Diluted Russell Viper Venom Time (dRVVT) has become the most popular test to detect Lupus Anticoagulant (LA). dRVVT is more sensitive than other global tests employed to detect LA and is not affected ...by inhibitors of factor VIII or IX. The test is most successfully implemented if you observe three steps in its execution: screening, mixing, and confirmatory studies. Interference due to the presence of heparin in tested plasma must be excluded by means of thrombin time (TT). The prior use of Vitamin K Antagonists (VKAs) or Non-vitamin K Oral Anticoagulants (NOACs) must also be evaluated by means of International Normalized Ratio, or specific tests, respectively.
Objective
To evaluate the subsequent rate of thrombosis among women with obstetric antiphospholipid syndrome (Ob‐APS) in a multicentre database of antiphospholipid antibody (aPL)‐positive patients, ...and the clinical utility of the adjusted Global Antiphospholipid Syndrome Score (aGAPSS), a validated tool to assess the likelihood of developing new thrombosis, in this group of patients.
Design
Retrospective study.
Setting
The Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking Clinical Database and Repository.
Population
Women with Ob‐APS.
Methods
Comparison of clinical and laboratory characteristics and measurement of aGAPSS in women with Ob‐APS, with or without thrombosis, after initial pregnancy morbidity (PM).
Main outcome measures
Risk factors for thrombosis and aGAPSS.
Results
Of 550 patients, 126 had Ob‐APS; 74/126 (59%) presented with thrombosis, and 47 (63%) of these women developed thrombosis after initial PM, in a mean time of 7.6 ± 8.2 years (4.9/100 patient years). Younger age at diagnosis of Ob‐APS, additional cardiovascular risk factors, superficial vein thrombosis, heart valve disease, and multiple aPL positivity increased the risk of first thrombosis after PM. Women with thrombosis after PM had a higher aGAPSS compared with women with Ob‐APS alone median 11.5 (4–16) versus 9 (4–13); P = 0.0089.
Conclusion
Based on a retrospective analysis of our multicentre aPL database, 63% of women with Ob‐APS developed thrombosis after initial obstetric morbidity; additional thrombosis risk factors, selected clinical manifestations, and high‐risk aPL profile increased the risk. Women with subsequent thrombosis after Ob‐APS had a higher aGAPSS at entry to the registry. We believe that aGAPSS is a valid tool to improve risk stratification in aPL‐positive women.
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More than 60% of women with obstetric antiphospholipid syndrome had thrombosis after initial pregnancy morbidity.
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More than 60% of women with obstetric antiphospholipid syndrome had thrombosis after initial pregnancy morbidity.
Most investigators currently advocate prophylactic-dose heparin plus low-dose aspirin as the preferred treatment of otherwise healthy women with obstetric antiphospholipid syndrome, whilst women with ...a history of vascular thrombosis alone or associated with pregnancy morbidity are usually treated with therapeutic heparin doses in association with low-dose aspirin in an attempt to prevent both thrombosis and pregnancy morbidity. However, the protocols outlined above fail in about 20 % of pregnant women with antiphospholipid syndrome. Identifying risk factors associated with pregnancy failure when conventional therapies are utilized is an important step in establishing guidelines to manage these high-risk patients. Some clinical and laboratory risk factors have been found to be related to maternal–foetal complications in pregnant women on conventional therapy. However, the most efficacious treatments to administer to high-risk antiphospholipid syndrome women in addition to conventional therapy in order to avoid pregnancy complications are as yet unestablished. This is a comprehensive review on this topic and an invitation to participate in a multicentre study in order to identify the best additional treatments to be used in this subset of antiphospholipid syndrome patients.
Venous or arterial thrombosis or pregnancy morbidity in the presence of circulating antiphospholipid antibodies (aPL) define the antiphospholipid syndrome (APS). In terms of accepted APS criteria, ...aPL are detected by one coagulation test (lupus anticoagulant; LAC) and two immunoassays (anticardiolipin antibodies and anti-β2-glycoptrotein I antibodies). In patients with APS, a single positive test carries a much lower risk of thrombosis recurrence or new pregnancy loss than does multiple (or triple) positivity. The same holds true for aPL carriers, namely subjects with laboratory tests but without clinical criteria for APS. Thus, very different risk categories exist among patients with APS as well as in carriers of aPL. Triple positivity apparently identifies the pathogenic autoantibody (antidomain I-II of β2-glycoptrotein I); it is in this category of patients that trials on new therapeutic strategies should focus.
Abstract Among the so called antiphospholipid (aPL) antibodies Lupus Anticoagulant (LAC) is considered the strongest risk factor for thromboembolic events. In individuals without a previous ...thromboembolic event (carriers), LAC is a risk factor when associated with the presence of anticardiolipin (aCL) and aβ2-Glycoprotein I (aβ2GPI) antibodies. On the other hand, data on carriers of isolated LAC positivity are sparse and inconclusive. The aim of this study was to prospectively determine the incidence of thrombosis in a cohort of carriers of isolated LAC positivity. One-hundred seventy-nine carriers of LAC confirmed twelve weeks apart and in a reference laboratory were studied. During a total follow up of 552 person-years, there were seven thromboembolic events (1.3% person-y). All the seven patients had at least one adjunctive major risk factor for thrombosis. The cumulative incidence of thromboembolic events was 3.1% (95% CI 0.6-5.6) after 2 years, and 5.9% (95% CI 1.2-10.6) after 5 and 10 years. On a multivariate regression analysis considering age, sex, autoimmune disease, risk factors for arterial and venous thrombosis, use of aspirin, only age was found to be an independent predictor of thromboembolic events (HR = 1.1, 95% CI 1.0-1.2, p = 0.02). These data might be relevant in clinical practice and underline the importance of differentiating LAC carriers in terms of isolated positivity or positivity associated with the presence of antibodies to aCL and β2-glycoprotein I.
Objective
Although systemic lupus erythematosus (SLE) is the most common autoimmune disease associated with antiphospholipid antibodies (aPL), limited data exist regarding the impact of SLE on the ...clinical phenotype of aPL‐positive patients. The primary objective of this study was to compare the clinical, laboratory, and treatment characteristics of aPL‐positive patients with SLE with those of aPL‐positive patients without SLE.
Methods
A secure web‐based data capture system was used to store patient demographic characteristics and aPL‐related clinical and laboratory characteristics. Inclusion criteria included positive aPL according to the updated Sapporo classification criteria. Antiphospholipid antibody–positive patients fulfilling the American College of Rheumatology criteria for the classification of SLE (“aPL with SLE”) and those with no other autoimmune diseases (“aPL only”) were included in the analysis.
Results
Six hundred seventy‐two aPL‐positive patients were recruited from 24 international centers; 426 of these patients did not have other autoimmune disease, and 197 had SLE. The frequency of thrombocytopenia, hemolytic anemia, low complement levels, and IgA anti–β2‐glycoprotein I (anti‐β2GPI) antibodies was higher in the aPL‐positive patients with SLE, whereas the frequency of cognitive dysfunction and IgG anti‐β2GPI antibodies was higher in the aPL‐only group. The frequency of arterial and venous thromboses (including recurrent) as well as pregnancy morbidity was similar in the 2 groups. The prevalence of cardiovascular disease risk factors at the time of entry into the registry entry did not differ between the 2 groups, with the exception of current smoking, which was more frequent in aPL‐positive patients with SLE.
Conclusion
Although the frequencies of thrombosis and pregnancy morbidity are similar in aPL‐positive patients with and those without SLE, the diagnosis of SLE in patients with persistently positive aPL is associated with an increased frequency of thrombocytopenia, hemolytic anemia, low complement levels, and positive IgA anti‐β2GPI antibodies.
Objective
This study aimed to use cluster analysis (CA) to identify different clinical phenotypes among antiphospholipid antibodies (aPL)-positive patients.
Methods
The Alliance for Clinical Trials ...and International Networking (APS ACTION) Registry includes persistently positive aPL of any isotype based on the Sydney antiphospholipid syndrome (APS) classification criteria. We performed CA on the baseline characteristics collected retrospectively at the time of the registry entry of the first 500 patients included in the registry. A total of 30 clinical data points were included in the primary CA to cover the broad spectrum of aPL-positive patients.
Results
A total of 497 patients from international centres were analysed, resulting in three main exclusive clusters: (a) female patients with no other autoimmune diseases but with venous thromboembolism (VTE) and triple-aPL positivity; (b) female patients with systemic lupus erythematosus, VTE, aPL nephropathy, thrombocytopaenia, haemolytic anaemia and a positive lupus anticoagulant test; and (c) older men with arterial thrombosis, heart valve disease, livedo, skin ulcers, neurological manifestations and cardiovascular disease (CVD) risk factors.
Conclusions
Based on our hierarchical cluster analysis, we identified different clinical phenotypes of aPL-positive patients discriminated by aPL profile, lupus or CVD risk factors. Our results, while supporting the heterogeneity of aPL-positive patients, also provide a foundation to understand disease mechanisms, create new approaches for APS classification and ultimately develop new management approaches.
The challenges of lupus anticoagulants Chighizola, Cecilia Beatrice; Raschi, Elena; Banzato, Alessandra ...
Expert review of hematology,
04/2016, Letnik:
9, Številka:
4
Journal Article
Recenzirano
The term "lupus anticoagulant" (LA) refers to a heterogeneous group of immunoglobulins behaving as acquired in vitro inhibitors of coagulation. These antibodies, namely anti-β2GPI and ...anti-prothrombin antibodies, induce the in vitro elongation of clotting time interfering with phospholipid-dependent coagulation cofactors. Positive LA is associated with thrombosis and pregnancy complications, providing one of the three laboratory criteria for the classification of the anti-phospholipid syndrome. LA is the strongest predictor of clinical events, especially when associated with other anti-phospholipid antibodies. Much more controversial is the risk conveyed by isolated and weak LA. LA detection is technically laborious, envisaging screening, mixing and confirming tests. Hopefully critical issues in LA detection, such as the interference of anticoagulants, will be overcome, in the next future.
A unique coagulation inhibitor prolonging whole-blood clotting time was described more than 50 years ago in two patients with systemic lupus erythematosus (SLE). The immunoglobulin nature of the ...inhibitor and its interaction with antiphospholipid antibodies was later demonstrated and the term "lupus anticoagulant (LA)" was coined to describe this laboratory finding. It soon became apparent that LA was a misnomer as it is often found in plasma from patients with clinical conditions other than SLE and is associated with thromboembolic events that may occur in otherwise healthy individuals. Individuals with LA have circulating autoantibodies that inhibits blood coagulation. These are mostly of IgG or IgM class and mainly directed against a phospholipid (PL)-binding plasma protein, β2-glycoprotein I (β2GPI). The presence of β2GPI-dependent LA represents a well-recognized risk factor for venous and arterial thromboembolism, as well as pregnancy loss and morbidity. β2GPI-dependent LA in the presence of documented previous thromboembolism, or history of pregnancy loss/morbidity, identifies definite anti-PL syndrome. Laboratory diagnosis of LA is thus of particular importance, as it may assign patients with a common event (thrombosis) to a group with a high risk for recurrence, which is a prerequisite for long-term oral antithrombotic treatment.
The APS ACTION International Clinical Database and Repository includes a secure web-based data capture system storing patient information including demographics, antiphospholipid antibodies ...(aPL)-related medical history, and aPL tests. Despite efforts at harmonization, inter-assay variability remains a problem in aPL testing. As a clinical repository open to researchers, ensuring comparability between assays and consistency in results between APS ACTION laboratories is essential to the validity of studies emerging from this network.
To assess the level of agreement between an aPL-registry inclusion and core laboratory (core lab) anticardiolipin antibody (aCL) and anti-β2-glycoprotein-I antibody (aβ2GPI) ELISA testing results.
Patients are recruited from 25 international centers based on positive aPL tests at inclusion. All samples are retested at the corresponding national APS ACTION core lab to confirm aPL positivity based on standard validated protocols. We analysed the categorical agreement, degree of linear association, and correlation between inclusion (local laboratory) and core lab aPL tests. Samples were included in this study only if results of aPL testing with ELISA at baseline were available.
497 registry samples underwent confirmatory aPL tests. Categorical agreement between the inclusion and core lab values, as expressed by Cohen's kappa coefficients, ranged between 0.61 and 0.80 (as substantial agreement). The correlation between quantitative results in the aCL and aβ2GPI was better for IgM and IgA compared to IgG (Spearman rho 0.789 and 0.666 vs. 0.600 for aCL and rho 0.892 and 0.744 vs. 0.432 for aβ2GPI).
The results of inclusion for aCL and aβ2GPI tests used for recruitment into the registry were in agreement to the results obtained by the APS ACTION core laboratories; aCL and aβ2GPI results showed very good categorical agreement. This agreement increased when considering high titer (>40 units) samples. APS ACTION is a reliable and useful research resource for APS.
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