been found in Lupus Anticoagulant (LA) positive patients. Their prevalence and relative contribution to thromboembolic risk in LA-positive ...patients is not well defined. The aim of this study was to determine their presence and association with thromboembolic events in a large series of patients with confirmed LA. Methods Plasma from LA-positive patients was collected at Thrombosis Centers and sent to a reference central laboratory for confirmation. Positive plasma was tested using home-made ELISA for the presence of aPT and anti-β2 GPI antibodies. Results LA was confirmed in 231 patients. Sixty-one of 231 (26%, 95%CI 22-33) LA positive subjects were positive for IgG aPT and 62 (27%, 95% CI 21-33) were positive for IgM aPT antibodies. Clinical features of Antiphospholipid Syndrome (APS) were not associated with the presence of IgG aPT 43 APS in 61 (70%) positive and 109 APS in 170 (64%) negative IgG aPT subjects, p = ns or IgM aPT. Rate of positivity of IgG and IgM aβ2 GPI was significantly higher than that of IgG and IgM aPT. Clinical events accounting for APS occurred in 97 of 130 (75%) IgG aβ2 GPI positive and in 55 of 101 (54%) IgG aβ2 GPI negative patients (OR 2.4, 95% CI 1.4 to 4.3, p = 0.002). No significant association with clinical events in patients positive for both IgG aPT and IgG aβ2 GPI as compared to those positive for one or another test was found. When patients negative for both IgG aPT and IgG aβ2 GPI (LA positive only) were compared with remaining patients, a significantly lower association with clinical events was found (OR = 0.4, 95% CI: 0.2 to 0.7, p = 0.004). Conclusions As compared to IgG aβ2 GPI, the prevalence of IgG aPT in patients with LA is significantly lower and not associated with the clinical features of APS.
Abstract Background Determination of the three recommended tests for the diagnosis of antiphospholipid syndrome Lupus Anticoagulant (LA), anticardiolipin (aCL) and anti β2-Glycoprotein 1 (aβ2GP1) ...antibodies allow physicians to allocate patients into classification (risk) categories. Objectives To measure antibodies of IgG isotype directed towards Domain 4/5 (Dm4/5) of β2GP1. Patients/Methods. In this cross-sectional study we measured IgG aβ2GP1-Dm4/5 in a group of individuals 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). Results Geometric mean and standard deviation of IgG aβ2GP1 values expressed as Chemiluminescent Units (CU) in triple, double, single positive groups and in 40 healthy individuals were 1795 ± 783, 321 ± 181, 29 ± 8 and 5.0 ± 1.0, respectively (ANOVA p < 0.0001). Geometric mean and standard deviation of IgG aβ2GP1-Dm4/5 expressed as Optical Density (OD) in triple, double and single positive groups and in 40 healthy individuals were 0.16 ± 0.13, 0.16 ± 0.15 and 0.26 ± 0.15, 0.13 ± 0,11, respectively (ANOVA p < 0.002). Individuals in the single positive group, expressed significantly higher values with respect to triple (p = 0.04) and double (p = 0.03) positive groups. Approximate OD cut-off value (99° percentile) calculated in 40 normal control subjects is 0.404. Positivity to IgG aβ2GP1-Dm4/5 according to this cutoff was found in only 5 individuals, 3 in triple positive and 2 in single positive groups and was not associated with thromboembolism. Conclusion Mean level of IgG aβ2GP1-Dm4/5 is higher in single positive group. There is no association between positivity to IgG aβ2GP1-Dm4/5 and thromboembolic events.
Antiphospholipid syndrome (APS) is diagnosed in the presence of vascular thrombosis or pregnancy morbidity occurring in patients with circulating antiphospholipid antibodies (lupus anticoagulant LA ...and/or IgG/IgM anticardiolipin aCL and/or IgG/IgM anti-β2glycoprotein I aβ2GPI antibodies). Each test may identify different autoantibodies; a single test makes the diagnosis possible when positive on two or more occasions at least 12 weeks apart. However, single test positivity may be unrelated to pathogenic antibodies, which are now considered to be a subclass of aβ2GPI antibodies directed against the domain I of this protein. Conversely, all three positive tests identify a single class of aβ2GPI antibodies, thus identifying high-risk patients with APS.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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