Patients Receiving Anticoagulation Therapy Research Articles

Extracorporeal Shockwave for Intermittent Claudication and Quality of Life

Intermittent lower limb claudication limits function and quality of life. Supervised exercise programs are not readily available, and a noninvasive alternative is needed. To assess extracorporeal corporeal shockwave therapy in improving quality of life in patients with claudication. In this double-blind, placebo-controlled randomized clinical trial, patients in the outpatient setting at a single tertiary center for vascular surgery were randomized in a 1:1 ratio to extracorporeal shockwave therapy or placebo therapy with no shockwaves delivered. Recruitment was between June 2015 and January 2020, with 12-week follow-up ending in March 2020. A convenience sample of patients with claudication and conservative treatment requirements who refused or were unable to participate in supervised exercise were eligible. Patients receiving anticoagulation therapy or with an active cancer were excluded. Of 522 patients screened, 389 were eligible, 138 were enrolled, and 110 completed follow-up and were included in the primary analysis. Statistical analysis was completed by May 2021. In the intervention group, patients received 100 impulses of 0.1mJ/mm/cm2 in an area of the gastrocnemius muscle 3 times weekly for 3 weeks. The steps for treatment were replicated for the control group without delivering the treatment. The primary outcome was the Physical Functioning domain of the 36-item Short-Form Quality of Life Questionnaire at 12-week follow-up. Secondary outcomes included walking distances, ankle brachial pressure index, and other quality-of-life measures. Of 138 patients recruited and randomized, 92 (67%) were male, and the mean (SD) age of the study population was 67 (9.6) years. The intervention group had a significantly higher physical function score at 12 weeks (estimated median difference 3.8; 95% CI, 0.0-7.7; P = .03). However, this significance did not remain when adjusting for covariates. At 12 weeks, the intervention group had significantly longer pain-free and maximum walking distances (pain-free estimated median difference, 34.1, 95% CI, 11.4-56.8; P = .004; maximum estimated median difference, 51.4; 95% CI, 10.7-86.5; P = .01). To our knowledge, this is the first double-blind, placebo-controlled, randomized clinical trial to consider extracorporeal shockwave therapy for the management of intermittent claudication. It demonstrated efficacy for walking distances, may have a positive effect on quality of life, and may provide a safe, noninvasive alternative therapy for patients with intermittent claudication. ClinicalTrials.gov Identifier: NCT02652078.

Position Statement on In-hospital/Clinic Point-of-care Coagulation Testing for Anticoagulation Monitoring in Saudi Arabia.

Hospital overload is a persistent occurrence in daily practice. Interventions such as point-of-care testing (POCT) are needed to alleviate the pressure faced by healthcare providers and administrators. An invited panel of experts from Saudi Arabia was formed under the auspices of the Saudi Heart Association in order to discuss local treatment gaps in the management of patients receiving anticoagulation therapy. This was done in a series of meetings, which resulted in the development of official recommendations for the implementation of POCT for anticoagulation monitoring in the country. Recommendations were based on a comprehensive literature review and international guidelines taking into consideration local clinical practice, clinical gaps, and treatment/testing availabilities. Vitamin K antagonist (VKA)-based anticoagulation therapy requires routine monitoring. POCT is a promising model of care for the monitoring of International Normalized Ratio (INR) in patients receiving oral anticoagulation in terms efficacy, safety and convenience. The availability of POC INR testing should not replace the use of standard laboratory anticoagulation monitoring. However, there are several indications for implementing POCTINR monitoring that was agreed upon by the expert panel. POCT for anticoagulation monitoring should primarily be used in the warfarin (or other VKA) monitoring clinic in order to ensure treatment efficiency, cost-effectiveness of care, patient satisfaction, and quality of life improvement. The expert panel detailed the requirements for the establishment of a warfarin (or other VKA) monitoring clinic in terms of organization, safety, quality control, and other logistic and technical considerations. The limitations of POCT should be recognized and recommendations on best practices should be strictly followed. Core laboratory confirmation should be sought for patients with higher INR results (>4.7) on POCT. Proper training, quality control, and regulatory oversight are also critical for preserving the accuracy and reliability of POCT results. POCT enables more rapid clinical decision-making in the process of diagnosis (rule-in or rule-out), treatment choice and monitoring, and prognosis, as well as operational decision-making and resource utilization. POCT thus can fulfill an important role in clinical practice, particularly for patients receiving VKAs.

Diagnosis and treatment of venous thromboembolism and clinical application of inferior vena cava filter in China

ObjectiveThis study investigated the trend of venous thromboembolism (VTE) in China during the past 10 years and assessed the clinical application of inferior vena cava filters (IVCFs). MethodsA survey designed to investigate the diagnosis and management of VTE, specifically the application of IVCFs, was distributed nationally from January 2009 to December 2019. The respondents were mainly designated medical professionals and were asked to complete 4 major and 61 minor items in the survey. ResultsA total of 53 medical centers, including 27 radiologic and 26 vascular surgery centers, from 21 provinces in China participated in the study. These centers had diagnosed and treated 171,310 patients with VTE; 83,969 were inpatients (49%). During a 10-year period, an increasing trend of VTE diagnosis and inpatient management, 3.8-fold and 4.8-fold, respectively, was observed. The characteristics of the inpatients were as follows: 15% bilateral lower extremity deep vein thrombosis (DVT), 27% right lower extremity DVT, and 58% left lower extremity DVT. Anticoagulation therapy included unfractionated heparin with vitamin K antagonists (8%), low-molecular-weight heparin (LMWH) with vitamin K antagonists (21%), LMWH with transition to rivaroxaban (34.2%), LMWH with transition to dabigatran (2.4%), rivaroxaban alone (33.4%), and dabigatran alone (1.0%). The percentage of patients continuing anticoagulation therapy at 3, 6, 12, 24, and >24 months was 36%, 35%, 18%, 6.0%, and 5%, respectively. The in-hospital mortality for the patients with VTE was 3.2%, with DVT and pulmonary embolism responsible for 5.2% and DVT alone for 2.7%. Thrombolytic therapy was initiated for 39,046 of 83,969 patients (46.5%), including catheter-directed thrombolysis for 33,189 of the 39,046 patients (85%) and evaluation of the iliac vein using ultrasound and/or venography for 63,816 patients (76%). Urokinase was the main thrombolytic drug used (98%), followed by recombinant tissue-type plasminogen activator. Complete and partial thrombolysis was achieved in 70% and 30% of the patients, respectively. Bleeding complications were observed in 3.5% of patients, and 20% of the patients with bleeding complications required intervention. Between 2009 and 2019, 40,478 IVCFs (76% retrievable) were implanted in hospitalized VTE patients. During the enrollment period, the total number of IVCFs implanted increased by 3.8-fold, with a 4.8-fold increase in retrievable IVCFs and 7.5-fold decline in permanent IVCFs. The removal rate for the retrievable IVCFs was 72%. After IVCF implantation, 94.8% of patients received anticoagulation therapy for an average of 9.1 ± 8.6 months. The overall complication rate associated with IVCF placement was 15.5% (n = 6274 of 40,478 IVCFs), including tilting (54%), vena cava thrombosis (26.1%), caval penetration (12.6%), and migration (7.3%). No IVCF placement-related mortality occurred. ConclusionsA significant increase occurred in VTE diagnosis in China during the past decade. Anticoagulation therapy was the mainstay treatment, and catheter-directed thrombolysis was widely used. Most IVCFs placed were retrievable, and the use of permanent IVCFs has largely been discarded.

Clinical benefits and risks of anticoagulation therapy according to the degree of chronic kidney disease in patients with atrial fibrillation

BackgroundThe clinical benefits and risks of anticoagulation therapy in patients with chronic kidney disease (CKD) are still inconclusive. We describe the outcomes of patients with atrial fibrillation (AF) after anticoagulation therapy according to differences in creatinine clearance (CrCl). We also aimed to determine the patients who could benefit from anticoagulation therapy.MethodsThis is a retrospective observational review of patients with AF who were managed at Asan Medical Center (Seoul, Korea) between January 1, 2006, and December 31, 2018. Patients were categorized into groups according to their baseline CrCl by Cockcroft–Gault equation and their outcomes were evaluated (CKD 1, ≥ 90 mL/min; CKD2, 60–89 mL/min; CKD3, 30–59 mL/min; CKD4, 15–29 mL/min; CKD 5, < 15 mL/min). The primary outcome was NACE (net adverse clinical events), defined as a composite of all-cause mortality, thromboembolic events, and major bleeding.ResultsWe identified 12,714 consecutive patients with AF (mean 64.6 ± 11.9 years, 65.3% male, mean CHA2DS2-VASc score 2.4 ± 1.6 points) between 2006 and 2017. In patients receiving anticoagulation therapy (n = 4447, 35.0%), warfarin (N = 3768, 84.7%) was used more frequently than NOACs (N = 673, 15.3%). There was a higher 3-year rate of NACE with renal function deterioration (14.8%, 18.6%, 30.3%, 44.0%, and 48.8% for CKD stages 1–5, respectively).The clinical benefit of anticoagulation therapy was most prominent in patients with CKD 1 (hazard ratio [HR] 0.49, 95% confidence interval [CI] 0.37–0.67), 2 (HR 0.64 CI 0.54–0.76), and 3 (HR 0.64 CI 0.54–0.76), but not in CKD 4 (HR 0.86, CI 0.57–1.28) and 5 (HR 0.81, CI 0.47–1.40). Among patients with CKD, the benefit of anticoagulation therapy was only evident in those with a high risk of embolism (CHA2DS2-VASc score ≥ 4, HR 0.25, CI 0.08–0.80).ConclusionAdvanced CKD is associated with a higher risk of NACE. The clinical benefit of anticoagulation therapy was reduced with the increasing CKD stage.

Pulmonary Embolism in Critically Ill COVID-19 And Non-COVID-19 Patients: Systematic Analysis of Risk Factors, Diagnostic and Management Strategies, and Prognosis.

Background: Coronavirus disease of 2019 or COVID-19 is characterised by two main features: the first is the respiratory compromise which corresponds to acute respiratory distress syndrome while the second corresponds to the state of hypercoagulability responsible for thromboembolic complications particularly pulmonary embolism which is the subject of this work. Indeed, a high prevalence of pulmonary embolism has been reported throughout the pandemic period with a significant morbidity and mortality. This reflects the severity of this life-threatening emergency chiefly in the elderly, hemodynamically unstable patients, and patients with severe underlying conditions, mainly cardio-pulmonary comorbidities. The aim of our study is to point out the incidence, the risk factors, the clinical and paraclinical features, the management strategies, and the overall prognosis of pulmonary embolism in critically ill COVID-19 and non-COVID-19 patients. Patients and methods: It is a retrospective observational study carried out over a two-year-period from January 2019 (non-COVID-19) to December 2020 (COVID-19). Over the study period, 42 cases of COVID-19 and non-COVID-19 pulmonary embolism were collected from an overall set of 611 patients admitted to the medical intensive care unit of the IBN ROCHD university hospital of Casablanca. Results: The mean age in the COVID-19 group was 64-year-old versus 46-year-old in the non-COVID-19 group. The sex ratio was 1.2 and 0.94 in the non-COVID-19 and COVID-19 group, respectively. Clinical symptomatology was dominated by respiratory failure and chest pain in non-COVID-19 patients while in the COVID-19 group, semiology was dominated by dyspnea, cough, and chest pain. The major sign of severity in both groups was tachypnea. The chest X-ray was performed in all our patients, it displayed radiological abnormalities in all patients mainly hyper clarity in pulmonary fields. D-dimers were performed in all patients within the two study groups. A chest computed tomography angiogram was performed for all patients and showed unilateral pulmonary embolism in 61% of cases in the non-COVID-19 group versus 61.3% in the COVID-19 group. Cardiac ultrasound was performed for all patients. It showed dilatation of right cavities in both groups (81.8% in non-COVID-19 versus 93.5% in COVID-19 patients). Venous ultrasound of the lower limbs was performed in 96.8% of COVID-19 patients and in 72.7% of non-COVID-19 patients. With regards to management, all COVID-19 and non-COVID-19 patients received anticoagulation therapy based on standard heparin and anti-vitamin K. Mortality accounted for 54.5% in non-COVID-19 patients versus 74.2% in COVID-19 patients. Conclusion: COVID-19 pulmonary embolism is often associated with significantly higher morbidity and mortality as compared with non-COVID-19 pulmonary embolism.

Effectiveness of a Nursing Intervention Module on Adherence, Knowledge, Quality of Life, and Complications Among Patients Receiving Anticoagulation therapy-a Randomized Controlled Trial Protocol.

BackgroundCardiovascular diseases are one of the major causes of mortality at the global level. They account for approximately 17.9 million deaths per year. Warfarin and acenocoumarol are the commonly used oral anticoagulants to treat and prevent thromboembolic disorders in patients with cardiovascular diseases. In India, approximately 2–2.5 million patients with rheumatic heart disease are receiving oral anticoagulation therapy. Additionally, this therapy is provided for stroke prevention in the case of atrial fibrillation and the treatment of valvular heart disease, stroke, and deep vein thrombosis. As the therapeutic range of these drugs is narrow and is affected by many factors, their use is challenging. This study aims to evaluate the effectiveness of a nursing intervention module in terms of adherence to therapy, knowledge, quality of life, and complications among patients receiving oral anticoagulation therapy. Furthermore, this study will address factors that affect adherence and the risk for bleeding by using a randomized controlled trial design.MethodsThis single-blind, single-center, randomized controlled trial will focus on adherence to oral anticoagulation therapy. A total of 320 patients who are on oral anticoagulation therapy will be randomized into blocks and allocated to either the intervention or standard care group. The intervention will comprise the use of a nursing intervention module that includes a booklet, log sheet, and decision aid on oral anticoagulation therapy adherence. Outcome measures, that is, knowledge regarding oral anticoagulation therapy, adherence, complications, and quality of life, will be assessed at the baseline and during follow-ups.DiscussionPatient safety can be best achieved through patients’ adherence to medication dose and monitoring of blood test values. Thromboembolic and bleeding complications are likely to occur when either the patient does not adhere to the treatment or the therapeutic range of the international normalized ratio is not maintained. This study will assess the nonadherence behavior and the effectiveness of a nursing intervention module toward adherence behavior.Trial RegistrationThis research project is registered under the Clinical Trial Registry of India (CTRI/2019/06/019610).

The Effect of Anticoagulation on the Treatment of Dupuytren Contracture with Collagenase.

There have been no formal studies of the use of collagenase clostridium histolyticum (Xiaflex; Endo Pharmaceuticals, Malvern, Pa.) in the anticoagulated patient. Previous study on its use excluded patients receiving anticoagulation therapy. This study reviewed the effects of anticoagulation use in patients undergoing collagenase clostridium histolyticum injection and cord rupture to determine safety and efficacy. The authors retrospectively reviewed patients receiving collagenase clostridium histolyticum injections for Dupuytren contracture between 2010 and 2017. Outcomes included type of anticoagulation, skin tear, tendon rupture, lymphadenopathy, sensory abnormality, hematoma, and bleeding. A total of 388 injections were performed in 197 patients. The average clinical follow-up was 311 days. Fifty-two percent of patients (n = 201) were anticoagulated. The vast majority were taking aspirin (acetylsalicylic acid) (n = 182), followed by warfarin (n = 27), clopidogrel (n = 9), apixaban (n = 8), rivaroxaban (n = 4), and dabigatran (n = 2). There were 42 skin tears, 21 in the anticoagulated group. One tendon rupture occurred in the anticoagulated group (acetylsalicylic acid) and none occurred in the nonanticoagulated group (p = 0.34). No patients experienced sensory abnormalities, a hematoma requiring intervention, or uncontrollable bleeding. Anticoagulation is commonly encountered by hand surgeons treating Dupuytren contracture. There is no significant difference in complications in the anticoagulated patient versus the nonanticoagulated patient. It is safe to perform collagenase clostridium histolyticum injections for Dupuytren contracture in the anticoagulated patient, regardless of the type of anticoagulation. Therapeutic, III.

Anticoagulation Practice in Patients with Cancer-Associated Thrombosis: Insights from GeCAT, a German Prospective Registry Study

Introduction: Cancer-associated venous thrombosis (CAT) is a common and serious complication of active malignancies, increasing in frequency during systemic treatment and radiotherapy. Due to a high risk of recurrence and bleeding, the administration of anticoagulants for initial treatment and secondary prevention of CAT is challenging. We conducted a prospective registry study of patients with acute CAT to evaluate the way treatment is given to these patients in routine practice. Methods: From May 2015 to May 2017, all consecutive patients with acute venous thromboembolism (VTE) admitted to specialty or emergency departments of the participating hospitals in Berlin, Germany, were entered into the registry. Patients with cancer underwent extensive baseline evaluation including the type and location of thrombosis and use of anticoagulant therapy. Follow-up assessments were made at discharge and by telephone interviews at 3 and 6 months. Results: A total of 382 patients with acute CAT were enrolled in the study, representing 24.5% of all patients with thrombosis. 70.4% of CAT patients had deep vein thromboses (DVT), 48.2% had pulmonary embolism (PE), and 18.6% had concurrent PE and DVT. A significant proportion of VTE (27%) was asymptomatic and was diagnosed only incidentally. At baseline, 97.9% of the patients received anticoagulant therapy, predominantly with low-molecular-weight heparin (LMWH) (n = 334, 87.4%). Direct oral anticoagulants (DOACs) were given to 5.8% of patients, and vitamin K antagonists were rarely used (<2% of patients). Changes in the prescription of antithrombotic agents were seen at discharge from hospital and during follow-up. Overall, the use of LMWH declined during follow-up, while the proportion of patients treated with DOACs increased to 32.4% at 6 months. At baseline, the most frequently used LMWH were enoxaparin and nadroparin, but many patients were switched to once daily tinzaparin prior to discharge. Initially and after discharge, the majority of patients were treated by oncologists. Overall, 263 (68.8%) and 222 (58.1%) patients were still alive and could be contacted at 3 and 6 months of follow-up, respectively. Of these, 84.0% and 71.6% were still on anticoagulant therapy (58.6% and 36.5% on LMWH). Conclusion: In accordance with the guidelines, the majority of CAT patients received anticoagulation therapy for the recommended minimum duration of 3–6 months. LMWH remained the preferred option throughout the study, demonstrating good patient adherence. In deviation from guideline recommendations and available study results during the study period, more than a quarter of CAT patients were treated with DOACs. Only recently, DOACs have been established as another option for anticoagulation in CAT patients.

Effectiveness and safety of catheter removal alone versus standard anticoagulation therapy after catheter removal for peripherally inserted central catheter (PICC)-related thrombosis

BackgroundCurrently, peripherally inserted central catheters (PICCs) are widely used; however, there are associated problems due to catheter-related thrombosis (CRT). According to the existing literature and guidelines, 3–6 months of anticoagulation therapy is recommended, but these recommendations are based on analogous deep vein thrombosis of the lower limbs. More specific management strategies need to be developed, and the safety and effectiveness of these strategies needs to be investigated.MethodsSome studies have suggested that catheter removal alone is a reasonable option, especially for patients with a higher risk of bleeding. We conducted a retrospective study of hospitalized patients from a single center who were diagnosed with PICC-related thrombosis. Among the 85 patients who met the inclusion criteria, 63 patients were treated with catheter removal alone, and 22 patients received anticoagulation therapy after catheter removal. The progression of thrombosis and bleeding in the two groups were compared. Most patients who underwent catheter removal alone had hematological malignancies, and thrombocytopenia had occurred during chemotherapy.ResultsAfter PICC removal, no patients in the anticoagulation therapy group developed progressive thrombosis, while 10 patients in the catheter removal alone group developed progressive thrombosis or pulmonary embolism (PE), including one case of PE, four cases of secondary upper extremity deep vein thrombosis (UEDVT), and five patients showed obvious aggravation of thrombosis after catheter removal, and were administered repeated anticoagulant therapy. In the PICC removal + anticoagulation treatment group, major bleeding increased significantly (28.6% vs. 4.7%, P=0.006).ConclusionsCompared to the PICC removal + anticoagulation treatment group, the risk of major bleeding in the catheter removal alone group was significantly reduced. In some patients with an increased bleeding risk, catheter removal alone may be a safer and more effective option than catheter removal with anticoagulation treatment for CRT.

Incidence of Bleeding Events in Acute Myeloid Leukemia (AML) Patients Receiving Anticoagulation Therapy for Treatment of Deep Vein Thrombosis (DVT) or Pulmonary Embolism (PE) Who Are Also Undergoing Induction or Re-Induction Therapy

Background/Rationale:Venous thromboembolic events (VTE) remain a prevalent complication in cancer patients. Despite this increased risk, the decision on whether or not to treat and/or use prophylactic therapy remains highly debatable among clinicians. Induction and re-induction therapy, in combination with the pathophysiology of the disease can cause profound thrombocytopenia. Additionally, leukemic cells can cause an inappropriate release of procoagulants directly into the bloodstream, initiating the clotting cascade and causing simultaneous clot formation and hemorrhage leading to disseminated intravascular coagulation (DIC). Another major factor to consider in this patient population is central venous access. Although the National Comprehensive Cancer Network (NCCN) guidelines recommend ≥3 months of therapeutic anticoagulation for catheter-associated VTEs, clinicians use anticoagulation cautiously in the AML population due to severe thrombocytopenia and the increased risk of bleeding. Data that can be used to optimize treatment strategies for catheter-associated VTE in patients with acute leukemia are needed as the risk versus benefit for anticoagulation is currently unclear. A recent article by Rajasekhar and colleagues investigated this risk and noted that among patients with severe thrombocytopenia (platelets <50,000/μL) who received therapeutic anticoagulation, 27% experienced a significant bleeding event compared to only 2% of patients who did not receive therapeutic anticoagulation. In order to establish the bleeding complications associated with patients receiving induction or re-induction therapy for AML, we conducted a retrospective chart review evaluating the incidence of bleeding in patients receiving therapeutic anticoagulation for treatment of VTE.Objective:The primary outcome of this study is incidence of bleeding events in AML patients receiving anticoagulation therapy for treatment of DVT or PE who are also undergoing induction or re-induction therapy. Secondary outcomes include incidence of chemical and non-chemical DVT prophylaxis, as well as the difference in incidence of bleeding events among agents.Methods:This is a retrospective chart review evaluating the incidence of bleeding in AML patients receiving anticoagulation for treatment of VTE during induction or re-induction therapy at WFBH from October 2012 to October 2016. AML patients who were >18 years of age who had undergone induction or re-induction chemotherapy and developed a VTE were included in the study. Clinical diagnosis of VTE was confirmed by objective imaging procedures. The following induction or re-induction regimens were excluded: azacitidine or decitabine. Descriptive statistics were used for data analysis.Results: Out of 523 patients screened, 24 met eligibility criteria for a total VTE incidence of 4.6%. The age range for the patients included was 22 to 77, with 14 patients (58.3%) being female and 10 patients (41.7%) being male. Of the patients who developed a VTE, 18 (75%) received non-chemical DVT prophylaxis. Twenty (83.3%) of the 24 VTEs were catheter-associated DVTs. Twenty-two of 24 patients received therapeutic anticoagulation with either heparin (n=21) or enoxaparin (n=1). The 2 patients who did not receive anticoagulation did not have a bleeding event. Patients who developed a bleed were more likely to have supratherapeutic PTTs (defined as PTTs ≥ 90 seconds); however, supratherapeutic levels were isolated and not associated with the time of the bleed. Of the patients who received therapeutic anticoagulation, 8 (36.4%) had a major bleed and 9 (40.9%) had a minor bleed, for an overall bleeding rate of 77.3%. There were no deaths as a result of bleeding events. Of the 20 patients with catheter-associated VTEs, 7 (35%) had a major bleed; 4 of these patients required anticoagulation reversal with protamine.Conclusions:AML patients who received induction or re-induction therapy had a low incidence of VTE overall. However, when patients received anticoagulation for VTE treatment there was a high incidence of bleeding. The results found in this retrospective chart review showed that for patients with catheter-associated VTEs, the risk of bleeding outweighed the risk of VTE. We recommend a risk-adapted strategy where patients do not receive therapeutic anticoagulation until platelet recovery. DisclosuresPowell:Rafael Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees. Ellis:Alexion: Speakers Bureau. Pardee:Rafael Pharmaceuticals: Employment, Research Funding.

Real-World Data on Characteristics and Management of Community Patients Receiving Anticoagulation Therapy Who Presented with Acute Bleeding to the Emergency Department at a Regional Australian Hospital: A Prospective Observational Study.

ObjectiveTo study patients receiving anticoagulants with or without antiplatelet therapy presenting at a regional Australian hospital with bleeding. The main aims are to explore: (1) patients’ characteristics and management provided; (2) association between the type of anticoagulant and antiplatelet agent used and the requirement of reversal; (3) and the length of hospital stay (LoS) in conjunction with bleeding episode and management.MethodsA prospective cross-sectional review of medical records of all patients who presented at a tertiary referral centre with bleeding while receiving anticoagulation therapy between January 2016 and June 2018. Data included: patients, demographics, investigations (kidney and liver function tests, coagulation profile, FBC), LoS, bleeding site, type of and reason for anticoagulation therapy, and management provided. Data analysis included descriptive statistics, χ2 association, and regression models.ResultsAmong the 144 eligible patients, 75 (52.1%) were male, and the mean age was 76 years (SD=11.1). Gastrointestinal tract bleeding was the most common (n=48, 33.3%), followed by epistaxis (n=32, 22.2%). Atrial fibrillation was the commonest reason for anticoagulation therapy (n=65, 45.1%). Warfarin was commonly used (n=74, 51.4%), followed by aspirin (n=29, 20.1%), rivaroxaban (n=26, 18.1%), and apixaban (n=12, 8.3%). The majority had increased blood urea nitrogen (n=67, 46.5%), while 58 (40.3%) had an elevated serum creatinine level, and 59 (41.0%) had a mild reduction in eGFR. Thirty-five of the warfarinised patients (47.3%) had an INR above their condition’s target range despite normal liver function. Severe anaemia (Hb<80g/L) was reported in 88 patients (61.1%). DOACs were associated with a reduced likelihood of receiving reversal (B= −1.7, P=<.001), and with a shorter LoS (B= −4.1, P=.046) when compared with warfarin, LMWH, and antiplatelet therapy.ConclusionWarfarin use was common among patients who presented with acute bleeding, and the INR in many warfarinised patients exceeded the target for their condition. DOACs were associated with a reduced likelihood of receiving reversal and a shorter LoS than warfarin, LMWH, which might support a broader application of DOACs into community practice.

Iliopsoas Hematoma in Patients Undergoing Venovenous ECMO.

Iliopsoas hematoma occasionally occurs in patients receiving anticoagulation therapy. It may be a life-threatening complication and can cause disseminated intravascular coagulation, which could develop into abdominal compartment syndrome. The incidence of and factors associated with iliopsoas hematoma during venovenous extracorporeal membrane oxygenation (ECMO) have not been well studied. To describe the incidence of iliopsoas hematoma and associated factors among patients undergoing venovenous ECMO. A retrospective cohort study was conducted at Nippon Medical School Hospital from April 2015 to October 2018. All patients (>18 years old) with iliopsoas hematoma received a diagnosis based on computed tomography. During the study period, 54 patients were supported with venovenous ECMO. Iliopsoas hematoma occurred in 8 of those patients (15%), none of whom had disseminated intravascular coagulopathy or abdominal compartment syndrome develop. Univariate analysis indicated that management of ECMO while the patient was awake and mobilization beyond sitting on the edge of the bed were significantly different (P < .05) in patients with and patients without iliopsoas hematoma. Mortality, however, did not differ significantly between the 2 groups. Our findings emphasize that recognizing factors associated with iliopsoas hematoma and detecting them early are crucial during venovenous ECMO in order to treat patients with iliopsoas hematoma appropriately.

Incidence, clinical impact and treatment outcomes of valve thrombosis after transcatheter mitral valve implantation

Abstract Background Transcatheter mitral valve implantation (TMVI) is a new treatment option for high-risk surgical patients with degenerated bioprosthesis (ViV), failed annuloplasty rings (ViR) and severe mitral annular calcification (ViMAC). However, limited data exist on transcatheter heart valve thrombosis. Purpose The aim of this study was to report the incidence, clinical impact and treatment outcomes of transcatheter heart valve (THV) thrombosis in patients undergoing TMVI. Methods All consecutive patients undergoing TMVI in our center between July 2010 and September 2019 were included. A transoesophageal echocardiography and a computed tomography (CT) were performed before hospital discharge and at each clinical visit, at 3 months, at 1 year and yearly after. THV thrombosis was defined as the presence of at least one thickened leaflet with restricted motion suggestive of thrombus confirmed by TOE and/or contrast CT. All patients received anticoagulation therapy with vitamin K antagonists (VKA) and a low dose of aspirin for the first 3 months. Results A total of 132 patients underwent TMVI (62 ViV, 36 ViR and 34 ViMAC). Among them, 16 (12.1%) patients had a THV thrombosis. Median age was 67 years old and 56.2% of patients were women. Median time to diagnosis of THV thrombosis was 78 days. Early THV thrombosis was observed in 7 (43.7%) and in 13 (81.2%) patients THV thrombosis occurred within the first 6 months after the procedure. 8 out 9 patients with subacute or late THV thrombosis were not anticoagulated or with subtherapeutic anticoagulation. No stroke or thromboembolic events occurred in these patients. No change in mitral gradient was observed in 14 out 16 patients. VKA were indicated in all patients. THV thrombosis resolved in all but one patient. Conclusion THV thrombosis is frequent after TMVI, occurs mainly within the first 6-months after the procedure, are mostly subclinical and resolves after optimization of anticoagulation treatment. An anticoagulation therapy for at least 6 months may be necessary. Timing of THV thrombosis Funding Acknowledgement Type of funding source: None

Characteristics of aged ischemic stroke patients indicative of cardioembolism.

The treatment of ischemic stroke has recently witnessed dramatic developments. However, there are limited data on ischemic stroke characteristics in aged patients. As part of the South Tochigi Acute Ischemic Stroke Registry, we prospectively enrolled 636 consecutive acute ischemic stroke patients (within 7days after the onset) who were ≥ 60years of age and who were admitted to two independent institutes from April 1, 2016 to February 28, 2019. We analyzed three groups divided by age: early-aged (60-69years), middle-aged (70-79years), and oldest-aged (≥ 80years). From the 636 subjects, 194 were early-aged, 215 were middle-aged, and 227 were oldest-aged. There were significant differences in the ischemic stroke subtypes in each aging group (p < 0.01). The proportion of cardioembolism was 22.2% in early-aged, 27.4% in middle-aged, and 41.4% in the oldest-aged patients. The proportion of patients with a modified Rankin Scale of 0-2 at 1 year after onset decreased to 42.2% in middle-aged and 17.8% in oldest-aged with cardioembolic ischemic stroke. The proportion of patients receiving anticoagulation therapy before admission was 25.6% (36.7% of atrial fibrillation [AF]) in early-aged, 39.0% (52.3% of AF) in middle-aged, and 18.1% (21.0% of AF) in oldest-aged patients (p < 0.001). Our study reports characteristics of clinical ischemic stroke in an aging population. The assessment of cardiogenic embolism is important for an aging population.

Clinical characteristics and long-term outcomes of Libman-Sacks endocarditis in patients with systemic lupus erythematosus.

Treatment of Libman-Sacks (LS) endocarditis in patients with systemic lupus erythematosus (SLE) is challenging due to the lack of data. This study aimed to identify the clinical characteristics of SLE patients and LS endocarditis, and to investigate the treatment and prognosis of LS endocarditis. Of all the patients with SLE who underwent echocardiography between 2010 and 2019, 11 and 29 patients with and without LS endocarditis, respectively, were included. We compared the inflammatory and thrombotic profiles between patients with and without LS endocarditis, and investigated the treatment and long-term outcome of LS endocarditis. No significant differences were observed in disease activity, clinical characteristics and inflammatory marker levels between patients with and without LS endocarditis. Patients with LS endocarditis had a significantly higher prevalence of antiphospholipid antibody (aPL) but a lower prevalence of SLE-specific antibody. Triple positivity of aPL was found in 72.7% and 13.8% of patients with and without LS endocarditis, respectively. Of 11 patients with LS endocarditis, six patients received anticoagulation therapy, and five patients received augmented immunosuppressive therapies. One patient who did not receive anticoagulation therapy developed cerebral infarction. Nine (82%) patients with LS endocarditis were classified as having antiphospholipid syndrome (APS). Despite the residual vegetation and valve dysfunction, surgical intervention was not required during the follow-up period of 56.8 months. A significant correlation was observed between APS and LS endocarditis. Anticoagulation therapy should be considered to prevent thromboembolic complications in SLE patients with LS endocarditis.

Health literacy and the quality of pharmacist-patient communication among those prescribed anticoagulation therapy

Adequate counseling from a pharmacist concerning anticoagulation therapy is crucial to the wellbeing of patients. No studies have fully examined the relationship between health literacy, patient-pharmacist communication, and anticoagulation control. To evaluate the relationship between health literacy and the perceived quality of patient-pharmacist communication among those receiving anticoagulation therapy. This investigation utilized structured telephone interviews to evaluate the relationship between health literacy and perceived quality patient-pharmacist communication among patients receiving anticoagulation therapy. Two hundred-twenty participants prescribed anticoagulation therapy continuously for at least 6-months served as the sample for this study. A previously validated one-item screening tool was utilized to estimate health literacy. The primary outcome was patients' perceptions regarding the general communication process with pharmacists, according to the Interpersonal Process of Care questionnaire. Patients possessing inadequate health literacy reported significantly less favorable ratings for the perceived quality of pharmacist communication on the domains of general clarity (p=0.02), responsiveness to patient concerns (p=<0.01), empowerment (p=0.01), and consideration of patients' desire and ability to comply with recommendations (p=0.01). Inadequate health literacy was found to be independently associated with poorer quality interpersonal processes of care across the domains of responsiveness to patient concerns and empowerment, (β=-0.207, P = <0.01 and β=-0.137, P=0.04, respectively). Patients with inadequate health literacy did not differ significantly from those with adequate health literacy in terms of time within therapeutic INR range or percent of INRs in therapeutic range over the previous 12 months. Patients receiving anticoagulation therapy and possessing inadequate health literacy appear more likely to percieve poorer communication with pharmacists. This seems especially true as it relates to the percieved time and attention pharmacist devote to the communication encounter, as well as the sense pharmacists provide patients concerning their ability to influence health outcomes.

Outcome in German and South African peripartum cardiomyopathy cohorts associates with medical therapy and fibrosis markers

AimsThis study aims to compare the clinical course of peripartum cardiomyopathy (PPCM) cohorts from Germany (G‐PPCM) and South Africa (SA‐PPCM) with fibrosis‐related markers to get insights into novel pathomechanisms of PPCM.Methods and resultsG‐PPCM (n = 79) and SA‐PPCM (n = 72) patients and healthy pregnancy‐matched women from Germany (n = 56) and South Africa (n = 40) were enrolled. Circulating levels of procollagen type‐I (PINP) and type‐III (PIIINP) N‐terminal propeptides, soluble ST2, galectin‐3, and full‐length and cleaved osteopontin (OPN) were measured at diagnosis (baseline) and 6 months of follow‐up. Both cohorts received standard heart failure therapy while anticoagulation therapy was applied in 100% of G‐PPCM but only in 7% of SA‐PPCM patients. In G‐PPCM patients, baseline left ventricular ejection fraction (LVEF) was lower, and outcome was better (baseline LVEF, 24 ± 8%, full recovery: 52%, mortality: 0%) compared with SA‐PPCM patients (baseline LVEF: 30 ± 9%, full recovery: 32%, mortality: 11%; P < 0.05). At baseline, PINP/PIIINP ratio was lower in SA‐PPCM and higher in G‐PPCM compared with respective controls, whereas total OPN was elevated in both collectives. Cleaved OPN, which increases PIIINP levels, is generated by thrombin and was reduced in patients receiving anticoagulation therapy. High baseline galectin‐3, soluble ST2, and OPN levels were associated with poor outcome in all PPCM patients.ConclusionsSA‐PPCM patients displayed a more profibrotic biomarker profile, which was associated with a less favourable outcome despite better cardiac function at baseline, compared with G‐PPCM patients. Use of bromocriptine and anticoagulation therapy in G‐PPCM may counteract fibrosis and may in part be responsible for their better outcome.

Clinical efficacy and safety of anticoagulation therapy for Pyrrolizidine alkaloids-induced hepatic sinusoidal obstruction syndrome: a retrospective multicenter cohort study.

Pyrrolizidine alkaloids-induced hepatic sinusoidal obstruction syndrome(PA-HSOS) has been reported to have high mortality. We evaluated the efficacy and safety of anticoagulation therapy for the patients with PA-HSOS. We collected clinical data on 249 PA-HSOS patients from January 2012 to December 2017 at four tertiary care hospitals. Among them, 151 patients received anticoagulation therapy, and 98 patients received supportive treatment. The outcomes were analyzed using the Fine and Gray competing risk analysis method and Cox regression model. The cumulative complete response rate was higher in the anticoagulation group than in the supportive group (60.9 vs 36.7%; P < 0.0001). The cumulative mortality was 12.6% in the anticoagulation group compared with 43.9% in the supportive group (P < 0.0001). In subgroup analysis, for mild, moderate, severe, and very severe groups, the adjusted hazard ratios [95% confidence interval (CI)] for complete response rates were 7.05 (3.00-16.59), 5.26 (2.31-12.42), 2.59 (0.85-7.87), and 2.05 (0.61-6.92), respectively; and the adjusted hazard ratios (95% CI) for mortalities were 0.02 (0.01-0.09), 0.04 (0.01-0.14), 0.19 (0.01-3.98), and 0.07 (0.02-1.27), respectively (P < 0.0001). There was no significant difference between both groups in the incidence of bleeding events (P = 0.674). Anticoagulation therapy improves clinical remission and the survival in selected patients with mild or moderate PA-HSOS. Anticoagulation therapy has a similar safety profile to supportive therapy.

The correlational research between G allele expression of matrix metalloproteinase 2 and complications after cardiac valve replacement

Objective To investigate the relationship between G allele of matrix metalloproteinase 2 (MMP-2) and complications after cardiac valve replacement. Methods 187 patients who underwent heart valve replacement in our hospital from January 2015 to January 2018 were selected, all patients received anticoagulation therapy after operation, the complications were observed and the MMP-2 genotype was detected by gene sequencing. Results During the follow-up period, the incidence of complications was 28.88%; The proportion of MMP-2 gene GG + GC genotype in patients with complications was 62.96%, which was significantly higher than that in patients without complications (P<0.05); The international standardized ratio (INR) of patients with GG + GC genotype was (2.87±0.45), which was significantly higher than that of patients with CC genotype (P<0.05); The age and INR of the patients with complications were (57.01±6.79) years old and (2.70±0.65) years old, which were significantly higher than those of the patients without complications (P<0.05); Logistic regression analysis showed that INR value, age and MMP-2 gene GG+ GC type were risk factors for complications after cardiac valvle replacement [odds ratio (OR)=3.751, 3.013 and 2.440, P<0.05]. Conclusion The G allele of MMP-2 is a risk factor for complications after cardiac valve replacement, is worth further study. Key words: Matrix metalloproteinase 2; G allele; Cardiac valve replacement; Complications

Gallbladder cancer accompanied by uncontrollable eosinophilia: report of a case.

A 48-year-old male was referred to our hospital for evaluation of motor speech disorders and difficulty in the movement of both the hands. The clinical diagnosis was Trousseau's syndrome due to advanced gallbladder cancer (cT3aN1M0). The patient received anticoagulation therapy and systemic chemotherapy (gemcitabine and cisplatin). Motor speech disorders and difficulty in movement of both hands were recovered. After 2 courses of chemotherapy, the primary tumor developed a massive hepatic invasion and the peripheral blood eosinophils increased gradually. The patient was admitted to our hospital for abdominal distension, fever, right upper quadrant pain, systemic edema, loss of appetite, and general malaise. The peripheral blood eosinophil count was markedly elevated to 45,900/μl (90.3%). The serum level of GM-CSF was high and there was no evidence of leukemia, allergic status and other diseases. The patient was diagnosed as paraneoplastic eosinophilia with advanced gallbladder cancer, which was suspected to produce GM-CSF. The patient received palliative support and died of disseminated intravascular coagulation 15days after admission. We herein reported a fatal case of gallbladder cancer suspected of producing GM-CSF.