Cessation Of Anticoagulant Therapy Research Articles

Antiphospholipid Syndrome and Catastrophic Antiphospholipid Syndrome: A Comprehensive Review of Pathogenesis, Clinical Features, and Management Strategies.

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by the presence of antiphospholipid antibodies (aPLs) that predispose individuals to thrombotic events and pregnancy-related complications. APS can occur as a primary condition or in association with other autoimmune diseases, most commonly systemic lupus erythematosus (SLE). Catastrophic APS (CAPS) is a rare, severe variant of APS, marked by rapid-onset, widespread thrombosis leading to multi-organ failure, often triggered by infections, surgical procedures, or cessation of anticoagulation therapy. Both APS and CAPS present significant clinical challenges due to their potential for severe morbidity and mortality. This comprehensive review aims to provide a detailed overview of the pathogenesis, clinical features, diagnostic criteria, and management strategies for APS and CAPS. The review highlights the immunological mechanisms underlying APS, including the role of aPLs, complement system activation, and endothelial cell dysfunction in developing thrombosis. It also outlines the clinical manifestations of APS, such as venous and arterial thrombosis, pregnancy morbidity, and neurological symptoms, along with the diagnostic criteria based on clinical and laboratory findings. The review delves into its pathogenesis, clinical presentation, and diagnostic challenges in the context of CAPS, emphasizing the need for immediate and intensive therapy to manage this life-threatening condition. Current management strategies for APS, including anticoagulant therapy, immunomodulatory treatments, and specific interventions for pregnancy-related complications, are discussed. The review highlights the importance of a multidisciplinary approach for CAPS, combining anticoagulation, high-dose corticosteroids, plasma exchange, and intravenous immunoglobulin. The review also addresses the prognosis and long-term outcomes for patients with APS and CAPS, underlining the necessity for ongoing monitoring and follow-up to prevent recurrent thrombotic events and manage chronic complications. Finally, future directions in research are explored, focusing on emerging therapies, biomarkers for early diagnosis, and the need for clinical trials to advance the understanding and treatment of these complex syndromes. By enhancing the understanding of APS and CAPS, this review aims to improve diagnosis, treatment, and patient care, ultimately leading to better health outcomes for those affected by these conditions.

Hormonal contraceptive use after a first venous thrombotic event and the risk of recurrence in premenopausal women

BackgroundExtensive evidence is available on hormonal contraceptive (HC) use and the risk of a first venous thromboembolism (VTE) event. Despite recommendations to discontinue combined HC (CHC) use, some women continue or start its use after a first VTE. ObjectivesWe aimed to evaluate the VTE recurrence risk associated with HC use in premenopausal women. MethodsPremenopausal women with a first VTE included in the Multiple Environmental and Genetic Assessment of Venous Thrombosis study between 1999 and 2004 were followed for a recurrence until 2010. Data on HC use were available through linkage to the Dutch Foundation for Pharmaceutical Statistics. The risk of recurrence was assessed 1) during anticoagulant therapy and 2) after cessation of anticoagulant therapy. Time-dependent Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% CIs adjusted for age and body mass index at baseline and thromboprophylaxis use during follow-up. ResultsSix hundred fifty women were uniquely linked and followed for a total of 3538 person-years (median, 6.1 years), during which 57 VTE recurrences occurred. Five occurred (8.8%) during anticoagulation treatment, with no clear risk difference for CHC use vs nonuse (HR, 0.8; 95% CI, 0.1-8.2). After anticoagulation cessation, CHC use was associated with a 2.4-fold higher risk of recurrence (HR, 2.4; 95% CI, 1.2-5.0) compared with nonuse. Recurrence risk for levonorgestrel-releasing intrauterine device use was similar to that for nonuse (HR, 0.9; 95% CI, 0.3-3.1). ConclusionCHC use after a first VTE is safe during anticoagulant use but substantially increases the risk of a recurrent VTE event in absence of anticoagulant use. This study adds to the evidence regarding the use of a levonorgestrel-releasing intrauterine device as a safe alternative.

Acute caval thrombosis leading to obstructive shock in the early post insertion period of an inferior vena cava filter: a case report and literature review

BackgroundObstructive shock is extremely rare in clinical practice and is caused by acute blood flow obstruction in the central vessels of either the systemic or pulmonary circulation. Utilizing inferior vena cava filters (IVCFs) to prevent pulmonary embolism (PE) is associated with some potential complications, such as inferior vena cava thrombosis (IVCT). Shock as a direct result of IVCT is rare. We present a case of obstructive shock secondary to extensive IVCT caused by inadequate anticoagulant therapy after the placement of an IVCF.Case presentationA 63-year-old male patient with a traffic accident injury presented orthopaedic trauma and lower limb deep vein thrombosis (DVT). He experienced sudden and severe abdominal pain with hypotension, tachycardia, tachypnea, oliguria and peripheral oedema 5 days after IVCF placement and 3 days after cessation of anticoagulant therapy. Considering that empirical anti-shock treatment lasted for a while and the curative effect was poor, we finally recognized the affected vessels and focused on the reason for obstructive shock through imaging findings—inferior vena cava thrombosis and occlusion. The shock state immediately resolved after thrombus aspiration. The same type of shock occurred again 6 days later during transfer from the ICU to general wards and the same treatment was administered. The patient recovered smoothly in the later stage, and the postoperative follow-up at 1, 3, and 12 months showed good results.ConclusionThis case alerts clinicians that it is crucial to ensure adequate anticoagulation therapy after IVCF placement, and when a patient presents with symptoms such as hypotension, tachycardia, and lower limb and scrotal oedema postoperatively, immediate consideration should be given to the possibility of obstructive shock, and prompt intervention should be based on the underlying cause.

Development of multifocal ischemic stroke after cessation of anticoagulant therapy in a patient with antiphospholipid syndrome

The clinical case presents a young patient with antiphospholipid syndrome, which was the cause of recurrent acute ischemic cerebrovascular accidents and pathology of pregnancy. During the clinical and laboratory examination, the patient was diagnosed with systemic lupus erythematosus. To determine the etiology of ischemic strokes and recurrent pregnancy loss, the patient underwent an immunological blood test which led to diagnosing the antiphospholipid syndrome. The patient failed to comply with the doctor's recommendations for taking an anticoagulant in the early postpartum period that resulted in the development of multifocal ischemic stroke. After treatment, the patient's condition improved, focal neurological symptoms partially regressed, and laboratory parameters returned to normal. As a secondary prevention of thrombosis, the patient was prescribed anticoagulant therapy.

From a DOAC to Warfarin: Reasons Why Patients Switch

1. IntroductionThe introduction of direct oral anticoagulants (DOACs) has led to their widespread use for stroke prevention in patients with non-valvular atrial fibrillation (AF) and as first-line treatment in acute venous thromboembolism (VTE), and also as secondary thromboprophylaxis in patients with a history of VTE. In addition, many patients previously taking vitamin K antagonists (VKAs) have switched to a DOAC for reasons including erratic international normalised ratio (INR) control, medication interactions, convenience, possible lower major bleeding risk and possible improved stroke prevention rates. Although DOACs are well tolerated, little is known about the numbers of patients switching from a DOAC to (or back to) a VKA or the reasons for doing so.2. MethodsThis study was an analysis of prospectively-collected data from a four-year period surveying a computer-based VKA (warfarin) dose adjustment clinic in a large city centre hospital. The primary objective was to identify the reasons for patients switching from a DOAC to warfarin. Secondary objectives included assessing indication for anticoagulant therapy and choice of DOAC. The time in therapeutic range (TTR) once switched back to VKA and clinical events following commencement of warfarin were also determined.3. ResultsIn our VKA clinic with 1791 patients annually under review, 39 patients were identified as having switched from a DOAC to warfarin. The mean age of the patients was 68.5 years +/- 13.8 and the majority (N=24) were female. AF was the most common condition necessitating anticoagulation (N=24); VTE accounted for 12 cases; arterial thromboembolism (N=2) and cardiac thrombus (N=1) were less common causes and one patient had been started on a DOAC in the setting of valvular replacement. Of the patients who were switched to warfarin, seven (17.9%) had originally been anticoagulated with a VKA prior commencing on a DOAC. In terms of anticoagulant choice, the majority of patients (N = 27) were taking rivaroxaban with 6 patients each on dabigatran and apixaban. The causes for switching in this cohort are outlined in table 1. Interesting cases of note include one patient who had a splenic infarction while taking rivaroxaban for atrial fibrillation and one patient who developed a new thumb arterial embolus while taking rivaroxaban for a PE.Following warfarin commencement, there was a total of eight clinical events reported (21.1% of patients). There were seven bleeding events recorded with two serious events necessitating hospital admission and five minor events; in five of these (71.4%), the original reason for switching back to warfarin had been a bleed while on a DOAC. One further patient had a high INR necessitating administration of vitamin K. The mean TTR of this cohort was 61.4% +/- 22.3. 33 patients (84.6%) of patients still attend the warfarin clinic, with cessation of anticoagulant therapy having occurred in three patients (7.7%) and death occurring in one patient (2.6%); two patients (5.1%) have been recommenced on a DOAC.4. DiscussionDOACs have several advantages over warfarin for many patients; they do not require monitoring and the dose remains stable. Index trials have demonstrated at least non-inferiority to warfarin in stroke prevention in non-valvular AF and treatment of VTE, with at least no significant difference in bleeding outcomes. However, warfarin can be an attractive option in complicated cases as it can be rapidly reversed, and there continues to be greater levels of clinician experience with its use. In the present study, we report data regarding the switch back to warfarin in a DOAC cohort, an area into which little research has been conducted. There were only 39 patients reported over a four-year period; this represents only a small minority of the full cohort. As expected, the majority of patients required a switch because of re-thrombosis or a bleeding event. Patients also required an appropriate switch in situations outside of the licence of the DOACs i.e. renal deterioration or valvular AF. The authors are not aware of any data regarding arterial embolisation in rivaroxaban users, and acute hepatitis has been rarely described in rivaroxaban use. These data confirm that switching from a DOAC to warfarin is seldom deemed necessary by clinicians. However, familiarity and experience may guide therapy in complicated cases, and vigilance is required to ensure adherence to the licence when prescribing a DOAC. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Effects of heparinoid bridging in patients with mechanical heart valves.

Patients with mechanical heart valves (MHVs) require long-term oral anticoagulation therapy to protect against thromboembolisms. Invasive procedures with high bleeding risks require oral anticoagulation therapy cessation. Currently, guidelines recommend the use of either subcutaneous low-molecular-weight heparin or intravenous unfractionated heparin in the perioperative period. It is unclear whether the evidence supports the use of one heparinoid over the other. To compare the effectiveness of low-molecular-weight heparin and unfractionated heparin bridging based on the adverse outcomes of thromboembolisms, major bleeding, and death during the perioperative period. A literature search was conducted using PubMed, EMBASE, CINAHL, and the Cochrane Library. Five studies comparing the two bridging therapies in chronically anticoagulated MHV patients met the inclusion criteria. No statistical significance was found for the endpoints of thromboembolism and death. One study found a statistically significant higher occurrence of major bleeding in patients treated with unfractionated heparin. In all the studies, major bleeding occurred more often than thromboembolisms. Findings were limited by the study designs and methodologies. Based on the available evidence, neither low-molecular-weight heparin nor intravenous heparin bridging was found to be more effective in reducing the occurrence of adverse events. This may be due in part to the study designs and lack of standardized bridging protocols used in the studies reviewed. Nurse practitioners should remain informed about bridging protocols and weigh the risk versus benefit of each bridging agent when caring for patients with MHVs.

Recurrent Intracranial Hemorrhage and Venous Thromboembolism Following Initial Intracranial Hemorrhage in Patients with Brain Tumors on Anticoagulation

Introduction Both venous thromboembolism (VTE) and intracranial hemorrhage (ICH) are common potentially life-threatening complications of primary and metastatic brain tumors. Despite emerging evidence regarding the safety of anticoagulation in patients with brain tumors, there is little evidence on appropriate management of VTE following an ICH. Potential management options after an ICH in patients with brain tumors include resumption of full or modified dose anticoagulation or cessation of anticoagulant therapy with or without placement of an inferior vena cava (IVC) filter. We evaluated rates of recurrent VTE and ICH following an initial ICH occurring on anticoagulant therapy. Methods A retrospective cohort study was performed using a hospital-based online medical record database (CQ2) which links ICD-9 and ICD-10 codes with prescription medication records. Cases were identified based on coding for primary brain tumors or brain metastases, after which charts were manually reviewed for a diagnosis of ICH. A blinded review of radiographic imaging was performed, and the initial ICH was categorized as either trace, measurable, or major. Measurable intracranial hemorrhages were those defined as greater than 1 mL in volume and major intracranial hemorrhages were defined as greater than 10 mL in volume, symptomatic, or requiring surgical intervention. The electronic medical record was reviewed to ascertain longitudinal anticoagulation status after the initial ICH. The primary endpoints of the study were recurrent ICH and venous thromboembolism (VTE) within 12 months from the initial ICH. Gray's test was used to compare the cumulative incidence of recurrent ICH and VTE between the groups, with death as a competing risk. Results A total of 79 patients with primary brain tumors or brain metastases and confirmed ICH were included in the study. Fifty-four patients (68.4%) restarted anticoagulation after ICH and 25 patients discontinued anticoagulation entirely. The cohorts were well-matched for tumor diagnosis, age, and comorbidities that portend an increased risk of ICH such as hypertension, chronic kidney disease, and concomitant aspirin use (Table 1). The cumulative incidence of recurrent ICH (95% CI) at one year was 6.1% (1.5 - 15.3) in the restart cohort compared to 4.2% (0.3 - 18.3) in patients who did not restart anticoagulation. Median time from anticoagulation restart to recurrent ICH was 36 days. A total of 16 of 31 patients with major ICH restarted anticoagulation and among these patients two developed subsequent ICH (cumulative incidence 14.5%, 95% CI 2.1 - 38.3). Among the 15 patients with a major ICH who did not restart anticoagulation, the cumulative incidence was 6.7% (0.3 - 27.5). Eleven of 15 patients with measurable ICH restarted anticoagulation and among these patients one subsequently developed ICH (cumulative incidence 0.1%, 95% CI 0.0 - 0.3). No recurrent ICH events were observed in 33 patients with trace initial hemorrhages regardless of restart status. All recurrent ICH events met criteria for classification as a major hemorrhage on the basis of clinical symptoms, and 30-day mortality after recurrent ICH was 100%. The cumulative incidence of recurrent VTE was significantly lower in the restart cohort compared to cohort of patients who did not restart anticoagulation (8.1 vs. 35.3, P=0.003, Figure 1). There were a total of five VTE events in the restart cohort, three deep vein thrombi (DVT) and two pulmonary emboli (PE). Two of the DVT were associated with an IVC filter. There were a total of nine VTE events in patients who did not restart anticoagulation, seven DVT and two PE. Five of the DVT were associated with an IVC filter. The two PE were both submassive events requiring ICU admission. Conclusions Recurrent VTE events are less frequent and less severe in patients who restart anticoagulation following ICH in patients with brain tumors on anticoagulation. Restarting anticoagulation after smaller ICH (trace or measurable) appears safe. However, approximately 1 in 7 patients with major initial ICH who restarted anticoagulation subsequently developed recurrent major ICH that was associated with a very high mortality rate. This raises serious questions as to the safety of restarting therapeutic anticoagulation following major hemorrhage in the setting of brain tumors. Disclosures Neuberg: Pharmacyclics: Research Funding; Madrigal Pharmaceuticals: Equity Ownership; Celgene: Research Funding. Zwicker:Quercegen: Research Funding; Daiichi: Consultancy; Seattle Genetics: Consultancy; Parexel: Consultancy; Incyte: Research Funding; Bayer: Consultancy; Portola: Consultancy.

P2773Evaluation of the bleeding prediction score VTE-BLEED for predicting recurrent VTE

Abstract Introduction VTE-BLEED is a validated score for identification of patients at a 3 to 5-fold increased risk of major bleeding during extended anticoagulation for venous thromboembolism (VTE; table 1). It is unknown whether VTE-BLEED high-risk patients also have an increased risk for recurrent VTE, which would limit the potential usefulness of the score. Methods This was a post-hoc analysis of the randomised double-blind placebo-controlled PADIS-PE trial, in which patients with a first unprovoked pulmonary embolism (PE) initially treated for 6 months were randomised to receive an additional 18-month of warfarin versus placebo. Primary outcome of the current analysis was recurrent VTE during 2-year follow-up after anticoagulant discontinuation, i.e. after the initial 6-month treatment in the placebo arm and after 24 months of anticoagulation in the active treatment arm. This rate, adjusted on study treatment allocation, was compared between patients in the high- versus low-risk VTE-BLEED group. Results In complete case analysis (n=308; 82.4% of total population), 89 (28.9%) patients were classified as VTE-BLEED high risk. A total of 44 VTE events occurred after anticoagulant discontinuation during 668 patient-years. The cumulative incidence of recurrent VTE was 16.4% (95% CI 10.0–26.1%; 14 events) and 14.6% (95% CI 10.4–20.3%; 30 events) in the high-risk and low-risk VTE-BLEED groups, respectively, for an adjusted Hazard Ratio of 1.16 (95% CI 0.62–2.19; Figure 1). Figure 1 Conclusion In this study, patients with unprovoked PE classified at high risk of major bleeding by VTE-BLEED did not have a higher incidence of recurrent VTE after cessation of anticoagulant therapy, supporting the potential yield of the score for making management decisions on the optimal duration of anticoagulant therapy.

Evaluation of the predictive value of the bleeding prediction score VTE‐BLEED for recurrent venous thromboembolism

IntroductionVTE‐BLEED is a validated score for identification of patients at increased risk of major bleeding during extended anticoagulation for venous thromboembolism (VTE). It is unknown whether VTE‐BLEED high‐risk patients also have an increased risk for recurrent VTE, which would limit the potential usefulness of the score. MethodsThis was a post hoc analysis of the randomized, double‐blind, placebo‐controlled PADIS‐PE trial that randomized patients with a first unprovoked pulmonary embolism (PE) initially treated during 6 months to receive an additional 18‐month of warfarin vs. placebo. The primary outcome of this analysis was recurrent VTE during 2‐year follow‐up after anticoagulant discontinuation, that is, after the initial 6‐month treatment in the placebo arm and after 24 months of anticoagulation in the active treatment arm. This rate, adjusted for study treatment allocation, was compared between patients in the high‐ vs. low‐risk VTE‐BLEED group. ResultsIn complete case analysis (n = 308; 82.4% of total population), 89 (28.9%) patients were classified as high risk; 44 VTE events occurred after anticoagulant discontinuation during 668 patient‐years. The cumulative incidence of recurrent VTE was 16.4% (95% confidence interval [CI], 10.0%‐26.1%; 14 events) and 14.6% (95% CI, 10.4%‐20.3%; 30 events) in the high‐risk and low‐risk VTE‐BLEED groups, respectively, for an adjusted hazard ratio of 1.16 (95% CI, 0.62‐2.19). ConclusionIn this study, patients with unprovoked PE classified at high risk of major bleeding by VTE‐BLEED did not have a higher incidence of recurrent VTE after cessation of anticoagulant therapy, supporting the potential yield of the score for making management decisions on the optimal duration of anticoagulant therapy.

Cessation of anticoagulation therapy following endovascular thrombus removal and stent placement for acute iliofemoral deep vein thrombosis.

Background: The optimal duration of anticoagulation therapy (AT) following catheter-based therapy of acute iliofemoral deep vein thrombosis (IFDVT) with stent placement is unknown. Theoretically, resolving the underlying obstructive iliac vein lesion by a stent may eliminate the main trigger for recurrence, the post-thrombotic syndrome (PTS), and the need for extended-duration AT. Patients and methods: From 113 patients with acute IFDVT who underwent endovascular thrombus removal and stent placement, we compared patency rates and clinical outcomes between 58 patients on limited-duration AT (3-12 month) and 55 patients on extended-duration AT (>12 months). Results: Mean follow-up duration was 26±18 (range 3-77) months; it was 24±18 (range 3-69) months after cessation of AT in the limited-duration AT group. In comparison to patients with extended-duration AT, patients with limited-duration AT were younger (38 versus 54 years; p<0.001), more often female (74% versus 49%; p=0.01), and had less often prior venous thromboembolism (VTE) (9% versus 35%; p=0.001). May-Thurner syndrome was more frequent in the limited-duration AT group (66% versus 38%; p=0.004). Overall, primary and secondary patency rates at 24 months were 80% (95% CI, 70-87%) and 95% (95% CI, 88-98%), respectively, with no difference between the groups. Overall, 17 (15%) patients developed recurrent VTE, of which 14 (82%) events were thrombotic stent occlusions, and 13 (76%) events occurred during AT. In the limited-duration AT group, 98% patients were free from the PTS at two years with a VTE recurrence rate of 3.5 per 100 patient years after cessation of AT. Conclusions: In selected patients with acute IFDVT and patent venous stent, particularly in younger and otherwise healthy patients with May-Thurner syndrome, it appears to be safe to discontinue AT 3-12 months after endovascular treatment. Clinical Trial Registration: The study is registered on the National Institutes of Health website (ClinicalTrials.gov; identifier NCT02433054).

COMPARISON OF SCHEMES OF PERIOPERATIONAL ANTICOAGULATION IN ATRIAL FIBRILLATION PATIENTS DEMANDING FOR SURGERY

A literature review provided, on the usage of various schemes of perioperational anticoagulation therapy (ACT) in atrial fibrillation patients undergoing scheduled surgery. It is noted that clinicians quite often pass through a situation when patients taking ACT require invasive investigations and surgery. Perioperational management of such category of patients is complicated as, on the one hand, the surgery under ACT is associated with intraoperational hemorrhagic complications, and, on the other hand, ACT cessation might increase the risk of thrombotic complications. The variants assessed, of different periprocedural ACT in patients taking vitamin K antagonists. It was found that as an alternative to continuous ACT recently, bridge therapy with low molecular weight heparins applied, aiming the decrease of the risk of bleeding in adequate thromboprophylaxis. The results of clinical trials provided on the assessment of bridge therapy in surgery. Risk stratification approaches presents for thromboembolic and hemorrhagic complications in surgery.

Biological versus mechanical heart valve prosthesis during pregnancy in women with congenital heart disease

BackgroundWe evaluate pregnancy outcome and anticoagulation regimes in women with mechanical and biological prosthetic heart valves (PHV) for congenital heart disease. MethodsRetrospective multicenter cohort studying pregnancy outcomes in an existing cohort of patients with PHV. Results52 women had 102 pregnancies of which 78 pregnancies (46 women) ≥20 weeks duration (59 biological, 19 mechanical PHV). Miscarriages (n = 19, ≤20 weeks) occurred more frequently in women using anticoagulation (P < .05). During 42% of pregnancies of women with mechanical PHV a combined low molecular weight heparin (LMWH) vitamin-K-antagonist anticoagulation regime was used (n = 8). Overall, cardiovascular, obstetric and fetal/neonatal complications occurred in 17% (n = 13), 68% (n = 42) and 42% (n = 27) of the pregnancies. Women with mechanical PHV had significantly higher cardiovascular (12% vs 32%, P < .05), obstetric (59% vs 85%, P = .02) and fetal/neonatal (34% vs 61%, P < .05) complication rates than women with biological PHV. This was related to PHV thrombosis (n = 3, P < .02), post-partum hemorrhage (P < .02), cesarean section (P < .02), low birth weight and small for gestational age (both P < .05). PHV thrombosis occurred in 3 pregnancies, including 2/5 pregnancies with pulmonary mechanical PHV. PHV thrombosis was related to necessary cessation of anticoagulation therapy or insufficient monitoring of LMWH. Other cardiovascular complications occurred equally frequent in both groups. ConclusionComplications occur more often in pregnancies of women with a mechanical PHV than in women with a biological PHV, mainly caused by PHV thrombosis and bleeding complications. Meticulous monitoring of anticoagulation in pregnant women is necessary. Women with a pulmonary mechanical PHV are at high risk of complications.

Accidents in patients under anticoagulant therapy in the Department of Cardiology at the Yalgado Ouedraogo Teaching Hospital, Ouagadougou (Burkina Faso)

Etudier le profil des patients hospitalisés pour hémorragie sous traitement anticoagulant. Il s’est agi d’une étude rétrospective à visée descriptive sur une période de 02 ans allant du 1er Janvier 2007 au 31 Décembre 2008, dans le Service de Cardiologie du Centre Hospitalier Universitaire-Yalgado Ouédraogo. Tous les patients hospitalisés présentant une hémorragie sous anticoagulant ont été inclus dans l'étude. L’âge moyen des patients était de 49,31 ± 17,68 ans, le sex-ratio était de 2,17. L’infarctus du myocarde était la première indication du traitement anticoagulant avec une fréquence de 21,05%. L’anti Vitamine K (AVK) a été pourvoyeur d’hémorragies dans 63,16% (n = 12) des cas contre 36,84% (n = 7) pour les Héparines de Bas Poids Moléculaire (HBPM); Il s’agissait de 10 cas d’hémorragie majeure et de neuf cas d’hémorragie mineure. La durée moyenne du traitement AVK était de 16 semaines ± 58 semaines. Le saignement par le tractus digestif était le plus fréquent (31,58%) et dans 89,47% des cas, le traitement était associé à un antiagrégant plaquettaire. L’arrêt définitif de l’anticoagulant constituait la prise en charge de l’accident hémorragique dans 73,68%. Il y avait quatre (21,05%) décès. L’inaccessibilité des antidotes comme le sulfate de protamine et les PPSD (Prothrombine Proconvertine Stuart B) constituent un véritable frein à la prise en charge adéquate des complications; mais une meilleure éducation de patients utilisateur de ces drogues constituerait la plus importante des préventions, car plus de 50% de ces accidents sont évitables.

Recurrent Bioprosthetic Valve Thrombosis — Should Long-Term Anticoagulation Be Considered?

Bioprosthetic valve thrombosis (BPVT) is an important and potentially reversible cause of valvular dysfunction. This complication can occur many years after surgery and understanding of the precise mechanisms and risk factors is limited. Anticoagulation therapy has been demonstrated to be effective in improving BPVT. However, the optimal duration of therapy and the risk of recurrence are unknown. Herein, we describe two cases-one of late BPVT and one of recurrence of BPVT after cessation of anticoagulation therapy.

Postoperative Outcomes Associated With Neuraxial vs General Anesthesia Following Bilateral Total Knee Arthroplasty

BackgroundThere is sparse evidence on the benefit of neuraxial (NA) vs general anesthesia (GA) as the primary anesthetic in postoperative outcomes following bilateral total knee arthroplasty. We sought to elucidate differences in outcomes in this surgical population using a national database. MethodsWe used data from the National Surgical Quality Improvement Program from 2007 to 2013 and compared rates of various postoperative outcomes in propensity-matched cohorts (NA vs GA). ResultsAfter exclusion, there were 1957 patients included in the final analysis, of which 26% received NA as the primary anesthetic. Propensity-matched cohorts were generated to ensure no differences in various comorbidities (including bleeding disorders or inadequate cessation of anticoagulation therapy), case duration, and patient demographics between both cohorts. Among the matched cohorts, there were no differences in preoperative platelet count, hematocrit, or international normalized ratio. NA was associated with decreased blood transfusion requirement and decreased total number of units of blood products transfused (P < .0001 for both outcomes). However, there were no differences in other outcomes, including hospital length of stay, pulmonary embolism, deep vein thrombosis, or urinary tract infections. ConclusionOur study demonstrates that in matched cohorts, NA is associated with decreased blood transfusion requirements in patients undergoing bilateral total knee arthroplasty when compared to GA as the primary anesthetic.

D‐dimer at venous thrombosis diagnosis is associated with risk of recurrence

Essentials Whether D-dimer at incident venous thromboembolism (VTE) can predict recurrence-risk is unknown. We explored this association in 454 cancer-free patients with a first lifetime VTE. A low D-dimer at first VTE diagnosis was associated with a low recurrence risk. The association was predominant in patients with deep vein thrombosis and unprovoked VTE. Click to hear Dr Cannegieter's presentation on venous thrombosis: prediction of recurrence SUMMARY: Background Venous thromboembolism (VTE) is a common disease with a high recurrence rate. D-dimer measured after cessation of anticoagulant therapy predicts recurrence, and is used to decide on treatment prolongation. However, whether D-dimer measured at first VTE diagnosis can be used to assess recurrence-risk is unknown. Aims To investigate the association between D-dimer, measured at first VTE diagnosis and risk of recurrent VTE. Methods Information on clinical risk factors and laboratory markers were collected in 454 cancer-free patients with a first VTE. Recurrent VTEs and deaths during follow-up (1994-2012) were recorded. Results During a median follow-up of 3.9 years, 84 patients experienced a recurrent VTE. The crude recurrence rate was 1.7 (95% confidence interval [CI], 1.0-2.9) per 100 person-years in the lower quartile of D-dimer (≤ 1500 ng mL-1 ), and 4.9 (95% CI, 3.9-6.1) per 100 person-years in the upper three quartiles combined, yielding an absolute risk difference of 3.2 per 100 person-years. Patients with D-dimer ≤ 1500 ng mL-1 had 54% lower recurrence-risk than patients with D-dimer > 1500 ng mL-1 (HR, 0.46; 95% CI, 0.25-0.82). The association was particularly pronounced among patients with unprovoked events and deep vein thrombosis, showing a 66% (HR, 0.34; 95% CI, 0.15-0.74) and 68% (HR, 0.32; 95% CI, 0.14-0.71) lower recurrence risk among patients with D-dimer ≤ 1500 ng mL-1 , respectively. Conclusions A low D-dimer (≤ 1500 ng mL-1 ) measured at first VTE diagnosis was associated with a low recurrence risk, particularly among patients with DVT and unprovoked events. Our findings suggest that a clinical decision to avoid prolonged anticoagulant treatment could be considered based on low D-dimer at the time of VTE diagnosis.

Extended Anticoagulant and Aspirin Treatment for the Secondary Prevention of Thromboembolic Disease: A Systematic Review and Meta-Analysis.

BackgroundPatients who have had an unprovoked deep venous thrombosis (DVT) or pulmonary embolus (PE) are at a high risk for recurrent venous thromboembolism (VTE). Extended “life-long” anticoagulation has been recommended in these patients. However, the risk benefit ratio of this approach is controversial and the role of the direct oral anticoagulants (DOACs) and aspirin is unclear. Furthermore, in some patients with a “weak provoking factor” there is clinical equipoise regarding continuation or cessation of anticoagulant therapy after treatment of the acute VTE event.ObjectiveA systematic review and meta-analysis to determine the risks (major bleeding) and benefits (recurrent VTE and mortality) of extended anticoagulation with vitamin k antagonists (VKA), DOACs and aspirin in patients with an unprovoked VTE and in those patients with clinical equipoise regarding continuation or cessation of anticoagulant therapy. In addition, we sought to determine the risk of recurrent VTE events once extended anti-thrombotic therapy was discontinued.Data SourcesMEDLINE, Cochrane Register of Controlled Trials, citation review of relevant primary and review articles.Study SelectionRandomized placebo-controlled trials (RCTs) that compared the risk of recurrent VTE in patients with an unprovoked DVT or PE who had been treated for at least 3 months with a VKA or a DOAC and were then randomized to receive an oral anti-thrombotic agent or placebo for at least 6 additional months. We included studies that included patients in whom clinical equipoise existed regarding the continuation or cessation of anticoagulant therapy.Data ExtractionIndependent extraction of articles by both authors using predefined data fields, including study quality indicators. Data were abstracted on study size, study setting, initial event (DVT or PE), percentage of patients where the initial VTE event was unprovoked, the number of recurrent VTE events, major bleeds and mortality during the period of extended anticoagulation in the active treatment and placebo arms. In addition, we recorded the event rate once extended treatment was stopped. Meta-analytic techniques were used to summarize the data. Studies were grouped according to the type of anti-thrombotic agent.Data SynthesisSeven studies which enrolled 6778 patients met our inclusion criteria; two studies evaluated the extended use of Coumadin, three studies evaluated a DOAC and two studies evaluated the use of aspirin. The duration of followup varied from 6 to 37 months. In the Coumadin and aspirin studies 100% of the randomized patients had an unprovoked VTE, while in the DOAC studies between 73.5% and 93.2% of the VTE events were unprovoked. In the control group recurrent VTE occurred in 9.7% of patients compared to 2.8% in the active treatment group (OR 0.21; 95% CI 0.11–0.42, p<0.0001). VKA, DOACs and aspirin significantly reduced the risk of recurrent VTE, with VKA and DOACs being significantly more effective than aspirin. Major bleeding events occurred in 12 patients in the control group (0.4%) and 25 of 3815 (0.6%) patients in the active treatment group (OR 1.64; 95% CI 0.69–3.90, NS). There were 39 (1.3%) deaths in control patients and 33 (0.9%) deaths in the anti-thrombotic group during the treatment period (OR 0.73; 95% CI 0.40–1.33, NS). Patients whose initial VTE event was a PE were more likely to have a recurrent PE than a DVT. The annualized event rate after discontinuation of extended antithrombotic therapy was 4.4% in the control group and 6.5% in the active treatment arm.ConclusionsVKA, DOACs and aspirin significantly reduced the risk of recurrent VTE, with DOACs and VKA being more effective than aspirin. The decision regarding life-long anticoagulation following an unprovoked DVT or PE should depend on the patients’ risk for recurrent PE as well as the patients’ values and preferences.

Long-term clinical course of acute pulmonary embolism

The long-term clinical course of acute pulmonary embolism (PE) is complicated by high rates of serious adverse events, both before and after cessation of anticoagulant therapy. These adverse events include recurrent venous thromboembolism, chronic thromboembolic pulmonary hypertension, arterial thrombotic events and increased risk of death, all compared to patients without thromboembolic disease. Several pharmacological options are available that may beneficially influence patients' prognosis. Nonetheless, because of insufficient knowledge of the benefit-to-harm ratio of these pharmacological agents, unambiguous recommendations are scarcely available. This review will cover the epidemiological aspects of the various possible complications in the long-term clinical course of acute PE as well as the latest evidence on preventive strategies. In addition, the unresolved issues regarding frequency, duration and focus of medical follow-up after acute PE are discussed.

Apixaban for Extended Treatment of Venous Thromboembolism

BackgroundApixaban, an oral factor Xa inhibitor that can be administered in a simple, fixed-dose regimen, may be an option for the extended treatment of venous thromboembolism.MethodsIn this randomized, double-blind study, we compared two doses of apixaban (2.5 mg and 5 mg, twice daily) with placebo in patients with venous thromboembolism who had completed 6 to 12 months of anticoagulation therapy and for whom there was clinical equipoise regarding the continuation or cessation of anticoagulation therapy. The study drugs were administered for 12 months.ResultsA total of 2486 patients underwent randomization, of whom 2482 were included in the intention-to-treat analyses. Symptomatic recurrent venous thromboembolism or death from venous thromboembolism occurred in 73 of the 829 patients (8.8%) who were receiving placebo, as compared with 14 of the 840 patients (1.7%) who were receiving 2.5 mg of apixaban (a difference of 7.2 percentage points; 95% confidence interval [CI], 5.0 to 9.3) and 14 of the 813 patients (1.7%) who were receiving 5 mg of apixaban (a difference of 7.0 percentage points; 95% CI, 4.9 to 9.1) (P<0.001 for both comparisons). The rates of major bleeding were 0.5% in the placebo group, 0.2% in the 2.5-mg apixaban group, and 0.1% in the 5-mg apixaban group. The rates of clinically relevant nonmajor bleeding were 2.3% in the placebo group, 3.0% in the 2.5-mg apixaban group, and 4.2% in the 5-mg apixaban group. The rate of death from any cause was 1.7% in the placebo group, as compared with 0.8% in the 2.5-mg apixaban group and 0.5% in the 5-mg apixaban group.ConclusionsExtended anticoagulation with apixaban at either a treatment dose (5 mg) or a thromboprophylactic dose (2.5 mg) reduced the risk of recurrent venous thromboembolism without increasing the rate of major bleeding. (Funded by Bristol-Myers Squibb and Pfizer; AMPLIFY-EXT ClinicalTrials.gov number, NCT00633893.)

An interaction between tacrolimus and pristinamycin resulting in an elevated tacrolimus level.

We report a case of interaction between tacrolimus and pristinamycin. A 62-year-old man, Mr TM, presented with a 2-day history of increased pain and left knee swelling after a twisting injury. This occurred 1 year after renal transplantation for end-stage kidney disease from membranous glomerulonephropathy, complicated by an episode of acute rejection requiring intravenous immunoglobulin, plasma exchange, pulsed glucocorticoids and antithymocyte globulin. His allograft function had ultimately stabilized (Cr 140 μmol/L) on an immunosuppressive regimen including 5 mg tacrolimus twice daily, 720 mg mycophenolate sodium (Myfortic) twice daily and prednisolone 10 mg daily. Other relevant medical history includes epilepsy controlled with stable doses of levetiracetam, carbamazepine and sodium valproate as well as multiple venous thromboembolic events including pulmonary emboli despite inferior vena cava filter, thus requiring anticoagulation with Enoxaparin. Haemarthrosis was diagnosed after aspirating frank blood (erythrocytes 243 200 × 106/L, 3080 × 106/L leucocytes, negative gram stain). Initially managed conservatively, together with cessation of anticoagulant therapy, Mr TM deteriorated, becoming tachycardic, hypotensive and delirious. Septic screen yielded a positive aerobic blood culture with methicillin-resistant Staphylococcus epidermidis (MRSE); thus IV flucloxacillin 2 g 6-hourly and vancomycin 1 g daily (when level <20 g/L) were commenced to treat for septic arthritis. A washout of his affected knee was performed but cultured no organisms. Mr TM improved with antibiotic therapy following the procedure, until fevers developed on Day 4 post washout and antibiotics escalated to ticarcillin/clavulanate 3.1 g 6-hourly and vancomycin. Trough tacrolimus levels were monitored regularly; these remained stable between 4.8 and 5.2 μg/L. Maintaining intravenous access was an ongoing difficulty; thus IV antibiotics were converted to oral pristinamycin 1 g 8-hourly and amoxicillin/clavulanic acid 875/125 mg twice daily after remaining afebrile for 5 days. Following six doses of pristinamycin, the trough tacrolimus level was significantly elevated at 20.9 μg/L. The next two doses of tacrolimus were withheld, and intravenous antibiotics reinstituted. Tacrolimus level 24 h later, although trending lower, remained elevated at 9.1 μg/L. We recommenced tacrolimus at Mr TM’s usual dosing and subsequent levels normalized. Reviewing the literature, for many years, pristinamycin and cyclosporin have been known to interact. [1, 2] This interaction is attributed to the metabolism of both medications. Pristinamycin is a streptogramin antibacterial synergistically combining a macrolide (Pristinamycin I) with a depsipeptide (Pristinamycin II) [3], and its use is becoming increasingly common, particularly for methicillin-resistant pathogens. It is an inhibitor of cytochrome P450 3A4, while calcineurin inhibitors such as cyclosporin are metabolized by CYP3A4 [3, 4]. This combination results in elevated cyclosporin blood concentrations and potential toxicity. Tacrolimus was approved by the Therapeutic Goods Administration in September 1998 for use in kidney transplantation. Its use has been steadily increasing; however, its drug interaction profile is less well known, relative to cyclosporin. As a calcineurin inhibitor, it is also metabolized by CYP3A4 [5] leading to significant potential for interactions with pristinamycin and other CYP3A4 inhibitory medications. In our case, there were no other medications or dietary changes in the days between his normal and elevated tacrolimus levels to explain these changes. Mr TM did not suffer any adverse effects from this transient increase in serum tacrolimus concentration. From this case, we recommend frequent monitoring of calcineurin inhibitor levels in patients while changing other medications, especially antibiotics in view of the increasing use of both tacrolimus and pristinamycin.