rivaroxaban and Antiphospholipid-Syndrome

Thromboprophylaxis is the cornerstone strategy for thrombotic antiphospholipid syndrome (APS). Data comparing direct oral anticoagulants (DOACs) to Vitamin K antagonists (VKAs) in the secondary prevention of thrombosis in APS patients remain contentious. We aim to review and analyse literature on the efficacy and safety of DOACs compared with VKAs in treating patients with APS. A literature search was performed from inception to 31 December 2021. Subgroups were analysed based on the risk stratification of APS profiles and different DOAC types. A total of nine studies with 1131 patients were included in the meta-analysis. High-risk APS patients (triple positive APS) who used DOACs displayed an increased risk of recurrent thrombosis [risk ratio = 3.65, 95% confidence interval (95% CI): 1.49-8.93; I2  = 29%, P  = 0.005] compared with those taking VKAs. Similar risk of recurrent thrombosis or major bleeding was noted in low-risk APS patients (single or double antibody-positive) upon administering DOACs or VKAs. The utilization of Rivaroxaban was associated with a high risk of recurrent thromboses (RR = 2.63; 95% CI: 1.56-4.42; I2  = 0, P  = 0.0003), particularly recurrent arterial thromboses (RR = 4.52; 95% CI: 1.99-10.29; I2  = 0, P  = 0.18) in overall APS patients. Comparisons of the rate of recurrent thrombosis events and major bleeding events when using dabigatran or apixaban versus VKAs yielded no statistical differences. In the absence of contraindications, this meta-analysis suggests that VKAs remain the first-choice treatment for high-risk APS patients, with DOACs a more appropriate option for low-risk APS patients. Different DOACs may exhibit different levels of efficacy and safety for thromboprophylaxis in APS patients and require further exploration.

Topics: Administration, Oral; Anticoagulants; Antiphospholipid Syndrome; Dabigatran; Fibrinolytic Agents; Hemorrhage; Humans; Rivaroxaban; Thrombosis; Venous Thromboembolism; Vitamin K

Herein, we report a case-based review of the Sneddon Syndrome (SS), a rare chronic condition which affects small to medium blood vessels. It is known by its skin presentation, livedo racemosa (LRC), and the relapsing cerebrovascular events. However, neither LRC nor cerebrovascular events are exclusive to SS. A 36-year-old female with history of mitral valve prolapse, hypothyroidism, Raynaud phenomenon, hypertension, migraines, and four episodes of transient ischemic attacks (TIA), presented to our clinic with new skin findings, suggestive of LRC. Based on her previous history, current presentation and skin biopsy results, she was diagnosed with SS secondary to antiphospholipid syndrome. The present report illustrates the difficulty in recognizing SS and how the heterogeneity of the disease may be contributing to the difficulty making a distinct diagnosis.

Topics: Adult; Antiphospholipid Syndrome; Antirheumatic Agents; Factor Xa Inhibitors; Female; Humans; Hydroxychloroquine; Rivaroxaban; Skin; Sneddon Syndrome

Despite vitamin K antagonists (VKA) being the gold standard in the prevention of thromboembolic events in antiphospholipid syndrome (APS), non-vitamin K antagonists oral anticoagulants/direct oral anticoagulants (DOACs) have been used off-label.. We aimed to perform a systematic review comparing DOACs to VKA regarding prevention of thromboembolic events, occurrence of bleeding events and mortality in patients with APS.. An electronic database search was performed through MEDLINE, CENTRAL and Web of Science. After data extraction, we pooled the results using risk ratio (RR) and 95% CI. Heterogeneity was assessed using the I². The outcomes considered were all thromboembolic events as primary, and major bleeding, all bleeding events and mortality as secondary. Evidence confidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation methodology.. We included 7 studies and a total of 835 patients for analyses. Thromboembolic events were significantly increased in DOACs arm, compared with VKA-RR 1.69, 95% CI 1.09 to 2.62, I²-24%, n=719, 6 studies. In studies using exclusively rivaroxaban, which was the most representative drug in all included studies, the thromboembolic risk was increased threefold (RR 3.36, 95% CI 1.53 to 7.37). The risks of major bleeding, all bleeding events and mortality were not significantly different from control arm. The grade of certainty of our results is very low.. Current evidence suggests DOACs use, particularly rivaroxaban, among patients with APS, is less effective than VKA since it is associated with 69% increased risk of thromboembolic events.. CRD42020216178.

Topics: Anticoagulants; Antiphospholipid Syndrome; Hemorrhage; Humans; Rivaroxaban; Vitamin K

Direct oral anticoagulants (DOACs) interfere with lupus anticoagulant (LAC) testing. DOAC-Stop (D-S) represents a preanalytical strategy to cope with this issue.. To assess D-S's ability to remove DOACs from plasma and overcome DOAC interference in LAC assays and to evaluate D-S's applicability in a representative patient cohort with routine LAC request.. Apixaban (30-933 ng/mL), edoxaban (31-1060 ng/mL), rivaroxaban (35-1020 ng/mL), and dabigatran (20-360 ng/mL) were spiked to normal plasma. Aliquots were treated with D-S or untreated before DOAC and LAC testing. Patient samples containing DOAC (n = 43), vitamin K antagonists (n = 25), heparins (n = 21), or no anticoagulants (n = 63) were tested for LAC before and after D-S.. Spiking experiments revealed false-positive LAC from low concentrations of DOACs except for apixaban. Following D-S, DOAC levels were below lower limits of quantification, except for apixaban at the highest concentration, and no false-positive LAC was obtained. DOAC levels were below lower limits of quantification after D-S in 39/43 DOAC-containing patient samples. For 23/29 LAC-positive DOAC-containing samples, LAC tests became negative after D-S, whereas 3/6 samples remaining positive were from patients with (high probability for) antiphospholipid syndrome. In the non-DOAC-treated groups, LAC changed from positive to negative in 10 and vice versa in 2 cases.. D-S limits DOAC interference in LAC assays. DOAC concentration measurement should be performed in D-S treated samples because incomplete removal may occur. Applying D-S to vitamin K antagonist-containing, heparin-containing, or not-anticoagulated samples may lead to erroneous LAC results. Therefore, D-S should only be used in plasma from DOAC-treated patients.

Topics: Administration, Oral; Adsorption; Anticoagulants; Antiphospholipid Syndrome; Dabigatran; Humans; Lupus Coagulation Inhibitor; Pyridones; Rivaroxaban

Anticoagulant treatment is recommended in patients with thrombosis and antiphospholipid syndrome (APS). Conflicting results have been reported on the role of direct oral anticoagulants (DOACs) in these patients. We performed a meta-analysis of randomized controlled trials (RCTs) focused on this issue.. We searched MEDLINE and EMBASE for RCTs comparing DOACs and vitamin K antagonists (VKAs) for secondary thromboprophylaxis in patients with thrombotic APS. The primary objective was to assess the efficacy of DOACs compared to VKAs to prevent recurrence of thromboembolic events. Risk difference (RD) was reported as weighted RD according to Mantel-Haenszel random-effect method.. Three RCTs (426 patients) were included, all comparing rivaroxaban with VKAs. The proportion of recurrences (either arterial or venous) was higher among rivaroxaban patients when compared with those receiving VKAs (9.5% vs 2.8%; RD 6%, 95% CI, -0.05 - 0.18, p=0.29), although non-statistically significant. In patients with an arterial index event, thromboembolic recurrences were more frequent in those treated with rivaroxaban compared to those treated with VKAs (25% vs 6.2%; RD 19%, 95% CI, 0.04 - 0.33; p =0.01; I. The use of rivaroxaban in APS patients is associated with an increased rate of thromboembolic recurrences compared to VKAs, at least in those with arterial index event or triple aPL positivity.

Topics: Administration, Oral; Anticoagulants; Antiphospholipid Syndrome; Humans; Neoplasm Recurrence, Local; Rivaroxaban; Vitamin K

Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by arterial or venous thrombosis (or both), and/or pregnancy morbidity in association with the presence of antiphospholipid antibodies. The prevalence of APS is estimated at 40 to 50 cases per 100,000 people. The most common sites of thrombosis are cerebral arteries and deep veins of the lower limbs. People with a definite APS diagnosis have an increased lifetime risk of recurrent thrombotic events.. To assess the effects of antiplatelet (AP) or anticoagulant agents, or both, for the secondary prevention of recurrent thrombosis, particularly ischemic stroke, in people with APS.. We last searched the MEDLINE, Embase, CENTRAL, Cochrane Stroke Group Trials Register, and ongoing trials registers on 22 November 2019. We checked reference lists of included studies, systematic reviews, and practice guidelines. We also contacted experts in the field.. We included randomized controlled trials (RCTs) that evaluated any anticoagulant or AP agent, or both, in the secondary prevention of thrombosis in people with APS, according to the criteria valid when the study took place. We did not include studies specifically addressing women with obstetrical APS.. Pairs of review authors independently worked on each step of the review, following Cochrane methods. We summarized the evidence using the GRADE approach.. We identified eight studies including 811 participants that compared different AP or anticoagulant agents. NOAC (non-VKA oral anticoagulant: rivaroxaban 15 or 20 mg/d) versus standard-dose VKA (vitamin K antagonist: warfarin at moderate International Normalized Ratio [INR] - 2.5) or adjusted [INR 2.0-3.0] dose): In three studies there were no differences in any thromboembolic event (including death) and major bleeding (moderate-certainty evidence), but an increased risk of stroke (risk ratio [RR] 14.13, 95% confidence interval [CI] 1.87 to 106.8; moderate-certainty evidence). One of the studies reported a small benefit of rivaroxaban in terms of quality of life at 180 days measured as health state on Visual Analogue Scale (mean difference [MD] 7 mm, 95% CI 2.01 to 11.99; low-certainty evidence), but not measured as health utility on a scale from 0 to 1 (MD 0.04, 95% CI -0.02 to 0.10; low-certainty evidence). High-dose VKA (warfarin with a target INR of 3.1 to 4.0 [mean 3.3] or 3.5 [mean 3.2]) versus standard-dose VKA (warfarin with a target INR of 2.0 to 3.0 [mean 2.3] or 2.5 [mean 2.5]): In two studies there were no differences in the rates of thrombotic events and major bleeding (RR 2.22, 95% CI 0.79 to 6.23, low-certainty evidence), but an increased risk of minor bleeding in one study during a mean of 3.4 years (standard deviation [SD] 1.2) of follow-up (RR 2.55, 95% CI 1.07 to 6.07). In both trials there was evidence of a higher risk of any bleeding (hazard ratio [HR] 2.03 95% CI 1.12 to 3.68; low-certainty evidence) in the high-dose VKA group, and for this outcome (any bleeding) the incidence is not different, only the time to event is showing an effect. Standard-dose VKA plus a single AP agent (warfarin at a target INR of 2.0 to 3.0 plus aspirin 100 mg/d) versus standard-dose VKA (warfarin at a target INR of 2.0 to 3.0): One high-risk-of-bias study showed an increased risk of any thromboembolic event with combined treatment (RR 2.14, 95% CI 1.04 to 4.43; low-certainty evidence) and reported on major bleeding with five cases in the combined treatment group and one case in the standard-dose VKA treatment group, resulting in RR 7.42 (95% CI 0.91 to 60.7; low-certainty evidence) and no differences for secondary outcomes (very low- to low-certainty evidence). Single/dual AP agent and standard-dose VKA (pooled results): Two high-risk-of-bias studies compared a combination of AP and VKA (aspirin 100 mg/d plus warfarin or unspecified VKA at a target INR of. The evidence identified indicates that NOACs compared with standard-dose VKAs may increase the risk of stroke and do not appear to alter the risk of other outcomes (moderate-certainty evidence). Using high-dose VKA versus standard-dose VKA did not alter the risk of any thromboembolic event or major bleeding but may increase the risk of any form of bleeding (low-certainty evidence). Standard-dose VKA combined with an AP agent compared with standard-dose VKA alone may increase the risk of any thromboembolic event and does not appear to alter the risk of major bleeding or other outcomes (low-certainty evidence). The evidence is very uncertain about the benefit or harm of using standard-dose VKA plus AP agents versus single or dual AP therapy, or dual versus single AP therapy, for the secondary prevention of recurrent thrombosis in people with APS (very low-certainty evidence).

Topics: Anticoagulants; Antiphospholipid Syndrome; Cause of Death; Factor Xa Inhibitors; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Rivaroxaban; Secondary Prevention; Stroke; Thromboembolism; Warfarin

We respond to comments by Dufrost et al. about the RAPS trial, in particular, showing that the trial did achieve its target sample size; pointing out that thrombin potential is not synonymous with overall thrombin generation; confirming that overall, no increased thrombotic risk was evident comparing rivaroxaban with warfarin; and that high-risk patients (28% were triple positive, representative of patients with venous thromboembolism requiring standard-intensity anticoagulation) were included; and clarifying our rationale for using a laboratory surrogate primary outcome measure instead of a clinical one.

Topics: Anticoagulants; Antiphospholipid Syndrome; Humans; Rivaroxaban; Venous Thromboembolism; Warfarin

We present the case of a patient with primary APS who had a recurrence of thrombotic event while on treatment with rivaroxaban and had to be restarted on warfarin. The current literature on recurrence of thrombotic events in patients with antiphospholipid syndrome (APS) treated with newer oral anticoagulants (NOAC) is also reviewed. Relevant case reports and case series were identified by searching the Medline database using the key words antiphospholipid syndrome, anticoagulants and names of the NOACs, and data on individual patients was abstracted. We identified several reports on the failure of newer anticoagulants in APS, as well as cases and clinical trial results reporting efficacy. We conclude that treatment strategies for APS should be tailored cautiously when using NOACs.

Topics: Administration, Oral; Anticoagulants; Antiphospholipid Syndrome; Female; Humans; Middle Aged; Rivaroxaban; Thrombosis; Warfarin

Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by arterial or venous thrombosis (or both) and/or pregnancy morbidity in association with the presence of antiphospholipid antibodies. The prevalence is estimated at 40 to 50 cases per 100,000 people. The most common sites of thrombosis are cerebral arteries and deep veins of the lower limbs. People with a definite APS diagnosis have an increased lifetime risk of recurrent thrombotic events.. To assess the effects of antiplatelet or anticoagulant agents, or both, for the secondary prevention of recurrent thrombosis, particularly ischemic stroke, in people with antiphospholipid syndrome.. We searched the Cochrane Stroke Group Trials Register (February 2017), CENTRAL (last search February 2017), MEDLINE (from 1948 to February 2017), Embase (from 1980 to February 2017), and several ongoing trials registers. We also checked the reference lists of included studies, systematic reviews, and practice guidelines, and we contacted experts in the field.. We included randomized controlled trials (RCTs) that evaluated any anticoagulant or antiplatelet agent, or both, in the secondary prevention of thrombosis in people diagnosed with APS according to the criteria valid when the study took place. We did not include studies specifically addressing women with obstetrical APS.. Pairs of review authors independently selected studies for inclusion, extracted data, and assessed the risk of bias for the included studies. We resolved any discrepancies through discussion or by consulting a third review author and, in addition, one review author checked all the extracted data.. We included five studies involving 419 randomized participants with APS. Only one study was at low risk of bias in all domains. One study was at low risk of bias in all domains for objective outcomes but not for quality of life (measured using the EQ-5D-5L questionnaire). We judged the other three studies to be at unclear or high risk of bias in three or more domains.The duration of intervention ranged from 180 days to a mean of 3.9 years. One study compared rivaroxaban (a novel oral anticoagulant: NOAC) with standard warfarin treatment and reported no thrombotic or major bleeding events, but it was not powered to detect such differences (low-quality evidence). Investigators reported similar rates of clinically relevant non-major bleeding (risk ratio (RR) 1.45, 95% confidence interval (CI) 0.25 to 8.33; moderate-quality evidence) and minor bleeding (RR 1.21, 95% CI 0.51 to 2.83) for participants receiving rivaroxaban and the standard vitamin K antagonists (VKA). This study also reported some small benefit with rivaroxaban over the standard VKA treatment in terms of quality of life health state measured at 180 days with the EQ-5D-5L 100 mm visual analogue scale (mean difference (MD) 7 mm, 95% CI 2.01 to 11.99; low-quality evidence) but not measured as health utility (MD 0.04, 95% CI -0.02 to 0.10 [on a scale from 0 to 1]).Two studies compared high dose VKA (warfarin) with moderate/standard intensity VKA and found no differences in the rates of any thrombotic events (RR 2.22, 95% CI 0.79 to 6.23) or major bleeding (RR 0.74, 95% CI 0.24 to 2.25) between the groups (low-quality evidence). Minor bleeding analyzed using the RR and any bleeding using the hazard ratio (HR) were more frequent in participants receiving high-intensity warfarin treatment compared to the standard-intensity therapy (RR 2.55, 95% CI 1.07 to 6.07; and HR 2.03, 95% CI 1.12 to 3.68; low-quality evidence).In one study, it was not possible to estimate the RR for stroke with a combination of VKA plus antiplatelet agent compared to a single antiplatelet agent, while for major bleeding, a single event occurred in the single antiplatelet agent group. In one study, comparing combined VKA plus antiplatelet agent with dual antiplatelet therapy, the RR of the risk of stroke over three years of observation was 5.00 (95% CI 0.26 to 98.0). In a single small study, the RR for stroke during one year of observation with a dual antiplatelet therapy compared to single antiplatelet drug was 0.14 (95% CI 0.01. There is not enough evidence for or against NOACs or for high-intensity VKA compared to the standard VKA therapy in the secondary prevention of thrombosis in people with APS. There is some evidence of harm for high-intensity VKA regarding minor and any bleeding. The evidence was also not sufficient to show benefit or harm for VKA plus antiplatelet agent or dual antiplatelet therapy compared to a single antiplatelet drug. Future studies should be adequately powered, with proper adherence to treatment, in order to evaluate the effects of anticoagulants, antiplatelets, or both, for secondary thrombosis prevention in APS. We have identified five ongoing trials mainly using NOACs in APS, so increasing experimental efforts are likely to yield additional evidence of clinical relevance in the near future.

Topics: Anticoagulants; Antiphospholipid Syndrome; Factor Xa Inhibitors; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Rivaroxaban; Secondary Prevention; Stroke; Warfarin

Lupus anticoagulant (LAC) is an in vitro phenomenon determining a phospholipid-dependent elongation of clotting times. The presence of LAC associated with anticardiolipin (aCL) and anti-β2 glycoprotein I (anti-β2GPI) antibodies is strongly associated with thrombosis and pregnancy morbidity. Direct oral anticoagulants (DOACs) targeting thrombin and factor Xa are currently widely use to prevent and treat venous and arterial thromboembolism. Some concern has, however, been expressed about the possibility of false laboratory results during LAC assessment in patients taking these drugs. Several in vitro studies, spiking DOACs into normal plasma as well as ex vivo at peak levels in treated patients, led in false-positive LAC. The dilute Russell Viper Venom time is the assay that is most influenced by rivaroxaban, edoxaban, dabigatran and less by apixaban. Both screening and confirmatory tests have resulted equally prolonged for activated partial thromboplastin time and have not led to false-positive results, but this may depend on the type of reagent used for the test. Taipan/Ecarin snake venoms ratios, has been recommend by some investigators as they do not seem to be affected by rivaroxaban or edoxaban, but these tests are neither standardized nor generally available in clinical practice. In conclusion, for the time being it does not seem advisable to carry out LAC testing during anti-factor Xa and anti-factor IIa treatment because of the risk of false-positive results. Whenever needed in deciding the suspension of DOACs or in case of recurrent thrombosis, LAC determination should be carried out at trough better if DOAC concentration is known.

Topics: Administration, Oral; Anticoagulants; Antiphospholipid Syndrome; Dabigatran; Humans; Lupus Coagulation Inhibitor; Rivaroxaban

The anti-phospholipid syndrome (APS) is an autoimmune disorder characterized by vascular thrombosis and/or pregnancy morbidity, associated with a persistent positivity for anti-phospholipid antibodies (aPL). The current classification criteria for APS include three laboratory tests: lupus anti-coagulant (LA), anti-cardiolipin (aCL), and anti-β2 glycoprotein-I (β2GPI). To date, the therapeutic approach for thrombotic APS mainly centers on long-term anti-coagulation with a vitamin K antagonist (VKA). APS management may represent a challenge for the treating physicians. Patients with different aPL profiles need a tailored risk-stratified approach. Moreover, in patients with recurrent thrombotic events despite therapy with VKA, or in those with microvascular involvement, new therapeutic options are highly needed. In this review, we aim to elucidate recent findings about new aPL specifities, available risk scoring models, and novel therapeutic approaches in APS management.

Topics: Adult; Antibodies, Anticardiolipin; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Anticoagulants; Antiphospholipid Syndrome; beta 2-Glycoprotein I; Female; Fibrinolytic Agents; Humans; Hydroxychloroquine; Lupus Coagulation Inhibitor; Pregnancy; Pregnancy Complications; Risk Assessment; Rivaroxaban; Thrombosis

The cornerstone of thrombotic antiphospholipid syndrome (APS) patients' management is to prevent recurrent thrombosis by long-term anticoagulation.. 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.. 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. 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.

Topics: Anticoagulants; Antiphospholipid Syndrome; Humans; Rivaroxaban; Secondary Prevention; Thrombosis; Warfarin

The current mainstay of treatment of thrombotic APS is long-term anticoagulation with oral vitamin K antagonists (VKA) such as warfarin. However, the use of warfarin is problematic, particularly in patients with antiphospholipid syndrome (APS). The new oral anticoagulants (NOAC) include dabigatran etexilate (Pradaxa®), a direct thrombin inhibitor, and rivaroxaban (Xarelto®), Apixaban (Eliquis) and Edoxaban (Lixiana®), which are direct anti-Xa inhibitors. Unlike warfarin, these agents do not interact with dietary constituents and alcohol, have few reported drug interactions, and monitoring of their anticoagulant intensity is not routinely required due to their predictable anticoagulant effects. In this chapter, we discuss clinical and laboratory aspects of NOAC. These agents have been approved for several therapeutic indications based on phase III prospective randomised controlled clinical trials using warfarin at a target INR of 2.5 (i.e. range 2.0-3.0) as the comparator. However these trials may not be directly applicable to patients with antiphospholipid syndrome (APS) where prospective clinical studies of NOAC are the way forward.

Topics: Administration, Oral; Adult; Animals; Anticoagulants; Antiphospholipid Syndrome; Benzimidazoles; beta-Alanine; Breast Feeding; Clinical Trials, Phase III as Topic; Contraindications; Dabigatran; Drug Monitoring; Female; Humans; Infant, Newborn; Maternal Exposure; Morpholines; Pregnancy; Pyrazoles; Pyridines; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Thiazoles; Thiophenes

Trial of Rivaroxaban in AntiPhospholipid Syndrome was a prospective randomized, open-label, noninferiority study conducted in 14 centers in Italy. Rivaroxaban was compared with warfarin for the prevention of thromboembolic events, major bleeding, and vascular death in high-risk, triple-positive patients with antiphospholipid syndrome.. The aim of this paper is to report the events during the 2-year follow-up after the study closure.. On January 28, 2018, the trial was prematurely stopped by adjudication and safety committee for an excess of events in the rivaroxaban group. Randomized patients were advised on trial results and those randomized to rivaroxaban were solicited to switch to warfarin. All 14 participating centers were asked and accepted to follow their patients for clinical events. This report describes the rate of events that occurred between January 28, 2018, and January 28, 2020.. Of 120 randomized patients, 115 were available for follow-up. Outcome events were two in six (33.3%) patients who remained on direct oral anticoagulants (DOACs) and six in 109 (5.7%) patients on warfarin (hazard ratio [HR] 6.9; 95% confidence interval [CI] 1.4-34.5, P = .018). The two patients on DOACs (one taking dabigatran and one taking rivaroxaban) suffered from thromboembolic events, whereas of the six patients with composite outcomes on warfarin, three had thromboembolic events (HR for thrombosis 13.3; 95% CI 2.2-79.9, P = .005).. These data further support the use of warfarin in high-risk patients with antiphospholipid syndrome.

Topics: Administration, Oral; Anticoagulants; Antiphospholipid Syndrome; Atrial Fibrillation; Dabigatran; Humans; Italy; Prospective Studies; Rivaroxaban; Stroke; Warfarin

The potential role of new oral anticoagulants in antiphospholipid antibody syndrome (APS) remains uncertain.. To determine whether rivaroxaban is noninferior to dose-adjusted vitamin K antagonists (VKAs) for thrombotic APS.. 3-year, open-label, randomized noninferiority trial. (EU Clinical Trials Register: EUDRA [European Union Drug Regulatory Authorities] code 2010-019764-36).. 6 university hospitals in Spain.. 190 adults (aged 18 to 75 years) with thrombotic APS.. 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).. 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.. 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.. Anticoagulation intensity was not measured in the rivaroxaban group.. 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.. Bayer Hispania.

Topics: Adult; Anticoagulants; Antiphospholipid Syndrome; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Recurrence; Rivaroxaban; Secondary Prevention; Stroke; Thrombosis; Vitamin K; Warfarin

Topics: Anticoagulants; Antiphospholipid Syndrome; Humans; Prospective Studies; Rivaroxaban; Warfarin

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-β2-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.

Topics: Adult; Anticoagulants; Antiphospholipid Syndrome; Factor Xa Inhibitors; Female; Humans; Italy; Male; Middle Aged; Prospective Studies; Rivaroxaban; Thromboembolism; Treatment Outcome; Warfarin

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.. 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.. The methods and the study design should be appropriate to achieve study results that are both scientifically valid and relevant to clinical practice.

Topics: Adolescent; Adult; Aged; Anticoagulants; Antiphospholipid Syndrome; Blood Coagulation; Clinical Protocols; Factor Xa Inhibitors; Female; Hemorrhage; Humans; International Normalized Ratio; Male; Middle Aged; Research Design; Risk Assessment; Risk Factors; Rivaroxaban; Thromboembolism; Treatment Outcome; Warfarin; Young Adult

Rivaroxaban is established for the treatment and secondary prevention of venous thromboembolism, but whether it is useful in patients with antiphospholipid syndrome is uncertain.. This randomised, controlled, open-label, phase 2/3, non-inferiority trial, done in two UK hospitals, included patients with antiphospholipid syndrome who were taking warfarin for previous venous thromboembolism, with a target international normalised ratio of 2·5. Patients were randomly assigned 1:1 to continue with warfarin or receive 20 mg oral rivaroxaban daily. Randomisation was done centrally, stratified by centre and patient type (with vs without systemic lupus erythematosus). The primary outcome was percentage change in endogenous thrombin potential (ETP) from randomisation to day 42, with non-inferiority set at less than 20% difference from warfarin in mean percentage change. Analysis was by modified intention to treat. Other thrombin generation parameters, thrombosis, and bleeding were also assessed. Treatment effect was measured as the ratio of rivaroxaban to warfarin for thrombin generation. This trial is registered with the ISRCTN registry, number ISRCTN68222801.. Of 116 patients randomised between June 5, 2013, and Nov 11, 2014, 54 who received rivaroxaban and 56 who received warfarin were assessed. At day 42, ETP was higher in the rivaroxaban than in the warfarin group (geometric mean 1086 nmol/L per min, 95% CI 957-1233 vs 548, 484-621, treatment effect 2·0, 95% CI 1·7-2·4, p<0·0001). Peak thrombin generation was lower in the rivaroxaban group (56 nmol/L, 95% CI 47-66 vs 86 nmol/L, 72-102, treatment effect 0·6, 95% CI 0·5-0·8, p=0·0006). No thrombosis or major bleeding were seen. Serious adverse events occurred in four patients in each group.. ETP for rivaroxaban did not reach the non-inferiority threshold, but as there was no increase in thrombotic risk compared with standard-intensity warfarin, this drug could be an effective and safe alternative in patients with antiphospholipid syndrome and previous venous thromboembolism.. Arthritis Research UK, Comprehensive Clinical Trials Unit at UCL, LUPUS UK, Bayer, National Institute for Health Research Biomedical Research Centre.

Topics: Anticoagulants; Antiphospholipid Syndrome; Equivalence Trials as Topic; Factor Xa Inhibitors; Female; Follow-Up Studies; Humans; Lupus Erythematosus, Systemic; Male; Middle Aged; Prevalence; Rivaroxaban; Survival Rate; Thrombosis; Treatment Outcome; United Kingdom; Warfarin

The current mainstay of the treatment of thrombotic antiphospholipid syndrome (APS) is long-term anticoagulation with vitamin K antagonists (VKAs) such as warfarin. Non-VKA oral anticoagulants (NOACs), which include rivaroxaban, have been shown to be effective and safe compared with warfarin for the treatment of venous thromboembolism (VTE) in major phase III prospective, randomized controlled trials (RCTs), but the results may not be directly generalizable to patients with APS.. The primary aim is to demonstrate, in patients with APS and previous VTE, with or without systemic lupus erythematosus (SLE), that the intensity of anticoagulation achieved with rivaroxaban is not inferior to that of warfarin. Secondary aims are to compare rates of recurrent thrombosis, bleeding and the quality of life in patients on rivaroxaban with those on warfarin.. Rivaroxaban in antiphospholipid syndrome (RAPS) is a phase II/III prospective non-inferiority RCT in which eligible patients with APS, with or without SLE, who are on warfarin, target international normalized ratio (INR) 2.5 for previous VTE, will be randomized either to continue warfarin (standard of care) or to switch to rivaroxaban. Intensity of anticoagulation will be assessed using thrombin generation (TG) testing, with the primary outcome the percentage change in endogenous thrombin potential (ETP) from randomization to day 42. Other TG parameters, markers of in vivo coagulation activation, prothrombin fragment 1.2, thrombin antithrombin complex and D-dimer, will also be assessed.. If RAPS demonstrates i) that the anticoagulant effect of rivaroxaban is not inferior to that of warfarin and ii) the absence of any adverse effects that cause concern with regard to the use of rivaroxaban, this would provide sufficient supporting evidence to make rivaroxaban a standard of care for the treatment of APS patients with previous VTE, requiring a target INR of 2.5.

Topics: Anticoagulants; Antiphospholipid Syndrome; Blood Coagulation Tests; Factor Xa Inhibitors; Female; Fibrin Fibrinogen Degradation Products; Humans; International Normalized Ratio; Lupus Erythematosus, Systemic; Male; Prospective Studies; Quality of Life; Recurrence; Rivaroxaban; Thrombin; Venous Thromboembolism; Warfarin

Topics: Anticoagulants; Antiphospholipid Syndrome; Blood Coagulation; Blood Coagulation Tests; False Positive Reactions; Humans; Lupus Coagulation Inhibitor; Morpholines; Partial Thromboplastin Time; Predictive Value of Tests; Prothrombin Time; Rivaroxaban; Thiophenes; Treatment Outcome; Venous Thromboembolism; Warfarin

Direct oral anticoagulants (DOACs) interfere with many coagulation assays, mostly in lupus anticoagulant (LA) detection, causing false positive and negative results. Despite guidelines recommendations, LA testing may be important during anticoagulation when the clinician has to decide whether to prolong or discontinue the drug.. In this study, the effect of activated charcoal (DOAC-Stop, DS) as a DOAC-adsorbent was investigated on samples from DOACs treated and untreated patients.. 165 plasma samples with a LA request were collected in three laboratories: 105 were from patients receiving DOACs and 60 were from nonanticoagulated patients with 30 LA negative and 30 LA positive. All coagulation screening assays and LA assays were evaluated before and after DS treatment.. The adsorption technique reduced DOACs concentration below the Lower Limit of Quantification. For nonanticoagulated patients: no significant difference in ratio results of coagulation screening (prothrombin time, activated partial thromboplastin time and thrombin time) and LA tests were observed before and after addition of DS in LA positive and negative patients. Every LA was correctly classified. For anticoagulated patients: a statistically significant difference was found for coagulation screening assays and LA assays. Final LA conclusions changed after DS addition from positive to negative in 58.9% of patients (more frequently with Rivaroxaban) and from negative to positive in 8% of patients (more frequently with Apixaban).. Our study suggests that DOAC-Stop can be used in daily laboratory practice to remove DOACs interference for a more accurate assessment of LA that is essential for diagnosis and management of APS patients.

Topics: Administration, Oral; Adsorption; Anticoagulants; Antiphospholipid Syndrome; Blood Coagulation Tests; Humans; Laboratories; Lupus Coagulation Inhibitor; Rivaroxaban

Antiphospholipid syndrome (APS) can affect different organ systems, including the heart and adrenal glands. Despite being known for its prothrombotic characteristics, APS can have serious bleeding complications. Occasionally, thrombotic and bleeding episodes can present simultaneously in an APS patient. Whenever these events co-occur, resuming anticoagulation becomes a topic of debate. As such, we present the case of a 43-year-old male with triple positive antiphospholipid antibodies, indicating APS, who presented with chest pain. Anticoagulants were switched one month before presentation from warfarin to a direct oral anticoagulant, rivaroxaban. Non-ST elevation myocardial infarction, as well as new-onset left-sided adrenal hemorrhage, were diagnosed. The patient developed adrenal insufficiency; therefore, corticosteroids were administered, and warfarin was resumed to prevent further thrombotic episodes.

Topics: Adult; Antiphospholipid Syndrome; Hemorrhage; Humans; Male; Myocardial Infarction; Rivaroxaban; Warfarin

Warfarin is recognized as the standard treatment for thrombotic antiphospholipid syndrome (APS); however, direct oral anticoagulants (DOACs) represent appealing therapeutic alternatives given their lack of monitoring and limited drug interactions. A few randomized controlled trials comparing rivaroxaban with warfarin showed an increased risk of recurrent thromboembolism, specifically arterial thrombosis, in patients with high risk forms of APS such as those that are triple antibody positive. We conducted a single-center, retrospective cohort study of all patients within our health system from 2015 to 2020 with a diagnosis of APS (single or double antibody positive) and history of venous thromboembolism. We sought to compare the proportion of patients with a recurrent thrombosis when prescribed a DOAC versus warfarin. Among 96 patients included, 57 were prescribed warfarin and 39 were prescribed a DOAC (90% rivaroxaban). The proportion of patients with a recurrent thromboembolism was almost three times higher in the DOAC group (15.4%) compared to the warfarin group (5.3%), although this was not statistically significant (p = 0.15). Major bleeding was not different between groups. Our findings suggest that rivaroxaban may pose an increased risk for recurrent thromboembolism in low risk APS patients that are single or double-antibody positive compared to warfarin. Results of our study should be cautiously applied to DOACs besides rivaroxaban given their small representation in this study.

Topics: Administration, Oral; Anticoagulants; Antiphospholipid Syndrome; Humans; Retrospective Studies; Rivaroxaban; Thrombosis; Venous Thromboembolism; Warfarin

Sample freezing is a part of routine laboratory tasks because some coagulation parameters are analysed in batches to optimize reagent consumption. The coagulation parameter stability in fresh and frozen samples has been described, but data are scarcer after thawing. This study objective was to determine the stability of the main coagulation parameters (from blood withdrawn on siliconized CTAD tubes and double-centrifuged) after one freeze/thaw cycle to generate procedures for appropriate handling, storage and testing.. Prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, D-dimers, clotting factors (F), protein C, protein S, antithrombin, lupus anticoagulant (LA)-sensitive aPTT and diluted-Russel's viper venom time (dRVVT) were assessed in 60 plasma samples (n=30, normal range and n=30, outside the normal range). Thirty samples from anticoagulated patients [unfractionated heparin (UFH), low-molecular weight heparin (LMWH), apixaban or rivaroxaban] were assessed using specific anticoagulant assays. Frozen samples were thawed, and assays were performed at 15 min, 2, 4 and 6 h after thawing. The coagulation parameter stability was assessed with the method of rejection limit.. After thawing, aPTT, PT, fibrinogen, D-dimers, FII, FV, FX, FIX, FXI, FXII, PC and UFH anti-Xa activity remained stable for at least 6 h, FVII for 5 h, PS, AT, dRVVT screen assay and LMWH anti-Xa activity for 4 h, and LA-sensitive aPTT and apixaban-specific anti-Xa activity for 3 h. FVIII, dRVVT confirm assay and rivaroxaban specific anti-Xa activity were stable for 2 h.. These results suggest that sample stability for some haemostasis assays is limited after thawing.

Topics: Anticoagulants; Antiphospholipid Syndrome; Blood Coagulation Tests; Fibrinogen; Freezing; Heparin; Heparin, Low-Molecular-Weight; Humans; Lupus Coagulation Inhibitor; Partial Thromboplastin Time; Rivaroxaban; Temperature

Topics: Administration, Oral; Anticoagulants; Antiphospholipid Syndrome; Humans; Rivaroxaban; Warfarin

Topics: Antiphospholipid Syndrome; Blood Coagulation; Factor Xa Inhibitors; Humans; Retrospective Studies; Rivaroxaban; Thrombosis; Treatment Outcome

A 34-year-old Japanese woman with systemic lupus erythematosus (SLE) was admitted to our hospital for exacerbation of renal dysfunction, hemolytic anemia and thrombocytopenia. Twenty-two years before admission, she was diagnosed with SLE. Eight years before, lupus anticoagulant (LAC) positivity was detected without any thrombotic findings. Fourteen months before, renal function started to worsen. Three months before, unprovoked left leg swelling appeared. She was diagnosed with deep vein thrombosis (DVT) by ultrasonography. Blood examination revealed mild anemia, thrombocytopenia, and renal dysfunction. Rivaroxaban was started after which the left leg swelling subsided. When she was referred to our hospital, LAC was positive, but hypocomplementemia nor elevation of serum anti-double-stranded DNA antibodies was detected. Renal biopsy showed acute and chronic thrombotic microangiopathy (TMA) without concurrent lupus nephritis. Brain magnetic resonance imaging showed new small multiple cerebral infarcts. Antiphospholipid antibody syndrome (APS), causing renal TMA, new cerebral infarction, and DVT was diagnosed. Rivaroxaban was changed to warfarin. Two months after admission, renal impairment improved, and the complete disappearance of DVT and brain infarcts was confirmed. This case suggests that warfarin may be more effective than direct oral anticoagulants in the treatment of APS-associated renal TMA.

Topics: Adult; Antiphospholipid Syndrome; Female; Humans; Kidney Diseases; Lupus Erythematosus, Systemic; Lupus Nephritis; Rivaroxaban; Thrombotic Microangiopathies; Treatment Outcome; Warfarin

Lupus anticoagulant (LA)-detection in anticoagulated patients is an unmet need, which becomes even more cogent with the introduction of direct oral anticoagulants (DOAC) that may lead to false-positive results.. We aimed to investigate the effect of a commercially available DOAC absorbent on residual drug concentrations, and on integrated procedures for LA-detection.. Blood from patients treated for atrial fibrillation with either dabigatran (n = 39), rivaroxaban (n = 55), apixaban (n = 47) or edoxaban (n = 47) were collected at peak and trough, and centralized for testing with two LA integrated procedures [i.e., the silica clotting time (SCT) and dilute Russel viper venom (dRVVT)] before and after DOAC absorbent exposure.. The commercially available DOAC absorbent investigated in this study proved effective in reducing the concentrations of all the investigated DOAC, although small residual drug was detected after absorption, especially in patients on edoxaban. Results mimicking LA were observed in patients on DOAC before absorbent exposure, especially for rivaroxaban when testing was performed with dRVVT (88% rate at peak and 20% at trough) and much less with SCT (12% at peak and 8% at trough). The correspondent rate of results mimicking LA in patients on rivaroxaban after exposure was reduced [dRVVT (peak 8%, trough 4%); SCT (peak and trough 8%)], but not abolished.. Overall, in vitro DOAC absorbance by active charcoal compounds is a useful laboratory tool for LA-detection in patients on DOAC. Caution should however be exerted when used in daily practice.

Topics: Administration, Oral; Anticoagulants; Antiphospholipid Syndrome; Dabigatran; Humans; Lupus Coagulation Inhibitor; Pyridones; Rivaroxaban

Thrombin generation assay (TGA) is a useful tool to evaluate the initiation, propagation and inhibition of coagulation. TGA is a global test that is used to assess hemorrhagic risk in hemophilia patients, but it can also be used to study hypercoagulable states. The interest of TGA is to screen for cardiovascular risk, which is regularly associated with autoimmune disease (AID) such as antiphospholipid syndrome. Indeed, TGA has been used to evaluate hypercoagulability in patients with antiphospholipid syndrome treated with rivaroxaban versus warfarin. In other AIDs without thrombotic events, TGA measurement is elevated, mainly in rheumatoid arthritis (RA), systemic lupus erythematosus and Behçet's disease. These findings in RA are correlated with the inflammatory activity of the disease. In systemic lupus erythematosus and Behçet's disease, TGA appears to reflect disease activity. In conclusion, TGA remains relatively under used in the clinical evaluation of AID, but it could play a greater role in the evaluation of certain potentially thrombogenic treatments in AID. Finally, TGA helps measuring AID activity, due to the clearlink between coagulation and inflammation, despite some limitations of interpretation mainly due to a lack of standardization.

Topics: Antiphospholipid Syndrome; Autoimmune Diseases; Blood Coagulation; Humans; Rivaroxaban; Thrombin

Despite controversies, direct oral anticoagulants (DOACs) are increasingly used in antiphospholipid syndrome (APS). We investigated the safety and efficacy of DOACs versus vitamin K antagonists (VKAs) in real-life consecutive APS patients.. In a cohort study of 176 APS patients, which included 82 subjects who preferred DOACs or had unstable anticoagulation with VKAs, we recorded venous thromboembolism (VTE), cerebrovascular ischemic events or myocardial infarction, along with major bleeding or clinically relevant non-major bleeding (CRNMB).. APS patients were followed for a median time of 51 (interquartile range 43-63) months. Patients on DOACs and those on VKAs were similar with regard to baseline characteristics. APS patients treated with DOACs had increased risk of recurrent thromboembolic events and recurrent VTE alone compared with those on VKAs (hazard ratio (HR) = 3.98, 95% confidence interval (CI): 1.54-10.28,. During long-term follow-up of real-life APS patients, DOACs are less effective and less safe as VKAs in the prevention of thromboembolism.

Topics: Adult; Antiphospholipid Syndrome; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Proportional Hazards Models; Prospective Studies; Pyrazoles; Pyridones; Rivaroxaban; Venous Thromboembolism; Vitamin K

Catastrophic antiphospholipid syndrome is the most severe complication of antiphospholipid syndrome. Vitamin K antagonists are the reference treatment for preventing relapsing thrombotic complications in patients with antiphospholipid syndrome. Direct oral anticoagulants are nonetheless sometimes used in this setting. We report two cases of women who were triple-positive for antiphospholipid antibodies and developed catastrophic antiphospholipid syndrome in the week after the introduction of rivaroxaban. The first patient, who had had a previous thrombotic event, had multiorgan failure 3 days after vitamin K antagonists was replaced by rivaroxaban, and the second developed a similar clinical presentation 7 days after introduction of the same treatment. Both catastrophic antiphospholipid syndrome episodes were successfully treated with heparin followed by vitamin K antagonists, corticosteroids, and plasmapheresis. These two cases highlight for the inefficacy of rivaroxaban preventing severe thrombotic events such as catastrophic antiphospholipid syndrome and thus provide further support for recommendations that vitamin K antagonists must remain the reference anticoagulant in patients with triple-positive antiphospholipid antibodies.

Topics: Adrenal Cortex Hormones; Adult; Aged; Antibodies, Antiphospholipid; Anticoagulants; Antiphospholipid Syndrome; Catastrophic Illness; Female; Heparin; Humans; Rivaroxaban; Thrombosis

Topics: Anticoagulants; Antiphospholipid Syndrome; Factor Xa Inhibitors; Humans; Rivaroxaban; Vitamin K

Topics: Anticoagulants; Antiphospholipid Syndrome; Factor Xa Inhibitors; Humans; Rivaroxaban; Vitamin K

Topics: 4-Hydroxycoumarins; Adult; Aftercare; Anticoagulants; Antiphospholipid Syndrome; England; Factor Xa Inhibitors; Fibrin Fibrinogen Degradation Products; Heparin, Low-Molecular-Weight; Humans; Incidence; Indenes; International Normalized Ratio; Neoplasms; Pyrazoles; Pyridones; Risk Assessment; Rivaroxaban; State Medicine; Systematic Reviews as Topic; Thrombophilia; Vena Cava Filters; Venous Thromboembolism; Vitamin K

A 46-year-old man with antiphospholipid syndrome (APS) and previous pulmonary embolism on anticoagulation with rivaroxaban was brought in to the hospital after a syncopal episode. He was found to be hypotensive and tachycardic and later admitted to the intensive care unit. Clinical presentation and laboratory findings were consistent with adrenal insufficiency. MRI revealed bilateral adrenal haemorrhage and he received appropriate steroid replacement therapy. Symptoms slowly subsided and anticoagulation regimen was changed to warfarin. Adrenal haemorrhage was likely caused by APS and rivaroxaban, which brings into question whether novel oral anticoagulants are safe in this patient population.

Topics: Adrenal Gland Diseases; Adrenal Insufficiency; Anticoagulants; Antiphospholipid Syndrome; Hemorrhage; Heparin; Humans; Male; Middle Aged; Pulmonary Embolism; Rivaroxaban; Treatment Outcome; Warfarin

Topics: Anticoagulants; Antiphospholipid Syndrome; Factor Xa Inhibitors; Humans; Rivaroxaban; Vitamin K

Topics: Administration, Oral; Antibodies, Antiphospholipid; Anticoagulants; Antiphospholipid Syndrome; beta 2-Glycoprotein I; Factor Xa Inhibitors; Humans; Lupus Coagulation Inhibitor; Meta-Analysis as Topic; Prospective Studies; Randomized Controlled Trials as Topic; Rivaroxaban; Thromboembolism; Vitamin K; Warfarin

Topics: Anticoagulants; Antiphospholipid Syndrome; Humans; Rivaroxaban; Vitamin K; Warfarin

Topics: Anticoagulants; Antiphospholipid Syndrome; Equivalence Trials as Topic; Factor Xa Inhibitors; Hemorrhage; Humans; Recurrence; Rivaroxaban; Secondary Prevention; Stroke; Thrombosis; Vitamin K; Warfarin

Topics: Anticoagulants; Antiphospholipid Syndrome; Humans; Rivaroxaban; Thrombosis; Vitamin K

Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterised by thromboembolic events including venous thromboembolism (VTE) in association with the presence of antiphospholipid antibodies. The standard treatment of VTE historically consists of anticoagulation therapy with warfarin, a vitamin K antagonist. Recently, direct oral anticoagulants, including rivaroxaban have become available for the treatment of VTE. However, the choice of anticoagulant, and the duration of anticoagulation in patients with APS has not been determined yet due to lack of evidence. Here, we report a case of recurrent venous thrombosis after discontinuation of rivaroxaban therapy and avoiding sedentary lifestyle in a patient with APS. We suggest that indefinite anticoagulation therapy might be needed even in low-risk APS cases.

Topics: Aftercare; Antiphospholipid Syndrome; Factor Xa Inhibitors; Fibrin Fibrinogen Degradation Products; Humans; Male; Middle Aged; Pulmonary Embolism; Recurrence; Rivaroxaban; Tomography, X-Ray Computed; Treatment Outcome; Venous Thromboembolism; Venous Thrombosis

We and others have previously highlighted the potential problems with testing of lupus anticoagulants (LA) in patients on anticoagulant therapy, including most recently as related to the direct oral anticoagulants (DOACs). Thus, current DOACs in use (e.g., dabigatran, a direct thrombin inhibitor, and apixaban and rivaroxaban, both direct Xa inhibitors), affect a wide variety of coagulation assays, including those used in LA investigation. The Russell viper venom time (RVVT) assay in particular, key to the investigation of LA, is highly sensitive to DOACs. LA is a marker of thrombophilia, and patients who have had a thrombosis may be placed on a DOAC. Thus, there is a high likelihood that LA testing will be requested on patients whilst they are on DOACs. In the current report, we have assessed data from our facility for the past two and a half years for all LA tests performed by RVVT testing, and have evaluated this data with respect to patient anticoagulant status. In total, there were 7170 test requests for RVVT associated testing during the period of data capture. Most LA-RVVT screen results (5008; ∼70%) were within normal limits, thereby excluding LA by RVVT method in most of the patient cohort. All DOACs led to a prolongation in both RVVT screen and confirm assays. However, rivaroxaban affected the screen more than the confirm, leading to higher RVVT ratios, whereas apixaban affected the confirm more than the screen, leading to lower RVVT ratios. LA testing in the presence of DOACs also led to lower intra-patient consistency in LA test results. We conclude that ex-vivo data appears to confirm the potential for false positive (with rivaroxaban) and potential for false negative (with apixaban) identification of LA in patients on DOAC treatment. We also make some recommendations in regards to such testing.

Topics: Anticoagulants; Antiphospholipid Syndrome; Blood Coagulation; Blood Coagulation Tests; Dabigatran; False Negative Reactions; False Positive Reactions; Humans; Lupus Coagulation Inhibitor; Prothrombin Time; Rivaroxaban; Thrombophilia

Background Direct oral anticoagulants (DOACs) cause false positive lupus anticoagulant (LA) results. We assessed the impact of DOAC-Stop, reversing in vitro effects of DOACs, on LA testing in anticoagulated patients. Methods We assessed 75 venous thromboembolism patients aged 44.5±14.6 years. Blood samples were collected 2-28 h since intake of DOACs, including 50 patients on rivaroxaban, 20 on dabigatran and five on apixaban. LA testing was performed at baseline and after DOAC-Stop treatment. Positive LA was defined as the normalized (patient/standard plasma clotting time) LA screening and screening (LA1)/confirmation (LA2) ratios exceeding 1.2. Results LA diluted Russell's viper venom time (dRVVT) normalized screening test revealed abnormal results in 73 (97.3%) and activated partial thromboplastin time (APTT)-LA in 49 (65.3%) patients. In six (8%) patients, antiphospholipid syndrome (APS) was diagnosed. dRVVT LA1/LA2 was abnormal in 35 (50.7%) patients taking DOACs. The APTT ratio was normal in all studied subjects. DOAC-Stop completely removed dabigatran and reduced by 98% rivaroxaban and by 92.3% apixaban concentrations (all p<0.05). After DOAC-Stop screening dRVVT remained prolonged in 34 (49.3%) patients (p<0.001), while dRVVT LA1/LA2 was abnormal in six (8.7%) subjects, with no association with DOAC concentrations at baseline and after DOAC-Stop. The APTT-LA screening test remained prolonged in five (7.2%) patients, while the APTT LA1/LA2 ratio was normal in those subjects. DOAC-Stop did not influence LA testing in APS patients. Conclusions Application of DOAC-Stop effectively reduced plasma DOAC concentrations leading to appropriate dRVVT results in up to 97% of VTE patients.

Topics: Administration, Oral; Adult; Anticoagulants; Antiphospholipid Syndrome; Blood Coagulation; Blood Coagulation Tests; Dabigatran; Factor Xa Inhibitors; False Positive Reactions; Female; Humans; Lupus Coagulation Inhibitor; Male; Middle Aged; Partial Thromboplastin Time; Plasma; Prothrombin Time; Pyrazoles; Pyridones; Rivaroxaban; Venous Thromboembolism

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.

Topics: Administration, Oral; Anticoagulants; Antiphospholipid Syndrome; Factor Xa Inhibitors; Female; Humans; Middle Aged; Rivaroxaban; Secondary Prevention; Thrombosis; Warfarin

Topics: Anticoagulants; Antiphospholipid Syndrome; Humans; Rivaroxaban; Warfarin

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.. 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.. 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.

Topics: Anticoagulants; Antiphospholipid Syndrome; Female; Humans; Middle Aged; Prospective Studies; Pyrazoles; Pyridones; Rivaroxaban

: 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 69 ± 11%: 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 (12 012 vs. 446.4 euros, P < 0.0001), and in spite of lower laboratory (738 vs. 1853 euros, P < 0.0001) and human costs (774.6 vs. 4841 euros), RRX thromboprophylaxis still yielded a hefty bill (13 525 vs. 7140 euros, P < 0.0001). 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.

Topics: Administration, Oral; Anticoagulants; Antiphospholipid Syndrome; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Rivaroxaban; Warfarin

Topics: Anticoagulants; Antiphospholipid Syndrome; Factor Xa Inhibitors; Humans; Rivaroxaban; Thrombosis

Topics: Anticoagulants; Antiphospholipid Syndrome; Factor Xa Inhibitors; Humans; Rivaroxaban; Thrombosis

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.

Topics: Acute Disease; Aged; Antiphospholipid Syndrome; Diagnosis, Differential; Factor Xa Inhibitors; Female; Humans; Mesenteric Veins; Rivaroxaban; Tomography, X-Ray Computed; Treatment Outcome; Venous Thrombosis

Topics: Anticoagulants; Antiphospholipid Syndrome; Humans; Rivaroxaban; Stroke; Warfarin

Topics: Antiphospholipid Syndrome; Cerebral Infarction; Diagnosis, Differential; Edema; Electrocardiography; Factor Xa Inhibitors; Female; Humans; Leg; Middle Aged; Rivaroxaban

Topics: Adult; Anticoagulants; Antiphospholipid Syndrome; Female; Humans; Rivaroxaban; Warfarin

Background Direct oral anticoagulants (DOACs) demonstrate a lower risk-benefit ratio than vitamin K antagonists (VKAs) for secondary thromboprophylaxis of thrombotic events. But there are no data on the efficacy of DOACs for the prevention of thrombotic recurrence in patients with antiphospholipid syndrome (APS). In this study, we evaluated the efficacy of DOACs to prevent recurrences of thrombotic events in patients with APS. Methods This was a single-center pilot, using a multi-step Fleming design. If seven or fewer patients presented treatment failure with rivaroxaban, the study could conclude efficacy. Results A total of 23 patients were included. APS involved the veins only ( n = 19), arteries only ( n = 2) or both ( n = 1) and 1 patient exhibited catastrophic antiphospholipid syndrome (CAPS). Overall, two patients were positive for lupus anticoagulant, anti-beta-2 glycoprotein I antibodies and anticardiolipid antibodies (triple positivity). The mean duration of follow up was 35.6 (range, 29-40) months. A total of six treatment failures were reported: one patient, with triple positivity, developed bilateral distal pulmonary embolism (PE) after 20 months of treatment with rivaroxaban, two patients refused to take rivaroxaban, the treatment was stopped in three other patients: two with adverse effects and one with chronic iron-deficiency anemia. Conclusions Rivaroxaban may represent an alternative for secondary thromboprophylaxis for thrombo-embolism in patients with APS, in particular, those with poor international normalized ratio (INR) control and those who are not at the highest risk of recurrent thrombosis, such as those with triple positivity.

Topics: Administration, Oral; Adult; Antibodies, Anticardiolipin; Anticoagulants; Antiphospholipid Syndrome; beta 2-Glycoprotein I; Cohort Studies; Female; Follow-Up Studies; Humans; Lupus Coagulation Inhibitor; Male; Middle Aged; Pilot Projects; Pulmonary Embolism; Rivaroxaban; Thrombosis; Young Adult

Topics: Adult; Anticoagulants; Antiphospholipid Syndrome; Female; Humans; Male; Middle Aged; Rivaroxaban; Thrombosis; Treatment Failure; Young Adult

Topics: Adult; Antiphospholipid Syndrome; Female; Humans; Rivaroxaban; Takayasu Arteritis

Topics: Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Antiphospholipid Syndrome; Antirheumatic Agents; Brain; Cerebral Veins; Diagnosis, Differential; Factor Xa Inhibitors; Humans; Hydroxychloroquine; Intracranial Thrombosis; Magnetic Resonance Imaging; Male; Plasma Exchange; Receptors, N-Methyl-D-Aspartate; Rivaroxaban; Treatment Outcome; Young Adult

Topics: Antiphospholipid Syndrome; Factor Xa Inhibitors; Humans; Lupus Erythematosus, Systemic; Rivaroxaban; Thrombosis; Warfarin

Direct oral anticoagulants have been shown safe and effective in the treatment of pulmonary emboli and deep vein thrombi. Their role in the treatment of patients with hypercoagulability is uncertain. We designed a retrospective exploratory analysis of all patients with definite heparin induced thrombocytopenia (HIT) and antiphospholipid syndrome (APS) that were treated with either apixaban or rivaroxaban from September 2011 through November 2015. Patients were reviewed for several clinico-pathologic features, including efficacy and safety. 23 patients were identified (12 patients with HIT and 11 patients with APS). Sixteen patients (70 %) were treated with apixaban and seven patients (30 %) were treated with rivaroxaban over a median follow up of 7 months (range 2-39). Zero patients developed recurrent thrombi. Two patients being treated for HIT developed major bleeding leading to discontinuation of all anticoagulation. Therefore, apixaban and rivaroxaban appear safe and effective for treatment of patients with HIT and APS in this small retrospective cohort and should be considered on an individual basis for patients who refuse, fail or are intolerant of warfarin. There were no sources of funding.

Topics: Adult; Aged; Anticoagulants; Antiphospholipid Syndrome; Female; Hemorrhage; Heparin; Humans; Male; Middle Aged; Pyrazoles; Pyridones; Recurrence; Retrospective Studies; Rivaroxaban; Thrombophilia; Thrombosis

Antiphospholipid syndrome (APS) is a common acquired thrombophilia associated with a high thrombotic risk, in which vitamin K antagonists (VKA) represent the mainstay of therapy. Case series involving up to 35 patients with APS suggested limited efficacy and safety of direct oral anticoagulants (DOACs).. In the prospective case series we followed 56 consecutive patients with APS (44 women and 12 men, aged from 22 to 64years), including 33 (60%) associated with systemic lupus erythematosus (SLE) and 16 (28.6%) with triple APS who were treated with DOACs due to their preferences or unstable anticoagulation with VKA. DOACs were started at least 3months since the thromboembolic event in patients with D-dimer below 500ng/ml.. Forty-nine (87.5%) patients were treated with rivaroxaban, 4 (7.3%) with dabigatran and 3 (5.4%) with apixaban. During follow-up of 2 to 43 (mean 22) months, 6 (10.7%, 5.8 per 100 patient-years) patients (4 women and 2 men, 4 with triple positive APS) experienced recurrent thrombosis, including deep vein thrombosis (n=4, including 2 episodes preceded by nonadherence), superficial vein thrombosis (n=1) and non-ST elevation myocardial infarction (n=1). The recurrence rate of VTE on DOACs was 5.8 per 100 patient-years. Two patients (3.6%) experienced severe bleeding.. This case-series suggests that DOACs are safe in patients with APS. These findings need to be confirmed in larger studies.

Topics: Administration, Oral; Adult; Anticoagulants; Antiphospholipid Syndrome; Dabigatran; Female; Hemorrhage; Humans; Male; Middle Aged; Prospective Studies; Pyrazoles; Pyridones; Rivaroxaban; Thrombosis; Vitamin K; Young Adult

Topics: Antiphospholipid Syndrome; Elapid Venoms; Female; Humans; Lupus Coagulation Inhibitor; Male; Rivaroxaban

The current treatment for antiphospholipid syndrome (APS) with thrombotic manifestation is long-term anticoagulation. Vitamin K antagonists (VKA) are usually the agents of choice. However, VKA limitations, such as unpredictable anticoagulation effects due to interaction with diet and other drugs, require regular monitoring. This may impact on patients' quality of life. Since the approval of new oral anticoagulants (NOAC) for non-valvular atrial fibrillation and deep vein thrombosis prevention, much has been speculated about its use in APS patients. We report here a series of eight APS patients with failure of thrombotic prevention during rivaroxaban use. All patients had venous thrombosis as the initial manifestation of APS, and two of them also had arterial manifestations. Three patients had triple antibody positivity. Five patients developed arterial events during the treatment with rivaroxaban. Until the results of ongoing trials of rivaroxaban for APS are presented, NOAC should not be recommended to APS patients. Our preliminary experience as well cases previously reported in the literature suggest that there is a high-risk group that is less protected with rivaroxaban, namely those with previous arterial thrombosis or triple positivity. VKA remains to be the mainstay treatment for thrombotic APS.

Topics: Adolescent; Adult; Anticoagulants; Antiphospholipid Syndrome; Female; Humans; Male; Middle Aged; Rivaroxaban; Thrombosis

The aim of this study was to describe a case series of patients with primary or secondary antiphospholipid syndrome (APS) treated with direct oral anticoagulants (DOACs).. Clinical charts of eight patients with thrombotic primary or secondary APS treated with direct oral anticoagulants (DOACs) between January 2012 and May 2015 were reviewed.. The mean age was 45 ± 14.36 (range 27-69 years). Four patients had secondary APS (50%). All patients were initially treated with warfarin by a mean time of 70.87 ± 57.32 months (range 17-153 months). Changes in anticoagulation were defined by recurring thrombosis in five patients (62.5%) and life-threatening bleeding in the other three cases. Seven patients (87.5%) received rivaroxaban treatment and one patient (12.5%) apixaban. The mean follow-up period with DOACs was 19 ± 10.06 months (range 2-36 months). There was no recurrence of thrombosis by the time of data collection.. Despite not being the standard treatment in APS, we propose DOACs as a rational alternative for the management of patients with this diagnosis. Further interventional clinical studies are necessary for possible standardization of this therapy in APS patients.

Topics: Administration, Oral; Adult; Aged; Anticoagulants; Antiphospholipid Syndrome; Female; Follow-Up Studies; Hemorrhage; Humans; Middle Aged; Pyrazoles; Pyridones; Recurrence; Retrospective Studies; Rivaroxaban; Thrombosis; Treatment Outcome; Warfarin

Topics: Antiphospholipid Syndrome; Bipolar Disorder; Disease Management; Factor Xa Inhibitors; Female; Heart Valve Prosthesis Implantation; Humans; Middle Aged; Mitral Valve Annuloplasty; Mitral Valve Insufficiency; Rivaroxaban; Stroke; Treatment Outcome; Venous Thrombosis

Essentials Complement activation has a pathogenic role in thrombotic antiphospholipid syndrome (APS). Coagulation proteases such as factor Xa can activate complement proteins. Complement activation markers were elevated in anticoagulated thrombotic APS patients. Complement activation decreased in APS patients switching from warfarin to rivaroxaban.. Background Complement activation may play a major role in the pathogenesis of thrombotic antiphospholipid syndrome (APS). Coagulation proteases such as factor Xa can activate complement proteins. Aims To establish whether rivaroxaban, a direct factor Xa inhibitor, limits complement activation compared with warfarin in APS patients with previous venous thromboembolism (VTE). Methods A total of 111 APS patients with previous VTE, on warfarin target INR 2.5, had blood samples taken at baseline and at day 42 after randomization in the RAPS (Rivaroxaban in Antiphospholipid Syndrome) trial. Fifty-six patients remained on warfarin and 55 switched to rivaroxaban. Fifty-five normal controls (NC) were also studied. Markers of complement activation (C3a, C5a, terminal complement complex [SC5b-9] and Bb fragment) were assessed. Results APS patients had significantly higher complement activation markers compared with NC at both time-points irrespective of the anticoagulant. There were no differences between the two patient groups at baseline, or patients remaining on warfarin at day 42. In 55 patients randomized to rivaroxaban, C3a, C5a and SC5b-9 were lower at day 42 (median (ng mL

Topics: Adult; Anticoagulants; Antiphospholipid Syndrome; Blood Coagulation; Complement Activation; Factor Xa; Factor Xa Inhibitors; Female; Humans; Inflammation; International Normalized Ratio; Male; Middle Aged; Rivaroxaban; Thrombosis; Venous Thromboembolism; Warfarin

Topics: Antiphospholipid Syndrome; Humans; Lupus Erythematosus, Systemic; Rivaroxaban; Thrombosis; Warfarin

Topics: Adult; Anticoagulants; Antiphospholipid Syndrome; Female; Humans; Lupus Erythematosus, Systemic; Male; Middle Aged; Pregnancy; Pregnancy Complications; Rivaroxaban; Secondary Prevention; Venous Thromboembolism; Warfarin; Young Adult

Rivaroxaban can affect lupus anticoagulant (LA) testing and antiphospholipid antibodies (aPL) may interfere with the anticoagulant action of rivaroxaban.. To establish the influence of rivaroxaban on LA detection and of aPL on the anticoagulant action of rivaroxaban.. Rivaroxaban and 52 IgG preparations (20 LA+ve, 12 LA-ve thrombotic antiphospholipid syndrome [APS] patients, and 20 normal controls [NC]) were spiked into pooled normal plasma (PNP) for relevant studies. LA detection was also studied in APS patients receiving rivaroxaban 20 mg once daily.. In vitro spiking of samples with rivaroxaban showed no false positive LA with Textarin time, Taipan venom time/Ecarin clotting time (TVT/ECT), dilute prothrombin time (dPT) and in-house dilute Russell's viper venom time (DRVVT), but false positives in the majority of NC and LA negative IgG with two commercial DRVVT reagents at 250 ng/mL but not 50 ng/mL rivaroxaban. Ex vivo studies: six LA+ve patients on rivaroxaban remained LA positive with TVT/ECT and DRVVT at peak (162-278 ng/mL) and trough (30-85 ng/mL) rivaroxaban levels. Six LA-ve patients became (apparently) LA+ve with two DRVVT reagents (test/confirm ratio median [confidence interval], 1.6 [1.3-1.8], 1.6 [1.4-1.9]) but not with TVT/ECT at peak rivaroxaban levels, and remained LA-ve with both DRVVT reagents and TVT/ECT at trough levels. aPL positive IgG spiking of PNP had no effect on rivaroxaban's anticoagulant action on thrombin generation or rivaroxaban anti-Xa levels.. The TVT/ECT ratio and Textarin time were not affected even at peak rivaroxaban levels, enabling detection of LA ex vivo. aPL had no effects on rivaroxaban's anticoagulant action in vitro.

Topics: Antibodies, Antiphospholipid; Antiphospholipid Syndrome; Biomarkers; Blood Coagulation; Blood Coagulation Tests; Case-Control Studies; Factor Xa Inhibitors; False Positive Reactions; Humans; Immunoglobulin G; Lupus Coagulation Inhibitor; Predictive Value of Tests; Reproducibility of Results; Rivaroxaban; Thrombosis; Treatment Outcome

Topics: Adolescent; Adult; Aged; Anticoagulants; Antiphospholipid Syndrome; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Rivaroxaban; Venous Thromboembolism; Vitamin K; Young Adult

A 77-year-old woman with atrial fibrillation (AF) treated with warfarin had a cortical left middle cerebral artery (MCA) stroke (October 2009, international normalized ratio [INR], 1.6) and a cortical left frontal stroke (October 2011, INR, 1.9). Anticoagulation was adjusted. In October 2011, she had a right frontal stroke (INR, 2.3). Acetylsalicylic acid (ASA) was temporally added to the treatment. In June 2013, she had a left occipital stroke (INR, 2.3). Warfarin was changed to rivaroxaban. In August 2013, she had a right occipital stroke. ASA 100 was added to the treatment. On all occasions, repeated neurovascular studies and echocardiography were normal. Diagnoses were cardioembolic stroke. In November 2013, she was admitted because of a left MCA stroke. A complete blood analysis showed the presence of anticardiolipin, anti-b2-glycoprotein antibodies, and lupus anticoagulant. Primary antiphospholipid syndrome (APS) was later confirmed. APS should be considered in young stroke patients, however is not frequent in stroke patients older than 70 years with several cerebrovascular risk factors. The existence of AF in our patient with several embolic strokes made the cardiembolic etiology likely. Uncommon causes of stroke were not considered despite the repetition of the ischemic events. Thus, a wider etiological study should be made in all patients with a recurrent stroke regardless of age, such as a complete blood analysis including immunology study in order to exclude an APS of late onset.

Topics: Aged; Antiphospholipid Syndrome; Atrial Fibrillation; Female; Humans; Magnetic Resonance Imaging; Rivaroxaban; Stroke; Warfarin

We herein report a case presenting with cerebral venous sinus thrombosis (CVST) associated with primary antiphospholipid syndrome (APS). The patient developed recurrent CVST followed by a hemorrhagic ischemic stroke despite the use of warfarin during the appropriate therapeutic window. Thus, we substituted warfarin to rivaroxaban with prednisolone and obtained a good clinical course. In addition to the effect of prednisolone of inhibiting elevated lupus anticoagulants and the recurrence of arterial thrombosis, rivaroxaban may prevent CVST and inhibit hypercoagulability induced by corticosteroids. The combination of an anti-Xa inhibitor and corticosteroid may be an alternative treatment for CVST and arterial thrombus with warfarin-resistant APS.

Topics: Adrenal Cortex Hormones; Anticoagulants; Antiphospholipid Syndrome; Drug Therapy, Combination; Factor Xa Inhibitors; Humans; Male; Middle Aged; Rivaroxaban; Stroke; Thrombosis; Venous Thromboembolism; Warfarin

Topics: Administration, Oral; Adult; Anticoagulants; Antiphospholipid Syndrome; Antithrombins; Benzimidazoles; beta-Alanine; Dabigatran; Female; Humans; Male; Middle Aged; Morpholines; Rivaroxaban; Thiophenes; Venous Thromboembolism

Direct oral factor inhibitors (DOFIs) are an attractive alternative to vitamin K antagonists (VKA) for the treatment of patients with antiphospholipid syndrome (APS). In the absence of prospective, randomised trial data, reports of therapeutic failures in clinical practice alert clinicians to potential limitations of DOFI therapy for this indication. Data for all cases were collected from a centralised system that contains complete medical records of all patients treated and followed at Mayo Medical Center. We present here three consecutive APS patients who had had no thromboembolism recurrence on warfarin but were switched to DOFIs. The diagnosis of APS was established according to currently recommended criteria. The three cases were as follows: A woman with primary APS developed thrombotic endocarditis with symptomatic cerebral emboli after transition to dabigatran. A second woman with primary APS experienced ischemic arterial strokes and right transverse-sigmoid sinus thrombosis after conversion to rivaroxaban. A man with secondary APS suffered porto-mesenteric venous thrombosis after switching to rivaroxaban. None of these patients had failed warfarin prior to the transition to DOFIs. Based on these three cases, we advocate caution in using DOFIs for APS patients outside of a clinical trial setting, until further data becomes available.

Topics: Adult; Anticoagulants; Antiphospholipid Syndrome; Benzimidazoles; beta-Alanine; Cerebral Infarction; Dabigatran; Drug Substitution; Female; Humans; International Normalized Ratio; Lupus Erythematosus, Systemic; Male; Mesenteric Veins; Middle Aged; Morpholines; Portal Vein; Recurrence; Retrospective Studies; Rivaroxaban; Splenic Vein; Stroke; Thiophenes; Thromboembolism; Thrombophilia; Treatment Failure; Venous Thrombosis; Warfarin

Topics: Adult; Antiphospholipid Syndrome; Factor Xa Inhibitors; Female; Humans; Morpholines; Rivaroxaban; Thiophenes; Thrombophlebitis; Treatment Outcome

The diagnosis of the antiphospholipid syndrome (APS) is based on clinical and biological criteria including the persistent presence of antiphospholipid antibodies and thrombotic events or pregnancy morbidity. Heparins relayed by vitamin K antagonists (VKA) are the gold standard treatment for thrombosis.. We report a 17-year-old man who presented with an initially seronegative antiphospholipid syndrome, in whom the diagnosis was late, only obtained after anticoagulation withdrawing, when a catastrophic antiphospholipid syndrome (CAPS) with cutaneous lesions and disseminated intravascular coagulation syndrome occurred. For personal convenience, this patient was initially treated with fondaparinux followed by a new oral anticoagulant (rivaroxaban) before to return to the conventional VKA treatment.. The "seronegative" APS is a controversial concept reflecting the heterogeneity of antigenic targets for aPL. This diagnosis may be considered after a rigorous work-up, with the help of haemostasis laboratories testing new emerging aPL assays. In APS, the new anticoagulants represent an attractive option needing nevertheless prospective studies to evaluate their safety and efficacy. Lupus anticoagulant detection in patients treated by new oral anticoagulants is not easy by usually recommended coagulation tests.

Topics: Adolescent; Antibodies, Antiphospholipid; Anticoagulants; Antiphospholipid Syndrome; Disseminated Intravascular Coagulation; Factor Xa Inhibitors; Fondaparinux; Humans; Male; Morpholines; Polysaccharides; Rivaroxaban; Thiophenes

Topics: Animals; Anticoagulants; Antiphospholipid Syndrome; Biomarkers; Blood Coagulation; Blood Coagulation Tests; Case-Control Studies; Endopeptidases; Humans; Lupus Coagulation Inhibitor; Morpholines; Peptide Hydrolases; Predictive Value of Tests; Prothrombin; Rivaroxaban; Thiophenes; Time Factors