Targeted nanotherapeutics in the prophylaxis and treatment of thrombosis

Nanomedicine ◽  
2021 ◽  
Author(s):  
Vishnu Priya ◽  
Matte Kasi Viswanadh ◽  
Abhishesh Kumar Mehata ◽  
Dharmendra Jain ◽  
Sanjeev K Singh ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
Intravenous Administration ◽  
Cerebral Hemorrhage ◽  
Polymeric Nanoparticles ◽  
Local Effect ◽  
Bleeding Complications ◽  
Systemic Availability ◽  
Severe Bleeding ◽  
Theranostic Applications

Currently available anti-thrombotic therapy for the prophylaxis and treatment of arterial and venous thrombosis includes intravenous administration of anti-thrombotic drugs which lead to severe bleeding risks such as cerebral hemorrhage and stroke. Targeting approaches that utilize nanosystems to reach the thrombus sites are emerging to increase the local effect of anti-thrombotic drugs, as well as to decrease these severe bleeding complications by diminishing the systemic availability of these drugs. This review emphasizes the emerging targeted nanomedicines (liposomes, micelles, polymeric nanoparticles, material bases nanoparticles and other biological vectors) for the prophylaxis and treatment of thrombotic events as well as multifunctional nanomedicines for theranostic applications. Nanomedicine offers a promising platform for a smart, safe, and effective approach for the management of thrombosis.

Anticoagulation in addition to dual antiplatelet therapy has no impact on long-term follow-up after endovascular treatment of (sub)acute lower limb ischemia

VASA ◽  
2019 ◽  
Vol 48 (4) ◽  
pp. 321-329
Author(s):  
Mariya Kronlage ◽  
Erwin Blessing ◽  
Oliver J. Müller ◽  
Britta Heilmeier ◽  
Hugo A. Katus ◽  
...  
Keyword(s):  
Endovascular Treatment ◽  
Antiplatelet Therapy ◽  
Dual Antiplatelet Therapy ◽  
Limb Ischemia ◽  
Bleeding Complications ◽  
Severe Bleeding ◽  
Short Term ◽  
Long Term Follow Up

Summary. Background: To assess the impact of short- vs. long-term anticoagulation in addition to standard dual antiplatelet therapy (DAPT) upon endovascular treatment of (sub)acute thrombembolic occlusions of the lower extremity. Patient and methods: Retrospective analysis was conducted on 202 patients with a thrombembolic occlusion of lower extremities, followed by crirical limb ischemia that received endovascular treatment including thrombolysis, mechanical thrombectomy, or a combination of both between 2006 and 2015 at a single center. Following antithrombotic regimes were compared: 1) dual antiplatelet therapy, DAPT for 4 weeks (aspirin 100 mg/d and clopidogrel 75 mg/d) upon intervention, followed by a lifelong single antiplatelet therapy; 2) DAPT plus short term anticoagulation for 4 weeks, followed by a lifelong single antiplatelet therapy; 3) DAPT plus long term anticoagulation for > 4 weeks, followed by a lifelong anticoagulation. Results: Endovascular treatment was associated with high immediate revascularization (> 98 %), as well as overall and amputation-free survival rates (> 85 %), independent from the chosen anticoagulation regime in a two-year follow up, p > 0.05. Anticoagulation in addition to standard antiplatelet therapy had no significant effect on patency or freedom from target lesion revascularization (TLR) 24 months upon index procedure for both thrombotic and embolic occlusions. Severe bleeding complications occurred more often in the long-term anticoagulation group (9.3 % vs. 5.6 % (short-term group) and 6.5 % (DAPT group), p > 0.05). Conclusions: Our observational study demonstrates that the choice of an antithrombotic regime had no impact on the long-term follow-up after endovascular treatment of acute thrombembolic limb ischemia whereas prolonged anticoagulation was associated with a nominal increase in severe bleeding complications.

Heparin Assays and Bleeding Complications in Treatment of Deep Venous Thrombosis with Particular Reference to Retroperitoneal Bleeding

1985 ◽  
Vol 53 (02) ◽  
pp. 278-281 ◽  
Author(s):  
H Asbjørn Holm ◽  
Ulrich Abildgaard ◽  
Sigmund Kalvenes
Keyword(s):  
Venous Thrombosis ◽  
Deep Venous Thrombosis ◽  
Major Bleeding ◽  
Bleeding Complications ◽  
Minor Bleeding ◽  
Thrombin Time ◽  
Heparin Infusion ◽  
Retroperitoneal Bleeding ◽  
Heparin Activity ◽  
The Difference

SummaryBleeding complications occurred in 30 (11%) out of 280 patients who received continuous heparin infusion for deep venous thrombosis (DVT). 22 (8%) had minor while 8 patients (3%) had major bleeding complications (1 intrathoracic [fatal], 2 gastrointestinal and 5 retroperitoneal). Heparin activity, in daily drawn blood samples, was determined by four assays (chromogenic substrate [CS] assay, activated partial thromboplastin time [APTT], thrombin time with citrated plasma [CiTT] and thrombin time with recalcified plasma [CaTT]). The differences in median heparin activity between patients with minor bleeding and patients with no bleeding did not reach significance for any of the tests. In patients with major bleeding, the differences were significant with the CS (p = .011) and the CaTT (p = .030) assays. Patients with retroperitoneal bleeding had significantly increased median activity judged by all four assays: CS (p = .002), CaTT (p = .003), APTT (p = .010), CiTT (p = .029). The difference was most pronounced after four days of heparin treatment, but there was a considerable overlap with patients without bleeding.

scholarly journals Topical vs. intravenous administration of tranexamic acid in knee arthroplasty and prevalence of deep venous thrombosis: a randomized clinical trial

2016 ◽  
Vol 15 (2) ◽  
pp. 120-125 ◽  
Author(s):  
Ari Zekcer ◽  
Ricardo Del Priori ◽  
Clauber Tieppo ◽  
Ricardo Soares da Silva ◽  
Nilson Roberto Severino
Keyword(s):  
Total Knee Arthroplasty ◽  
Tranexamic Acid ◽  
Venous Thrombosis ◽  
Deep Venous Thrombosis ◽  
Intravenous Administration ◽  
Knee Arthroplasty ◽  
Duplex Ultrasound ◽  
Control Group ◽  
Perioperative Bleeding ◽  
Total Knee

Abstract Background Tranexamic acid (TXA) is widely used in orthopedic surgery to reduce perioperative bleeding. Since TXA inhibits fibrinolysis, there is concern that it may increase the risk of thromboembolic events. Objectives To verify the prevalence of deep venous thrombosis (DVT) in patients receiving TXA during total knee arthroplasty and to compare topical with intravenous administration of the drug. Methods All patients admitted for total knee arthroplasty due to primary arthrosis between June and November of 2014 were recruited consecutively. Thirty patients were randomized to a “topical group” (1.5 g TXA diluted in 50ml saline sprayed over the area operated, before tourniquet release), 30 to an “intravenous group” (20mg/kg TXA in 100 ml of saline, given at the same time as anesthesia), and 30 to a control group (100 ml of saline, given at the same time as anesthesia). All patients had duplex ultrasound scans of the legs on the 15th postoperative day. Results Deep venous thrombosis events occurred in five of the 90 patients operated (one out of 30 in the topical group [3.3%], four out of 30 in the control group [13.3%], and zero in the intravenous group). All were confirmed by duplex ultrasound scans and all were asymptomatic. Prevalence rates of DVT were similar between groups (p = 0.112 for control vs. intravenous; p = 0.353 for control vs. topical; and p =1.000 for intravenous vs. topical, according to two-sided exact tests). Conclusions Both topical and intravenous administration of TXA are safe with regard to occurrence of DVT, since the number of DVT cases in patients given TXA was not different to the number in those given placebo.

Monotherapy Anticoagulation to Expedite Home Treatment of Patients Diagnosed With Venous Thromboembolism in the Emergency Department: A Pragmatic Effectiveness Trial

2021 ◽  
Author(s):  
Jeffrey A. Kline ◽  
David H. Adler ◽  
Naomi Alanis ◽  
Joseph R. Bledsoe ◽  
Daniel M. Courtney ◽  
...  
Keyword(s):  
Emergency Department ◽  
Venous Thromboembolism ◽  
Venous Thrombosis ◽  
The United States ◽  
Home Treatment ◽  
Low Risk ◽  
Severe Bleeding ◽  
Effectiveness Trial ◽  
Risk Of Death ◽  
Recurrent Vte

BACKGROUND: The objective was to test if low-risk emergency department patients with vitamin K antagonist (venous thromboembolism [VTE]; including venous thrombosis and pulmonary embolism [PE]) can be safely and effectively treated at home with direct acting oral (monotherapy) anticoagulation in a large-scale, real-world pragmatic effectiveness trial. METHODS: This was a single-arm trial, conducted from 2016 to 2019 in accordance with the Standards for Reporting Implementation Studies guideline in 33 emergency departments in the United States. Participants had newly diagnosed VTE with low risk of death based upon either the modified Hestia criteria, or physician judgment plus the simplified PE severity index score of zero, together with nonhigh bleeding risk were eligible. Patients had to be discharged within 24 hours of triage and treated with either apixaban or rivaroxaban. Effectiveness was defined by the primary efficacy and safety outcomes, image-proven recurrent VTE and bleeding requiring hospitalization >24 hours, respectively, with an upper limit of the 95% CI for the 30-day frequency of VTE recurrence below 2.0% for both outcomes. RESULTS: We enrolled 1421 patients with complete outcomes data, including 903 with venous thrombosis and 518 with PE. The recurrent VTE requiring hospitalization occurred in 14/1421 (1.0% [95% CI, 0.5%–1.7%]), and bleeding requiring hospitalization occurred in 12/1421 (0.8% [0.4%–1.5%). The rate of severe bleeding using International Society for Thrombosis and Haemostasis criteria was 2/1421 (0.1% [0%–0.5%]). No patient died, and serious adverse events occurred in 2.5% of venous thrombosis patients and 2.3% of patients with PE. Medication nonadherence was reported by patients in 8.0% (6.6%–9.5%) and was associated with a risk ratio of 6.0 (2.3–15.2) for VTE recurrence. Among all patients diagnosed with VTE in the emergency department during the period of study, 18% of venous thrombosis patients and 10% of patients with PE were enrolled. CONCLUSIONS: Monotherapy treatment of low-risk patients with venous thrombosis or PE in the emergency department setting produced a low rate of bleeding and VTE recurrence, but may be underused. Patients with venous thrombosis and PE should undergo risk-stratification before home treatment. Improved patient adherence may reduce rate of recurrent VTE. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03404635

Subcutaneous Heparin in the Prevention of Venous Thrombosis After Elective Aortic Bifurcation Graft Surgery

1979 ◽  
Author(s):  
J.J.F. Belch ◽  
G.D.O. Lowe ◽  
J.G. Pollock ◽  
C.D. Forbes ◽  
C.R.M. Prentice
Keyword(s):  
Venous Thrombosis ◽  
Deep Venous Thrombosis ◽  
Controlled Trial ◽  
Bleeding Complications ◽  
Aortic Bifurcation ◽  
Double Blind ◽  
Risk Of Bleeding ◽  
Subcutaneous Heparin ◽  
Calcium Heparin ◽  
Intravenous Sodium

In a randomised double-blind controlled trial 24 patients undergoing elective aortic bifurcation graft surgery received subcutaneous calcium heparin (2, 500 u preoperatively then 5,000 u 12 hourly or 7 days) and 25 control patients received saline injections. All patients received the routine dose of intravenous sodium heparin intraoperatively. The trial was terminated because of excess bleeding complications in patients on subcutaneous heparin (8 vs. 1, p<0.05). Deep venous thrombosis was diagnosed by 125I-fibrinogen scanning in 8 control patients and 3 patients on heparin (p>0.05). In this group of patients the risk of bleeding due to subcutaneous heparin appeared to outweigh the benefit of thrombotic prophylaxis.

Individualized antithrombotic therapy in high risk patients after coronary stenting. A double-edged sword between thrombosis and bleeding

2008 ◽  
Vol 99 (03) ◽  
pp. 487-493 ◽  
Author(s):  
Tobias Geisler ◽  
Meinrad Gawaz ◽  
Andreas May
Keyword(s):  
High Risk ◽  
Antiplatelet Therapy ◽  
Stent Thrombosis ◽  
Antithrombotic Therapy ◽  
Bleeding Complications ◽  
Severe Bleeding ◽  
High Risk Patients ◽  
Coronary Stent Implantation ◽  
Risk Patients ◽  
The Individual

SummaryDual antiplatelet therapy with aspirin and clopidogrel is currently the standard therapy after coronary stent implantation to prevent a life-threatening stent thrombosis. However, a variety of procedural and individual factors contribute to the individual patient risk and have to be taken into account to allow for an individual recommendation for both the duration and intensity of the antiplatelet therapy. Obviously, the benefit of the prevention of stent thrombosis by antithrombotic therapy has to outweigh the risk of severe bleeding complications. Depending on the individual clinical situation and procedural characteristics (stent type, length, angiographic result etc.), the recommended duration of the combined antiplatelet therapy currently varies from four weeks to at least one year.These recommendations are mainly based on large, prospective, randomized trials and evidence-based guidelines. However, in a subgroup of high-risk patients there is insufficient evidence for the benefit of conventional dual antiplatelet regimen.These include i) patients with an indication for anticoagulation, ii) patients with urgent need for an operation requiring a perioperative withholding of antiplatelet therapy, as well as iii) clopidogrel low responders.This review aims to provide a stratification to define patient collectives who may benefit from more individualized antithrombotic regimens on behalf of currently available literature and guidelines.

Bleeding and haemostasis disorders

2018 ◽  
Author(s):  
Pier Mannuccio Mannucci ◽  
Maddalena Lettino
Keyword(s):  
Artery Bypass ◽  
Coronary Intervention ◽  
Adverse Outcomes ◽  
High Rate ◽  
Bleeding Complications ◽  
Severe Bleeding ◽  
Preventive Strategy ◽  
Stent Deployment ◽  
Coronary Syndrome ◽  
Coronary Syndromes

The main cause of haemostasis defects and related bleeding complications in patients with acute coronary syndromes admitted to the intensive cardiac care unit is the use of multiple antithrombotic drugs, alone or concomitantly with invasive procedures such as percutaneous coronary intervention with stent deployment and coronary artery bypass surgery. These drugs, that act upon several components of haemostasis (platelet function, coagulation, fibrinolysis), are associated with bleeding complications, particularly in elderly patients (more so in women than in men), those who are underweight, and those with comorbid conditions such as renal and liver insufficiency and diabetes. The identification of patients at higher risk of bleeding is the most important preventive strategy. Red cell and platelet transfusions, which may become necessary in patients with severe bleeding, should be used with caution, because transfused patients with acute coronary syndrome have a high rate of adverse outcomes (death, myocardial infarction, and stroke).

Case 17: Severe bleeding complications, lymphocytosis and leukoerythroblastosis – disseminated intravascular coagulation in a patient with metastasizing carcinoma of the prostate and chronic lymphocytic leukemia

1999 ◽  
Vol 56 (9) ◽  
pp. 533-536 ◽  
Author(s):  
Solenthaler ◽  
Lämmle
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Disseminated Intravascular Coagulation ◽  
Lymphocytic Leukemia ◽  
Bleeding Complications ◽  
Severe Bleeding ◽  
Disseminierte Intravasale Gerinnung ◽  
Intravascular Coagulation ◽  
Carcinoma Of The Prostate

Blutungskomplikationen bei chronischer lymphatischer Leukämie (CLL) stehen meist in Zusammenhang mit einer Thrombozytopenie, bedingt entweder durch eine direkte Verdrängung der Megakaryopoese bei diffuser Knochenmarksinfiltration oder durch einen vermehrten peripheren Verbrauch im Rahmen einer (sekundären) Immunthrombozytopenie. Eine disseminierte intravasale Gerinnung (DIC) gehört nicht zum Spektrum hämatologischer Komplikationen einer CLL. Das hier geschilderte Fallbeispiel eines Patienten mit schweren Blutungskomplikationen, labormäßigen Zeichen einer DIC und neu entdeckter CLL ließ eine Ursache der DIC vermissen. Das leukoerythroblastäre Blutbild lieferte den Schlüssel zur Diagnose eines metastasierenden Prostatakarzinoms, welches durch die Knochenmarksbiopsie bestätigt wurde und als Trigger für die DIC verantwortlich war.

Bleeding complications in venous thrombosis patients on well-managed warfarin

2015 ◽  
Vol 41 (2) ◽  
pp. 351-358 ◽  
Author(s):  
Per Sandén ◽  
Henrik Renlund ◽  
Peter J. Svensson ◽  
Anders Själander
Keyword(s):  
Venous Thrombosis ◽  
Bleeding Complications
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