Need For Anticoagulation Therapy Research Articles

Antithrombotic Therapy in Cancer Patients with Cardiovascular Diseases: Daily Practice Recommendations by the Hemostasis Working Party of the German Society of Hematology and Medical Oncology (DGHO) and the Society for Thrombosis and Hemostasis Research (GTH e.V.).

Active cancer by itself but also chemotherapy is associated with an increased risk of cardiovascular disease (CVD) and especially coronary artery disease (CAD) and atrial fibrillation (AF). The frequency of CVD, CAD, and AF varies depending on comorbidities (particularly in older patients), cancer type, and stage, as well as the anticancer therapeutic being taken. Many reports exist for anticancer drugs being associated with CVD, CAD, and AF, but robust data are often lacking. Because of this, each patient needs an individual structured approach concerning thromboembolic and bleeding risk, drug-drug interactions, as well as patient preferences to evaluate the need for anticoagulation therapy and targeting optimal symptom control. Interruption of specific cancer therapy should be avoided to reduce the potential risk of cancer progression. Nevertheless, additional factors like thrombocytopenia and anticoagulation in the elderly and frail patient with cancer cause additional challenges which need to be addressed in daily clinical management. Therefore, the aim of these recommendations is to summarize the available scientific data on antithrombotic therapy (both antiplatelet and anticoagulant therapy) in cancer patients with CVD and in cases of missing data providing guidance for optimal careful decision-making in daily routine.

Mechanical Valves: Past, Present, and Future-A Review.

The mechanical valve was first invented in the 1950s, and since then, a wide variety of prostheses have been developed. Although mechanical valves have outstanding durability, their use necessitates life-long treatment with anticoagulants, which increases the risk of bleeding and thromboembolic events. The current guidelines recommend a mechanical prosthetic valve in patients under 50-60 years; however, for patients aged 50-70 years, the data are conflicting and there is not a clear-cut recommendation. In recent decades, progress has been made in several areas. First, the On-X mechanical valve was introduced; this valve has a lower anticoagulant requirement in the aortic position. Second, a potential alternative to vitamin K-antagonist treatment, rivaroxaban, has shown encouraging results in small-scale trials and is currently being tested in a large randomized clinical trial. Lastly, an innovative mechanical valve that eliminates the need for anticoagulant therapy is under development. We attempted to review the current literature on the subject with special emphasis on the role of mechanical valves in the current era and discuss alternatives and future innovations.

Hydrogel-polyurethane fiber composites with enhanced microarchitectural control for heart valve replacement.

Polymeric heart valves offer the potential to overcome the limited durability of tissue based bioprosthetic valves and the need for anticoagulant therapy of mechanical valve replacement options. However, developing a single-phase material with requisite biological properties and target mechanical properties remains a challenge. In this study, a composite heart valve material was developed where an electrospun mesh provides tunable mechanical properties and a hydrogel coating confers an antifouling surface for thromboresistance. Key biological responses were evaluated in comparison to glutaraldehyde-fixed pericardium. Platelet and bacterial attachment were reduced by 38% and 98%, respectively, as compared to pericardium that demonstrated the antifouling nature of the hydrogel coating. There was also a notable reduction (59%) in the calcification of the composite material as compared to pericardium. A custom 3D-printed hydrogel coating setup was developed to make valve composites for device-level hemodynamic testing. Regurgitation fraction (9.6 ± 1.8%) and effective orifice area (1.52 ± 0.34 cm2 ) met ISO 5840-2:2021 requirements. Additionally, the mean pressure gradient was comparable to current clinical bioprosthetic heart valves demonstrating preliminary efficacy. Although the hemodynamic properties are promising, it is anticipated that the random microarchitecture will result in suboptimal strain fields and peak stresses that may accelerate leaflet fatigue and degeneration. Previous computational work has demonstrated that bioinspired fiber microarchitectures can improve strain homogeneity of valve materials toward improving durability. To this end, we developed advanced electrospinning methodologies to achieve polyurethane fiber microarchitectures that mimic or exceed the physiological ranges of alignment, tortuosity, and curvilinearity present in the native valve. Control of fiber alignment from a random fiber orientation at a normalized orientation index (NOI) 14.2 ± 6.9% to highly aligned fibers at a NOI of 85.1 ± 1.4%. was achieved through increasing mandrel rotational velocity. Fiber tortuosity and curvilinearity in the range of native valve features were introduced through a post-spinning annealing process and fiber collection on a conical mandrel geometry, respectively. Overall, these studies demonstrate the potential of hydrogel-polyurethane fiber composite as a heart valve material. Future studies will utilize the developed advanced electrospinning methodologies in combination with model-directed fabrication toward optimizing durability as a function of fiber microarchitecture.

Incidence patterns and clinical implications of venous thromboembolisms (VTE) in patients (p) with neuroendocrine tumors (NET).

e24155 Background: Venous Thromboembolisms (VTE) is a common complication in cancer patients (p) and one of the lead causes of cancer-related death. Digestive neoplasms have specific characteristics in VTE incidence and treatment. There is a lack of data regarding VTE impact in p with neuroendocrine tumors (NET). Currently few studies have addressed VTE in NET, with an estimated incidence of 7.5%. Nevertheless, there is no evidence from large datasets to address specific implications of thrombosis in NET p. In the present study, we review incidence and treatment of VTE in NET in a large unicentric cohort. Methods: Consecutive p with gastroenteropancreatic (GEP) and thoracic NET treated in our institution were reviewed to study incidence of VTE including deep vein thrombosis (DVT), pulmonary embolisms (PE) and splanchnic venous thrombosis (SVT). Information regarding clinical characteristics and VTE treatment were collected. Results: 212 p were included in the analysis (38% Female; 42% Pancreatic, 35% Small Intestine, 6.5% lung). 50p presented any kind of thrombotic event (23.5%), and 23 were directly related to TNE (10.8%). Considering 23p with TNE-related VTE (82.3% Male; 82.3% Pancreatic), main origins included: SVT 11p (47.8%) and PE 7p (30.4%). Leading cause of SVT was splenic vein thrombosis. 80.9% of VTE cases received anticoagulant therapy, most of them with low-molecular weight heparin (82.6%) and indefinitely duration (58.8%). All cases that did not started anticoagulant therapy were splenic vein thrombosis due to physician decision. Any complication related to anticoagulant therapy was described in 5p (26.3%). No cases of VTE-related death were found. Conclusions: Patients with NET have a moderate risk of VTE events. Splenic thrombosis is the most common location but need of anticoagulant therapy in those cases remains controversial. Specific studies regarding VTE in NET population are needed.

Comparison of landiolol and amiodarone for the treatment of new-onset atrial fibrillation after cardiac surgery (FAAC) trial: study protocol for a randomized controlled trial

BackgroundPostoperative atrial fibrillation (PoAF) after cardiac surgery has a high incidence of 30%, but its management is controversial. Two strategies are recommended without evidence of a superiority of one against the other: rate control with beta-blocker or rhythm control with amiodarone. Landiolol is a new-generation beta-blocker with fast onset and short half-life. One retrospective, single-center study compared landiolol to amiodarone for PoAF after cardiac surgery with a better hemodynamic stability and a higher rate of reduction to sinus rhythm with landiolol, justifying the need for a multicenter randomized controlled trial. Our aim is to compare landiolol to amiodarone in the setting of PoAF after cardiac surgery with the hypothesis of a higher rate of reduction to sinus rhythm with landiolol during the 48 h after the first episode of POAF.MethodsThe FAAC trial is a multicenter single-blind two parallel-arm randomized study, which planned to include 350 patients with a first episode of PoAF following cardiac surgery. The duration of the study is 2 years. The patients are randomized in two arms: a landiolol group and an amiodarone group.Randomization (Ennov Clinical®) is performed by the anesthesiologist in charge of the patient if PoAF is persistent for at least 30 min after correction of hypovolemia, dyskalemia, and absence of pericardial effusion on a transthoracic echocardiography done at bedside.Our hypothesis is an increase of the percentage of patients in sinus rhythm from 70 to 85% with landiolol in less than 48 h after onset of PoAF (alpha risk = 5%, power = 90%, bilateral test).DiscussionThe FAAC trial was approved by the Ethics Committee of EST III with approval number 19.05.08. The FAAC trial is the first randomized controlled trial comparing landiolol to amiodarone for PoAF after cardiac surgery. In case of higher rate of reduction with landiolol, this beta-blocker could be the drug of choice used in this context as to reduce the need for anticoagulant therapy and reduce the risk of complications of anticoagulant therapy for patients with a first episode of postoperative atrial fibrillation after cardiac surgery.Trial registrationClinicalTrials.gov NCT04223739. Registered on January 10, 2020.

Effect of Anticoagulant Versus Non-Anticoagulant Therapy on Mortality of Sepsis-Induced Disseminated Intravascular Coagulation: A Systematic Review and Meta-Analysis.

Sepsis is a syndrome of severe systemic inflammatory response. When combined with disseminated intravascular coagulation, mortality is increased. The need for anticoagulant therapy is still the focus of debate. PubMed, Embase, Cochrane Library, and Web of Science were searched. Adult patients with sepsis-induced disseminated intravascular coagulation were included in this study. All-cause mortality as efficacy and serious bleeding complications as adverse effect were measured as primary outcomes. Methodological quality of included studies were assessed using the Methodological Index for Non-randomized Studies (MINORS). Meta-analysis was performed using R software (version 3.5.1) and Review Manager (version 5.3.5). There were nine eligible studies with 17,968 patients included. There were no significant reductions in mortality between the anticoagulant group and the non-anticoagulant group (RR, 0.89; 95% CI, 0.72-1.10; P = 0.27). The DIC resolution rate in the anticoagulation group has a statistically significant increase compared with the control group [OR: 2.62, 95% CI (1.54-4.45), P < 0.05]. And there was no significant difference in bleeding complications between the two groups (RR, 1.27; 95% CI, 0.77-2.09; P = 0.69). SOFA score reduction did not change significantly between the two groups (P = 0.13). Our study observed no significant benefit of anticoagulant therapy on mortality of sepsis-induced DIC. Anticoagulation therapy can promote DIC resolution in sepsis-induced DIC. In addition, anticoagulant therapy does not increase the risk of bleeding in these patients.

The Detection of Hypercoagulability in Patients with Acute Cerebral Infarction Using a Clot Waveform Analysis.

A few studies concerning hypercoagulable states have sufficiently been reported in patients with acute cerebral infarction (ACI), as ACI is generally considered to be caused by platelet activation. Clot waveform analyses (CWA) for activated partial thromboplastin time (APTT) and small amount of tissue factor FIX activation assay (sTF/FIXa) were examined in 108 patients with ACI, 61 patients without ACI, and 20 healthy volunteers. CWA-APTT and CWA-sTF/FIXa showed that the peak heights were significantly higher in ACI patients without anticoagulant therapy than in healthy volunteers. Absorbance exceeding 78.1 mm on the 1st DPH in the CWA-sTF/FIXa showed the highest odds ratio for ACI. The peak heights were significantly lower in the CWA-sTF/FIXa of ACI patients receiving argatroban therapy than in those of ACI patients without anticoagulant therapy. CWA can suggest a hypercoagulable state in ACI patients and may be useful for monitoring the need for anticoagulant therapy.

Evaluating the efficacy and safety of rivaroxaban as a warfarin alternative in chronic thromboembolic pulmonary hypertension patients undergoing pulmonary endarterectomy: A randomized clinical trial

Background and aimChronic thromboembolic pulmonary hypertension (CTEPH) is caused by the obstruction of the main pulmonary artery due to thrombosis and vascular remodeling. Regarding the need for anticoagulant therapy in CTEPH patients, this study aimed to compare rivaroxaban with warfarin in terms of its efficacy and safety in patients undergoing endarterectomy surgery. MethodsThe study was a parallel clinical trial in patients who underwent endarterectomy following CTEPH. A total of 96 patients were randomly selected and assigned to two groups: warfarin-treated (control) and rivaroxaban-treated (intervention). Patients were clinically assessed for re-thrombosis, re-admission, bleeding, and mortality in the first, third, and sixth months after surgery. ResultsThere was no significant difference in the occurrence of thrombosis between the two groups within the first, third-, and sixth-months post-surgery (p=0.52, 1, 0.38 respectively). Moreover, the mortality rate (p=0.9), bleeding rate (p=0.06), and re-admission rate (p=0.15) showed no significant differences between the two groups. ConclusionRivaroxaban may be as effective as warfarin in treating CTEPH patients after endarterectomy in the short term and can be used as an anticoagulant in these patients. However, studies with long-term follow-ups are needed to consolidate the strategy of treating these patients with rivaroxaban.

Prognosis after aortic valve replacement in dialysis patients: results from the Swedish Renal Registry

Abstract Background The choice of aortic valve prosthesis in aortic stenosis patients is based on patient preference, preoperative age, life expectancy, need for anticoagulant therapy and valve durability. Major uncertainties remain regarding optimal prosthetic valve choice in dialysis patients. Objectives The aim of the study was to compare the clinical outcomes after aortic valve replacement with mechanical (MAV) or bioprosthetic valves (BAV) in dialysis patients. Methods We used the observational, prospective, multicenter cohort from the Swedish Renal Registry, which includes all dialysis patients in Sweden. The study included 294 dialysis patients with aortic stenosis who underwent aortic valve replacement with MAV or BAV (obtained from surgical procedure codes) between 2005 and 2018, either before (n=155) or after dialysis start (n=139). Comorbidities and net adverse clinical events (bleeding events, stroke and reoperation) were obtained from national registries and defined by International Classification of Diseases codes (ICD-10). The incidence rate (IR) of primary endpoint comprised of all-cause death, bleeding events, stroke and aortic valve reoperation, as well as only all-cause death rates between recipients of MAV or BAV were estimated with Kaplan – Meier curves. Results The median age was 72 years (interquartile range [IQR]: 63.9, 77.3), 77% were males and 60% received mechanical valves. During a median follow-up of 1.49 years (IQR: 0.66–2.83), the primary endpoint occurred in 202 patients. Compared to BAV-recipients, those who received MAV had comparable IR of the primary end-point (40.1/100 person-years; [95% Confidence Interval (CI): 33.7–47.7], vs 36.2/100 person-years; [95% CI: 28.9–45.4], P=0.322) (Figure 1). Mortality rate at 1-year of follow-up was 28.9% without difference between recipients of MAV or BAV (68.8% in MAV-group and 57.6% with BAV; mortality rate MAV 33.3/100 person-year; (95% CI: 27.9–39.8) vs BAV 27.3/100 person-year; (95% CI: 21.5–34.6), P=0. 183)), (Figure 2). Additional statistical analysis of the secondary endpoint based on the occurrence of aortic valve intervention before or after dialysis start, was consistent with the main results. Conclusion There is no difference in mortality and complication rates in dialysis patients who underwent aortic valve replacement with MAV or BAV. Funding Acknowledgement Type of funding sources: None.

Intra-abdominal Bleeding due to Segmental Arterial Mediolysis and Coexisting Pulmonary Thromboembolism: a Case Report

Segmental arterial mediolysis (SAM) is a rare but important cause of abdominal haemorrhage and is usually treated with endovascular management. Surgical or conservative management can be performed depending on the patient’s situation. Since the course of conservative treatment is not well described in the existing literature, it must be used with caution. We describe the case of a 52-year-old man who was transferred to the emergency department because of abdominal pain, diarrhoea, and haematemesis. On arrival, he was haemodynamically unstable, with a blood pressure of 70/40 mmHg. After he was transfused and stabilised in the emergency department, contrast-enhanced computed tomography (CECT) revealed a haematoma around the transverse colon and ascites, without any evident extravasation. The peripheral branch of the middle colic artery (MCA) showed irregular calibre, suggesting SAM. Since the patient remained stable, we initially chose conservative management. However, a CECT scan performed on the third day of hospitalisation showed coexisting pulmonary thromboembolism (PTE). Because of the need for anticoagulation therapy, we performed open surgery. The pathological examination was consistent with SAM. Anticoagulation therapy was initiated the next day. A CECT scan performed on a postoperative day (POD) 13 showed no PTE. Although the patient defecated haemorrhagic stool and experienced hematemesis on PODs 19 and 23, respectively, colonoscopy, esophagogastroduodenoscopy, and repeated CECT scans revealed no evidence of rebleeding, and no recurrence was observed. Open surgery produced a relatively good postoperative course for the patient. Endovascular management, however, remains a reasonable first approach, considering its reportedly excellent outcomes.

Bronchoscopic Intrapulmonary Recombinant Factor VIIa for Diffuse Alveolar Hemorrhage-induced Acute Respiratory Failure in MPO-ANCA Vasculitis: A Case Report.

IntroductionDiffuse alveolar haemorrhage (DAH) is a potentially life-threatening disease, characterized by diffuse accumulation of red blood cells within the alveoli. It can be caused by a variety of disorders. In case DAH results in severe respiratory failure, veno-venous extracorporeal membrane oxygenation (VV-ECMO) can be required. Since VV-ECMO coincides with the need for anticoagulation therapy, this results in a major clinical challenge in DAH patients with hemoptysis.Case presentationWe report a patient case with severe DAH-induced acute respiratory failure and hemoptysis in need for VV-ECMO complicated by life-threatening membrane oxygenator thrombosis. The DAH-induced hemoptysis was successfully treated with local bronchoscopic recombinant factor VIIa (rFVIIa), allowing systemic anticoagulation to prevent further membrane oxygenator thrombosis. Neither systemic clinical side effects nor differences in the serum coagulation markers occurred after applying recombinant factor VIIa (rFVIIa) treatment endobronchially.ConclusionThis is, to our knowledge, the first case that reports the use of rFVIIa in a patient with DAH due to vasculitis and in need for VV-ECMO complicated by membrane oxygenator thrombosis.

PO-674-04 ANTICOAGULATION MANAGEMENT AND RISK OF THROMBOEMBOLISM IN HEALTHY YOUTH WITH ATRIAL FIBRILLATION: DATA FROM A MULTI-INSTITUTIONAL PACES COLLABORATIVE REGISTRY

Stroke is a well-defined complication of atrial fibrillation (AF) in adults. However, the risk of thromboembolism and need for anticoagulation therapy in children and young adults with AF are unknown. To describe the current anticoagulation practice and assess the risk of thrombosis in children and young adults with AF across 13 pediatric heart centers. Data was obtained from the multi-institutional PACES collaborative registry on atrial fibrillation. Patients ≤ 21 years of age with documented AF of an unknown cause from January 2004 to December 2018 were included. We included patients with AF with no structural heart disease, cardiomyopathy, ventricular pre-excitation, history of open heart surgery, hypertension, or thyroid disease. Of 241 subjects, 76 were prescribed oral anticoagulation at diagnosis and an additional 15 at time of AF recurrence. Aspirin was prescribed in 66 (73%) patients, warfarin in 14 (15%), novel oral anticoagulant in 7 (8%), combined therapy in 3 (3%), and unknown in 1 (1%). In a multivariable model, patients were less likely to be anticoagulated at a freestanding children’s hospital (OR 0.44, 95%CI [0.23-0.78], p=0.005) or if they had spontaneous cardioversion (OR 0.53, 95%CI [0.29-0.96], p=0.037), and more likely if prescribed an antiarrhythmic at time of initial diagnosis (OR 1.82, 95%CI [1.01-3.3], p=0.047). There was a trend towards anticoagulation in patients presenting with asymptomatic AF (OR 0.45, 95%CI [0.19-1.03], p=0.06]). Age at diagnosis, gender, and BMI were not associated with anticoagulation status. One patient (1/241, 0.4%) was found to have left atrial thrombus confirmed by transesophageal echocardiogram at time of presentation. This patient was treated with warfarin for 3 months and repeat echocardiogram showed thrombus resolution. No patient developed thromboembolic phenomenon over a mean follow up of 2.1 ± 2.6 years. Our study is the first to demonstrate that there is large practice variation in anticoagulation management with patients treated at a free-standing children’s hospital being less likely to be anticoagulated. AF associated thrombosis is rare in children and young adults.

Эффекты эноксапарина в лечебных и терапевтических дозах при COVID-19: систематический обзор и мета-анализ

Thrombotic complications are the most dangerous manifestations of COVID-19. This justifies the need for anticoagulant therapy in a new coronavirus infection. The effects of enoxaparin at therapeutic and prophylactic doses in COVID-19 were assessed from a meta-analysis of 5 randomized clinical trials (RCTs). Search for RCTs was performed in the MEDLINE, Cochrane, PubMed, and ClinicalTrials.gov databases. Odds ratio (OR) with 95% confidence interval and heterogeneity were calculated applying RevMan 5.4.1 software. Combined criterion for the effectiveness of anticoagulant therapy included mortality and thrombotic events (arterial and venous thrombosis). The safety of enoxaparin was assessed by the frequency of bleeding (secondary outcomes). There were no statistically significant differences in mortality in COVID-19 patients receiving enoxaparin at therapeutic doses compared with prophylactic doses [OR = 0.98; 95% CI 0.84 – 1.16; p = 0.85]. The frequency of thrombosis and thromboembolism when using enoxaparin in therapeutic doses was lower compared with prophylactic doses [OR = 0.80; 95% CI 0.66 – 0.98; p = 0.03], while the frequency of bleeding was higher [OR = 2.11; 95% CI 1.36 – 3.30; p = 0.0009]. This meta-analysis suggests a greater efficacy of enoxaparin at therapeutic doses in reducing the incidence of thrombotic complications in hospitalized COVID-19 patients, however, these data require clarification. Further multicenter randomized controlled trials are needed to determine the optimal anticoagulant regimens in COVID-19 patients.

Application of Hemostatic Agent “Haemoblock” for Pocket Hematoma Reduction. Design of the PEGAS study: a Multicenter Clinical Trial

Pocket hematoma (PH) is a common complication of pacemaker implantations which prolongs hospitalization and may demand surgical revision in some cases. According to the data from different researchers PH rate varies from 2 to 7%. It depends on number of factors including a need for anticoagulation therapy. We present a review of design of multicenter clinical trial evaluating safety and efficacy of application of hemostatic agent Haemoblock for pocket hematoma reduction in patients taking oral anticoagulants.

COVID-19 Sepsis: Pathogenesis and Endothelial Molecular Mechanisms Based on "Two-Path Unifying Theory" of Hemostasis and Endotheliopathy-Associated Vascular Microthrombotic Disease, and Proposed Therapeutic Approach with Antimicrothrombotic Therapy.

COVID-19 sepsis is characterized by acute respiratory distress syndrome (ARDS) as a consequence of pulmonary tropism of the virus and endothelial heterogeneity of the host. ARDS is a phenotype among patients with multiorgan dysfunction syndrome (MODS) due to disseminated vascular microthrombotic disease (VMTD). In response to the viral septicemia, the host activates the complement system which produces terminal complement complex C5b-9 to neutralize pathogen. C5b-9 causes pore formation on the membrane of host endothelial cells (ECs) if CD59 is underexpressed. Also, viral S protein attraction to endothelial ACE2 receptor damages ECs. Both affect ECs and provoke endotheliopathy. Disseminated endotheliopathy activates two molecular pathways: inflammatory and microthrombotic. The former releases inflammatory cytokines from ECs, which lead to inflammation. The latter initiates endothelial exocytosis of unusually large von Willebrand factor (ULVWF) multimers and FVIII from Weibel–Palade bodies. If ADAMTS13 is insufficient, ULVWF multimers activate intravascular hemostasis of ULVWF path. In activated ULVWF path, ULVWF multimers anchored to damaged endothelial cells recruit circulating platelets and trigger microthrombogenesis. This process produces “microthrombi strings” composed of platelet-ULVWF complexes, leading to endotheliopathy-associated VMTD (EA-VMTD). In COVID-19, microthrombosis initially affects the lungs per tropism causing ARDS, but EA-VMTD may orchestrate more complex clinical phenotypes, including thrombotic thrombocytopenic purpura (TTP)-like syndrome, hepatic coagulopathy, MODS and combined micro-macrothrombotic syndrome. In this pandemic, ARDS and pulmonary thromboembolism (PTE) have often coexisted. The analysis based on two hemostatic theories supports ARDS caused by activated ULVWF path is EA-VMTD and PTE caused by activated ULVWF and TF paths is macrothrombosis. The thrombotic disorder of COVID-19 sepsis is consistent with the notion that ARDS is virus-induced disseminated EA-VMTD and PTE is in-hospital vascular injury-related macrothrombosis which is not directly related to viral pathogenesis. The pathogenesis-based therapeutic approach is discussed for the treatment of EA-VMTD with antimicrothrombotic regimen and the potential need of anticoagulation therapy for coinciding macrothrombosis in comprehensive COVID-19 care.

MO755SPONTANEOUS SOFT TISSUE HEMATOMAS IN ESRD PATIENTS WITH SYMPTOMATIC SARS-CO-V2 INFECTION – THE EXPERIENCE OF AN EMERGENCY NEPHROLOGY AND DIALYSIS DEPARTMENT

Background and AimsWhile actual proofs plead for an increased thrombotic risk in SARS-Co-V2 infection and need for anticoagulant therapy in severe cases, we report suspicious occurrence of hemorrhagic events in a series of ESRD patients.Method59 patients with stage 5 CKD were hospitalized in a two months interval, since our hospital was designated for the admission of mild-severe SARS-Co-V2 patients exclusive. 8 patients were admitted for RRT initiation and 51 were maintenance dialysis patients admitted with SARS-Co-V2-associated complications. Beside hemodialysis and treatment of chronic complications of ESRD, all patients were treated, according to the stage and gravity of SARS-Co-V2 infection and under continuous supervision of an infectious disease physician, with antivirals, antibiotics, anticoagulants and IL-antagonists. Daily or at 2 days laboratory monitoring was performed and consisted in evaluation of inflammatory markers, clotting tests, complete hemogram, D-dimer testing, IL-1 and IL-6 serum levels, serum urea, creatinine and albumin.ResultsIn 6 cases spontaneous soft tissue hematomas were noted, totalizing a number of 9 hematomas documented through ultrasound and CT-scan. In order of frequency, the locations were: 4 rectus abdominalis hematoma, 2 in the external oblique, 2 in gluteus maximus muscle, and one in the right psoas muscle. The source of the bleeding could not be identified in any patient. The occurrence of spontaneous hematomas was correlated with the D-dimer values (p=0.02), prolonged anticoagulation (over 7 days), albumin levels (p=0.01), platelets count (p=0.05). We found no correlation with the serum urea, creatinine, hemoglobin, INR, or with the dialysis age. In all these cases cough was severe. A conservative approach was instituted, with daily US monitoring, withdrawal of anticoagulants and antiplatelet medication, and blood transfusions. 2 patients necessitated surgical procedures and two deaths were recorded.ConclusionIn this brief report, we observed that in chronic hemodialysis patients infected with SARS-Co-V2, risk of hemorrhagic manifestations may overcome the benefits of anticoagulant routine therapy. There is a need to explore further this risk in the future; until then, a careful individualized assessment of the safety and indications for anticoagulant therapy regimens is mandatory for ESRD patients with symptomatic new Coronavirus infection.

A case of rapidly progressive upper limb ischemic necrosis in a patient with COVID-19

BackgroundFor more than a year, health systems all over the world have been combating the global coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The disease was first described in the city of Wuhan in China, presenting as an atypical infection of the lower respiratory tract. MethodsCOVID-19 is characterized by multisystemic involvement, and mortality is attributed mainly to the respiratory system involvement, which may lead to severe acute respiratory distress syndrome and respiratory failure. Several COVID-19-associated complications are being increasingly reported, including arterial and venous thromboembolic events that may lead to amputation of the affected limbs. So far, a large number of reports have described hypercoagulability crises leading to amputation of the lower limbs. However, a search of the National Library of Medicine (MEDLINE) revealed no cases of urgent upper limb amputation in COVID-19 patients. ResultsThis article describes a novel case of upper limb ischemia in a COVID-19 patient, with rapid progression to hand necrosis, requiring urgent through-arm amputation of the upper limb. ConclusionsThis case emphasizes the need for anticoagulant therapy in COVID-19 patients and to maintain a constant awareness of the possible thromboembolic COVID-19-related sequelae.

Association of New-Onset Atrial Fibrillation After Noncardiac Surgery With Subsequent Stroke and Transient Ischemic Attack

Outcomes of postoperative atrial fibrillation (AF) after noncardiac surgery are not well defined. To determine the association of new-onset postoperative AF vs no AF after noncardiac surgery with risk of nonfatal and fatal outcomes. Retrospective cohort study in Olmsted County, Minnesota, involving 550 patients who had their first-ever documented AF within 30 days after undergoing a noncardiac surgery (postoperative AF) between 2000 and 2013. Of these patients, 452 were matched 1:1 on age, sex, year of surgery, and type of surgery to patients with noncardiac surgery who were not diagnosed with AF within 30 days following the surgery (no AF). The last date of follow-up was December 31, 2018. Postoperative AF vs no AF after noncardiac surgery. The primary outcome was ischemic stroke or transient ischemic attack (TIA). Secondary outcomes included subsequent documented AF, all-cause mortality, and cardiovascular mortality. The median age of the 452 matched patients was 75 years (IQR, 67-82 years) and 51.8% of patients were men. Patients with postoperative AF had significantly higher CHA2DS2-VASc scores than those in the no AF group (median, 4 [IQR, 2-5] vs 3 [IQR, 2-5]; P < .001). Over a median follow-up of 5.4 years (IQR, 1.4-9.2 years), there were 71 ischemic strokes or TIAs, 266 subsequent documented AF episodes, and 571 deaths, of which 172 were cardiovascular related. Patients with postoperative AF exhibited a statistically significantly higher risk of ischemic stroke or TIA (incidence rate, 18.9 vs 10.0 per 1000 person-years; absolute risk difference [RD] at 5 years, 4.7%; 95% CI, 1.0%-8.4%; HR, 2.69; 95% CI, 1.35-5.37) compared with those with no AF. Patients with postoperative AF had statistically significantly higher risks of subsequent documented AF (incidence rate 136.4 vs 21.6 per 1000 person-years; absolute RD at 5 years, 39.3%; 95% CI, 33.6%-45.0%; HR, 7.94; 95% CI, 4.85-12.98), and all-cause death (incidence rate, 133.2 vs 86.8 per 1000 person-years; absolute RD at 5 years, 9.4%; 95% CI, 4.9%-13.7%; HR, 1.66; 95% CI, 1.32-2.09). No significant difference in the risk of cardiovascular death was observed for patients with and without postoperative AF (incidence rate, 42.5 vs 25.0 per 1000 person-years; absolute RD at 5 years, 6.2%; 95% CI, 2.2%-10.4%; HR, 1.51; 95% CI, 0.97-2.34). Among patients undergoing noncardiac surgery, new-onset postoperative AF compared with no AF was associated with a significant increased risk of stroke or TIA. However, the implications of these findings for the management of postoperative AF, such as the need for anticoagulation therapy, require investigation in randomized trials.

Eligibility for extended antithrombotic therapy for secondary prevention of acute coronary syndrome

Introduction and ObjectivesRecent randomized controlled trials have evaluated the benefit of extended antithrombotic therapy in secondary prevention of acute coronary syndrome (ACS). However, the numerous and strict enrollment criteria may limit the validity and reproducibility of the published results in clinical practice. Our goal was to estimate the eligibility for participation in two randomized clinical trials in a group of patients followed for ACS. MethodsWe applied the enrollment criteria of two randomized clinical trials (PEGASUS and COMPASS) to consecutive patients who underwent percutaneous coronary intervention in an ACS registry between January 2016 and June 2017. ResultsA total of 780 patients were included in the final analysis. The proportion of patients fulfilling the trial enrollment criteria was 35.9% for PEGASUS and 32.1% for COMPASS. The proportion of patients eligible for both trials was 17.7% and 49.7% of patients were eligible for at least one trial. The need for anticoagulant therapy was the most common reason for exclusion on the PEGASUS criteria (46.2%) and the presence of high bleeding risk was the most common reason for exclusion on the COMPASS criteria (61.5%). ConclusionsApproximately 50% of real-world patients are not eligible for the antithrombotic strategies applied in these trials. Since this non-eligible population is at greater risk of events, further studies are needed to confirm the applicability of these strategies.

Atrial Fibrillation in Patients on Dialysis Therapy: Epidemiology, Prognosis and Choice of Anticoagulant Therapy

The review presents data on the prevalence of atrial fibrillation in patients on dialysis therapy. It is shown that dialysis-dependent patients with non-valve atrial fibrillation prognosis is extremely unfavorable, significantly increased risk of death due to both ischemic and hemorrhagic complications. Scales to assess the risk of thromboembolic and hemorrhagic complications in patients with atrial fibrillation on program dialysis are not validated. The lack of data from randomized clinical trials makes it much more difficult to choose anticoagulant therapy in patients with terminal stage of chronic kidney disease on dialysis who have undergone kidney transplantation. Therefore, the need for anticoagulant therapy and the choice of drugs in patients in this category should be made on the basis of a personalized multidisciplinary approach, taking into account comorbid pathology and the patient's preferences.