Early systemic anticoagulation reduces hospital readmission in acute necrotizing pancreatitis patients:A retrospective cohort study

Background:Early systemic anticoagulation(SAC)is a common practice in acute necrotizing pancreatitis(ANP),and its impact on in-hospital clinical outcomes had been assessed.However,whether it affects long-term outcomes is unknown.This study aimed to evaluate the effect of SAC on 90-day readmission and other long-term outcomes in ANP patients.Methods:During January 2013 and December 2018,ANP patients admitted within 7 days from the onset of abdominal pain were screened.The primary outcome was 90-day readmission after discharge.Cox proportional-hazards regression model and mediation analysis were used to define the relationship between early SAC and 90-day readmission.Results:A total of 241 ANP patients were enrolled,of whom 143 received early SAC during their hospitalization and 98 did not.Patients who received early SAC experienced a lower incidence of splanchnic venous thrombosis(SVT)[risk ratio(RR)=0.40,95%CI:0.26-0.60,P<0.01]and lower 90-day readmission with an RR of 0.61(95%CI:0.41-0.91,P=0.02)than those who did not.For the quality of life,patients who received early SAC had a significantly higher score in the subscale of vitality(P=0.03)while the other subscales were all comparable between the two groups.Multivariable Cox regression model showed that early SAC was an independent protective factor for 90-day readmission after adjusting for potential confounders with a hazard ratio of 0.57(95%CI:0.34-0.96,P=0.04).Mediation analysis showed that SVT mediated 37.0%of the early SAC-90-day readmission causality.Conclusions:The application of early SAC may reduce the risk of 90-day readmission in the survivors of ANP patients,and reduced SVT incidence might be the primary contributor.

Challenging anticoagulation therapy for multiple primary malignant tumors combined with thrombosis:A case report and review of literature

BACKGROUND Venous thromboembolism significantly contributes to patient deterioration and mortality.Management of its etiology and anticoagulation treatment is intricate,necessitating a comprehensive consideration of various factors,including the bleeding risk,dosage,specific anticoagulant medications,and duration of therapy.Herein,a case of lower extremity thrombosis with multiple primary malignant tumors and high risk of bleeding was reviewed to summarize the shortcomings of treatment and prudent anticoagulation experience.CASE SUMMARY An 83-year-old female patient was admitted to the hospital due to a 2-wk history of left lower extremity edema that had worsened over 2 d.Considering her medical history and relevant post-admission investigations,it was determined that the development of left lower extremity venous thrombosis and pulmonary embolism in this case could be attributed to a combination of factors,including multiple primary malignant tumors,iliac venous compression syndrome,previous novel coronavirus infection,and inadequate treatment for prior thrombotic events.However,the selection of appropriate anticoagulant medications,determination of optimal drug dosages,and establishment of an appropriate duration of anticoagulation therapy were important because of concurrent thrombocytopenia,decreased quantitative fibrinogen levels,and renal insufficiency.CONCLUSION Anticoagulant prophylaxis should be promptly initiated in cases of high-risk thrombosis.Individualized anticoagulation therapy is required for complex thrombosis.

Management of regional citrate anticoagulation for continuous renal replacement therapy:guideline recommendations from Chinese emergency medical doctor consensus

Continuous renal replacement therapy(CRRT)is widely used for treating critically-ill patients in the emergency department in China.Anticoagulant therapy is needed to prevent clotting in the extracorporeal circulation during CRRT.Regional citrate anticoagulation(RCA)has been shown to potentially be safer and more effective,and is now recommended as the preferred anticoagulant method for CRRT.However,there is still a lack of unified standards for RCA management in the world,and there are many problems in using this method in clinical practice.The Emergency Medical Doctor Branch of the Chinese Medical Doctor Association(CMDA)organized a panel of domestic emergency medicine experts and international experts of CRRT to discuss RCA-related issues,including the advantages and disadvantages of RCA in CRRT anticoagulation,the principle of RCA,parameter settings for RCA,monitoring of RCA(mainly metabolic acid-base disorders),and special issues during RCA.Based on the latest available research evidence as well as the paneled experts'clinical experience,considering the generalizability,suitability,and potential resource utilization,while also balancing clinical advantages and disadvantages,a total of 16 guideline recommendations were formed from the experts'consensus.

Therapeutic anticoagulation for splanchnic vein thrombosis in acute pancreatitis: A national survey and case-vignette study

BACKGROUND Splanchnic vein thrombosis(SVT)is a major complication of moderate and severe acute pancreatitis.There is no consensus on whether therapeutic anticoagulation should be started in patients with acute pancreatitis and SVT.AIM To gain insight into current opinions and clinical decision making of pancreatologists regarding SVT in acute pancreatitis.METHODS A total of 139 pancreatologists of the Dutch Pancreatitis Study Group and Dutch Pancreatic Cancer Group were approached to complete an online survey and case vignette survey.The threshold to assume group agreement was set at 75%.RESULTS The response rate was 67%(n=93).Seventy-one pancreatologists(77%)regularly prescribed therapeutic anticoagulation in case of SVT,and 12 pancreatologists(13%)for narrowing of splanchnic vein lumen.The most common reason to treat SVT was to avoid complications(87%).Acute thrombosis was the most important factor to prescribe therapeutic anticoagulation(90%).Portal vein thrombosis was chosen as the most preferred location to initiate therapeutic anticoagulation(76%)and splenic vein thrombosis as the least preferred location(86%).The preferred initial agent was low molecular weight heparin(LMWH;87%).In the case vignettes,therapeutic anticoagulation was prescribed for acute portal vein thrombosis,with or without suspected infected necrosis(82%and 90%),and thrombus progression(88%).Agreement was lacking regarding the selection and duration of long-term anticoagulation,the indication for thrombophilia testing and upper endoscopy,and about whether risk of bleeding is a major barrier for therapeutic anticoagulation.CONCLUSION In this national survey,the pancreatologists seemed to agree on the use of therapeutic anticoagulation,using LMWH in the acute phase,for acute portal thrombosis and in the case of thrombus progression,irrespective of the presence of infected necrosis.

The Effects of Lower Intensity Anticoagulation Therapy on Coagulation System in Patients With Mechanical Prosthetic Valves

Summary: To evaluate the effect of lower intensity anticoagulation therapy in patients with mechanical prosthetic valves, laboratory based hematological assays including prothrombin time (PT), activity of factor X, antithrombin Ⅲ (AT Ⅲ), D dimer, fibrinogen (Fg) and platel et al pha granular membrane protein (GMP 140) were performed in 65 patients who had been on warfarin treatment for over one month. The patients were assigned to 3 groups on the basis of their International Normalized Ratios (INR), ranging from 2.00 to 2.50; 2.51 to 3.00; 3.01 to 4.50, respectively. The results showed that the D dimer, Fg, GMP 140 levels were higher after mechanical valve replacement than those before operation, indicating the activation of coagulation and fibrinolysis system and the damage of platelets. Lower intensity anticoagulation therapy (INR 2 00 to 2.50) could effectively inhibit the activity of factor X and increase the level of AT Ⅲ. There were no appreciable differences among D dimer, Fg, GMP 140 and AT Ⅲ in the 3 anticoagulation intensity groups. These results suggest that in patients with new generation mechanical prosthetic valves, target anticoagulation level (INR 2 00 to 2.50) may result in good protection from thrombo embolism.

Anticoagulation therapy for pulmonary embolism involving a myxoma mimicking, giant type C thrombus: A case report

Right heart thrombus(RHTh) with concurrent acute pulmonary embolism(PE) is rare and can seriously destabilize hemodynamics, leading to an emergency situation with high mortality. Diagnosis and treatment of RHTh with acute PE are not yet standardized. There are few reports of acute PE concurrent with RHTh and even less is known about patients with a right heart mural thrombus. For physicians, the diagnostic choice and treatment of these patients are particularly difficult due to the lack of knowledge. Here, we report a rare case of partial mural RHTh(type C RHTh) with acute PE. The mural mass in the right heart was initially diagnosed as atrial myxoma according to transthoracic echocardiography(TTE), and both pulmonary embolus and the mural mass were completely absorbed after administering Rivaroxiban. This case suggests that TTE alone is insufficient to identify and diagnoses a right heart mural mass such as this. However, novel oral anticoagulants may be effective at alleviating PE with type C RHTh.

Systemic right ventricle complications in levo-transposition of the great arteries: A case report and review of literature

BACKGROUND Congenitally corrected levo-transposition of the great arteries(L-TGA)is a congenital heart disease in which the ventricles and great arteries are transposed from their typical anatomy.In L-TGA,the double discordance,atrioventricular and ventriculoarterial,create an acyanotic milieu which allows patients to survive their early decades,however,progressive systemic right ventricle(sRV)dys-function creates complications later in life.sRV dysfunction and remodeling predisposes patients to intracardiac thrombus(ICT)formation.CASE SUMMARY A 40-year-old male with L-TGA presented with symptoms of acute decom-pensated heart failure.In childhood,he had surgical repair of a ventricular septal defect.In adulthood,he developed sRV dysfunction,systemic tricuspid valve(sTV)regurgitation,and left-bundle branch block for which he underwent cardiac resynchronization therapy.Transthoracic echocardiogram showed a sRV ejection fraction of 40%,severe sTV regurgitation,and a newly identified sRV ICT.ICT was confirmed by ultrasound-enhancing agents and transesophageal echocardio-graphy.Our patient was optimized with guideline-directed medical therapy and diuresis.Anticoagulation was achieved with a vitamin K antagonist(VKA)and he was later referred for evaluation by advanced heart failure and heart transplant services.CONCLUSION Anticoagulation with VKA is the mainstay of treatment in the absence of conclusive data supporting direct oral anticoagulant use in ICT in patients with congenital heart disease.This case illustrates the natural history of L-TGA and highlights the importance of surveillance and monitoring with dedicated cardiac imaging to identify complications.

Deciding the Gold Standard for Oral Anticoagulation Therapy

Healthcare practitioners have many anticoagulant options for treating various disease states pertaining to blood clots and blood clot formation. Each anticoagulant has pros and cons and the decision of which pharmacological agent to use can be confusing and difficult. In years past, Vitamin K antagonists have been the standard of care when treating specific disease states such as atrial fibrillation and venous thromboembolism based on habit and cost of care. The emergence of newer anticoagulants should be considered the new standard of care based on the evidence presented over the last several years.

Paper Analysis of the WATCHMAN on the Reduction of Stroke Compared to Anticoagulants: A Systematic Review of the Literature

Objective: Anticoagulants have been approved and used for decades as highly effective blood thinners. The objective of this study is to analyze the clinical trials in order to determine if the Watchman reduces the risk of stroke in patients with atrial fibrillation compared to those prescribed the traditional anticoagulants. This will contribute to the current body of knowledge and possibly provide beneficial clinical guidance with respect to providing an alternative option for those suffering from non-valvular Atrial fibrillation. Methods: A systematic literature search through the Saint James School of Medicine library resources as well as PubMed, Medscape, Google Scholar was conducted. Studies were included if the literature examined the comparison between the Watchman device and four specific anticoagulants (Xarelto, Eliquis, Pradaxa, and Warfarin) in association with reduction of risks of strokes in an atrial fibrillation population. The study includes a qualitative sub-analysis to explore additional clinical aspects that may affect risk of stroke and response of treatment. Results: Outcomes were significant for similar stroke occurrence, when compared to published clinical trials. Alternatively, there was a significant reduction in risk of bleeding and all-cause mortality in the Watchman™ device compared to traditional NOACs and warfarin. While examining the studies and trials, overall, the Watchman™ device offers a better long-term outcome therapy for non-valvular atrial fibrillation populations who are not possibilities for extended anticoagulation. The studies used for analysis examining the dosage found higher fatality with increased use of NOACs and more hospitalizations with decreased use. Conclusion: From the presented data, it is safe to say that the Watchman™ device is a viable and effective alternative for stroke prophylaxis in certain patient populations. Compared to traditional anticoagulant therapies for non-valvular atrial fibrillation, these studies suggest that the Watchman™ device can reduce bleeding time and, in most cases, the risk of stroke is less than or equal to traditional anti-coagulants.

临床药师参与1例心力衰竭、心肌梗死合并房颤患者的药物治疗

目的梳理复杂治疗方案后的抗栓方案,重整抗栓药物和疗程,纠正不合理用药,促进合理用药。方法临床药师介入1例心力衰竭、多次因心肌梗死植入多枚支架,合并房颤,行射频消融和左心耳封堵患者的药物治疗,重整抗栓药物方案,并全程监控治疗药物,就不合理用药提出警示。结果患者明显好转,住院及出院随访期间未发生不良事件。结论临床药师的参与有助于精细化管理患者的药物治疗方案,并及时纠正不合理用药,更好的为患者服务。

Effect of VEGF/GREDVY Modified Surface on Vascular Cells Behavior

We synthesized B-He/B-GREDVY and immobilized them on avidin-coated surfaces.To examine the immobilization of molecules in the material, the following experiments were performed:fluorescein isothiocyanate(FITC) fluorescence staining, water contact angle and atomic force microscopy(AFM) measurements. Besides, the biological evaluation experiments were also performed, such as platelets adhesion and activation, the culturing of smooth muscle cells(SMC) and endothelial cells(EC). These experimental results show that the modified surfaces could prevent the hyperproliferation of SMC, and promote the proliferation and migration of EC and EPC. Furthermore, the adding of VEGF improved the EC adhesion in a dynamic environment. Generally, it is expected that the modified surfaces could be used to accelerate the formation of the newly endothelial layer for the construction of platforms for coronary artery stent therapy.

Use of MLC901 in cerebral venous sinus thrombosis:Three case reports

BACKGROUND Cerebral venous sinus thrombosis(CVT)is rare cause of cerebrovascular disease.The incidence is 0.5%of all stroke.The majority of affected patients are young adults(mean age:35-40 years)with mild to moderate disabilities.Poor outcome with severe disability is seen in 13%of cases.Early diagnosis and treatment are important for good outcomes and preventing complications.Treatment options are limited and mostly based on consensus.NeuroAiD II™(MLC901;Moleac Pte,Ltd,Singapore)has a potential beneficial role in post-stroke recovery,by aiding the natural brain recovery process.CASE SUMMARY MLC901 consists of nine natural herbal ingredients.Studies have shown its safety profile and aid in post stroke recovery.The aim of this case series was to demonstrate the potential role of MLC901 in stroke recovery of patients with cerebral venous sinus thrombosis(CVST)who received MLC901 in addition to standard of care.The prescribed dose of MLC901 is 400 mg/cap two capsules,three times a day.Data from these patients were prospectively collected at baseline and at monthly visits,for a duration of 3 mo.Outcome measures included adherence to therapy,side effects,National Institutes of Health Stroke Scale,Glasgow Coma Scale,modified Rankin Scale,and the Short Orientation-Memory-Concentration Test.MLC901 was well tolerated and no side effects were reported.All patients were stable with improved condition.CONCLUSION This case series highlights the potential therapeutic effects of MLC901 on CVST and provides support for further studies.

Management of cerebral amyloid angiopathy and atrial fibrillation:We are still far from precision medicine

The use of anticoagulation therapy could prove to be controversial when trying to balance ischemic stroke and intracranial bleeding risks in patients with concurrent cerebral amyloid angiopathy(CAA)and atrial fibrillation(AF).In fact,CAA is an age-related cerebral vasculopathy that predisposes patients to intracerebral hemorrhage.Nevertheless,many AF patients require oral systemic dose-adjusted warfarin,direct oral anticoagulants(such as factor Xa inhibitors)or direct thrombin inhibitors to control often associated with cardioembolic stroke risk.The prevalence of both CAA and AF is expected to rise,due to the aging of the population.This clinical dilemma is becoming increasingly common.In patients with coexisting AF and CAA,the risks/benefits profile of anticoagulant therapy must be assessed for each patient individually due to the lack of a clear-cut consensus with regard to its risks in scientific literature.This review aims to provide an overview of the management of patients with concomitant AF and CAA and proposes the implementation of a risk-based decision-making algorithm.

Simultaneous portal vein thrombosis and splenic vein thrombosis in a COVID-19 patient:A case report and review of literature

BACKGROUND It is well-described that the coronavirus disease 2019(COVID-19)infection is associated with an increased risk of thrombotic complications.While there have been many cases of pulmonary emboli and deep vein thrombosis in these patients,reports of COVID-19 associated portal vein thrombosis(PVT)have been uncommon.We present a unique case of concomitant PVT and splenic artery thrombosis in a COVID-19 patient.CASE SUMMARY A 77-year-old-male with no history of liver disease presented with three days of left-sided abdominal pain.One week earlier,the patient was diagnosed with mildly symptomatic COVID-19 and was treated with nirmatrelvir/ritonavir.Physical exam revealed mild right and left lower quadrant tenderness,but was otherwise unremarkable.Significant laboratory findings included white blood cell count 12.5 K/μL,total bilirubin 1.6 mg/dL,aminoaspartate transferase 40 U/L,and alanine aminotransferase 61 U/L.Computed tomography of the abdomen and pelvis revealed acute PVT with thrombus extending from the distal portion of the main portal vein into the right and left branches.Also noted was a thrombus within the distal portion of the splenic artery with resulting splenic infarct.Hypercoagulable workup including prothrombin gene analysis,factor V Leiden,cardiolipin antibody,and JAK2 mutation were all negative.Anticoagulation with enoxaparin was initiated,and the patient’s pain improved.He was discharged on apixaban.CONCLUSION It is quite uncommon for PVT to present simultaneously with an arterial thrombotic occlusion,as in the case of our patient.Unusual thrombotic manifestations are classically linked to hypercoagulable states including malignancy and hereditary and autoimmune disorders.Viral infections such as Epstein-Barr virus,cytomegalovirus,viral hepatitis,and COVID-19 have all been found to increase the risk of splanchnic venous occlusions,including PVT.In our patient,prompt abdominal imaging led to early detection of thrombus,early treatment,and an excellent outcome.This case is unique in that it is the second known case within the literature of simultaneous PVT and splenic artery thrombosis in a COVID-19 patient.

Anticoagulation and delayed bowel resection in the management of mesenteric venous thrombosis

Acute mesenteric venous thrombosis is potentially lethal because it can result in mesenteric ischemia and,ultimately,bowel infarction requiring surgical intervention.Systemic anticoagulation for the prevention of thrombus propagation is a well-recognized treatment modality and the current mainstay therapy for patients with acute mesenteric venous thrombosis.However,the decision between prompt surgical exploration vs conservative treatment with anticoagulation is somewhat difficult in patients with suspected bowel ischemia.Here we describe a patient with acute mesenteric venous thrombosis who presented with bowel ischemia and was treated with anticoagulation and delayed short-segment bowel resection.

Atractylenolide Ⅰ protects against lipopolysaccharide-induced disseminated intravascular coagulation by anti-inflammatory and anticoagulation effect

Objective:To investigate whether atractylenolide Ⅰ(ATL-Ⅰ) has protective effect on lipopolysaccharide(LPS)-induced disseminated intravascular coagulation(DIC) in vivo and in vitro,and explore whether NF-κB signaling pathway is involved in ATL-Ⅰ treatment.Methods:New Zealand white rabbits were injected with LPS through marginal ear vein over a period of 6h at a rate of 600 μg/kg(10 mL/h).Similarly,in the treatment groups,1.0,2.0,or 5.0 mg/kg ATL-Ⅰ were given.Both survival rate and organ function were tested,including the level of alanine aminotransferase(ALT),blood urine nitrogen(BUN),and TNF-α were examined by ELISA.Also haemostatic and fibrinolytic parameters in serum were measured.RAW 264.7 macrophage cells were administered with control,LPS,LPS + ATL-Ⅰ and ATL-Ⅰ alone,and TNF-α,phosphorylation(P)-IκBα,phosphorylation(P)-NF-κB(P65) and NF-κB(P65) were determined by Western blot.Results:The administration of LPS resulted in 73.3%mortality rate,and the increase of serum TNF-α,BUN and ALT levels.When ATL-Ⅰ treatment significantly increased the survival rate of LPS-induced DIC model,also improved the function of blood coagulation.And protein analysis indicated that ATL-Ⅰ remarkably protected liver and renal as decreasing TNF-α expression.In vitro,ATL-Ⅰ obviously decreased LPS-induced TNF-αproduction and the expression of P-NF-κB(P65),with the decrease of P-IκBα.Conclusions:ATL-Ⅰ has protective effect on LPS-induced DIC,which can elevate the survival rate,reduce organ damage,improve the function of blood coagulation and suppress TNF-α expression by inhibiting the activation of NF-κB signaling pathway.

Incidence, clinical impact and risk of bleeding during oral anticoagulation therapy

Bleeding is the most important complication of oral anticoagulation (OAC) with vitamin K-antagonists. Whilst bleeding is unavoidably related to OAC, it may have a great impact on the prognosis of treated subjects by leading to discontinuation of treatment, permanent disability or death. The yearly incidence of bleeding during OAC is 2%-5% for major bleeding, 0.5%-1% for fatal bleeding, and 0.2%-0.4% for intracranial bleeding. While OAC interruption and/or antagonism, as well as administration of coagulation factors, represent the necessary measures for the management of bleeding, proper stratification of the individual risk of bleeding prior to start OAC is of paramount importance. Several factors, including advanced age, female gender, poor control and higher intensity of OAC, associated diseases and medications, as well as genetic factors, have been proven to be associated with an increased risk of bleeding. Most of these factors have been included in the development of bleeding prediction scores, which should now be used by clinicians when prescribing and monitoring OAC. Owing to the many limitations of OAC, including a narrow therapeutic window, cumber-some management, and wide interand intra-individual variability, novel oral anticoagulants, such as factor Xa inhibitors and direct thrombin inhibitors, have been recently developed. These agents can be given in f ixed doses, have little interaction with foods and drugs, and do not require regular monitoring of anticoagulation. While the novel oral anticoagulants show promise for effective thromboprophylaxis in atrial f ibrillation and venous thromboembolism, def initive data on their safety and eff icacy are awaited.

Antithrombotic management of patients on oral anticoagulation undergoing coronary artery stenting

Patients on oral anticoagulation(OAC),who are referred for coronary artery stenting account for about 5% of the whole population undergoing percutaneous coronary intervention(PCI).Although relatively small,this patient subset poses particular problems owing to the need to balance carefully the risk of bleeding against the risk of stent thrombosis and thromboembolism.Triple therapy(TT) of OAC,aspirin and clopidogrel appears as the most effective for prevention of stent thrombosis and thromboembolism.However,an increased incidence of major bleeding is to be expected during follow-up.Therefore,TT should be prolonged for as short a time as possible,and implantation of drug-eluting stents avoided.Frequent monitoring of international normalized ratio is also warranted,and the intensity of OAC should be targeted at the lower limit of the therapeutic range.Gastric protection should also be considered for all patients on medium-to long-term TT,owing to the observed highest incidence of bleeding at the gastrointestinal site.Peri-procedural management is cumbersome,and a substantial incidence of inhospital major bleeding has been reported.Since this latter is more related to procedural variables than to TT itself,choice of radial access,avoidance of glycoprotein Ⅱb/Ⅲa inhibitors,and preference for not interrupting effective OAC should be implemented.However,the evidence on which the recommendations for managing this patient subset are based is limited and of relative poor quality.While waiting for the results of ongoing,large prospective studies that are aimed at conclusively determining optimal medium-to long-term antithrombotic treatment,the official recommendations issued by the Working Group on Thrombosis of the European Society of Cardiology on the management of patients on OAC undergoing PCI with stenting should followed.

Anticoagulation with direct thrombin inhibitors during extracorporeal membrane oxygenation

Use of extracorporeal membrane oxygenation to support patients with critical cardiorespiratory illness is increasing.Systemic anticoagulation is an essential element in the care of extracorporeal membrane oxygenation patients.While unfractionated heparin is the most commonly used agent,unfractionated heparin is associated with several unique complications that can be catastrophic in critically ill patients,including heparin-induced thrombocytopenia and acquired antithrombin deficiency.These complications can result in thrombotic events and subtherapeutic anticoagulation.Direct thrombin inhibitors(DTIs)are emerging as alternative anticoagulants in patients supported by extracorporeal membrane oxygenation.Increasing evidence supports DTIs use as safe and effective in extracorporeal membrane oxygenation patients with and without heparininduced thrombocytopenia.This review outlines the pharmacology,dosing strategies and available protocols,monitoring parameters,and special use considerations for all available DTIs in extracorporeal membrane oxygenation patients.The advantages and disadvantages of DTIs in extracorporeal membrane oxygenation relative to unfractionated heparin will be described.