Thromboprophylaxis

血栓预防
  • DOI:
    文章类型: Journal Article
    确定静脉血栓栓塞(VTE)的危险因素有助于决定VTE的血栓预防。一项回顾性研究表明,在我们的人群中,高血压和糖尿病与VTE之间存在关联。这项研究的目的是确认这些发现,并确定完整的血细胞计数和凝血测试是否也可以作为对VTE患者进行分层预防的有用参数。
    这是一项性别和年龄匹配的前瞻性病例对照研究,研究对象为45例多普勒证实的DVT和43例明显健康的对照。
    确定的危险因素包括高血压病史,糖尿病,以前的DVT,最近的手术,最近的创伤,恶性肿瘤,脓毒症,和不动。这些病例的平均血细胞比容显着降低(33±7.4%vs38±4.6%,p<0.001)。尽管在病例和对照组之间没有观察到白细胞和血小板计数的差异,但两组之间的白细胞增多与白细胞减少(P=0.003)和血小板增多与血小板减少(P=0.045)分层存在差异。此外,病例中国际标准化比率(INR)较高(1.1±0.2vs1.0±0.1;P=0.001),分别在4.4%和28.9%的病例中观察到高凝状态(INR<0.9)和低凝状态(INR>1.2),而在对照组中没有观察到(P<0.001)。此外,aPTT>40秒分别见于4.4%和4.7%的病例和对照,aPTT<30秒见于22%的病例,但未见于对照(P=0.004)。
    高血压和糖尿病是传统上与DVT无关的危险因素。除了完整的血细胞计数和凝血测试之外,这些还可以用于对我们人群和其他类似社区中的患者进行分层以进行预防。
    UNASSIGNED: Identifying risk factors for venous thromboembolism (VTE) is useful in deciding thromboprophylaxis for VTE. A retrospective study had shown an association between hypertension and diabetes mellitus with VTE in our population. The objective of this study was to confirm these findings and to determine if the complete blood count and coagulation tests can also be useful parameters in stratifying VTE patients for prophylaxis.
    UNASSIGNED: This is a gender and age matched prospective case-control study of 45 Doppler\'s confirmed DVT and 43 apparently healthy controls.
    UNASSIGNED: Identified risk factors included history of hypertension, diabetes mellitus, previous DVT, recent surgery, recent trauma, malignancy, sepsis, and immobility. The cases had a significantly lower mean haematocrit (33±7.4% vs 38±4.6%, p<0.001). Though no differences were observed in leucocyte and platelet counts between cases and controls but stratification as leucocytosis vs leucopaenia (P=0.003) and thrombocytosis vs thrombocytopaenia (P=0.045) differed between both groups. Also, the International normalized ratio (INR) was higher in cases (1.1±0.2 vs 1.0±0.1;P=0.001), hypercoagulable state (INR<0.9) and hypocoagulable state (INR>1.2) were observed in 4.4% and 28.9% of cases respectively but not in controls (P <0.001). Also, aPTT>40 seconds was seen in 4.4% vs 4.7% of cases and controls respectively and aPTT< 30 seconds in 22% of cases but not in controls (P =0.004).
    UNASSIGNED: Hypertension and diabetes mellitus are identified risk factors not traditionally associated with DVT. These in addition to a complete blood count and coagulation tests can be useful in stratifying patients for prophylaxis in our population and other similar communities.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Editorial
    暂无摘要。
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    住院期间和出院后的内科疾病患者的血栓预防仍未得到充分利用。临床决策支持(CDS)如果嵌入工作流程中,可以满足这一需求,在电子健康记录(EHR)之间可互换,并锚定在一个经过验证的模型上。
    本研究的目的是评估基于静脉血栓栓塞加D-二聚体静脉血栓栓塞模型的国际医学预防注册的通用EHR整合CDS工具的临床影响。
    这是一项从2020年12月21日至2022年1月21日对4家三级学术医院进行的整群随机试验。60岁以上有主要医疗疾病的住院患者符合资格。我们在入院和出院时嵌入了CDS。医院被随机分为干预组(CDS;n=2)和常规护理组(n=2)。主要结果是适当的血栓预防率。次要结果包括静脉,动脉,和总血栓栓塞,大出血,以及出院后30天的全因死亡率。
    排除后,对19,823例患者中的10,699例进行了分析。干预组工具采用率为77.8%。干预医院增加了适当的血栓预防,均为住院患者(80.1%vs72.5%,OR:1.52,95%CI:1.39-1.67)和出院时(13.6%vs7.5%,OR:1.93,95%CI:1.60-2.33)。静脉较少(2.7%vs3.3%,OR:0.80,95%CI:0.64-1.00),动脉(0.25%vs0.70%,OR:0.35,95%CI:0.19-0.67),和总血栓栓塞(2.9%vs4.0%,OR:0.71,95%CI:0.58-0.88)在干预医院。大出血很少见,组间没有差异。干预医院的死亡率更高(9.1%vs7.0%,OR:1.32,95%CI:1.15-1.53)。
    在内科住院患者中,嵌入EHR的CDS增加了适当的血栓预防并减少了血栓栓塞,而不增加大出血。干预医院的死亡率较高。
    UNASSIGNED: Thromboprophylaxis for medically ill patients during hospitalization and postdischarge remains underutilized. Clinical decision support (CDS) may address this need if embedded within workflow, interchangeable among electronic health records (EHRs), and anchored on a validated model.
    UNASSIGNED: The purpose of this study was to assess the clinical impact of a universal EHR-integrated CDS tool based on the International Medical Prevention Registry on Venous Thromboembolism plus D-Dimer venous thromboembolism model.
    UNASSIGNED: This was a cluster randomized trial of 4 tertiary academic hospitals from December 21, 2020 to January 21, 2022. Inpatients over age 60 with key medical illnesses were eligible. We embedded CDS at admission and discharge. Hospitals were randomized to intervention (CDS; n = 2) vs usual care (n = 2) groups. The primary outcome was rate of appropriate thromboprophylaxis. Secondary outcomes included venous, arterial, and total thromboembolism, major bleeding, and all-cause mortality through 30 days postdischarge.
    UNASSIGNED: After exclusions, 10,699 of 19,823 patients were analyzed. Intervention group tool adoption was 77.8%. Appropriate thromboprophylaxis was increased at intervention hospitals, both inpatient (80.1% vs 72.5%, OR: 1.52, 95% CI: 1.39-1.67) and at discharge (13.6% vs 7.5%, OR: 1.93, 95% CI: 1.60-2.33). There were fewer venous (2.7% vs 3.3%, OR: 0.80, 95% CI: 0.64-1.00), arterial (0.25% vs 0.70%, OR: 0.35, 95% CI: 0.19-0.67), and total thromboembolisms (2.9% vs 4.0%, OR: 0.71, 95% CI: 0.58-0.88) at intervention hospitals. Major bleeding was rare and did not differ between groups. Mortality was higher at intervention hospitals (9.1% vs 7.0%, OR: 1.32, 95% CI: 1.15-1.53).
    UNASSIGNED: EHR-embedded CDS increased appropriate thromboprophylaxis and reduced thromboembolism without increasing major bleeding in medically ill inpatients. Mortality was higher at intervention hospitals.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Editorial
    暂无摘要。
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    静脉血栓栓塞症(VTE)是妊娠期死亡的主要原因之一。最大的风险是存在VTE的病史或家族史,死产,剖宫产和选择性血栓形成倾向。适当的血栓预防有可能将高危妊娠患者的VTE风险降低60-70%。基于此,作者回顾了PubMed,WebofScience和Scopus数据库,以确定高危VTE孕妇血栓预防的可能性。此外,他们在具体情况下总结了它的管理,如剖宫产或神经轴阻滞。目前,低分子量肝素(LMWH)由于给药简便且不良事件发生率较低,是妊娠和产后抗凝血栓预防的首选药物.
    Venous thromboembolism (VTE) represents one of the leading causes of death during pregnancy. The greatest risk for it is the presence of medical or family history of VTE, stillbirth, cesarean section and selected thrombophilia. Appropriate thromboprophylaxis has the potential to decrease the risk of VTE in at-risk pregnant patients by 60-70%. Based on this, the authors reviewed the PubMed, Web of Science and Scopus databases to identify the possibilities of thromboprophylaxis in pregnant patients with a high risk of VTE. Moreover, they summarized its management in specific situations, such as cesarean delivery or neuraxial blockade. Currently, low-molecular-weight heparins (LMWH) are the preferred drugs for anticoagulant thromboprophylaxis in the course of pregnancy and postpartum due to easy administration and a lower rate of adverse events.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    背景:与动脉粥样硬化相关的急性血栓形成导致的心肌梗塞(MI)是全球死亡和残疾的主要原因。抗血小板和抗凝血药物是预防和治疗MI的标准疗法。然而,所有临床使用的药物都与出血并发症有关,这最终限制了它们在出血风险高的患者中的使用。我们开发了一种新的重组药物,targ-HSA-TAP,结合了活化血小板的靶向和特异性抑制以及抗凝。这种药物的设计和测试延长了循环半衰期,使独特的血栓预防没有出血并发症。方法:Targ-HSA-TAP结合了单链抗体(scFv),该抗体靶向活化血小板上的活化糖蛋白IIb/IIIa,人血清白蛋白(HSA)延长循环,和tick抗凝血肽(TAP)用于凝血FX抑制。非结合scFv用作非靶向对照(非targ-HSA-TAP)。使用急性血栓形成和心脏缺血再灌注(I/R)损伤的小鼠模型在体内研究了其功效。结果:我们的实验证实了targ-HSA-TAP对活化血小板的靶向特异性,并证明了有效预防血小板聚集和血栓形成。以及FXa体外抑制。与非targ-HSA-TAP和PBS对照处理的小鼠相比,小鼠皮下预防血栓施用targ-HSA-TAP可防止氯化铁损伤后颈动脉闭塞。通过比较targ-TAP和targ-HSA-TAP的治疗效果,我们证明了HSA融合在延长药物的半衰期和延长其治疗窗口方面带来的显着改善,直至给药后16小时。重要的是,与临床使用的抗凝血依诺肝素相比,targ-HSA-TAP并未延长尾部出血时间.此外,在小鼠心脏I/R损伤模型中,在损伤前10小时给予targ-HSA-TAP的小鼠表现出保留的心功能,具有明显更高的射血分数和缩短分数,与非targ-HSA-TAP和PBS对照组相比。高级应变分析显示,与对照组相比,targ-HSA-TAP治疗的小鼠的心肌变形减少,组织学证实梗塞面积减少。结论:HSA的纳入代表了设计用于血栓预防的靶向治疗剂的显着进步。我们的活化血小板靶向targ-HSA-TAP是一种高效的抗血栓药物,具有抗凝血和抗血小板作用,同时保持正常止血。targ-HSA-TAP的长半衰期为使用这种抗血栓药物提供了独特的机会,持久和更安全的抗血栓预防。如果发生MI,这种预防策略降低了血栓负担,并有效减少了心脏I/R损伤.
    Background: Myocardial infarction (MI) as a consequence of atherosclerosis-associated acute thrombosis is a leading cause of death and disability globally. Antiplatelet and anticoagulant drugs are standard therapies in preventing and treating MI. However, all clinically used drugs are associated with bleeding complications, which ultimately limits their use in patients with a high risk of bleeding. We have developed a new recombinant drug, targ-HSA-TAP, that combines targeting and specific inhibition of activated platelets as well as anticoagulation. This drug is designed and tested for a prolonged circulating half-life, enabling unique thromboprophylaxis without bleeding complications. Methods: Targ-HSA-TAP combines a single-chain antibody (scFv) that targets activated glycoprotein IIb/IIIa on activated platelets, human serum albumin (HSA) for prolonged circulation, and tick anticoagulant peptide (TAP) for coagulation FX inhibition. A non-binding scFv is employed as a non-targeting control (non-targ-HSA-TAP). Its efficacy was investigated in vivo using murine models of acute thrombosis and cardiac ischemia-reperfusion (I/R) injury. Results: Our experiments confirmed the targeting specificity of targ-HSA-TAP to activated platelets and demonstrated effective prevention of platelet aggregation and thrombus formation, as well as FXa inhibition in vitro. Thromboprophylactic administration of targ-HSA-TAP subcutaneously in mice prevented occlusion of the carotid artery after ferric chloride injury as compared to non-targ-HSA-TAP and PBS-control treated mice. By comparing the therapeutic outcomes between targ-TAP and targ-HSA-TAP, we demonstrate the significant improvements brought by the HSA fusion in extending the drug\'s half-life and enhancing its therapeutic window for up to 16 h post-administration. Importantly, tail bleeding time was not prolonged with targ-HSA-TAP in contrast to the clinically used anticoagulant enoxaparin. Furthermore, in a murine model of cardiac I/R injury, mice administered targ-HSA-TAP 10 h before injury demonstrated preserved cardiac function, with significantly higher ejection fraction and fractional shortening, as compared to the non-targ-HSA-TAP and PBS control groups. Advanced strain analysis revealed reduced myocardial deformation and histology confirmed a reduced infarct size in targ-HSA-TAP treated mice compared to control groups. Conclusion: The inclusion of HSA represents a significant advancement in the design of targeted therapeutic agents for thromboprophylaxis. Our activated platelet-targeted targ-HSA-TAP is a highly effective antithrombotic drug with both anticoagulant and antiplatelet effects while retaining normal hemostasis. The long half-life of targ-HSA-TAP provides the unique opportunity to use this antithrombotic drug for more effective, long-lasting and safer anti-thrombotic prophylaxis. In cases where MI occurs, this prophylactic strategy reduces thrombus burden and effectively reduces cardiac I/R injury.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    由于外阴癌(VC)的发病率低,对静脉血栓栓塞症(VTE)的发生率和预测因素了解甚少.我们检查了接受VC手术的患者中与VTE相关的发生率和危险因素。
    我们从国家外科质量改进计划数据库中纳入了接受VC手术的患者。使用当前程序术语代码捕获术后30天内的VTE。比较有和没有VTE的患者的基线人口统计学和临床特征。使用单变量和多变量调整的精确逻辑回归模型来估计危险因素与VTE之间关联的比值比(OR)和95%置信区间(CI)。
    我们从NSQIP数据库中确定了1414例接受VC手术的患者。总的来说,11例(0.8%)患者发生VTE。VTE的单变量预测因素包括手术类型[与单纯外阴切除术相比:仅根治性外阴切除术(OR=7.97,95%CI=1.44,无限)和根治性外阴切除术加单侧IFN(OR=15.98,95%CI=2.70,无限)],计划外再入院(OR=11.56,95%CI=2.74,46.38),手术部位深部感染(OR=16.05,95%CI=1.59-85.50),术前血小板增多(OR=6.53,95%CI=0.00,34.86)。在多变量调整模型中,较长的手术时间(≥72分钟OR=11.33,95%CI=1.58~499.03)和术前功能状态[与完全独立性相比:总依赖性(OR=53.88,95%CI=0.85,无穷大)和部分依赖性(OR=53.88,95%CI=0.85,无穷大)]与VTE相关.
    在接受根治性外阴切除术的VC患者队列中,VTE发生率低。手术类型,更长的手术时间,依赖功能状态,伤口破裂被确定为危险因素。我们的发现强调了某些患者预防性干预的机会。
    UNASSIGNED: Due to low incidence of vulvar cancer (VC), incidence and predictors for development of venous thromboembolism (VTE) are poorly understood. We examined incidence and risk factors associated with VTE in patients undergoing surgery for VC.
    UNASSIGNED: We included patients who underwent surgery for VC from the National Surgical Quality Improvement Program database. VTE within the 30-day postoperative period was captured with Current Procedural Terminology codes. Baseline demographics and clinical characteristics were compared between patients with and without VTE. Univariable and multivariable-adjusted exact logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between risk factors and VTE.
    UNASSIGNED: We identified 1414 patients undergoing procedures for VC from the NSQIP database. Overall, 11 (0.8 %) patients developed VTE. Univariable predictors of VTE included surgery type [compared with simple vulvectomy: radical vulvectomy only (OR = 7.97, 95 % CI = 1.44, infinity) and radical vulvectomy plus unilateral IFN (OR = 15.98, 95 % CI = 2.70, infinity)], unplanned readmission (OR = 11.56, 95 % CI = 2.74, 46.38), deep surgical site infection (OR = 16.05, 95 % CI = 1.59-85.50), and preoperative thrombocytosis (OR = 6.53, 95 % CI = 0.00, 34.86). In a multivariable-adjusted model, longer operative time (≥72 min OR = 11.33, 95 % CI = 1.58-499.03) and preoperative functional status [compared with complete independence: total dependence (OR = 53.88, 95 % CI = 0.85, infinity) and partial dependence (OR = 53.88, 95 % CI = 0.85, infinity)] were associated with VTE.
    UNASSIGNED: In this cohort of patients with VC undergoing radical vulvectomy, VTE incidence was low. Surgery type, longer operative time, dependent functional status, and wound disruption were identified as risk factors. Our findings highlight opportunities for prophylactic intervention in certain patients.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    背景:静脉血栓栓塞(VTE)是一种严重的,频繁,以及住院患者可预防的医疗并发症。尽管已经证明了预防(药理和/或机械)的功效,在国际和国家层面,对预防的依从性很差。
    目的:确定乌拉圭住院患者预防血栓药物的适应证和使用。
    方法:观察性,描述性,描述性横截面,进行了涉及31个全国性医疗机构的多中心研究。与入院相关的基线特征,有血栓预防指征的人口百分比,并评估接受药物血栓预防的患者百分比.使用内科患者的Padua评分确定VTE风险;手术患者的Caprini评分;皇家妇产科学院(RCOG)妊娠产后患者指南。
    结果:纳入1925例患者,代表乌拉圭26%的住院患者。71.9%的患者有发生VTE的风险。在所有有静脉血栓栓塞风险的患者中,58.6%接受药物血栓预防。未接受血栓预防的原因是16.1%的病例中的处方遗漏,15.9%和9.4%的患者因其他原因已经抗凝治疗.总的来说,只有68%的患者受到“保护”以预防VTE。70.1%的高危患者遵循主要血栓预防指南的建议。
    结论:尽管在坚持血栓预防指征方面取得了进展,不坚持仍然是一个问题,影响乌拉圭六分之一有静脉血栓栓塞风险的患者。
    BACKGROUND: Venous thromboembolism (VTE) is a serious, frequent, and preventable medical complication in hospitalized patients. Although the efficacy of prophylaxis (pharmacological and/or mechanical) has been demonstrated, compliance with prophylaxis is poor at international and national levels.
    OBJECTIVE: To determine the indication and use of pharmacological thromboprophylaxis in hospitalized patients in Uruguay.
    METHODS: An observational, descriptive, cross-sectional, multicentre study involving 31 nationwide healthcare facilities was conducted. Baseline characteristics associated with hospital admission, the percentage of the population with an indication for thromboprophylaxis, and the percentage of patients receiving pharmacological thromboprophylaxis were assessed. The VTE risk was determined using the Padua score for medical patients; the Caprini score for surgical patients; the Royal College of Obstetricians and Gynaecologists (RCOG) guidelines for pregnant-postpartum patients.
    RESULTS: 1925 patients were included, representing 26% of hospitalized patients in Uruguay. 71.9% of all patients were at risk of VTE. Of all patients at risk of VTE, 58.6% received pharmacological thromboprophylaxis. The reasons for not receiving thromboprophylaxis were prescribing omissions in 16.1% of cases, contraindication in 15.9% and 9.4% of patients were already anticoagulated for other reasons. Overall, just 68% of patients were \"protected\" against VTE. Recommendations of major thromboprophylaxis guidelines were followed in 70.1% of patients at risk.
    CONCLUSIONS: Despite the progress made in adherence to thromboprophylaxis indications, nonadherence remains a problem, affecting one in six patients at risk of VTE in Uruguay.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    目的:静脉血栓栓塞症(VTE)是肺癌开胸手术患者的严重并发症。然而,因为证据不足,目前尚无明确的指南,VTE的预防措施差异很大.这项全国范围的队列研究是一项比较研究,调查了外科部门的VTE风险,与常规使用低分子量肝素(LMWH)进行院内血栓预防相比,没有。
    方法:我们确定了2010-2021年在丹麦接受手术的所有非小细胞肺癌(NSCLC)患者。胸外科手术仅在四所大学医院进行。自2000年以来,三家医院实施了院内血栓预防作为标准护理,而第四家医院于2016年9月采用了这种做法。随访6个月,根据医院和研究期间评估VTE事件,使用逆概率的治疗加权方法。
    结果:我们确定了9,615例患者。在六个月的随访中,共观察到190例VTE事件,导致每100人年4.5个事件的加权率和2.2%的绝对风险.根据医院场所或医院内血栓预防的使用,没有明确的趋势,不使用血栓预防的医院风险为2.2%,而使用血栓预防的医院风险为1.7%-3.1%。
    结论:使用院内血栓预防并不影响NSCLC手术后VTE的风险,提示仅依靠院内血栓预防可能不足以减轻这些患者的VTE风险.进一步的研究是必要的,以调查延长血栓预防在降低选定的NSCLC手术患者的VTE风险的潜在益处。
    OBJECTIVE: Venous thromboembolic event (VTE) is a severe complication in patients with lung cancer undergoing thoracic surgery. Nevertheless, because of insufficient evidence, there are no clear guidelines, and VTE prophylaxis practices vary widely. This nationwide cohort study was a comparative study investigating VTE risk in surgical departments that routinely administered in-hospital thromboprophylaxis with low-molecular-weight heparin compared to those that did not.
    METHODS: We identified all patients with non-small-cell lung cancer (NSCLC) who underwent surgery in Denmark during 2010-2021. Thoracic surgery was exclusively performed in the 4 university hospitals. Three hospitals implemented in-hospital thromboprophylaxis as standard care since 2000, while the fourth adopted this practice in September 2016. VTE events were assessed at 6-month follow-up according to hospital and study period, using an inverse probability of treatment weighting approach.
    RESULTS: We identified 9615 patients. During 6-month follow-up, a total of 190 VTE events were observed, resulting in a weighted rate of 4.5 events per 100 person-years and an absolute risk of 2.2%. There was no clear trend according to hospital site or use of in-hospital thromboprophylaxis with a 2.2% risk in the hospital not using thromboprophylaxis compared to 1.7-3.1% in those that did.
    CONCLUSIONS: Use of in-hospital thromboprophylaxis did not affect the risk of VTE after surgery for NSCLC, suggesting that relying solely on in-hospital thromboprophylaxis may be insufficient to mitigate VTE risk in these patients. Further research is warranted to investigate the potential benefits of extended thromboprophylaxis in reducing VTE risk in selected NSCLC surgical patients.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    背景:激肽释放酶-激肽系统是参与血压维持的关键调节级联,止血,炎症和肾功能。目前,批准的药物仍然限于罕见疾病遗传性血管性水肿。然而,越来越多的有希望的候选药物用于进一步适应症,这表明人们对该系统的兴趣越来越大。
    方法:为了提供当前药物开发的概述,我们在2023年3月至12月进行了两阶段文献检索,以确定激肽释放酶-激肽系统中具有靶点的候选药物.首先,使用PubMed和Clinicaltrials.gov鉴定候选药物。第二,在PubMed中搜索了这些化合物的最新出版物/结果,Clinicaltrials.gov和谷歌学者。这些发现是按目标分类的,发展阶段,和预期的指示。
    结果:搜索确定了68种药物,其中10个被批准,25个正在临床开发中,和33在临床前发展。三个研究最多的适应症包括糖尿病视网膜病变,血栓预防和遗传性血管性水肿。后者仍然是大多数接近监管部门批准的候选药物的适应症(4个中的3个)。对于新出现的适应症,临床开发中很有前景的新候选药物是用于预防血栓的ixodesricinus接触相抑制剂和用于治疗糖尿病性黄斑水肿的RZ402和THR-149(均为2期).
    结论:靶向激肽释放酶-激肽系统的治疗效果不再局限于治疗遗传性血管性水肿。正在进行的对其他疾病的研究证明了针对激肽释放酶激肽系统的治疗干预的潜力,并将在未来为患者提供进一步的治疗选择。
    BACKGROUND: The kallikrein-kinin system is a key regulatory cascade involved in blood pressure maintenance, hemostasis, inflammation and renal function. Currently, approved drugs remain limited to the rare disease hereditary angioedema. However, growing interest in this system is indicated by an increasing number of promising drug candidates for further indications.
    METHODS: To provide an overview of current drug development, a two-stage literature search was conducted between March and December 2023 to identify drug candidates with targets in the kallikrein-kinin system. First, drug candidates were identified using PubMed and Clinicaltrials.gov. Second, the latest publications/results for these compounds were searched in PubMed, Clinicaltrials.gov and Google Scholar. The findings were categorized by target, stage of development, and intended indication.
    RESULTS: The search identified 68 drugs, of which 10 are approved, 25 are in clinical development, and 33 in preclinical development. The three most studied indications included diabetic retinopathy, thromboprophylaxis and hereditary angioedema. The latter is still an indication for most of the drug candidates close to regulatory approval (3 out of 4). For the emerging indications, promising new drug candidates in clinical development are ixodes ricinus-contact phase inhibitor for thromboprophylaxis and RZ402 and THR-149 for the treatment of diabetic macular edema (all phase 2).
    CONCLUSIONS: The therapeutic impact of targeting the kallikrein-kinin system is no longer limited to the treatment of hereditary angioedema. Ongoing research on other diseases demonstrates the potential of therapeutic interventions targeting the kallikrein-kinin system and will provide further treatment options for patients in the future.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

公众号