RESUMEN
Systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS), and Sjögren's syndrome (SS) are heterogeneous autoimmune diseases. Severe manifestations and refractory/intolerance to conventional immunosuppressants demand other options, namely biological drugs, and small molecules. We aimed to define evidence and practice-based guidance for the off-label use of biologics in SLE, APS, and SS. Recommendations were made by an independent expert panel, following a comprehensive literature review and two consensus rounds. The panel included 17 internal medicine experts with recognized practice in autoimmune disease management. The literature review was systematic from 2014 until 2019 and later updated by cross-reference checking and experts' input until 2021. Preliminary recommendations were drafted by working groups for each disease. A revision meeting with all experts anticipated the consensus meeting held in June 2021. All experts voted (agree, disagree, neither agree nor disagree) during two rounds, and recommendations with at least 75% agreement were approved. A total of 32 final recommendations (20 for SLE treatment, 5 for APS, and 7 for SS) were approved by the experts. These recommendations consider organ involvement, manifestations, severity, and response to previous treatments. In these three autoimmune diseases, most recommendations refer to rituximab, which aligns with the higher number of studies and clinical experience with this biological agent. Belimumab sequential treatment after rituximab may also be used in severe cases of SLE and SS. Second-line therapy with baricitinib, bortezomib, eculizumab, secukinumab, or tocilizumab can be considered in SLE-specific manifestations. These evidence and practice-based recommendations may support treatment decision and, ultimately, improve the outcome of patients living with SLE, APS, or SS.
Asunto(s)
Síndrome Antifosfolípido , Productos Biológicos , Lupus Eritematoso Sistémico , Síndrome de Sjögren , Humanos , Síndrome Antifosfolípido/diagnóstico , Síndrome Antifosfolípido/tratamiento farmacológico , Síndrome de Sjögren/diagnóstico , Síndrome de Sjögren/tratamiento farmacológico , Rituximab/uso terapéutico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Productos Biológicos/uso terapéutico , Terapia BiológicaRESUMEN
BACKGROUND: The differential diagnosis of abdominal pain in pregnant women is broad. Liver diseases as the origin of abdominal pain in pregnancy are rare, and severe forms occur in less than 0.1% of pregnancies. Some disorders, such as hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome and preeclampsia, are unique to pregnancy, while others, such as antiphospholipid antibody syndrome, may manifest in pregnancy but have consequences beyond the current pregnancy. All of them require prompt identification and treatment. CASE PRESENTATION: A 27-year-old Caucasian woman who was 15+1 weeks pregnant reported to the emergency department twice due to stabbing right-upper-quadrant abdominal pain. Initial laboratory testing revealed mild leukocytosis and slightly elevated liver enzymes. On second presentation, the patient was febrile and had an increased C-reactive protein concentration. Over the course of the next days, nonhemolytic anemia and thrombocytopenia emerged with elevated liver enzymes. Coagulation studies also revealed a prolongation of activated partial thromboplastin time. Magnetic resonance imaging showed nonspecific alterations in the right liver lobe, possibly corresponding to infection or infarction. A hepatic viral infection was ruled out. At that time, the most likely diagnosis was cholangitis with liver abscess formation, and antibiotic therapy was started. Further worsening of the anemia and thrombocytopenia, development of proteinuria, together with a miscarriage on the fourth day of hospitalization resulted in the tentative diagnosis of (triple-positive) antiphospholipid antibody syndrome, which was confirmed 12 weeks after the initial investigation. Treatment consisted of prompt anticoagulation with heparin and later on with a vitamin K antagonist as well as high-dose glucocorticoid therapy. There was no need for intravenous immunoglobulin therapy or plasma exchange, although we suspected a catastrophic form of antiphospholipid antibody syndrome due to infarctions of the liver, placenta, and possibly kidneys (proteinuria). The outcome was favorable. CONCLUSION: We report a 27-year-old pregnant woman whose abdominal pain was caused by liver infarctions as the first manifestation of catastrophic antiphospholipid antibody syndrome. The antiphospholipid antibody syndrome was possibly secondary to hitherto clinically silent systemic lupus erythematosus since the antinuclear antibodies were increased later on. Hydroxychloroquine therapy was initiated to prevent antiphospholipid antibody syndrome recurrence in a future pregnancy.
Asunto(s)
Aborto Espontáneo , Síndrome Antifosfolípido , Síndrome HELLP , Infarto Hepático , Preeclampsia , Adulto , Síndrome Antifosfolípido/complicaciones , Síndrome Antifosfolípido/diagnóstico , Síndrome Antifosfolípido/tratamiento farmacológico , Femenino , Humanos , EmbarazoRESUMEN
Introduction: Some patients with positive antiphospholipid antibodies (aPL) have not been included in randomized clinical trials or observational registries and, therefore, information on their risk of obstetric or thrombotic recurrence and optimal treatment is scarce.Areas covered: In the present review, the existing evidence regarding the management of two laboratory scenarios not covered by the guidelines is presented: (1) patients with antiphospholipid syndrome (APS) clinical manifestations and aPL positivity not fulfilling APS laboratory criteria, and (2) the possibility of discontinuing anticoagulation in APS patients whose aPL become persistently negative.Expert opinion: Growing evidence suggests a role for low titers and 'non-criteria' aPL, especially in obstetric APS. Treatment is not formally recommended but might be considered according to the individual's risk profile. Regarding the question of whether or not to discontinue anticoagulants after the 'spontaneous' disappearance of aPL, there is no definite answer. Retrospective studies seem to suggest that withdrawal of anticoagulation could be safe in certain patients with APS, especially in those with a first provoked venous thrombosis and whose aPL became persistently negative during follow-up. Still, before the withdrawal can be recommended in routine clinical practice, multicenter and prospective studies are required to validate this hypothesis.
Asunto(s)
Síndrome Antifosfolípido , Trombosis , Anticuerpos Antifosfolípidos , Síndrome Antifosfolípido/diagnóstico , Síndrome Antifosfolípido/tratamiento farmacológico , Femenino , Humanos , Laboratorios , Estudios Multicéntricos como Asunto , Embarazo , Estudios Retrospectivos , Trombosis/etiología , Trombosis/prevención & controlAsunto(s)
Síndrome Antifosfolípido/tratamiento farmacológico , Inhibidores del Factor Xa/uso terapéutico , Rivaroxabán/uso terapéutico , Trombosis/tratamiento farmacológico , Síndrome Antifosfolípido/sangre , Síndrome Antifosfolípido/complicaciones , Coagulación Sanguínea/efectos de los fármacos , Humanos , Estudios Retrospectivos , Trombosis/sangre , Trombosis/etiología , Resultado del TratamientoRESUMEN
Ginger is known to have antiinflammatory and antioxidative effects and has traditionally been used as an herbal supplement in the treatment of various chronic diseases. Here, we report antineutrophil properties of 6-gingerol, the most abundant bioactive compound of ginger root, in models of lupus and antiphospholipid syndrome (APS). Specifically, we demonstrate that 6-gingerol attenuates neutrophil extracellular trap (NET) release in response to lupus- and APS-relevant stimuli through a mechanism that is at least partially dependent on inhibition of phosphodiesterases. At the same time, administration of 6-gingerol to mice reduces NET release in various models of lupus and APS, while also improving other disease-relevant endpoints, such as autoantibody formation and large-vein thrombosis. In summary, this study is the first to our knowledge to demonstrate a protective role for ginger-derived compounds in the context of lupus. Importantly, it provides a potential mechanism for these effects via phosphodiesterase inhibition and attenuation of neutrophil hyperactivity.
Asunto(s)
Catecoles/farmacología , Alcoholes Grasos/farmacología , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/inmunología , Neutrófilos/efectos de los fármacos , Neutrófilos/inmunología , Animales , Anticuerpos Antifosfolípidos/biosíntesis , Síndrome Antifosfolípido/tratamiento farmacológico , Síndrome Antifosfolípido/inmunología , Síndrome Antifosfolípido/metabolismo , Catecoles/sangre , Catecoles/farmacocinética , Modelos Animales de Enfermedad , Trampas Extracelulares/efectos de los fármacos , Trampas Extracelulares/inmunología , Alcoholes Grasos/sangre , Alcoholes Grasos/farmacocinética , Femenino , Humanos , Técnicas In Vitro , Lupus Eritematoso Sistémico/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Neutrófilos/metabolismo , Inhibidores de Fosfodiesterasa 4/farmacología , Inhibidores de Fosfodiesterasa/sangre , Inhibidores de Fosfodiesterasa/farmacocinética , Inhibidores de Fosfodiesterasa/farmacología , Fitoterapia , Especies Reactivas de Oxígeno/metabolismo , Trombosis de la Vena/tratamiento farmacológico , Trombosis de la Vena/patologíaRESUMEN
Functional tests for lupus anticoagulants (LA) as part of a thrombophilia workup are commonly performed in patients under anticoagulant therapy that may interfere with assay results. There is no consensus on how these tests should be assessed in patients on direct oral anticoagulants (DOACs). In this retrospective cohort study, we analysed data from patients with a history of thrombosis in whom dilute Russell viper venom time (dRVVT), LA-sensitive aPTT, and solid phase assays for antiphospholipid antibodies (aPL) were performed (n = 3,147, thereof 588 on rivaroxaban, 144 on apixaban, 1,179 on other anticoagulant drugs). The dRVVT ratio was correlated with rivaroxaban (r = 0.30, P < 10-4) but not with apixaban plasma levels. The LA-sensitive aPTT/aPTT ratio showed no correlation with DOAC levels. Correspondingly, the rate of patients with abnormal dRVVT test was significantly higher (P < 10-4) under rivaroxaban (88%) than in thrombosis patients without anticoagulant medication (6%), independent from their aPL plasma levels. No isolated positive results of functional LA testing in patients on anticoagulants could be confirmed in repeated testing after discontinuation of the medication (n = 40). These data indicate that rivaroxaban should be discontinued before functional LA testing is performed. However, viable interpretation of these tests appears to be less affected in patients on apixaban.
Asunto(s)
Anticoagulantes/uso terapéutico , Inhibidor de Coagulación del Lupus/uso terapéutico , Trombosis/tratamiento farmacológico , Administración Oral , Adulto , Anticuerpos Antifosfolípidos/uso terapéutico , Síndrome Antifosfolípido/tratamiento farmacológico , Coagulación Sanguínea/efectos de los fármacos , Pruebas de Coagulación Sanguínea/métodos , Dabigatrán/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tiempo de Tromboplastina Parcial/métodos , Tiempo de Protrombina/métodos , Pirazoles/uso terapéutico , Piridonas/uso terapéutico , Estudios Retrospectivos , Rivaroxabán/uso terapéutico , Trombofilia/tratamiento farmacológicoRESUMEN
Background: The potential role of new oral anticoagulants in antiphospholipid antibody syndrome (APS) remains uncertain. Objective: To determine whether rivaroxaban is noninferior to dose-adjusted vitamin K antagonists (VKAs) for thrombotic APS. Design: 3-year, open-label, randomized noninferiority trial. (EU Clinical Trials Register: EUDRA [European Union Drug Regulatory Authorities] code 2010-019764-36). Setting: 6 university hospitals in Spain. Participants: 190 adults (aged 18 to 75 years) with thrombotic APS. Intervention: Rivaroxaban (20 mg/d or 15 mg/d, according to renal function) versus dose-adjusted VKAs (target international normalized ratio, 2.0 to 3.0, or 3.1 to 4.0 in patients with a history of recurrent thrombosis). Measurements: The primary efficacy outcome was the proportion of patients with new thrombotic events; the primary safety outcome was major bleeding. The prespecified noninferiority margin for risk ratio (RR) was 1.40. Secondary outcomes included time to thrombosis, type of thrombosis, changes in biomarker levels, cardiovascular death, and nonmajor bleeding. Results: After 3 years of follow-up, recurrent thrombosis occurred in 11 patients (11.6%) in the rivaroxaban group and 6 (6.3%) in the VKA group (RR in the rivaroxaban group, 1.83 [95% CI, 0.71 to 4.76]). Stroke occurred more commonly in patients receiving rivaroxaban (9 events) than in those receiving VKAs (0 events) (corrected RR, 19.00 [CI, 1.12 to 321.9]). Major bleeding occurred in 6 patients (6.3%) in the rivaroxaban group and 7 (7.4%) in the VKA group (RR, 0.86 [CI, 0.30 to 2.46]). Post hoc analysis suggested an increased risk for recurrent thrombosis in rivaroxaban-treated patients with previous arterial thrombosis, livedo racemosa, or APS-related cardiac valvular disease. Limitation: Anticoagulation intensity was not measured in the rivaroxaban group. Conclusion: Rivaroxaban did not show noninferiority to dose-adjusted VKAs for thrombotic APS and, in fact, showed a non-statistically significant near doubling of the risk for recurrent thrombosis. Primary Funding Source: Bayer Hispania.
Asunto(s)
Anticoagulantes/uso terapéutico , Síndrome Antifosfolípido/tratamiento farmacológico , Inhibidores del Factor Xa/uso terapéutico , Rivaroxabán/uso terapéutico , Trombosis/prevención & control , Warfarina/uso terapéutico , Adulto , Femenino , Hemorragia/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , Prevención Secundaria , Accidente Cerebrovascular/epidemiología , Trombosis/epidemiología , Vitamina K/antagonistas & inhibidoresAsunto(s)
Anticoagulantes/uso terapéutico , Síndrome Antifosfolípido/tratamiento farmacológico , Inhibidores del Factor Xa/uso terapéutico , Rivaroxabán/uso terapéutico , Trombosis/prevención & control , Warfarina/uso terapéutico , Estudios de Equivalencia como Asunto , Hemorragia/epidemiología , Humanos , Recurrencia , Prevención Secundaria , Accidente Cerebrovascular/epidemiología , Trombosis/epidemiología , Vitamina K/antagonistas & inhibidoresRESUMEN
The antiphospholipid-syndrome (APS) is one of the most severe forms of thrombophilia, which may not only lead to recurrent venous but also to arterial thromboembolic events (TE), and to severe pregnancy complications, respectively. APS is defined by clinical symptoms and specific laboratory findings: 1. Lupus anticoagulant (LA), 2. anticardiolipin-antibodies (ACA), and 3. ß2-Glycoprotein I-antibodies (ß2GPI-Ab). All test results have to be confirmed after at least 12 weeks. The thrombotic risk is highest, if all 3 test groups are positive. It must be pointed out that the presence of UFH, VKA or DOACs may lead to false positive LA-test results; the addition of a specific absorber after blood sampling may provide reliable results in the presence of DOACs. A prospective randomized controlled trial comparing warfarin and rivaroxaban (TRAPS-trial) including only high-risk patients with triple positive APS was terminated early because of an increased rate of TE in patients treated with rivaroxaban [19 %, mostly arterial, compared to 3 % with warfarin (HR 7.4;1.7-32.9)]. Subsequently, a warning letter was issued by the pharmaceutical manufacturers of DOACs, including a warning of DOAC use in APS-patients, particularly in triple-positive high-risk patients. Conclusions: 1. Clinical suspicion of APS requires careful diagnostic testing. Because of inadequate diagnostic workup, many patients may not even have an APS, and these patients could be adequately treated with a DOAC. 2. Patients with single or double positive antiphospholipid antibodies but without positive LA may have a comparably low thrombotic risk and may also be treated with a DOAC in venous TE - sufficient evidence for that conclusion is not yet available but is suggested by the results of meta-analyses. 3. Triple positive patients or those with APS who suffered from arterial thromboembolism have a very high recurrence risk of thrombosis; the TRAPS-Study shows that these patients should be treated with VKA instead of a DOAC.
Asunto(s)
Síndrome Antifosfolípido , Anticoagulantes/uso terapéutico , Síndrome Antifosfolípido/tratamiento farmacológico , Humanos , Estudios Prospectivos , Rivaroxabán/uso terapéutico , Warfarina/uso terapéuticoAsunto(s)
Anticoagulantes/uso terapéutico , Síndrome Antifosfolípido/tratamiento farmacológico , Inhibidores del Factor Xa/uso terapéutico , Rivaroxabán/uso terapéutico , Vitamina K/antagonistas & inhibidores , Warfarina/uso terapéutico , Administración Oral , Anticuerpos Antifosfolípidos/sangre , Anticoagulantes/administración & dosificación , Síndrome Antifosfolípido/sangre , Síndrome Antifosfolípido/complicaciones , Inhibidores del Factor Xa/administración & dosificación , Humanos , Inhibidor de Coagulación del Lupus/sangre , Metaanálisis como Asunto , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto , Rivaroxabán/administración & dosificación , Tromboembolia/etiología , Warfarina/administración & dosificación , beta 2 Glicoproteína I/sangreRESUMEN
A 63-year-old woman with known antiphospholipid syndrome (APLS) presented with catastrophic APLS and multiorgan dysfunction after a change in her anticoagulation from warfarin to rivaroxaban. Evidence suggests direct-acting oral anticoagulants (DOACs) like rivaroxaban may be less effective than warfarin in secondary prevention of thrombotic events in high-risk APLS patients.
Asunto(s)
Síndrome Antifosfolípido/tratamiento farmacológico , Rivaroxabán/administración & dosificación , Prevención Secundaria , Trombosis/prevención & control , Administración Oral , Anticoagulantes/uso terapéutico , Síndrome Antifosfolípido/complicaciones , Inhibidores del Factor Xa/administración & dosificación , Inhibidores del Factor Xa/efectos adversos , Femenino , Humanos , Persona de Mediana Edad , Rivaroxabán/efectos adversos , Trombosis/etiología , Warfarina/uso terapéuticoRESUMEN
BACKGROUND: Previous clinical studies reported low molecular weight heparin (LMWH) monotherpay has been utilized for the treatment of recurrent abortion (RCA) with antiphospholipid system (APS). However, its efficacy is still inconclusive. This systematic review aims to assess its efficacy and safety for patients with RCA and APS. METHODS: A systematic literature search for article up to February 2019 will be conducted in 9 databases: Cochrane Library, EMBASE, MEDILINE, Cumulative Index to Nursing and Allied Health Literature, Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, VIP Information, and Wanfang Data. Inclusion criteria are randomized control trials of LMWH monotherpay for patients with RCA and APS. The Cochrane risk of bias tool will be used to evaluate the methodological quality for each qualified study. The summary results will be showed by using fixed-effects and random-effects models for pooling the data based on the heterogeneity of included studies. RESULTS: This systematic review will assess the clinical efficacy and safety of LMWH monotherpay in treating RCA with APS. The primary outcome is pregnancy loss. The secondary outcomes include frequency of preterm delivery, live birth rates, maternal and fetal complications, as well as adverse events. CONCLUSION: The findings of this study will summarize the present evidence to judge whether LMWH monotherpay is an effective therapy for patients with RCA and APS. DISSEMINATION AND ETHICS: The findings of this study will be published by through peer-reviewed journals. This study does not needs ethic documents, because it will not analyze individual patient data. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019121064.
Asunto(s)
Aborto Habitual/tratamiento farmacológico , Anticoagulantes/uso terapéutico , Síndrome Antifosfolípido/tratamiento farmacológico , Heparina de Bajo-Peso-Molecular/uso terapéutico , Aborto Habitual/etiología , Anticoagulantes/efectos adversos , Síndrome Antifosfolípido/complicaciones , Femenino , Heparina de Bajo-Peso-Molecular/efectos adversos , Humanos , Embarazo , Resultado del Embarazo/epidemiología , Proyectos de Investigación , Resultado del TratamientoRESUMEN
Antiphospholipid syndrome is characterized by abortions or thrombotic phenomena associated with specific antibodies. Anticoagulant therapy is based on vitamin K antagonists. We present two cases in which the use of rivaroxaban achieved control of the disease after the failure of acenocoumarol.
Asunto(s)
Acenocumarol/uso terapéutico , Anticoagulantes/uso terapéutico , Síndrome Antifosfolípido/tratamiento farmacológico , Inhibidores del Factor Xa/uso terapéutico , Rivaroxabán/uso terapéutico , Adulto , Trombosis de las Arterias Carótidas/diagnóstico por imagen , Humanos , Relación Normalizada Internacional , Masculino , Resultado del Tratamiento , Tromboembolia Venosa/tratamiento farmacológicoRESUMEN
Rivaroxaban is an effective and safe alternative to warfarin in patients with atrial fibrillation and venous thromboembolism. We tested the efficacy and safety of rivaroxaban compared with warfarin in high-risk patients with thrombotic antiphospholipid syndrome. This is a randomized open-label multicenter noninferiority study with blinded end point adjudication. Rivaroxaban, 20 mg once daily (15 mg once daily based on kidney function) was compared with warfarin (international normalized ratio target 2.5) for the prevention of thromboembolic events, major bleeding, and vascular death in patients with antiphospholipid syndrome. Only high-risk patients triple positive for lupus anticoagulant, anti-cardiolipin, and anti-ß2-glycoprotein I antibodies of the same isotype (triple positivity) were included in the study. The trial was terminated prematurely after the enrollment of 120 patients (59 randomized to rivaroxaban and 61 to warfarin) because of an excess of events among patients in the rivaroxaban arm. Mean follow-up was 569 days. There were 11 (19%) events in the rivaroxaban group, and 2 (3%) events in the warfarin group. Thromboembolic events occurred in 7 (12%) patients randomized to rivaroxaban (4 ischemic stroke and 3 myocardial infarction), whereas no event was recorded in those randomized to warfarin. Major bleeding occurred in 6 patients: 4 (7%) in the rivaroxaban group and 2 (3%) in the warfarin group. No death was reported. The use of rivaroxaban in high-risk patients with antiphospholipid syndrome was associated with an increased rate of events compared with warfarin, thus showing no benefit and excess risk. This trial was registered at www.clinicaltrials.gov as #NCT02157272.
Asunto(s)
Anticoagulantes/uso terapéutico , Síndrome Antifosfolípido/tratamiento farmacológico , Inhibidores del Factor Xa/uso terapéutico , Rivaroxabán/uso terapéutico , Tromboembolia/tratamiento farmacológico , Warfarina/uso terapéutico , Adulto , Anticoagulantes/administración & dosificación , Anticoagulantes/efectos adversos , Síndrome Antifosfolípido/complicaciones , Síndrome Antifosfolípido/epidemiología , Inhibidores del Factor Xa/administración & dosificación , Inhibidores del Factor Xa/efectos adversos , Femenino , Humanos , Italia/epidemiología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Rivaroxabán/administración & dosificación , Rivaroxabán/efectos adversos , Tromboembolia/complicaciones , Tromboembolia/epidemiología , Resultado del Tratamiento , Warfarina/administración & dosificación , Warfarina/efectos adversosRESUMEN
Endothelial cells are thought to play a central role in the pathogenesis of antiphospholipid syndrome (APS). Omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation has been shown to improve endothelial function in a number of diseases; thus, it could be of high clinical relevance in APS. The aim of this study was to evaluate the efficacy of n-3 PUFA supplementation on endothelial function (primary outcome) of patients with primary APS (PAPS). A 16-week randomized clinical trial was conducted with 22 adult women with PAPS. Patients were randomly assigned (1:1) to receive placebo (PL, n = 11) or n-3 PUFA (ω-3, n = 11) supplementation. Before (pre) and after (post) 16 weeks of the intervention, patients were assessed for endothelial function (peripheral artery tonometry) (primary outcome). Patients were also assessed for systemic markers of endothelial cell activation, inflammatory markers, dietary intake, international normalized ratio (INR), and adverse effects. At post, ω-3 group presented significant increases in endothelial function estimates reactive hyperemia index (RHI) and logarithmic transformation of RHI (LnRHI) when compared with PL (+13 vs. -12%, p = 0.06, ES = 0.9; and +23 vs. -22%, p = 0.02, ES = 1.0). No changes were observed for e-selectin, vascular adhesion molecule-1, and fibrinogen levels (p > 0.05). In addition, ω-3 group showed decreased circulating levels of interleukin-10 (-4 vs. +45%, p = 0.04, ES = -0.9) and tumor necrosis factor (-13 vs. +0.3%, p = 0.04, ES = -0.95) and a tendency toward a lower intercellular adhesion molecule-1 response (+3 vs. +48%, p = 0.1, ES = -0.7) at post when compared with PL. No changes in dietary intake, INR, or self-reported adverse effects were observed. In conclusion, 16 weeks of n-3 PUFA supplementation improved endothelial function in patients with well-controlled PAPS. These results support a role of n-3 PUFA supplementation as an adjuvant therapy in APS. Registered at http://ClinicalTrials.gov as NCT01956188.
Asunto(s)
Síndrome Antifosfolípido/tratamiento farmacológico , Proteínas Sanguíneas/inmunología , Suplementos Dietéticos , Endotelio Vascular/inmunología , Ácidos Grasos Omega-3/administración & dosificación , Adulto , Síndrome Antifosfolípido/sangre , Síndrome Antifosfolípido/inmunología , Síndrome Antifosfolípido/patología , Biomarcadores/sangre , Proteínas Sanguíneas/metabolismo , Método Doble Ciego , Endotelio Vascular/metabolismo , Endotelio Vascular/patología , Femenino , Humanos , Persona de Mediana EdadRESUMEN
Acute mesenteric venous thrombosis (MVT) is the rarest cause of acute mesenteric ischaemia, so thrombosis of a variant inferior mesenteric vein (IMV) is especially uncommon in the setting of antiphospholipid syndrome (APS). Here, we present such a case of seronegative APS initially manifesting as an anomalous IMV thrombosis in a 76-year-old woman. Although guidelines support anticoagulation with vitamin K antagonists in these patients, we anticoagulated with rivaroxaban (a direct oral anticoagulant (DOAC)) due to patient preference, which resulted in complete clinical and endoscopic resolution. IMV thrombosis is a rare form of MVT, only two case reports describe successful anticoagulation with DOACs in the setting of MVT and none report APS as an underlying aetiology. Therefore, this case provides the opportunity to review the pathophysiology of MVT, APS and their medical management including current trends in anticoagulation.
Asunto(s)
Síndrome Antifosfolípido/complicaciones , Síndrome Antifosfolípido/tratamiento farmacológico , Venas Mesentéricas/anomalías , Rivaroxabán/uso terapéutico , Trombosis de la Vena/complicaciones , Trombosis de la Vena/tratamiento farmacológico , Enfermedad Aguda , Anciano , Síndrome Antifosfolípido/diagnóstico por imagen , Diagnóstico Diferencial , Inhibidores del Factor Xa/uso terapéutico , Femenino , Humanos , Venas Mesentéricas/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Trombosis de la Vena/diagnóstico por imagenRESUMEN
: The objective of the study is to perform a cost comparison of 1 year of oral anticoagulation management with warfarin vs. hypothetical rivaroxaban (RRX) in thrombotic primary antiphospholipid syndrome. Longitudinal study on 20 primary antiphospholipid syndrome patients followed-up for 1 year after anticoagulation stabilisation with warfarin: a dedicated software calculated number of clinic visits, time in therapeutic range and warfarin consumption for each patient; for RRX, we considered a visit every 3 months (baseline done in hospital before attending anticoagulant clinic); knowing the cost of both anticoagulants, the laboratory cost and the human cost we calculated and compared the yearly expenditure. Average time in therapeutic international normalized ratio range was 69â±â11%: warfarin management required a total of 375 of visits compared with the 60 for RRX; the yearly cost of RRX was superior to that of warfarin (12â012 vs. 446.4 euros, Pâ<â0.0001), and in spite of lower laboratory (738 vs. 1853 euros, Pâ<â0.0001) and human costs (774.6 vs. 4841 euros), RRX thromboprophylaxis still yielded a hefty bill (13â525 vs. 7140 euros, Pâ<â0.0001). Switching from warfarin to RRX will be 48% more expensive to our Healthcare Authority; unless ongoing clinical trials demonstrate improved long-term outcomes for RRX over warfarin, we feel that a 69% time in therapeutic range does not warrant a change to RRX at a 48% increased cost.
Asunto(s)
Anticoagulantes/uso terapéutico , Síndrome Antifosfolípido/tratamiento farmacológico , Inhibidores del Factor Xa/uso terapéutico , Administración Oral , Anticoagulantes/farmacología , Síndrome Antifosfolípido/patología , Inhibidores del Factor Xa/farmacología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Rivaroxabán/farmacología , Rivaroxabán/uso terapéutico , Warfarina/farmacología , Warfarina/uso terapéuticoRESUMEN
WHAT IS KNOWN AND OBJECTIVES: At least four prospective trials have been initiated investigating the direct oral anticoagulants in the antiphospholipid syndrome. Preliminary reports have supported their use in patients with a history of venous thrombosis and a target INR of 2-3, but there have also been reports of failure of these agents in the antiphospholipid syndrome. The objective is to present a case report that illustrates there may be important dosing issues when considering the use of these agents in patients with the antiphospholipid syndrome. CASE SUMMARY: A 50-year-old woman with the antiphospholipid syndrome, manifesting clinically with recurrent pyoderma gangrenosum-like leg ulcers, was treated with apixaban, resulting in improved ulcer healing. For insurance purposes, she was switched to rivaroxaban with worsening of the ulcers which again improved when apixaban was resumed. WHAT IS NEW AND CONCLUSION: Despite a similar half-life, pharmacokinetics and pharmacodynamics, the manufacturer-recommended maintenance dosing of apixaban is twice daily and rivaroxaban once daily. We believe this difference in recommended dose accounts for the differential clinical response noted in the present case report and that twice daily dosing and a larger daily dose of these agents may be more efficacious in potent hypercoagulable disorders, such as the antiphospholipid syndrome.
Asunto(s)
Anticoagulantes/administración & dosificación , Anticoagulantes/uso terapéutico , Síndrome Antifosfolípido/tratamiento farmacológico , Femenino , Humanos , Persona de Mediana Edad , Estudios Prospectivos , Pirazoles/administración & dosificación , Pirazoles/uso terapéutico , Piridonas/administración & dosificación , Piridonas/uso terapéutico , Rivaroxabán/administración & dosificación , Rivaroxabán/uso terapéuticoRESUMEN
OBJECTIVE: Antiphospholipid syndrome (APS) leukocytes exhibit an oxidative perturbation, directly linked to alterations in mitochondrial dynamics and metabolism. This disturbance is related to the patients' prothrombotic status and can be prevented by in vitro treatment with coenzyme Q10. Our aim was to investigate short-term effects of in vivo ubiquinol (reduced coenzyme Q10 [Qred]) supplementation on markers related to inflammation and thrombosis in APS through a prospective, randomized, crossover, placebo-controlled trial. APPROACH AND RESULTS: Thirty-six patients with APS were randomized to receive Qred (200 mg/d) or placebo for 1 month. Thirty-three patients with APS completed the intervention, which increased plasma coenzyme Q10. Qred improved endothelial function and decreased monocyte expression of prothrombotic and proinflammatory mediators, inhibited phosphorylation of thrombosis-related protein kinases, and decreased peroxides and percentage of monocytes with depolarized mitochondria; mitochondrial size was increased, and mitochondrial biogenesis-related genes were upregulated. Qred ameliorated extruded neutrophil extracellular traps in neutrophils and downregulated peroxides, intracellular elastase, and myeloperoxidase. Nanostring microRNA profiling revealed 20 microRNAs reduced in APS monocytes, and 16 of them, with a preponderance of cardiovascular disease-related target mRNAs, were upregulated. Monocytes gene profiling showed differential expression of 29 atherosclerosis-related genes, 23 of them changed by Qred. Interaction networks of genes and microRNAs were identified. Correlation studies demonstrated co-ordinated effects of Qred on thrombosis and endothelial function-associated molecules. CONCLUSIONS: Our results highlight the potential of Qred to modulate the overexpression of inflammatory and thrombotic risk markers in APS. Because of the absence of clinically significant side effects and its potential therapeutic benefits, Qred might act as safe adjunct to standard therapies in APS. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02218476.