Chronic Anticoagulation in Patients with Atrial Fibrillation and COVID-19: A Systematic Review and Meta-Analysis. / Anticoagulação Crônica em Pacientes com Fibrilação Atrial e COVID-19: Uma Revisão Sistemática e Metanálise.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with hypercoagulability. It remains uncertain whether ongoing anticoagulation for atrial fibrillation (AF) in patients who later contract COVID-19 improves clinical outcomes. OBJECTIVES: To compare chronic oral anticoagulation with no previous anticoagulation in patients with AF who contracted a COVID-19 infection concerning the outcomes of all-cause mortality, COVID-19 mortality, intensive care unit (ICU) admission, and hospitalization. METHODS: We systematically searched PubMed, Embase, and Cochrane Library for eligible studies from inception to December 2022. We included studies comparing COVID-19 outcomes in patients with versus without prior chronic anticoagulation for AF. Risk ratios (RR) with 95% confidence intervals (CI) were pooled with a random-effects model. The level of significance was set at p < 0.05. Quality assessment and risk of bias were performed according to Cochrane recommendations. RESULTS: Ten studies comprising 1,177,858 patients with COVID-19 and AF were identified, of whom 893,772 (75.9%) were on prior chronic anticoagulation for AF. In patients with COVID-19, being on chronic anticoagulation for AF significantly reduced all-cause mortality (RR 0.75; 95% CI 0.57 to 0.99; p = 0.048; I2 = 89%) and COVID-19-related mortality (RR 0.76; 95% CI 0.72 to 0.79; p < 0.001; I2 = 0%) when compared with no prior anticoagulation. In contrast, there was no difference between groups regarding hospitalization (RR 1.08; 95% CI 0.82 to 1.41; p = 0.587; I2 = 95%) or ICU admission (RR 0.86; 95% CI 0.68 to 1.09; p = 0.216; I2 = 69%). CONCLUSIONS: In this meta-analysis, chronic anticoagulation for patients with AF who contracted COVID-19 was associated with significantly lower rates of all-cause mortality and COVID-19-related mortality as compared with no previous anticoagulation.

FUNDAMENTO: A doença por coronavírus 2019 (COVID-19) está associada à hipercoagulabilidade. Permanece incerto se a anticoagulação contínua para fibrilação atrial (FA) em pacientes que posteriormente contraem COVID-19 melhora os desfechos clínicos. OBJETIVOS: Comparar a anticoagulação oral crônica com ausência de anticoagulação prévia em pacientes com FA que contraíram uma infecção por COVID-19 em relação aos desfechos de mortalidade por todas as causas, mortalidade por COVID-19, admissão em unidade de terapia intensiva (UTI) e hospitalização. MÉTODOS: Buscamos sistematicamente no PubMed, Embase e Cochrane Library estudos elegíveis desde o início até dezembro de 2022. Incluímos estudos que compararam desfechos de COVID-19 em pacientes com e sem anticoagulação crônica prévia para FA. Foram agrupadas razões de risco (RR) com intervalos de confiança (IC) de 95% por meio de um modelo de efeitos aleatórios. O nível de significância foi estabelecido em p < 0,05. As avaliações da qualidade e do risco de viés foram realizadas de acordo com as recomendações da Cochrane. RESULTADOS: Foram identificados 10 estudos abrangendo 1.177.858 pacientes com COVID-19 e FA, dos quais 893.772 (75,9%) estavam em anticoagulação crônica prévia para FA. Em pacientes com COVID-19, a anticoagulação crônica para FA reduziu significativamente a mortalidade por todas as causas (RR 0,75; IC 95% 0,57 a 0,99; p = 0,048; I2 = 89%) e a mortalidade relacionada à COVID-19 (RR 0,76; IC 95% 0,72 a 0,79; p < 0,001; I2 = 0%) quando comparada com a ausência de anticoagulação prévia. Em contrapartida, não houve diferença entre os grupos em relação à hospitalização (RR 1,08; IC 95% 0,82 a 1,41; p = 0,587; I2 = 95%) ou internação em UTI (RR 0,86; IC 95% 0,68 a 1,09; p = 0,216; I2 = 69%). CONCLUSÕES: Nesta metanálise, a anticoagulação crônica para pacientes com FA que contraíram COVID-19 foi associada a taxas significativamente mais baixas de mortalidade por todas as causas e mortalidade relacionada à COVID-19 em comparação com a ausência de anticoagulação anterior.

Early unfractionated heparin treatment in patients with STEMI - trial design and rationale.

The early unfractionated heparin (UFH) treatment in patients with ST-elevation myocardial infarction (STEMI) is a single-center, open-label, randomized controlled trial. The study population are patients with STEMI that undergo primary percutaneous coronary intervention (PPCI). The trial was designed to investigate whether early administration of unfractionated heparin immediately after diagnosis of STEMI is beneficial in terms of patency of infarct-related coronary artery (IRA) when compared to established UFH administration at the time of coronary intervention. The patients will be randomized in 1:1 fashion in one of the two groups. The primary efficacy endpoint of the study is Thrombolysis in myocardial infarction (TIMI) flow grades 2 and 3 on diagnostic coronary angiography. Secondary outcome measures are: TIMI flow after PPCI, progression to cardiogenic shock, 30-day mortality, ST-segment resolution, highest Troponin I and Troponin I values at 24 hours. The safety outcome is bleeding complications. The study of early heparin administration in patients with STEMI will address whether pretreatment with UFH can increase the rate of spontaneous reperfusion of infarct-related coronary artery.

The prevalence of clinically relevant delayed intracranial hemorrhage in head trauma patients treated with oral anticoagulants is very low: a retrospective cohort register study.

BACKGROUND: Current guidelines from Scandinavian Neuro Committee mandate a 24-hour observation for head trauma patients on anticoagulants, even with normal initial head CT scans, as a means not to miss delayed intracranial hemorrhages. This study aimed to assess the prevalence, and time to diagnosis, of clinically relevant delayed intracranial hemorrhage in head trauma patients treated with oral anticoagulants. METHOD: Utilizing comprehensive two-year data from Region Skåne's emergency departments, which serve a population of 1.3 million inhabitants, this study focused on adult head trauma patients prescribed oral anticoagulants. We identified those with intracranial hemorrhage within 30 days, defining delayed intracranial hemorrhage as a bleeding not apparent on their initial CT head scan. These cases were further defined as clinically relevant if associated with mortality, any intensive care unit admission, or neurosurgery. RESULTS: Out of the included 2,362 head injury cases (median age 84, 56% on a direct acting oral anticoagulant), five developed delayed intracranial hemorrhages. None of these five cases underwent neurosurgery nor were admitted to an intensive care unit. Only two cases (0.08%, 95% confidence interval [0.01-0.3%]) were classified as clinically relevant, involving subdural hematomas in patients aged 82 and 87 years, who both subsequently died. The diagnosis of these delayed intracranial hemorrhages was made at 4 and 7 days following initial presentation to the emergency department. CONCLUSION: In patients with head trauma, on oral anticoagulation, the incidence of clinically relevant delayed intracranial hemorrhage was found to be less than one in a thousand, with detection occurring four days or later after initial presentation. This challenges the effectiveness of the 24-hour observation period recommended by the Scandinavian Neurotrauma Committee guidelines, suggesting a need to reassess these guidelines to optimise care and resource allocation. TRIAL REGISTRATION: This is a retrospective cohort study, does not include any intervention, and has therefore not been registered.

Coordination of oral anticoagulant care at hospital discharge (COACHeD): pilot randomised controlled trial.

OBJECTIVES: To evaluate whether a focused, expert medication management intervention is feasible and potentially effective in preventing anticoagulation-related adverse events for patients transitioning from hospital to home. DESIGN: Randomised, parallel design. SETTING: Medical wards at six hospital sites in southern Ontario, Canada. PARTICIPANTS: Adults 18 years of age or older being discharged to home on an oral anticoagulant (OAC) to be taken for at least 4 weeks. INTERVENTIONS: Clinical pharmacologist-led intervention, including a detailed discharge medication management plan, a circle of care handover and early postdischarge virtual check-up visits to 1 month with 3-month follow-up. The control group received the usual care. OUTCOMES MEASURES: Primary outcomes were study feasibility outcomes (recruitment, retention and cost per patient). Secondary outcomes included adverse anticoagulant safety events composite, quality of transitional care, quality of life, anticoagulant knowledge, satisfaction with care, problems with medications and health resource utilisation. RESULTS: Extensive periods of restriction of recruitment plus difficulties accessing patients at the time of discharge negatively impacted feasibility, especially cost per patient recruited. Of 845 patients screened, 167 were eligible and 56 were randomised. The mean age (±SD) was 71.2±12.5 years, 42.9% females, with two lost to follow-up. Intervention patients were more likely to rate their ability to manage their OAC as improved (17/27 (63.0%) vs 7/22 (31.8%), OR 3.6 (95% CI 1.1 to 12.0)) and their continuity of care as improved (21/27 (77.8%) vs 2/22 (9.1%), OR 35.0 (95% CI 6.3 to 194.2)). Fewer intervention patients were taking one or more inappropriate medications (7 (22.5%) vs 15 (60%), OR 0.19 (95% CI 0.06 to 0.62)). CONCLUSION: This pilot randomised controlled trial suggests that a transitional care intervention at hospital discharge for older adults taking OACs was well received and potentially effective for some surrogate outcomes, but overly costly to proceed to a definitive large trial. TRIAL REGISTRATION NUMBER: NCT02777047.

Effectiveness, utilisation and cost associated with implantable loop recorders versus external monitors after ischaemic or cryptogenic stroke.

OBJECTIVE: Implantable loop recorders (ILRs) are increasingly used for long-term rhythm monitoring after ischaemic and cryptogenic stroke, with the goal of detecting atrial fibrillation (AF) and subsequent initiation of oral anticoagulation to reduce risk of adverse clinical outcomes. There is a need to determine the effectiveness of different rhythm monitoring strategies in this context. METHODS: We conducted a retrospective cohort analysis of individuals with commercial and Medicare Advantage insurance in Optum Labs Data Warehouse who had incident ischaemic or cryptogenic stroke and no prior cardiovascular implantable electronic device from 1 January 2016 to 30 June 2021. Patients were stratified by rhythm monitoring strategy: ILR, long-term continuous external cardiac monitor (>48 hours to 30 days) or Holter monitor (≤48 hours). The primary outcome was risk-adjusted all-cause mortality at 12 months. Secondary outcomes included new diagnosis of AF and oral anticoagulation, bleeding, and costs. RESULTS: Among 48 901 patients with ischaemic or cryptogenic stroke, 9235 received an ILR, 29 103 long-term continuous external monitor and 10 563 Holter monitor only. Mean age was 69.9 (SD 11.9) years and 53.5% were female. During the 12-month follow-up period, patients who received ILRs compared with those who received long-term continuous external monitors had a higher odds of new diagnosis of AF and oral anticoagulant initiation (adjusted OR 2.27, 95% CI 2.09 to 2.48). Compared with patients who received long-term continuous external monitors, those who received ILRs had similar 12-month mortality (HR 1.00; 95% CI 0.89 to 1.12), with approximately $13 000 higher costs at baseline (including monitor cost) and $2500 higher costs during 12-month follow-up. CONCLUSIONS: In this large real-world study of patients with ischaemic or cryptogenic stroke, ILR placement resulted in more diagnosis of AF and initiation of oral anticoagulation, but no difference in mortality compared with long-term continuous external monitors.

Emulation of randomized trials of direct oral anticoagulants with claims data and implications for new Factor XI inhibitors.

Direct oral anticoagulants (DOACs) revolutionized the management of thromboembolic disorders. Clinical care may be further improved as Factor XIs undergo large-scale outcome trials. What role can non-randomized database studies play in expediting understanding of these drugs in clinical practice? The RCT-DUPLICATIVE Initiative emulated the design of eight DOAC randomized clinical trials (RCT) using non-randomized claims database studies. RCT study design parameters and measurements were closely emulated by the database studies and produced highly concordant results. The results of the single database study that did not meet all agreement metrics with the specific RCT it was emulating were aligned with a meta-analysis of six trials studying similar questions, suggesting the trial result was an outlier. Well-designed database studies using fit-for-purpose data came to the same conclusions as DOAC trials, illustrating how database studies could complement RCTs for Factor XI inhibitors-by accelerating insights in underrepresented populations, demonstrating effectiveness and safety in clinical practice, and testing broader indications.

The effect of preoperative use of anticoagulants on the hemostatic effect of intravenous application of tranexamic acid in PLIF: a case control study.

Intravenous application of tranexamic acid (TXA) in posterior lumbar interbody fusion (PLIF) can effectively reduce blood loss without affecting coagulation function. However, it has not been reported whether preoperative use of anticoagulants may affect the efficacy of TXA in PLIF. The purpose of this study is to observe the effect of preoperative use of anticoagulants on coagulation indicators and blood loss after PLIF receiving intravenous unit dose TXA. A retrospective analysis was conducted on data from 53 patients with PLIF between 2020.11 and 2022.9, who received intravenous application of a unit dose of TXA (1 g/100 mL) 15 min before the skin incision after general anesthesia. Those who used anticoagulants within one week before surgery were recorded as the observation group, while those who did not use anticoagulants were recorded as the control group. The main observation indicators include surgical time, intraoperative blood loss, postoperative drainage volume, blood transfusion, and red blood cell (RBC), hemoglobin (HB), and hematocrit (HCT) measured on the 1st, 4th, 7th, and last-test postoperative days. Secondary observation indicators included postoperative incision healing, deep vein thrombosis of lower limbs, postoperative hospital stay, and activated partial thrombin time (APTT), prothrombin time (PT), thrombin time (TT), fibrinogen (FIB), and platelets (PLT) on the 1st and 4th days after surgery. The operation was successfully completed in both groups, the incision healed well after operation, and no lower limb deep vein thrombosis occurred. There was no significant difference in surgical time, intraoperative blood loss, postoperative drainage volume, and blood transfusion between the two groups (p > 0.05). There was no significant difference in the RBC, HB, and HCT measured on the 1st, 4th, 7th, and last-test postoperative days between the two groups (p > 0.05). There was no statistically significant difference in APTT, PT, TT, FIB and PLT between the two groups on the 1st and 4th postoperative days (p > 0.05). There was no significant difference in postoperative hospital stay between the two groups (p > 0.05). The use of anticoagulants within one week before surgery does not affect the hemostatic effect of intravenous unit dose TXA in PLIF.

The influence of perioperative enoxaparin on bleeding after TORS oropharyngectomy.

Perioperative enoxaparin is often avoided in patients undergoing transoral robotic (TORS) oropharyngectomy. Our goal was to quantify the risk of postoperative hemorrhage (POH) in patients receiving enoxaparin after TORS oropharyngectomy. This was a retrospective database cohort study set up in 89 separate healthcare organizations. The TriNetX electronic database was queried for patients with OPSCC who underwent TORS oropharyngectomy. Propensity-score matching was used to create two cohorts, one receiving and one not receiving perioperative enoxaparin. Outcome measures were the POH rate within 1 day of surgery ("primary") and POH rate within 2-30 days of surgery ("secondary"). 1109 patients undergoing TORS for OPSCC were identified, 400 of which received perioperative enoxaparin. One-to-one propensity score matching resulted in 310 patients per cohort. After matching, the primary POH rates between patients receiving and not receiving enoxaparin were 3.23% for both cohorts (OR 1.000, 95% CI 0.410 to 2.438). The secondary POH rates between those receiving and not receiving enoxaparin were 5.47% vs. 3.54% (OR 1.577, 95% CI 0.726 to 3.424). The number needed to harm (NNH) with perioperative enoxaparin use for secondary POH after TORS was 53; no difference was found in primary POH rates. While not statistically significant, the use of perioperative enoxaparin after TORS is associated with increased odds of secondary POH with a NNH of 53; no difference was found in rates of primary POH. For patients undergoing TORS, enoxaparin use requires careful weighing of the risks and benefits.

[Is low-dose anticoagulation a therapeutic option for patients at high risk of bleeding with high-risk pulmonary thromboembolism].

This issue of Chinese Journal of Tuberculosis and Respiratory Diseases published an interesting case illustrating the identification, treatment, and post-treatment management of a high-risk pulmonary thromboembolism (PTE) that occurred during surgery. It was a high-risk case of PTE, but during treatment, the risk stratification changed to medium-high risk. We should dynamically assess risk stratification and develop diagnosis and treatment plans based on changes in the patient's condition. At the same time, there was a high risk of bleeding in this patient. We should try to decrease the risk of bleeding as much as possible, consider all the conditions that can be applied at that time and on a local level, and devise a safe and effective treatment plan. The socio-economic status of patients may have an impact on how the final diagnosis and treatment plan are implemented. We need to communicate fully with patients, consider comprehensively, and prepare contingency plans to ensure patients' life safety to the greatest extent possible.

[Successful treatment of high-risk pulmonary embolism with low-dose anticoagulation: a case report].

Reperfusion is considered as the cornerstone of the treatment of high-risk pulmonary embolism (PE). However, when thrombolysis is contraindicated and surgery or interventional therapy is not available, the treatment of high-risk PE becomes very difficult. To our knowledge, there are no reports of successful treatment of high-risk PE with low-dose anticoagulation. On November 30, 2021, a 56-year-old male patient with subarachnoid hemorrhage was admitted to the emergency department of the First Affiliated Hospital of Chongqing Medical University. On the second day of admission, the patient suddenly went into shock during aneurysm clipping. After implementing D-dimer, markers of myocardial injury, echocardiography and computed tomography pulmonary angiography, a high-risk PE was diagnosed. Due to the contraindication of thrombolysis and the refusal of endovascular treatment, he was eventually cured with low-dose anticoagulation combined with vasopressors.

Predictors of adherence to direct oral anticoagulants after cardiovascular or bleeding events in Medicare Advantage Plan enrollees with atrial fibrillation.

BACKGROUND: Direct oral anticoagulants (DOACs) are recommended for patients with atrial fibrillation (AF) given their improved safety profile. Suboptimal adherence to DOACs remains a significant concern among individuals with AF. However, the extent of adherence to DOACs following a cardiovascular or bleeding event has not been fully evaluated. OBJECTIVE: To evaluate the pattern of adherence trajectories of DOACs after a cardiovascular or bleeding event and to investigate the sociodemographic and clinical predictors associated with each adherence trajectory by using claims-based data. METHODS: This retrospective study was conducted among patients with AF prescribed with DOACs (dabigatran/apixaban/rivaroxaban) between July 2016 and December 2017 and who were continuously enrolled in the Texas-based Medicare Advantage Plan. Patients who experienced a cardiovascular or bleeding event while using the DOACs were further included in the analysis. The sample was limited to patients who experienced a clinical event such as a cardiovascular or bleeding event while using the DOACs. The clinical events considered in this study were cardiovascular (stroke, congestive heart failure, myocardial infarction, systemic embolism) and bleeding events. To assess adherence patterns, each patient with a DOAC prescription was followed up for a year after experiencing a clinical event. The monthly adherence to DOACs after these events was evaluated using the proportion of days covered (PDC). A group-based trajectory model incorporated the monthly PDC to classify groups of patients based on their distinct patterns of adherence. Predictors associated with each trajectory were assessed using a multinomial logistic regression model, with the adherent trajectory serving as the reference group in the outcome variable. RESULTS: Among the 694 patients with AF who experienced clinical events after the initiation of DOACs, 3 distinct adherence trajectories were identified: intermediate nonadherent (30.50%), adherent (37.7%), and low adherent (31.8%); the mean PDC was 0.47 for the intermediate nonadherent trajectory, 0.93 for the adherent trajectory, and 0.01 for low adherent trajectory. The low-income subsidy was significantly associated with lower adherence trajectories (odds ratio [OR] = 4.81; 95% CI = 3.07-7.51) and with intermediate nonadherent trajectories (OR = 1.57; 95% CI = 1.06-2.34). Also, nonsteroidal anti-inflammatory drug use was significantly associated with lower adherence trajectories (OR = 5.10; 95% CI = 1.95-13.36) and intermediate nonadherent trajectories (OR = 3.17; 95% CI = 1.26-7.93). Other predictors significantly associated with both nonadherent trajectories are type of DOACs (OR = 0.53; 95% CI = 0.35-0.79), presence of coronary artery disease (OR = 1.89; 95% CI = 1.01-3.55), and having 2 or more clinical events (OR = 1.65; 95% CI = 1.09-2.50). CONCLUSIONS: Predictors identified provide valuable insights into the suboptimal adherence of DOACs among Medicare Advantage Plan enrollees with AF, which can guide the development of targeted interventions to enhance adherence in this high-risk patient population.

Preoperative Drug Monitoring in Management of Patients with Hip Fracture on Treatment with Direct Oral Anticoagulants.

Purpose: Aim of the present study was to evaluate whether monitoring direct oral anticoagulant (DOAC) levels may improve management of anticoagulated patients who need surgery for hip fracture. Patients and Methods: A total of 147 out of 2231 (7.7%) patients with hip fracture admitted to a tertiary teaching hospital were on DOACs (group A), whereas 206 patients matched for age, sex, and type of fracture not on anticoagulant or P2Y12 platelet inhibitors were considered as control group (group B). Patients on DOACs were divided into two subgroups: A1 in which intervention was scheduled in relation to the last drug intake according to current guidelines, and A2 included patients in whom time of surgery (TTS) was defined according to DOAC levels. Neuraxial anesthesia was considered with DOAC levels <30 ng/mL, general anesthesia for levels in the range 30-50 ng/mL. Results and conclusions: TTS was significantly lower in controls than in DOAC patients: surgery within 48 hours was performed in 80.6% of group B versus 51% in group A (p<0.0001). In A2, 41 patients underwent surgery within 48 hours (56%) in comparison to 32 A1 patients (45.1%; p=0.03). TTS and length of hospitalization were on average 1 day lower in patients with assay of DOAC levels. Finally, 35/39 (89%) patients with DOAC levels <50 ng/mL had surgery within 48 hours (26 under neuraxial anesthesia, without any neurological complication, and 13 in general anesthesia). Conclusion: DOAC assay in patients with hip fracture may be useful for correct definition of time to surgery, particularly in patients who are candidates for neuraxial anesthesia. Two-thirds of patients with DOAC levels <50 ng/mL at 48 hours from last drug intake underwent uneventful neuraxial anesthesia, saving at least 24 hours in comparison to guidelines.

Direct Oral Anticoagulation in Lung Transplant Recipients.

OBJECTIVES: Presently, the management of direct oral anticoagulants lacks specific guidelines for patients before and after transplant, particularly for lung transplant recipients. We aimed to consolidate the existing literature on direct oral anticoagulants and explore their implications in lung transplant recipients. MATERIALS AND METHODS: We conducted a comprehensive search in PubMed and Google Scholar databases for studies published between January 2000 and December 2022, using specific search terms. We only included studies involving lung transplant recipients and focusing on direct oral anticoagulants. RESULTS: Five relevant publications were identified, providing varied insights. None of the studies specifically addressed bleeding complications associated with direct oral anticoagulants in lung transplant recipients. Limited details were available on the type of solid-organ transplant or the specific direct oral anticoagulant used in these studies. CONCLUSIONS: Varied bleeding complications associated with direct oral anticoagulants in lung transplant recipients were reported, but studies lacked specificity on transplant type and direct oral anticoagulant variations. Notably, the incidence of venous thrombotic embolism in lung transplant recipients was comparatively higher than in other solid-organ transplant recipients, potentially linked to factors such as corticosteroid therapy, calcineurin inhibitors, and cytomegalovirus infections. Our synthesis on findings of use of direct oral anticoagulant in lung transplant recipients emphasized challenges of managing these medications in urgent transplant situations. Recommendations from experts suggested caution in initiation of direct oral anticoagulants posttransplant until stability in renal and hepatic function is achieved. The limited evidence on safety of direct oral anticoagulants in lung transplant recipients underscores the need for further research and guidance in this specific patient population.

Effect of Splenectomy on Coagulation and Platelet Function in Adult Liver Transplant Recipients Assessed With Rotational Thromboelastometry and Standard Coagulation Tests.

OBJECTIVES: Splenectomy during liver transplant can affect platelet function. In this study, our primary aim was to assess the perioperative platelet function by rotational thromboelastometry and the effects of splenectomy on platelet function. MATERIALS AND METHODS: We studied 40 consecutive liver transplant recipients with end-stage liver disease (50% as a result of hepatitis C). Patients with splenectomy were compared with patients without splenectomy (n = 20/group). Three platelet function parameters by rotational thromboelastometry were studied: platelet activation with arachidonic acid, platelet activation with adenosine diphosphate, and platelet activation with thrombin receptor-activating peptide 6. Patients were monitored perioperatively and until postoperative day 21. Heparin was infused for 2 days postoperatively (60-180 U/kg/day), followed by administration of subcutaneous low-molecular-weight heparin (40 mg/24 h) on postoperative days 2 and 3 and oral acetylsalicylic acid when platelet count was >50 × 103/µL. RESULTS: Liver disease contributed to low perioperative platelet count and function. Patients showed significant improvement by postoperative day 14 and day 21, particularly after splenectomy. Platelet count was significantly correlated with the 3 platelet function parameters by rotational thromboelastometry (P < .001). Acetyl salicylic acid was required earlier (postoperative day 3) for patients with splenectomy (8/20) but only affected the platelet function represented by platelet activation with arachidonic acid, whereas other platelet activation pathways were less affected. Patients received no transfusions of platelet units. CONCLUSIONS: End-stage liver disease significantly contributed to low platelet function and counts before transplant. Two weeks were required for recovery of patients posttransplant, with further enhancement by splenectomy. Some recipients showed recovery that exceeded the normal reference range, which warranted monitoring. Acetyl salicylic acid only affected 1 platelet activation receptor.

Study Design of a Brazilian Observational Study of Edoxaban in Patients with Atrial Fibrillation (EdoBRA). / Desenho de Estudo de um Estudo Observacional Brasileiro sobre o uso de Edoxabana em Pacientes com Fibrilação Atrial (EdoBRA).

BACKGROUND: Clinical trials showed the safety of Edoxaban, a non-vitamin K-dependent oral anticoagulant (NOAC), and its efficacy to prevent stroke and systemic embolism in non-valvular atrial fibrillation (NVAF) patients and also to prevent and treat venous thromboembolism. However, additional research is needed to evaluate the safety and effectiveness of Edoxaban in a real-world scenario in the Brazilian population. OBJECTIVE: In order to understand the risks and benefits of Edoxaban use in routine clinical settings, the EdoBRA study is being conducted to gain insight into the safety and effectiveness of Edoxaban use in non-preselected patients with NVAF in Brazil. METHODS: The EdoBRA study is a multicenter, prospective, observational study conducted in 36 sites in Brazil. NVAF patients ≥ 18 years treated with commercially available Edoxaban who initiated treatment for at least 14 days and no longer than 90 days prior to enrollment, and who are not simultaneously participating in any interventional study are eligible for this study. Seven hundred patients are planned to be enrolled and one-year of follow up, with data collections expected at baseline and 3, 6, and 12 months after the study enrollment. The primary safety objective is ISTH Clinically Relevant Bleeding, and the secondary effectiveness objective focuses on relevant cardiovascular outcomes related to NVAF. CONCLUSION: EdoBRA observational study will generate relevant additional information about NOAC Edoxaban on various aspects of patient management in routine care, such as its safety and effectiveness profile in patients with NVAF in Brazil.

FUNDAMENTO: Os ensaios clínicos demonstraram a segurança da Edoxabana, um anticoagulante oral não dependente de vitamina K (NOAC), e a sua eficácia na prevenção de acidente vascular cerebral e embolia sistémica em pacientes com fibrilação atrial não valvar (FANV) e também na prevenção e tratamento de tromboembolismo venoso. No entanto, pesquisas adicionais são necessárias para avaliar a segurança e a eficácia da Edoxabana em um cenário real na população brasileira. OBJETIVO: A fim de compreender os riscos e benefícios do uso da Edoxabana em cenários clínicos de rotina, o estudo EdoBRA está sendo conduzido para obter informações sobre a segurança e eficácia do uso da Edoxabana em pacientes não pré-selecionados com FANV no Brasil. MÉTODOS: O estudo EdoBRA é um estudo multicêntrico, prospectivo e observacional, realizado em 36 centros no Brasil. São elegíveis para este estudo pacientes com FANV, ≥ 18 anos de idade, tratados com Edoxabana disponível comercialmente, que iniciaram o tratamento por pelo menos 14 dias e não mais do que 90 dias antes da data de inclusão no estudo, e que não estão participando de nenhum outro estudo de intervenção. Ao todo, 700 pacientes devem ser inscritos e acompanhados por um ano, com coletas de dados programadas para o período basal e 3, 6 e 12 meses após a inscrição no estudo. O objetivo primário de segurança é o sangramento clinicamente relevante (de acordo com critérios da Sociedade Internacional de Trombose e Hemostasia - ISTH), e o objetivo secundário de eficácia são desfechos cardiovasculares relevantes relacionados à FANV. CONCLUSÃO: O estudo observacional EdoBRA gerará informações adicionais relevantes sobre a Edoxabana enquanto NOAC em diversos aspectos do manejo de pacientes no atendimento clínico de rotina, como perfil de segurança e efetividade em pacientes com FANV no Brasil.