Target INR Research Articles

Nonalcoholic fatty liver disease impacts the control of the international normalized ratio in patients with atrial fibrillation.

BackgroundIt is unclear whether the therapeutic effect of warfarin in patients with atrial fibrillation (AF) and normal liver function differs between those with and without nonalcoholic fatty liver disease (NAFLD). With this in mind, we aimed to evaluate the impact of NAFLD on the international normalized ratio (INR) control in warfarin-treated AF patients with normal liver function.MethodsWe enrolled 600 AF patients aged 28–94 (median 68) with normal liver function who were receiving daily warfarin therapy, 172 with NAFLD and 428 without. The INR and INR/warfarin dosage rate were measured. Four nested multivariable linear regression models adjusted for potential confounders were used to assess whether there were differences in INR and INR/warfarin dose rate between patients with and without NAFLD.ResultsThe INR, the percentage of patients with INR within the target range of 2.0–3.0, and the INR/warfarin dose rate were lower in patients with NAFLD than those without. In the maximally adjusted multivariable linear regression models, the INR in NAFLD patients (0.22±0.07, P=0.003) was lower than in non-NAFLD patients, and the INR/warfarin dose rate was slightly lower (0.09±0.06, P=0.10) in NAFLD than in non-NAFLD patients.ConclusionsOur findings suggest that among AF patients, the therapeutic effect of warfarin is impaired in patients who have NAFLD. Therefore, a slightly higher or personally optimized dosage of warfarin might be necessary among AF patients with NAFLD in order to achieve the INR target range.

Impact of bariatric surgery on oral anticoagulants pharmacology, and consequences for clinical practice: a narrative review.

The prevalence of obesity has been steadily increasing in recent years worldwide. At the same time bariatric surgery, the best therapeutic strategy to date in terms of sustainable weight loss and improvement of associated comorbidities has been also increasing. However, these surgeries, whether primarily restrictive or malabsorptive, raise questions about the pharmacology of oral drugs. Among widely used drugs, anticoagulants are the referent therapy to treat some cardiovascular diseases such as atrial fibrillation and venous thromboembolism. How bariatric surgery may impact pharmacological properties of oral anticoagulants, and more specifically, direct oral anticoagulants (DOACs) are difficult to anticipate. In this review, we describe available data concerning the potential impact of bariatric surgery on the pharmacology of oral anticoagulants. The vitamin K antagonists (VKAs) requirements for the same international normalized ratio target are reduced after bariatric surgery. Limited data available for dabigatran 150mg twice daily indicate a risk of insufficient efficacy in atrial fibrillation after gastric bypass due to probable impaired absorption. Data for rivaroxaban at the prophylactic dose of 10mg per day suggest no impact of bariatric surgery from 3days to 8months post-surgery. However, no conclusive data are available for other anticoagulants or the use of DOACs at therapeutic doses. To date, DOACs are not recommended in patients who have undergone bariatric surgery, because of limited available data. Pending new studies to confirm the predictable pharmacokinetics and safety of DOACs in this population, especially at therapeutic doses, VKAs remain the first option for chronic anticoagulation.

Multi-centered evaluation of a novel fixed-dose four-factor prothrombin complex concentrate protocol for warfarin reversal

IntroductionPrevious studies have shown fixed-dose 4PCC to be as effective as standard-dose 4PCC for warfarin reversal. However, certain patient populations such as those with high total body weight (TBW) or elevated baseline INR may be at increased risk for treatment failure. The purpose of this study was to validate the efficacy of a novel fixed-dose 4PCC protocol for warfarin reversal. MethodsThis was a multi-centered observational comparison of patients who received 4PCC for warfarin reversal. Fixed-dose patients received 1500 units of 4PCC with the dose increased to 2000 units in patients with a baseline INR ≥ 7.5, a TBW ≥ 100 kg, or for intracranial hemorrhage (ICH). Standard-dosing followed manufacturer recommendations. The primary outcome was achievement of a post-4PCC INR of ≤1.4. Secondary outcomes included target INR achievement among patients with a baseline INR ≥ 7.5, a TBW ≥ 100 kg, or neurologic bleeding indications; hospital length of stay; cost of therapy; and thromboembolic complications. ResultsA total of 116 patients were included in the standard-dose group and 75 in the fixed-dose group. There was no difference in the primary outcome (65% vs 57%, p = 0.32). There was no difference in secondary outcomes aside from cost of therapy in which fixed-dose 4PCC was less expensive than standard-dose 4PCC. ConclusionA fixed-dose 4PCC regimen for warfarin reversal of 1500 units, with an increased dose of 2000 units for select patients, is as effective as standard-dose 4PCC for INR reversal.

Safety and effectiveness of a four-factor prothrombin complex concentrate for vitamin K antagonist reversal following a fixed-dose strategy

ObjectivesEarly reversal of anticoagulation improves outcomes in major bleeding and emergency surgery. To reverse vitamin K antagonists (VKA), vitamin K in addition to prothrombin complex concentrate (PCC) is recommended. Dosing...

Safety of low intensity oral anticoagulant therapy in patients with bileaflet mechanical aortic valve prosthesis: A propensity weighted study

BackgroundScarce data are available on the long-term outcomes of different regimens of oral anticoagulation in an all comer population of patients undergoing aortic valve replacement with a bileaflet mechanical heart valve. MethodsOutcomes of 88 patients discharged with a target INR of 2.0 (LOW-INR) were compared to 147 contemporary patients who have been recommended a target INR of 2.5 (CONV). Primary outcome was the composite of any thromboembolic or haemorrhagic events. Secondary outcomes were the individual components of the primary outcome, cardiovascular mortality and stroke. To reduce selection bias, a propensity weighted analysis was performed. ResultsAfter inverse probability of treatment weighting, the primary endpoint occurred in 0.7% of patient in the LOW-INR group and in 7.0% in the CONV group (p = .0255). Linearized event rate were significantly lower in the LOW-INR group (primary endpoint: rate difference − 12.0 per 1000 patient/years, p = .0052; haemorrhage: −5.8 per 1000 patient/years, p = .0330; neurological events: −7.6 per 1000 patient/years, p = .0140). Conventional target INR was associated with an increased hazard of the composite endpoint (HR 11.193, 95% CI 1.424–88.003, p = .0217). ConclusionsLowering the intensity of oral anticoagulation resulted in a relevant clinical benefit of reduced rates of haemorrhagic and neurological adverse events in the mid-term follow-up. This report confirms the safety profile of the low INR regimen in an all comer population undergoing aortic valve replacement with an Abbott mechanical valve.

International Normalized Ratio Test Frequency in Left Ventricular Assist Device Patients Affects Anticoagulation Quality and Adverse Events.

Anticoagulation therapy in patients using left ventricular assist device (LVAD) is essential to reduce hemocompatibility related adverse events (HRAEs). Vitamin K-antagonist dosage must be adapted and monitored by INR point-of-care testing (POCT) in outpatients. The study aims to determine if the frequency of INR POCT in LVAD outpatients has an influence on the quality of anticoagulation therapy (ACQ), HRAEs, and outcomes. This retrospective study included n = 48 patients who received LVAD implantation (HMII, HM3, and HVAD) between 2013 and 2017. ACQ (% of INR tests in range, PTR), outcomes and HRAEs using Kaplan-Meier curves were compared in a daily (n = 36) and 3×/week (n = 12) INR POCT group. Further, based on the achieved PTR ranging from 0-60% (poor), 61-70% (acceptable), and 71-100% (well controlled), HRAEs and outcomes were compared. Daily and 3×/week groups were similar in perioperative risk factors and INR target (p = 0.28). Freedom from any HRAE (38.9% vs. 25.0%, p = 0.44), any readmission (72.2% vs. 75.0%, p = 0.97), and 1 year survival (91.7% vs. 91.7%, p = 0.98) were comparable in both groups. The PTR was significantly higher with the daily self-assessments (73.5% vs. 68.4%, p = 0.006). Well vs. poorly controlled INR POCT patients more often had (p = 0.01) a daily POCT frequency (92%) vs. poorly controlled (54%) and significantly higher freedom from neurologic events (96.0 vs. 69.2%, p = 0.024) as well as hemorrhagic strokes (100% vs. 76.9%, p = 0.011). Well-controlled anticoagulation of LVAD outpatients is associated with less neurologic events. The frequency of INR POCT could be one of the key factors in the reduction of HRAEs, so future prospective, large-scale studies should help to clarify the effects.

P569Efficacy and safety of direct Xa oral inhibitors versus warfarin in patients with atrial fibrillation and cancer: a meta-analysis of randomized controlled trials

Abstract Background Patients with cancer are at higher risk of atrial fibrillation (AF) compared with the general population. Furthermore, cancer per se and anti-cancer treatments have been associated with thromboembolic complications and increased bleeding risk. Considering that only 12% of cancer patients can achieve a stable International Normalized Ratio target and the frequent need for invasive procedures, warfarin is not an ideal option. Direct oral anticoagulants may theoretically represent a valid alternative although their use in this population has been scarcely investigated. Purpose To compare efficacy and safety of direct oral Xa inhibitors (DOXaI) versus warfarin in patients with atrial fibrillation and cancer. Methods We searched electronic databases for randomized controlled trials (RCTs) that analyzed the use of DOXaI versus warfarin in patients with AF and cancer. The primary efficacy outcome was stroke or systemic embolism (SE). The secondary efficacy outcomes were ischemic stroke, myocardial infarction and all-cause death. The primary safety outcome was major bleeding; secondary safety outcomes were major or clinically relevant non-major bleeding, intracranial bleeding and any bleeding. The net clinical benefit was estimated as the composite of the two primary outcomes. A sensitivity analysis was performed to better define the incidence of these outcomes in patients with active cancer. The statistical software ProMeta 3 was used to estimate the risk ratio with a random-effect model. Results 3 RCTs counting a total of 3029 cancer patients (1682 on DOXaI and 1347 on warfarin), 1354 of whom with active cancer (856 on DOXaI and 502 on warfarin), were included in the analysis. Mean age was 75.6 ± 1.2 years, and 32% were female. Mean follow-up period was 2.2 ± 0.6 years. The most common cancer sites were prostate (23%), gastrointestinal tract (22.2%), breast (12.1%) and genitourinary tract (10.6%). The mean CHADS2 score was 2.9 ± 0.6 and the mean HAS-BLED score was 2.6 ± 0.4. There were no significant differences in the risk of stroke or SE (RR 0.76; 95% CI 0.52-1.10) as well as for all the other secondary efficacy outcomes. DOXaI significantly reduced the incidence of major bleeding in the overall cancer population (RR 0.79; 95% CI 0.63-0.99; p = 0.039); this finding was consistent also in patients with active cancer (RR 0.79; 95% CI 0.59-1.05) although the effect was not statistically significant. DOXaI also significantly reduced intracranial bleeding in overall cancer population (RR 0.12; 95% CI 0.02-0.63; p = 0.013) and any bleeding in active cancer patients (RR 0.87; 95% CI 0.77-0.98; p = 0.026). Furthermore, DOXaI significantly reduced the composite endpoints of major bleeding and stroke or SE in overall cancer population (RR 0.78; 95% CI 0.64-0.94; p = 0.008). Conclusions Our metanalysis shows that, in patients with atrial fibrillation and cancer, DOXaI are safer and have a similar efficacy compared with warfarin. Abstract Figure. Primary efficacy and safety outcomes

Emergent Warfarin Reversal With Fixed-Dose 4-Factor Prothrombin Complex Concentrate

Four-factor prothrombin complex concentrate (4FPCC) is used for emergent warfarin reversal, but dosing remains controversial. Following approval, further studies have evaluated a variety of fixed-dose regimens. The studies utilized lower doses as compared with package insert dosing and provided data in regard to efficacy, safety, and cost savings. Further data are needed, however, to determine which fixed-dose regimen provides optimal efficacy and safety for emergent warfarin reversal. The purpose of this study is to evaluate the efficacy, safety, and cost-savings of a fixed-dose 4FPCC protocol. This multicentered, retrospective chart review of adult patients requiring 4FPCC for emergent warfarin reversal utilized a fixed-dose regimen of 1500 units. The 2 primary outcomes were the proportion of patients who achieved a post-4FPCC international normalized ratio (INR) of ≤1.5 and ≤2. Secondary outcomes included thrombotic events within 7 days of 4FPCC administration and survival to discharge. A cost analysis was also performed to identify potential cost savings. Of the 64 patients included, 44 (68.8%) achieved a post-4FPCC INR ≤1.5, and 61 (95.3%) achieved a post-4FPCC INR ≤2.0. No thrombotic events were reported; 55 (85.9%) patients survived to hospital discharge. More than $1000 was saved per patient via utilization of the fixed-dose protocol. A fixed-dose of 1500 units of 4FPCC successfully achieved a target INR of ≤1.5 in the majority of patients and resulted in no thrombotic events. This study adds to the data evaluating alternative 4FPCC dosing regimens in comparison to package insert recommended dosing.

Effect of post-operative anticoagulation management in patients who have undergone On-X mechanical heart valve replacement surgery on post-discharge warfarin therapy.

We evaluated the effect of the proportion of time maintained within the target international normalized ratio (INR) postoperatively in hospitalized patients who underwent On-X mechanical heart valve replacement on warfarin therapy after discharge. Inclusion was patients who were ≥18years, received warfarin for a minimum of 10days without any interruptions during hospitalization and followed by the anticoagulation service (ACS) clinic after discharge between June 2006 and June 2016. Patients were excluded if they had incomplete medical records, INR goal changes, known as warfarin resistance, transferred to another facility or expired during the study. The patients were divided into 3 groups according to the proportion of time maintained within therapeutic INR range (TTR) from day 4 to 10 of warfarin initiation (low: <30%, moderate: ≥30% to <70%, and high: ≥70%). The number of days needed to reach target INR for 2 consecutive measurements after discharge and the number of ACS visits was compared among the groups. Among 539 postoperative patients, 273 were included. The baseline demographics were similar among the 3 groups. The mean time needed to reach target INR for 2 consecutive measurements was 68.6±106.1days. The low group required time needed to reach target INR for 2 consecutive measurements of 94.0±140.9days compared with 44.8±57.1days in the high group (P=.007). Additionally, the low group had more ACS visits than the high group (low, 6.6±5.2 vs high, 4.6±3.9; P=.025). Patient compliance affected the time needed to reach target INR for 2 consecutive measurements (compliant, 42.36±58.5days vs non-compliant, 132.0±157.1days, P<.001). The study implicated that high postoperative TTR would reduce the time to require post-discharge target INR and the number of ACS visits.

Real-world investigation on discontinuation of oral anticoagulation after paroxysmal atrial fibrillation catheter ablation in China.

To find out the real-world investigation on discontinuation of oral anticoagulation after paroxysmal atrial fibrillation (AF) catheter ablation China. We enrolled in our study 1,508 consecutive paroxysmal AF patients who underwent catheter ablation from five centers. Patients' clinical data and follow-up data were collected. Clinical data included on-admission characteristics such as gender, age, type and duration of AF, type of ablation, ablation sessions, history of diseases, CHA2DS2-VASc score, echocardiographic variables, medication, and blood test variables. Follow-up data included duration of follow-up, the status of oral anticoagulant (OAC) therapy, adverse events, and recurrence of AF. A total of 1,491 patients were included in the final analysis, while the other 17 patients lost contact. The follow-up duration was 12 to 74 months (27.8±14.6 months). Of 1,491 patients, 989 (66.3%) patients stopped OAC therapy 3 to 14 months after successful ablation during follow-up. Stroke or transient ischemic attack (TIA) occurred in 37 (2.5%) patients. Major bleeding occurred in 24 (1.6%) patients. Six (0.4%) patients died at follow-up. Patients who stopped OAC had lower CHA2DS2-VASc score (1.5±1.4 vs. 2.4±1.7, P<0.05) and lower incidence of major bleeding (11/989 vs. 13/502, P<0.05). Of 989 patients who stopped OAC, 318 stopped according to doctor's prescription, and 671 stopped on their own decision. In patients who underwent brain MRI, patients who stopped OAC had a lower incidence of silent cerebral infarction (SCI) (37/904 vs. 38/419, P<0.05). Among patients who did not stop warfarin therapy, there were 117 (117/397, 29.5%) patients had not to achieve target INR. The incidence of adverse events was relatively low in paroxysmal AF patients who stopped OAC. The patient partly determined when OAC was discontinued. Target INR was not achieved in many patients who had not to stop OAC.

Pharmacist-led anticoagulation monitoring can significantly improve the effectiveness and safety of warfarin for patients during hospitalization

To investigate the role of pharmacist-led anticoagulation monitoring service for warfarin anticoagulation therapy in patients during hospitalization. We retrospectively analyzed the data of 421 patients receiving warfarin anticoagulation therapy during hospitalization between April, 2016 and December, 2017. Of these patients, 316 received daily pharmacist-led anticoagulation monitoring service including checking the patients' International Normalized Ratio (INR) and other pertinent laboratory test results and reviewing medication changes and the patients' clinical status (monitoring group); the other 105 patients receiving warfarin anticoagulation therapy without pharmaceutical care served as the control group. The data including compliance rate of anticoagulant indicators, incidence and rate of prompt management of INR alert, thrombosis and bleeding events during hospitalization were analyzed among these patients. Compared with the control patients, the patients in the monitoring group showed a significantly higher percentage time within target INR range [(73.20±9.46)% vs (46.32±17.11)%, P &lt; 0.001] and a higher qualified rate of INR before discharge (98.42% vs 60.95%, P &lt; 0.001) as well as a higher proper INR-monitoring frequency (97.15% vs 66.67%, P &lt; 0.001). The patients in the monitoring group showed a significantly lower incidence of INR alert than the control patients (8.23% vs 20.00%, P &lt; 0.001) with also a much higher rate of prompt management (96.15% vs 33.33%). The two groups had similar incidences of clinical events except that the control group reported a higher incidence of minor bleeding episodes (9.52% vs 2.53%, P=0.005). Pharmacist-led anticoagulation monitoring service can significantly improve the effectiveness and safety of warfarin anticoagulation therapy for patients during hospitalization.

Pharmacogenetic-guided and clinical warfarin dosing algorithm assessments with bleeding outcomes risk-stratified by genetic and covariate subgroups

BackgroundSafe administration of warfarin presents challenges due to a narrow therapeutic INR range and significant variability in inter-individual dose response. Bleeding secondary to warfarin use is a leading cause of hospitalization. MethodsFive warfarin dosing algorithms were assessed for accuracy of predicted compared to the INR target dose for patients with a HAS-BLED score ≥3 participating in the ENGAGE-AF TIMI 48 trial. Three warfarin metabolism subgroups (normal, sensitive, and highly sensitive responders) were established based on genotype. Mean differences between calculated and prescribed dose were determined for each algorithm across groups. ResultsA total of 7036 patients were analyzed and 1846 participants with HAS-BLED ≥3 were genotyped. The mean absolute error of predicted versus INR target dose for warfarin ranged from 8.1 mg/week on the pharmacogenetic-guided International Warfarin Pharmacogenetics Consortium (IWPC) and Gage algorithms to 11.3 mg/week on fixed dose. Overestimation of INR target dose occurred in 98% of highly sensitive responders by 21 mg/week for subjects on fixed dose. Pharmacogenetic-guided IWPC saw 89% overestimation with mean difference of 8.3 mg/week for highly sensitive responders. Major or clinically relevant non-major bleeding in the first 90 days of beginning warfarin was 3.27 times more likely for highly sensitive than normal responders. ConclusionsInitial doses were higher than INR target doses in high-risk bleeding subpopulations as defined by the modified HAS-BLED and genotype sensitivity analysis when compared to established algorithms. Clinical and pharmacogenetic-guided algorithms improved dosing in highly sensitive responders with HAS-BLED ≥3 compared to fixed dosing.

Comparison of different bridging anticoagulation therapies used after mechanical heart valve replacement in Chinese patients - a prospective cohort study

ObjectiveTo assess different bridging anticoagulation therapies early after mechanical heart valve replacement (MHVR) in Chinese patients.MethodsWe performed a prospective, single-center, observational cohort study of 305 patients who underwent elective MHVR with different bridging anticoagulation regimens. Patients enrolled in the study were divided into three bridging therapy groups: the unfractionated heparin (UFH) group (n = 109), the low-molecular-weight heparin (LMWH) group (n = 97), and the UFH with sequential LMWH (UFH-LMWH) group (n = 99). All patients were followed for 4 weeks.ResultsTwo patients experienced thromboembolic stroke events in the UFH group. The LMWH group was associated with an increase in the incidence of bleeding events compared with the UFH group (10.3% VS 2.8%; P = 0.03). With a comparison of LMWH and UFH group in secondary endpoints, the statistical test for significance indicated a trend of reduced ICU length of stay (P = 0.08), postoperative length of stay (P = 0.08) and time of achieving target INR (P = 0.06). The creatinine level (odds ratio = 1.03; 95% confidence interval = 1.01 to 1.05; P = 0.02) and hypertension (odds ratio = 3.72; 95% confidence interval = 1.35 to 10.28; P = 0.01) were risk factors for bleeding events.ConclusionFor Chinese patients, the LMWH bridging anticoagulation presents the increased the incidence of bleeding events, but enables patients to benefit from achieving an early anticoagulation effect. Close follow-up and personalized management are required in patients with thromboembolic and bleeding risk factors.Trial registrationChinese Clinical Trial Registry ChiCTR1800019841. Registered 2 December 2018 retrospectively.

Successful percutaneous occlusion of a large left circumflex coronary artery fistula draining into the coronary sinus using a ventricular septal defect occluder: a case report

BackgroundCoronary artery fistula (CAF) is a congenital anomaly of the coronaries that can lead to significant intracardiac shunting and myocardial ischaemia.Case summaryWe describe the case of a 15-year-old male with an incidentally documented precordial cardiac murmur. An evidently dilated coronary sinus (CS) on transthoracic echocardiography prompted further investigation. A computed tomography (CT) revealed the presence of a large CAF from the left circumflex coronary artery to the CS. No other structural heart defects were detected. A haemodynamically significant intracardiac shunt was confirmed during cardiac catheterization, and it was decided to close the fistula. This was successfully performed using a ventricular septal defect (VSD) occluder (Konar 10-8, Lifetech Scientific) that was deployed through a 6 Fr right coronary guiding catheter. A partial thrombotic occlusion of the CS behind the closure device was noted during follow-up which led to anticoagulation in a higher target INR range and concomitant start of low dose carbasalate calcium to reduce further retrograde thrombus extension. Patient is doing well at over 1 year of follow-up, and no further thrombotic extension into the CS was seen on a recent CT.DiscussionThis report illustrates the diagnostic workup and a percutaneous treatment strategy of a CAF using a VSD occluder. We also describe a not previously reported complication, thrombotic CS occlusion. Improving transcatheter techniques and marketing of novel devices with a broad spectrum of applications can offer new opportunities for treating CAF and avoiding surgical correction often involving cardiopulmonary bypass, reserving this option for patients with complex anatomy or failed transcatheter closure.

CYP2C9 and VKORC1 genotyping for the quality of long-standing warfarin treatment in Russian patients.

A total of 263 warfarin naive patients with indications to long-term anticoagulation were included in prospective multicenter study and randomized into Pharmacogenetics and Standard dosing groups. The loading warfarin dose in Pharmacogenetics group was calculated by Gage algorithm and corrected starting on day 5 of treatment according to INR. In Standard dosing group warfarin initial dose was 5 mg and starting on day 3 of treatment it was titrated according to INR. Pharmacogenetics dosing in comparison with prescription of starting dose of 5 mg decreased major bleedings (0 vs. 6, p = 0.031), time to target INR (11 [9-14] vs. 17 [15-24] days, p = 0.046), and frequency of INR fluctuations ≥4.0 (11% vs. 30.9%, p = 0.002). The advantages of the pharmacogenetics dosing were mainly achieved due to the patients with increased warfarin sensitivity.

Treatment of Vascular Thrombosis in Antiphospholipid Syndrome: An Update.

The antiphospholipid syndrome (APS) is an acquired autoimmune disorder associated with arterial, venous, or microvascular thrombosis and/or pregnancy complications mainly in young age. The diagnosis is made by the persistent detection of anticardiolipin antibodies, β2-glycoprotein I antibodies (β2GPIA), and/or lupus anticoagulants (LAs) for at least 12 weeks. Patients should present with at least one clinical and one laboratory criterion. Patients presenting with all three types of antibodies and vascular events are high-risk patients and should receive vitamin K antagonists (VKAs) as long as the antibodies persist. In patients with prior arterial thrombosis, VKA with or without low-dose aspirin is the current treatment of choice. The international normalized ratio (INR) should be between 2 and 3 although in some cases keeping the target INR above 3 may be necessary. Patients with venous thrombosis and negative LA may alternatively be treated with direct oral anticoagulants although more data are needed. Minimizing vascular risk factors is always necessary in APS patients. Aspirin can be given as primary prevention in asymptomatic patients with positive antiphospholipid antibodies without thrombosis or pregnancy complications especially when additional vascular risk factors are present. Catastrophic APS occurs in less than 1% of APS patients and presents as a thrombotic storm. Early use of a combined triple therapy such as anticoagulation, plasma exchange, and steroids with either or not addition of immunoglobulins is important to reduce mortality.

Anticoagulant and anti-thrombotic therapy in acute type B aortic dissection: when real-life scenarios face the shadows of the evidence-based medicine

BackgroundEvidence-based recommendations about anticoagulation in acute type B aortic dissection (TBAD) are completely missing, but there is a diffuse conviction that it could prevent the healing process of the dissected aorta’s false lumen. However, several clinical conditions may lead to the necessity to start anticoagulant therapy among patients with acute type B aortic dissection, ranging from atrial fibrillation to more complicated clinical scenarios and the correct management in this kind of patients is still an open issue.Case presentationWe are presenting a 51-years-old man with multi-infarct encephalopathy referred to us for an acute TBAD and a first diagnosis of ischemic cardiomyopathy complicated by left ventricular (LV) thrombus formation. Coronary angiography revealed a critical stenosis of left anterior descending artery (LAD) treated with drug-eluting stent deployment. The patient was addressed to triple antithrombotic therapy with acetylsalicylic acid, clopidogrel and warfarin with target INR 2.0–2.5. After 6 months, computed tomography angiography revealed the stability of the dissection flap. Cardiac magnetic resonance imaging, however, confirmed the persistence of a small thrombotic formation in LV apex, thus double antithrombotic therapy with warfarin and clopidogrel was instituted. The patient remained asymptomatic during the follow-up period but was advised to suspend his job and physical activities.ConclusionCurrent guidelines do not discuss anticoagulant therapy in the setting of TBAD and large randomized trials are lacking. Despite it is generally considered unsafe to administer anticoagulants in patients with TBAD, we present a case in which triple antithrombotic therapy was well tolerated and did not lead to progression of the intimal flap after 6 months.

Short-term prognosis of breakthrough venous thromboembolism in anticoagulated patients

BackgroundEvidence for guideline recommendations for the treatment of venous thromboembolism (VTE) during anticoagulant therapy is scarce. We aimed to observe and to describe the management of VTE occurring during anticoagulant therapy. MethodsThis prospective multi-center, observational study included patients with objectively confirmed VTE during anticoagulant therapy (breakthrough event), with a follow-up of 3 months, after the breakthrough event. ResultsWe registered 121 patients with a breakthrough event, with a mean age of 56 years (range, 19 to 90); 61 were male (50%). Fifty-eight patients (48%) had an active malignancy. At the time of the breakthrough event, 57 patients (47%) were treated with a vitamin K antagonist (VKA), 53 patients (44%) with low-molecular-weight heparin (LMWH) and 11 patients (9%) with direct oral anticoagulants, unfractionated heparin, or VKA plus LMWH. A total of 21 patients (17%) were receiving a subtherapeutic dose of an anticoagulant. The main regimens to treat recurrence in patients on VKA were: switch to LMWH (33%), temporary double treatment with LMWH and VKA (23%), and VKA with a higher target INR (19%). In patients with a breakthrough on LMWH, the most frequently chosen regimen was a permanent dose increase (74%). During 3-month follow-up, 7% of patients had a second breakthrough event and 8% experienced major or clinically relevant non-major bleeding. ConclusionThere is wide variation in the management of VTE during anticoagulant treatment, reflecting a heterogeneous and complex clinical situation. Despite intensifying anticoagulation, the risk of a second breakthrough event in this population is 7%.

Association between polymorphisms in microRNA seed region and warfarin stable dose

BackgroundThe optimal dose of anticoagulant warfarin varies among patients to achieve the target international normalised ratio. Although genetic variations related to warfarin pharmacokinetics and vitamin K cycle are important factors...

Evaluation of self-testing INR in a French GUCH population with mechanical valve

The Coaguchek INRange® is a self testing meter to measure the INR, that is reimbursed by French Social Security since August 2017 for patients with mechanical valve. We evaluated the use of this anticoagulation method in a French population of GUCH (Grown-Up patients with Congenital Heart Disease) with mechanical valve. Since September 2018, 52 patients of 37 ± 11 years old were asked to attend a training of 2 hours on anticoagulation and Coaguchek INRange® use, provided by specialized nurses, before getting home with the machine. Patients had to attend a 3 months re-evaluation appointment. Twenty-nine (56%) patients had an aortic mechanical valve, 12 (23%) a mitral one, 8 (15%) a double aortic and mitral one, 2 (4%) a double aortic and pulmonary one and 1 (2%) a tricuspid one. 28 patients (54%) had a mechanical valve for ≥ 10 years (group 1). In group 1, patients were older (41 ± 10 years old vs. 34 ± 10, P = 0.01). Fluindione was the preferred oral anticogulant (30 patients, 57%), and more frequent in group 1 (18 patients, 64%). In group 1, 61% of patients usually managed themselves dosage adjustment whereas in the other group, 52% of patients referred to their doctor. Thirty-one patients (62%) had a higher target of INR than recommended in the last European guidelines. Concerning follow-up, 26 patients (50%) did not attend the 3 months appointment and had to be rescheduled or contacted by phone. Eight patients (15%) did not use the device at 3 months: 5 for variation > 15% compared to laboratory plasma technique and 3 for not trusting the new device. INR at 3 months was obtained in only 40 (77%) patients, and was in the attended target in 62% of cases. GUCH patients with mechanical valves, especially when present for ≥ 10 years, seem to validate Coaguchek, even though evaluation is hard since a great proportion of them did not attend follow-up appointment, stick to their old INR target and did not use the device as often as recommended.