Oral anti-coagulants use in Chinese hospitalized patients with atrial fibrillation

Background:Oral anti-coagulants(OAC)are the intervention for the prevention of stroke,which consistently improve clinical outcomes and survival among patients with atrial fibrillation(AF).The main purpose of this study is to identify problems in OAC utilization among hospitalized patients with AF in China.Methods:Using data from the Improving Care for Cardiovascular Disease in China-Atrial Fibrillation(CCC-AF)registry,guideline-recommended OAC use in eligible patients was assessed.Results:A total of 52,530 patients with non-valvular AF were enrolled from February 2015 to December 2019,of whom 38,203 were at a high risk of stroke,9717 were at a moderate risk,and 4610 were at a low risk.On admission,only 20.0%(6075/30,420)of patients with a diagnosed AF and a high risk of stroke were taking OAC.The use of pre-hospital OAC on admission was associated with a lower risk of new-onset ischemic stroke/transient ischemic attack among the diagnosed AF population(adjusted odds ratio:0.54,95%confidence interval:0.43-0.68;P<0.001).At discharge,the prescription rate of OAC was 45.2%(16,757/37,087)in eligible patients with high stroke risk and 60.7%(2778/4578)in eligible patients with low stroke risk.OAC utilization in patients with high stroke risk on admission or at discharge both increased largely over time(all P<0.001).Multivariate analysis showed that OAC utilization at discharge was positively associated with in-hospital rhythm control strategies,including catheter ablation(adjusted odds ratio[OR]11.63,95%confidence interval[CI]10.04-13.47;P<0.001),electronic cardioversion(adjusted OR 2.41,95%CI 1.65-3.51;P<0.001),and anti-arrhythmic drug use(adjusted OR 1.45,95%CI 1.38-1.53;P<0.001).Conclusions:In hospitals participated in the CCC-AF project,>70%of AF patients were at a high risk of stroke.Although poor performance on guideline-recommended OAC use was found in this study,over time the CCC-AF project has made progress in stroke prevention in the Chinese AF population.Registration:ClinicalTrials.gov,NCT02309398.

Anticoagulation therapy in intra-aortic balloon counterpulsation： Does IABP really need anti-coagulation ？

Objective: To investigate if intra-aortic balloon pump(IABP) is contraindicated without anticoag-ulation therapy. Methods: Some 153 IABP patients in the King Abdulaziz Cardiac Center(KSA) were random-ly assigned into two groups. Anticoagulation group( Group A) consisted of 71 patients who were given heparin intravenously with target aPTT 50 - 70 seconds. Non-anticoagulation group( Group B) consisted of 82 patients without intravenous heparin during balloon pumping. Hematological parameters including platelet count, D-dimer, Plasminogen activator inhibitor-1 (PAI-1) and fibrinogen degradation products(FDP) were checked respectively at the point of baseline, 24 hours, 48 hours and 24 hours post IABP counterpulsation. Clot deposits on balloon surface, vascular complications from IABP including bleeding and limb ischemia were recorded.Results: Platelet count and PAI-1 level decreased at 24 hours and 48 hours in both groups ( P < 0.05) . D-dimer and FDP level increased at 24 hours and 48 hours in both groups( P < 0.05), but returned to the baseline level 24 hours post IABP removal( P > 0.05) . Three patients in Group A and 2 patients in Group B developed minor limb ischemia( P > 0.05). No major limb ischemia in either group. Two patients in Group A suffered major bleeding and required blood transfusion or surgical intervention, whereas no patient had major bleeding in Group B. Eight patients had minor bleeding in Group A, but only 2 patients in Group B ( P <0.05). No clot deposit developed on IABP surface in either group. Conclusion: IABP is safe without routine anticoagulation therapy. Selecting appropriate artery approach and early detection intervention are key methods for preventing complications.

Preparation of Polyporus Albicans Teng Sulfate andIts Anti-coagulation Activity

More studies have indicated that polysaccharide sulfate has anti-coagulant activity.Now,heparin is the most popular anticoagulant used in clinic,however,its side effects have also caused highly concern.It is still under intensive investigations to synthesize effective safe polysaccharide sulfate as heparin substitute.We extracted water-soluble polysaccharide from fermented mycelium of edible polyporus albicans（Imaz.） teng,and got the water-soluble polyporus albicans teng sulfate（PATS） by modifying the water-solubility polyose with the method of chlorosulfonic acid-pyridine.The anti-coagulant assay of PATS in vitro towards normal human plasma indicates its remarkable anticoagulant activity,while the dose could be as low as 5 mg/L for anticoagulation.The anti-coagulant effect was equivalent to that of heparin about 150 U when the concentration of PATS was 10 mg/L.The study on anti-coagulation mechanism suggests that PATS got involved in the intrinsic pathway.The anti-coagulation activity of PATS was due to the inhibition of the coagulation factors IIa and Xa activities mediated by antithrombin Ⅲ（ATIII）.The anti-coagulation mechanism of PATS is absolutely identical to that of heparin.In conclusion,we suggest that PATS has the similar anti-coagulation characteristic to heparin,but with a better anti-coagulation effect.Meanwhile,derived from edible fungus-polysaccharide,PATS has more bio-safety advantage.Therefore,PATS has promising future to be developed and used as an ideal substitute for heparin in clinic.

局部枸橼酸抗凝与全身肝素抗凝治疗脓毒症急性肾损伤的效果对比

目的比较局部枸橼酸抗凝与全身肝素抗凝在脓毒症急性肾损伤(AKI)治疗中的效果和安全性。方法纳入2013年3月至2016年3月期间的脓毒症AKI病人82例,按照抗凝治疗方法的不同分为观察组(局部枸橼酸抗凝治疗)和对照组(全身肝素抗凝治疗),比较2组的凝血功能、血液净化效果、滤器的使用寿命以及不良事件发生情况。结果治疗后,观察组凝血酶原时间(PT)、活化部分凝血时间(APTT)等凝血指标明显优于对照组,血小板计数(PLT)明显高于对照组,肌酸激酶同工酶(CK-MB)以及肌酐(Cr)水平较对照组显著降低;观察组滤器的使用寿命明显高于对照组,而出血事件发生率明显低于对照组;2组间比较差异均具有统计学意义(P<0.05)。结论局部枸橼酸抗凝治疗对脓毒症AKI病人的凝血功能影响甚微,其可提高血液净化效果,降低出血事件的发生率。

Fondaparinux:A cornerstone drug in acute coronary syndromes

In acute coronary syndrome(ACS),the use of anticoagulants in conjunction with antiplatelet agents in the acute phase has resulted in reduced ischemic events and is more effective than either class of drug used alone.Though parenteral anticoagulation is essential at the time of diagnosis,a balance must be made between ischemic benefit and the increased risk of bleeding when prescribing anticoagulants.Adverse events associated with anticoagulants,such as heparin-induced thrombocytopenia,bleeding problems,and the need for close monitoring of anticoagulant activity,have contributed to finding agents that reduce these limitations.Studies like the Organization to Assess Strategies in Ischemic Syndromes 5 and 6 and their meta-analysis have proven the efficacy of Fondaparinux over the entire ACS spectrum.The convenience of administration(once daily),lack of monitoring,reduction in mortality,and better safety profile make Fondaparinux a simple and effective anti-coagulant for the management of ACS.

Isolated Superior Mesenteric Vein Thrombosis in Acute Pancreatitis: A Case Report

The most common vascular complication of acute pancreatitis is thrombosis of the splenic vein. Isolated thrombosis of the superior mesenteric vein is rare and may lead to mesenteric ischemia and bowel infarction. We report the case of a 39 years old patient received for acute pancreatitis with a Ranson score less than 3 and image scanner for a grade C of Balthazar and a superior mesenteric vein thrombosis. The outcome was favorable with improvement of symptoms under medical treatment including anti-coagulant therapy. The contrast enhancing abdominal CT showed an absence of superior mesenteric thrombosis.

Septic thrombophlebitis of the porto-mesenteric veins as a complication of acute appendicitis

Pylephlebitis, a rare complication of acute appendicitis, is defined as thrombophlebitis of the portal venous system. Pylephlebitis usually occurs due to secondary infection in the region drained into the portal system. We report a case of pylephlebitis caused by acute appendicitis. The patient was transferred from a private clinic 1 wk after appendectomy with the chief complaints of high fever and abdominal pain. He was diagnosed with pylephlebitis of the portal vein and superior mesenteric vein by CT-scan. The patient was treated with antibiotics and anticoagulation therapy, and discharged on the 25th day and follow-up CT scan showed a cavernous transformation of portal thrombosis.

Recurrent Implantation Failure and Low Molecular Weight Heparin

Implantation of the embryo into the endometrium is the first step in the establishment of pregnancy. This process is complex, and depends on many factors. Recurrent implantation failure is a source of distress to patients and specialists. It is defined as failure to achieve a viable pregnancy, following “>3 embryo transfers with high quality embryos or the transfer of ≥ 10 embryos in multiple transfers”. Thrombophilic conditions that contribute to recurrent implantation failure are the main concern in this review. The mechanism of implantation failure is believed to be due to decreased blood flow to the endometrium and placenta which can hinder normal endometrial receptivity leading to miscarriage. Defects in early placentation resulting in pregnancy failure, have focused attention on the therapeutic potential of low molecular weight heparin in the implantation process. Heparin has a role at all stages of implantation to improve pregnancy outcomes. There are controversies in literature regarding the association between thrombophilia and recurrent implantation failure and available literature regarding this issue is very heterogeneous. Various investigators, have shown that women with RIF are more likely to have a thrombophilia disorder, yet a clear cause cannot be acknowledged from these studies. Heparin treatment has been evaluated in several studies, showing conflicting evidence. However, several studies have pointed out that it may play a role in a subset of patients who presents a thrombophilia mutation, thus the group of patients that might benefit is needed to be identified. This review is dedicated to evaluate the published literature about the role of low molecular weight heparin in case of recurrent implantation failure with or without the presence of thrombophilia.

A strategy for mechanically integrating robust hydrogeltissue hybrid to promote the anti-calcification and endothelialization of bioprosthetic heart valve

Bioprosthetic heart valve(BHV)replacement has been the predo-minant treatment for severe heart valve diseases over decades.Most clinically available BHVs are crosslinked by glutaraldehyde(GLUT),while the high toxicity of residual GLUT could initiate calcification,severe thrombosis,and delayed endothelializa-tion.Here,we construed a mechanically integrating robust hydrogel-tissue hybrid to improve the performance of BHVs.In particular,recombinant humanized coilagen type Ⅲ(rhCOLⅢ),which was precisely customized with anti-coagulant and pro-endothelialization bioactivity,was first incorporated into the polyvinyl alcohol(PVA)-based hydrogel via hydrogen bond interactions.Then,tannic acid was introduced to enhance the mechanicalperfo of PVA-based hvdrogel and interfacial bonding between the hydrogel layer and bio-derived tissue due to the strong affinity for a wide range of substrates.In vitro and in vivo experimental results confirmed that the GLUT-crosslinked BHVs modified by the robust PVA-based hydrogel embedded rhCOLII and TA possessed long-term anti-coagulant,accelerated endothelialization,mild inflammatory response and anti-calcification properties.Therefore,our mechanically integrating robust hydrogel-tissue hybrid strategy showed the potential to enhance the service function and prolong the service life of the BHVs after implantation.

A biomimetic tri-phasic scaffold with spatiotemporal patterns of gastrodin to regulate hierarchical tissue-based vascular regeneration

Clinical use of small-diameter vascular grafts remains a challenging issue in neovessel regeneration in view of thrombosis and intimal hyperplasia.Developing a vascular graft with structure and function similar to those of the native vessels necessitates a major direction of vascular tissue regeneration.Thus,this study sought to design and fabricate a range of tri-phasic scaffolds(0,2,and 5 wt%gastrodin-polyurethane(PU))with spatiotemporally defined structure and gastrodin-release for regulating the highly coordinated processes in growth of the intima and media.While the small pores of inner layer guided infiltration of human umbilical vein endothelial cells(HUVECs),the bigger pores of medial layer could offer smooth muscle cell(SMC)-friendly habitat,and external fibers conferred adequate mechanical properties.Correspondingly,spatial distribution and differential regulation of key proteins in HUVECs and SMCs were mediated by hierarchical release of gastrodin,of which rapid release in inner layer elicited enhanced HUVEC proliferation and migration against those of the SMC via activated endothelial nitric oxide synthase(eNOS)and heat shock protein 70(HSP70)signal.Of note,superior anti-coagulation was reflected in 2 wt%gastrodin-PU ex vivo extracorporeal blood circulation experiment.After in vivo implantation for 12 weeks,there was no formation of obvious thrombosis and intimal hyperplasia in 2 wt%gastrodin-PU.The scaffold maintained high patency and improved vascular remodeling,including the formation of thin endothelialization in lumen and dense extracellular matrix deposition in medial layer.Taken together,the results demonstrate the positive function of hierarchical releasing system that responded to tri-phasic structure,which not only suppressed intimal thickening but also tightly controlled tissue regeneration.

Functional non-glutaraldehyde treated porcine pericardium for anti-coagulation,anti-calcification,and endothelial proliferation bioprosthetic heart valves

In the last decade,the number of transcatheter heart valve replacement for severe heart valve disease has increased exponentially.Although the bioprosthetic artificial heart valve(BHV)has similar fluid dynamics performance to the original heart valve compared with mechanical heart valve so that there is no need to take long-term anticoagulant drugs to prevent thromboembolism,transcatheter BHV replacement are still at risk for thrombosis during the first few months according to the clinical data.However,the use of antithrombotic drugs can also increase the risk of bleeding.Therefore,it is particularly important to improve the anticoagulant properties for the BHV itself.In this work,a kind of non-glutaraldehyde cross-linked BHV material with excellent antithrombotic ability has been prepared from carboxylated oxazolidine treated porcine pericardium(consisting of collagen,elastin and glycoprotein)with the further graft of the anticoagulant heparin sodium via hydrophilic modified chitosan.Along with the similar mechanical properties and collagen stability comparable to the glutaraldehyde cross-linked porcine pericardium(PP),these functional non-glutaraldehyde cross-linked PPs exhibit better biocompatibility,promoted endothelial proliferation and superior anti-calcification ability.More importantly,excellent anticoagulant activity can be observed in the hematological experiments in vivo and in vitro.In summary,these excellent performances make these functional non-glutaraldehyde cross-linked PPs great potentialities in the BHV applications.

An extracellular matrix-mimetic coating with dual bionics for cardiovascular stents

Anti-inflammation and anti-coagulation are the primary requirements for cardiovascular stents and also the widely accepted trajectory for multi-functional modification.In this work,we proposed an extracellular matrix(ECM)-mimetic coating for cardiovascular stents with the amplified functionalization of recombinant humanized collagen type III(rhCOL III),where the biomimetics were driven by structure mimicry and component/function mimicry.Briefly,the structure-mimic was constructed by the formation of a nanofiber(NF)structure via the polymerization of polysiloxane with a further introduction of amine groups as the nanofibrous layer.The fiber network could function as a three-dimensional reservoir to support the amplified immobilization of rhCoL III.The rhCOL III was tailored for anti-coagulant,anti-inflammatory and endothelialization promotion properties,which endows the ECM-mimetic coating with desired surface functionalities.Stent implantation in the abdominal aorta of rabbits was conducted to validate the in vivo re-endothelialization of the ECM-mimetic coating.The mild inflammatory responses,anti-thrombotic property,promotion of endothelialization and suppression of excessive neointimal hyperplasia confirmed that the ECM-mimetic coating provided a promising approach for the modification of vascular implants.

Why anticoagulant studies on sepsis fail frequently-start with SCARLET

The Sepsis Coagulopathy Asahi Recombinant LE Thrombomodulin(SCARLET)trial has many defects,and thus cannot be the terminator of recombinant thrombomodulin(rTM).On the contrary,it provides sufficient evidence for further research.Based on analysis focusing on the failure of SCARLET and several previous anticoagulant studies,it is most important for new studies to grasp the following two points:(1)The enrolled cases should have sufficient disease severity and a clear standard for disseminated intravascular coagulation;(2)Heparin should not be used in combination with the investigated drugs.Multiple post-hoc analyses show that no combination of heparin will not increase the risk of thromboembolism.In fact,the combination of heparin can mask the true efficacy of the investigated drug.Due to the complexity of sepsis treatment and the limitations of clinical studies,the results of all treatment studies should be repeatedly verified,rather than be determined at one stroke.Some research conclusions contrary to disease physiology,pharmacology and clinical practice may be deceptive,and should be cautious rather than be simply accepted.On the other hand,the dissenting voices in the"consensus"scene are often well discussed by the authors and should be highly valued.

Syntheses and characterization of anti-thrombotic and anti-oxidative Gastrodin-modified polyurethane for vascular tissue engineering

Vascular grafts must avoid negative inflammatory responses and thrombogenesis to prohibit fibrotic deposition immediately upon implantation and promote the regeneration of small diameter blood vessels(<6 mm inner diameter).Here,polyurethane(PU)elastomers incorporating anti-coagulative and anti-inflammatory Gastrodin were fabricated.The films had inter-connected pores with porosities equal to or greater than 86%and pore sizes ranging from 250 to 400μm.Incorporation of Gastrodin into PU films resulted in desirable mechanical properties,hydrophilicity,swelling ratios and degradation rates without collapse.The released Gastrodin maintained bioactivity over 21 days as assessed by its anti-oxidative capability.The Gastrodin/PU had better anti-coagulation response(less observable BSA,fibrinogen and platelet adhesion/activation and suppressed clotting in whole blood).Red blood cell compatibility,measured by hemolysis,was greatly improved with 2Gastrodin/PU compared to other Gastrodin/PU groups.Notably,Gastrodin/PU upregulated anti-oxidant factors Nrf2 and HO-1 expression in H2O2 treated HUVECs,correlated with decreasing pro-inflammatory cytokines TNF-αand IL-1β in RAW 264.7 cells.Upon implantation in a subcutaneous pocket,PU was encapsulated by an obvious fibrous capsule,concurrent with a large amount of inflammatory cell infiltration,while Gastrodin/PU induced a thinner fibrous capsule,especially 2Gastrodin/PU.Further,enhanced adhesion and proliferation of HUVECs seeded onto films in vitro demonstrated that 2Gastrodin/PU could help cell recruitment,as evidenced by rapid host cell infiltration and substantial blood vessel formation in vivo.These results indicate that 2Gastrodin/PU has the potential to facilitate blood vessel regeneration,thus providing new insight into the development of clinically effective vascular grafts.

New Perspectives on Pharmacological Treatment of Atrial Fibrillation

Despite the huge development of radiofrequency catheter ablation, surgical operation, pacemaker implantation, and drug therapy remains the first line treatment of atrial fibrillation. Several new anti-arrhythmic drugs and anticoagulation drugs have come out recently, and have made the drug therapy of atrial fibrillation a more promising choice. This article provides a contemporary highlight on the new anti-arrhythmic agents of atrial fibrillation. （ S Chin J Cardiol 2009 ; 10 （4） ： 244 - 249 ）

Advanced practice nurses transitional care promotes anticoagulation therapy of warfarin in atrial fibrillation patients in South China

Background Advanced practice chronic conditions. However, nurse transitional care has been proofed to be important for older adults with such effectiveness has never been studied in the management of appropriate Warfarin use in clinical practice. Methods A total of 97 patients were randomly distributed into control group who received usual care, and interventional group who received transitional care provided by APNs. A 12-month observation of both groups were recorded by physicians and APNs and the impact of APNs on the managing of Warfarin therapy was also evaluated based on time in the therapeutic range （TTR）. Results APNs transitional care significantly （P 〈 0.01） improved patients＇ adherence, increased TTR and high TTR ratio compared with control group. Re-admission due to stroke was significantly （P 〈 0.01） reduced by APNs transitional care. Conclusion APNs transitional care improves patients＇ knowledge on AF and reduces stroke risk. The current research strongly suggest the necessity of APNs transitional interventional in managing anticoagulation therapy in AF patients in China.