Towards evidence-based treatment of thrombotic antiphospholipid syndrome

Lupus ◽  
2010 ◽  
Vol 19 (4) ◽  
pp. 470-474 ◽  
Author(s):  
Rhwm Derksen ◽  
PG de Groot

Thrombosis in the presence of persistently positive tests for antiphospholipid antibodies is termed thrombotic antiphospholipid syndrome (APS). At present, ‘standard’ secondary thromboprophylaxis in thrombotic APS is treatment with moderate intensity oral anticoagulants for life after a first venous thrombosis and with high intensity oral anticoagulation after non-embolic ischaemic stroke. These recommendations differ from those applied in the general population, where a restricted period of anticoagulation is common practice after venous thrombosis and antiplatelet drugs are the first choice after ischaemic stroke. From an extensive literature review we conclude that the available data are insufficient to apply a different strategy for secondary thromboprophylaxis in patients with thrombotic APS than the one that holds for the general population.

2017 ◽  
Vol 44 (05) ◽  
pp. 419-426 ◽  
Author(s):  
Cecilia Chighizola ◽  
Maria Raimondo ◽  
Pier Meroni

AbstractPersistent serum positivity for antiphospholipid antibodies (aPL) is required to diagnose antiphospholipid syndrome (APS), an autoimmune disease characterized by recurrent vascular thrombosis and/or pregnancy morbidity. The current therapeutic management of patients with thrombotic APS aims at preventing recurrences and long-term complications by attenuating the procoagulant state. There is overall consensus to reserve moderate-intensity anticoagulation to aPL-positive patients with a previous venous thrombosis; the therapeutic options for those with a history of arterial event comprise antiplatelet agents and high-intensity anticoagulation. Unfortunately, thrombotic occurrences might occur despite adequate anticoagulation, carrying a significant burden of morbidity and mortality. The management of refractory thrombotic APS and catastrophic APS is still not clear, warranting the issue of recommendations. Vitamin-K antagonists are limited by significant side effects, and a careful weighting of risks and benefits should be performed to reserve the optimal treatment to each patient. To overcome these limitations, novel oral anticoagulants have been introduced in the market, but their efficacy in thrombotic APS has still to be unraveled. The poor safety profile and the scarce efficacy of drugs acting on the coagulation cascade explain why novel therapeutic approaches are currently under investigation, to identify pharmacological tools specifically counteracting aPL-mediated prothrombotic effects.


1997 ◽  
Vol 77 (05) ◽  
pp. 0839-0844 ◽  
Author(s):  
Vittorio Pengo ◽  
Fabio Barbero ◽  
Alberto Banzato ◽  
Elisabetta Garelli ◽  
Franco Noventa ◽  
...  

SummaryBackground. The long-term administration of oral anticoagulants to patients with mechanical heart valve prostheses is generally accepted. However, the appropriate intensity of oral anticoagulant treatment in these patients is still controversial.Methods and Results. From March 1991 to March 1994, patients referred to the Padova Thrombosis Center who had undergone mechanical heart valve substitution at least 6 months earlier were randomly assigned to receive oral anticoagulants at moderate intensity (target INR = 3) or moderate-high intensity (target INR = 4). Principal end points were major bleeding, thromboembolism and vascular death. Minor bleeding was a secondary end-point.A total of 104 patients were assigned to the target 3 group and 101 to the target 4 group; they were followed for from 1.5 years to up 4.5 years (mean, 3 years). Principal end-points occurred in 13 patients in the target 3 group (4 per 100 patient-years) and in 20 patients in the target 4 group (6.9 per 100 patient-years). Major hemorrhagic events occurred in 15 patients, 4 in the target 3 group (1.2 per 100 patient-years) and 11 in the target 4 group (3.8 per 100 patient-years) (p = 0.019). The 12 recorded episodes of thromboembolism, 4 of which consisted of a visual deficit, were all transient ischemic attacks, 6 in the target 3 group (1.8 per 100 patient-years) and 6 in the target 4 group (2.1 per 100 patient- years). There were 3 vascular deaths in each group (0.9 and 1 per 100 patient-years for target 3 and target 4 groups, respectively). Minor bleeding episodes occurred 85 times (26 per 100 patient-years) in the target 3 group and 123 times (43 per 100 patient-years) in the target 4 group (p = 0.001).Conclusions. Mechanical heart valve patients on anticoagulant treatment who had been operated on at least 6 months earlier experienced fewer bleeding complications when maintained on a moderate intensity regimen (target INR = 3) than those on a moderate-high intensity regimen (target INR = 4). The number of thromboembolic events and vascular deaths did not differ between the two groups.


BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sara Esmaeili ◽  
Meysam Abolmaali ◽  
Sobhan Aarabi ◽  
Mohammad Reza Motamed ◽  
Samira Chaibakhsh ◽  
...  

Abstract Background New Oral Anticoagulants (NOACs) such as Rivaroxaban are introduced as alternatives to conventional vitamin-K antagonists in the long-term treatment of thrombotic events due to their lower bleeding risk. There is a lack of evidence on the effectiveness and safety of Rivaroxaban in Cerebral venous thrombosis (CVT). This study aims to assess the effectiveness and bleeding risk of Rivaroxaban in comparison with Warfarin for the treatment of CVT. Materials and methods 36 patients with diagnosis of CVT were included. Clinical and background information was assessed on admission and patients were followed for at least 12 months. Measured outcomes were modified Rankin Scale (mRS), evidence of recanalization on contrast-enhanced Brain MR venography (MRV) and major or minor bleeding. Patients were divided into two groups according to the type of oral anticoagulant (Rivaroxaban vs Warfarin). Groups were compared in terms of final outcomes and side effects. Result Overall, 13 (36.11%) patients received Warfarin and 23 (63.89%) received Rivaroxaban. Optimal mRS score (0–1) was attained in 9 of 10 (90%) of patients treated with Rivaroxaban and 19 of 22 (86.36%) of patients received Warfarin. MRV showed complete or partial recanalization in 12 of 14 (85.71%) patients treated with Rivaroxaban and all patients in the Warfarin group. There was no significant difference between the two groups in terms of major and minor hemorrhage. Conclusion Rivaroxaban holds promise for the treatment of CVT.


BMJ Open ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. e043963
Author(s):  
Jorge López Fernández ◽  
Alejandro López-Valenciano ◽  
Xián Mayo ◽  
Elizabeth Horton ◽  
Ivan Clavel ◽  
...  

Objectives(1) To describe the physical activity (PA) levels of the members of a Spanish leisure centre operator according to age and gender; (2) to describe the differences in the three PA levels between the members of a Spanish leisure centre operator and the general Spanish population considering the PA Eurobarometer data according to their gender and age and (3) to explore the intensity origin of the PA either in Spanish members of leisure centres or the Spanish population considering their gender.DesignDescriptive epidemiology study.ParticipantsData from 16 Spanish leisure centres (n=3627) and from the 2017 Eurobarometer 472 for Spain (n=1002) were used for this research.Primary and secondary outcomes measuresThe PA levels were analysed with the International Physical Activity Questionnaire short version, and respondents were grouped into physical inactivity (PIA), moderate-PA and high-PA. Moreover, gender (men or women) and age (18–29 years; 30–44 years; 45–59 years; 60–69 years; ≥70 years) were considered. Total metabolic equivalent (MET)-min/week, as well as total MET-min/week for walking intensity, moderate intensity and vigorous intensity were recorded.ResultsLeisure centres showed a lower prevalence of PIA and a higher prevalence of high-PA than the general population (p<0.05). Women displayed a higher prevalence of PIA and lower prevalence of high-PA than men (p<0.05). The prevalence of PIA increases with age while the prevalence of high-PA decreases.ConclusionLeisure centres engage most of their members in regular PA, including women and older adults, and these members also perform a higher number of MET in vigorous PA, than the general population.


1984 ◽  
Vol 55 (3) ◽  
pp. 251-253 ◽  
Author(s):  
Bart A. Swierstra ◽  
Frank J. van Oosterhout ◽  
Bert Ausema ◽  
Willem H. Bakker ◽  
Willem B. van der Pompe ◽  
...  

2018 ◽  
Vol 118 (12) ◽  
pp. 2162-2170 ◽  
Author(s):  
Kamilla Steensig ◽  
Kevin Olesen ◽  
Troels Thim ◽  
Jens Nielsen ◽  
Svend Jensen ◽  
...  

Background Patients with atrial fibrillation (AF) have an increased risk of ischaemic stroke. The risk can be predicted by the CHA2DS2-VASc score, in which the vascular component refers to previous myocardial infarction, peripheral artery disease and aortic plaque, whereas coronary artery disease (CAD) is not included. Objectives This article explores whether CAD per se or extent provides independent prognostic information of future stroke among patients with AF. Materials and Methods Consecutive patients with AF and coronary angiography performed between 2004 and 2012 were included. The endpoint was a composite of ischaemic stroke, transient ischaemic attack and systemic embolism. The risk of ischaemic events was estimated according to the presence and extent of CAD. Incidence rate ratios (IRR) were calculated in reference to patients without CAD and adjusted for parameters included in the CHA2DS2-VASc score and treatment with anti-platelet agents and/or oral anticoagulants. Results Of 96,430 patients undergoing coronary angiography, 12,690 had AF. Among patients with AF, 7,533 (59.4%) had CAD. Mean follow-up was 3 years. While presence of CAD was an independent risk factor for the composite endpoint (adjusted IRR, 1.25; 1.06–1.47), extent of CAD defined as 1-, 2-, 3- or diffuse vessel disease did not add additional independent risk information. Conclusion Presence, but not extent, of CAD was an independent risk factor of the composite thromboembolic endpoint beyond the components already included in the CHA2DS2-VASc score. Consequently, we suggest that significant angiographically proven CAD should be included in the vascular disease criterion in the CHA2DS2-VASc score.


2017 ◽  
Vol 76 (9) ◽  
pp. 1544-1549 ◽  
Author(s):  
Elizabeth V Arkema ◽  
Elisabet Svenungsson ◽  
Mia Von Euler ◽  
Christopher Sjöwall ◽  
Julia F Simard

ObjectiveTo study the occurrence of ischaemic and haemorrhagic stroke in systemic lupus erythematosus (SLE) compared with the general population by age, sex and time since SLE diagnosisMethodsAdults with incident SLE were identified from the Swedish National Patient Register (NPR, n=3390) and general population comparators from the Total Population Register were matched on age, sex and county (n=16730). Individuals were followed prospectively until first of death, December 2013, emigration or incident stroke (identified from the NPR, Cause of Death Register and the Stroke Register). Incidence rates, rate differences and HR were estimated comparing SLE with non-SLE. Estimates were stratified by sex, age and time since diagnosis.ResultsWe observed 126 strokes in SLE and 304 in the general population. Individuals with SLE had a twofold increased rate of ischaemic stroke compared with the general population (HR 2.2; 95% CI 1.7 to 2.8). The HR for intracerebral haemorrhage was 1.4 (95% CI 0.7 to 2.8). There was effect modification by sex and age, with the highest HRs for females and individuals <50 years old. The HR for ischaemic stroke was highest in the first year of follow-up (3.7; 95% CI 2.1 to 6.5).ConclusionsThe relative risk of ischaemic stroke in SLE was more than doubled compared with the general population, and importantly, the highest relative risks were observed within the first year after SLE diagnosis. Thus, the first encounter with patients presents an opportunity for rheumatologists to screen for risk factors and intervene.


2012 ◽  
Vol 56 (5) ◽  
pp. 2598-2603 ◽  
Author(s):  
Wei Liu ◽  
Yi Sun ◽  
Wei Chen ◽  
Weixia Liu ◽  
Zhe Wan ◽  
...  

ABSTRACTWith voriconazole (VRC) being approved as the first choice in treating invasive aspergillosis (IA) and its increasing use in treatment, a VRC-resistant strain ofAspergillus flavus, the second leading cause of IA afterAspergillus fumigatus, has emerged. The VRC-resistant strain ofA. flavuswas isolated for the first time from the surgical lung specimen of an IA patient with no response to VRC therapy. In order to ascertain the mechanism of VRC resistance, the azole target enzyme genes in this strain ofA. flavuswere cloned and sequenced, and 4 mutations generating amino acid residue substitutions were found in thecyp51Cgene. To further determine the role of this mutated gene for VRC resistance inA. flavus, anAgrobacterium tumefaciens-mediated gene replacement approach was applied. Consequently, the mutatedcyp51Cgene from thisA. flavusstrain was proven to confer the VRC resistance. Finally, to discern the one out of the four mutations in thecyp51Cgene that is responsible for contributing to VRC resistance, a site-directed gene mutagenesis procedure combined with a gene replacement method was performed. As a result, the T788G missense mutation in thecyp51Cgene was identified as responsible for VRC resistance inA. flavus. These findings indicated that the detection of this mutation inA. flavuscould serve as an indicator for physicians to avoid the use of VRC during IA treatment. Further comprehensive surveillance for antifungal susceptibility, as well as intensive study on the mechanism of azole resistance inA. flavuscausing IA, would be required to fully understand this mechanism.


2015 ◽  
Vol 2015 ◽  
pp. 1-3 ◽  
Author(s):  
Murat Sahin ◽  
Ayten Oguz ◽  
Dilek Tuzun ◽  
Serife Nur Boysan ◽  
Bülent Mese ◽  
...  

Background. Antiphospholipid syndrome (APS) characterized by thrombosis and abortus may rarely cause primary adrenal failure.Case Presentations. A 34-year-old male presented with hypotension, hypoglycemia, hyperpigmentation on his skin and oral mucosa, scars on both legs, and loss of consciousness. In laboratory examinations, hyponatremia (135 mmol/L), hyperpotassemia (6 mmol/L), and thrombocytopenia (83 K/µL) were determined. Cortisol (1.91 µg/dL) and adrenocorticotropic (550 pg/mL) hormone levels were also evaluated. The patient was hospitalized with a diagnosis of acute adrenal crisis due to primary adrenal insufficiency. A Doppler ultrasound revealed venous thrombosis. The patient was diagnosed with antiphospholipid syndrome after the detection of venous thrombosis, thrombocytopenia, elevated aPTT, and anticardiolipin antibody levels. Anticoagulation treatment was started for antiphospholipid syndrome. The patient is now following up with hydrocortisone, fludrocortisone, and warfarin sodium.Conclusion. Antiphospholipid syndrome is a rare reason for adrenal failure. Antiphospholipid syndrome should be suspected if patients have morbidity secondary to venous-arterial thrombosis.


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