Introduction
Coronavirus disease (COVID‐19) is associated with a high incidence of thrombosis and mortality despite standard anticoagulant thromboprophylaxis. There is equipoise regarding the optimal ...dose of anticoagulant intervention in hospitalized patients with COVID‐19 and consequently, immediate answers from high‐quality randomized trials are needed.
Methods
The World Health Organization's International Clinical Trials Registry Platform was searched on June 17, 2020 for randomized controlled trials comparing increased dose to standard dose anticoagulant interventions in hospitalized COVID‐19 patients. Two authors independently screened the full records for eligibility and extracted data in duplicate.
Results
A total of 20 trials were included in the review. All trials are open label, 5 trials use an adaptive design, 1 trial uses a factorial design, 2 trials combine multi‐arm parallel group and factorial designs in flexible platform trials, and at least 15 trials have multiple study sites. With individual target sample sizes ranging from 30 to 3000 participants, the pooled sample size of all included trials is 12 568 participants. Two trials include only intensive care unit patients, and 10 trials base patient eligibility on elevated D‐dimer levels. Therapeutic intensity anticoagulation is evaluated in 14 trials. All‐cause mortality is part of the primary outcome in 14 trials.
Discussion
Several trials evaluate different dose regimens of anticoagulant interventions in hospitalized patients with COVID‐19. Because these trials compete for sites and study participants, a collaborative effort is needed to complete trials faster, conduct pooled analyses and bring effective interventions to patients more quickly.
Objective
The aim of the study was to describe clinical and biological characteristics and thrombotic relapses of patients diagnosed with antiphospholipid syndrome (APS) after the age of 65 years, in ...comparison with patients diagnosed with APS before 65.
Methods
This retrospective multicenter study was performed to 2005 from 2017 and included patients diagnosed with APS after the age of 65 years, in accordance with Sydney criteria. We compared these patients with APS patients diagnosed before the age of 65 years, and with control thrombotic patients older than 65 years.
Results
Fifty-eight APS patients over the age of 65 years were compared to 127 APS patients aged less than 65 and to 58 controls. In elderly APS versus younger APS, there was a male predominance (58.6% vs 36.2% p = .001); myocardial infarction and lower limb deep vein thrombosis (LLDVT) were more frequent in elderly, respectively, 12.1% versus 1.6% (p = .005), and 44.8% versus 29.9% (p = .048). Anticardiolipin antibody (aCL) IgM was more frequently found in old patients compared to younger patients (33.9% vs 18.1%, p = .02), contrary to lupus anticoagulant (LAC) (52.8% vs 66.9%, p = .02). Older patients were more often diagnosed with single positive APS (82.8% vs 59.8% p = .002). The thrombotic relapse free survival was lower in elderly APS patients (p = .044) compared to younger APS. Elderly APS patients had more recurrent arterial and venous thrombosis (p = .03) and had poorer overall survival (p = .004) than elderly controls.
Conclusion
In this study, APS was different in patients aged more than 65 years, with a male predominance and more myocardial infarctions and LLDVT at diagnosis. Single antiphopholipid positivity and aCL IgM were more frequent in older patients. Older patient with APS had more thrombotic recurrence during follow-up. Compared to elderly controls, elderly APS patients had more thrombosis recurrences and poorer survival.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
To investigate the validity of the global APS score (GAPSS) to predict thrombosis in patients with autoimmune diseases.
This prospective cohort study included consecutive patients with aPL or SLE. ...aPL, aPS-PT and GAPSS were determined. A Cox proportional hazards model assessed the validity of GAPSS and identified other potential independent predictors of thrombosis.
One hundred and thirty-seven patients 43.5 (s.d. 15.4) years old; 107 women were followed up for a mean duration of 43.1 (s.d. 20.7) months. Mean GAPSS was significantly higher in patients who experienced a thrombotic event compared with those without 10.88 (s.d. 5.06) vs 8.15 (s.d. 5.31), respectively, P = 0.038. In univariate analysis, age hazard ratio (HR) = 1.04 (95% CI 1.01, 1.08) and GAPSS above 16 HR = 6.86 (95% CI 1.90, 24.77) were each significantly associated with thrombosis during follow-up, while history of arterial thrombosis HR = 2.61 (95% CI 0.87, 7.82) failed to reach significance. Among aPL assays, IgG aPS/PT--a component of the GAPSS--was significantly associated with thrombosis HR = 2.95 (95% CI 1.02, 8.51). In multivariate analysis, GAPSS above 16 remained the only significant predictor of thrombosis HR = 6.17 (95% CI 1.70, 22.40).
This first external validation study confirmed that GAPSS can predict thrombosis in patients with aPL and associated autoimmune diseases.
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.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The gold standard for secondary thromboprophylaxis in APS is long term anticoagulation with vitamin K antagonists (VKAs). Because of their widespread use and potential advantages of directs oral ...anticoagulants (DOACs) over VKAs, they have been prescribed in APS without definitive evidence of their safety and efficacy in this context. Recent specific randomized controlled trials (RCT) in APS and results from pivotal RCTs comparing DOACs vs VKAs are now available. Their results are conflicting but these studies have been conducted in different APS populations.
To summarize available data from RCT and determine risks of recurrent thrombosis and bleeding.
Four studies were included and 23 and 10 thrombotic events were recorded among 282 and 294 APS patients treated with DOACs and warfarin respectively. Overall recurrent thrombotic events were not significantly increased during DOACs treatment (OR = 2.22 95% CI, 0.58–8.43) compared to VKAs. However, when different types of thrombosis were analyzed separately, there was an increased risk of recurrent arterial thrombosis (5.17 95% CI, 1.57–17.04) with DOACs compared to warfarin but no significant higher risk of venous thrombosis (OR 0.69 95% CI, 0.23–2.06). No increased risk of bleeding was found.
In APS patients treated with DOACs compared to those treated with warfarin, no evidence of a higher risk of recurrent venous thromboembolism was found however there was a significantly increased risk of recurrent arterial thrombosis. Moreover risk of recurrent arterial thrombosis tended to be more frequent in patients with a history of arterial thrombosis. These results are in line with international guidelines which recommend not to use DOACs in APS patients with a history of arterial thrombosis but raise the question of the efficacy of DOACs to prevent venous thrombosis in a subset of APS patients without a history of arterial thrombosis.
•APS patients had more arterial recurrent thromboses with DOACs than with VKAs (80).•No increased risk of recurrent venous thrombosis was found for DOACs over VKAs (81).•A trend for an increased risk of overall thrombosis on DOACs was not significant (83).
Unexpected cause of bleeding Dufrost, Virginie; Risse, Jessie, MD; Malgras, Aurélie, MD ...
The American journal of medicine,
09/2017, Letnik:
130, Številka:
9
Journal Article
Background
The cornerstone of thrombotic antiphospholipid syndrome (APS) patients’ management is to prevent recurrent thrombosis by long-term anticoagulation.
Purpose of review
The purpose of the ...review is to summarize available literature on direct oral anticoagulants (DOACs) use in APS patients through a systematic review and to determine factors associated with thrombosis recurrence.
Recent findings
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.
Summary
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.
Antiphospholipid syndrome (APS) is a condition in which the presence of antibodies against phospholipid-binding proteins is associated with thrombophilia and/or pregnancy morbidity. Although ...antiphospholipid antibodies have anticoagulant characteristics in vitro, they are associated with thromboembolic complications. Thrombin generation (TG) is a sensitive global test of coagulation, and elevated TG is associated with thrombosis. Increased TG can be caused by increased prothrombin conversion, decreased thrombin inactivation, or a combination of both. In this study, we measured TG in APS patients and healthy controls with and without vitamin K antagonist (VKA) treatment at 1 and 5 pM tissue factor and with thrombomodulin. Prothrombin conversion and thrombin inactivation were determined by thrombin dynamics analysis. The TG peak was increased in nontreated APS patients at 1 pM TF compared with nontreated controls. Prothrombin conversion was significantly increased in nontreated APS patients. In contrast, prothrombin conversion did not differ in controls and patients that were on VKA therapy. Thrombin inactivation was comparable between controls and APS patients in the presence and absence of VKAs. Both TG (peak and ETP) and prothrombin conversion were significantly higher in APS patients with prior thrombosis compared with patients without a history of thrombosis. In this study, we demonstrate that in APS, the hemostatic balance shifts toward a more prothrombotic phenotype due to elevated prothrombin conversion but unchanged thrombin inactivation rates. Within the group of APS patients, increased TG and prothrombin conversion are associated with a history of thrombosis.
•The rate of prothrombin conversion is elevated in APS patients, causing a hemostatic imbalance.•TG and prothrombin conversion are higher in APS patients with prior thrombosis than in patients without thrombosis.
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