Treatment Of Acute Deep Vein Thrombosis Research Articles

Diagnosis and treatment of deep vein thrombosis of the lower and upper limbs. 2024 recommendations of the venous thromboembolism group of the Spanish Society of Internal Medicine

Deep vein thrombosis (DVT) of the limbs is a common disease and causes significant morbidity and mortality. It is frequently the prelude to pulmonary embolism (PE), it can recur in 30% of patients and in 25–40% of cases they can develop post-thrombotic syndrome (PTS), with a significant impact in functional status and quality of life. This document contains the recommendations on the diagnosis and treatment of acute DVT from the Thromboembolic Disease group of the Spanish Society of Internal Medicine (SEMI).PE and thrombosis of unusual venous territories (cerebral, renal, mesenteric, superficial, etc.) are outside its scope, as well as thrombosis associated with catheter and thrombosis associated with cancer, which due to their peculiarities will be the subject of other positioning documents of the Thromboembolic Disease group of the Spanish Society of Internal Medicine (SEMI).

Targeted microbubbles combined with low-power focused ultrasound promote the thrombolysis of acute deep vein thrombosis.

Introduction: The side effects of conventional therapy for acute deep vein thrombosis (DVT) are severe, with inflammatory reactions playing a pivotal role. It is particularly important to explore new ways of treatment thrombosis by targeting inflammatory factors. Methods: A targeted microbubble contrast agent was prepared using the biotin-avidin method. The 40 DVT model rabbits were established and divided into four groups according to different treatment regimens. The four coagulation indexes, TNF-α, and D-dimer content of experimental animals were measured before modeling and before and after treatment, and the thrombolysis was assessed by ultrasound imaging. Finally, the results were verified by pathology. Results and Discussion: Fluorescence microscopy verified the successful preparation of targeted microbubbles. Among the groups, PT, APTT, and TT in Group II-IV were longer than those in Group I (all p < 0.05). FIB and D-dimer content were lower than those in Group I (all p < 0.05), and TNF-α content in Group IV was lower than that in Group I-III (all p < 0.05). Pairwise comparison before modeling and before treatment and after treatment showed that, after treatment, the PT, APTT, and TT in Group II-IV were longer than those before modeling (all p < 0.05). The contents of FIB and D-dimer were lower than those before modeling and before treatment (all p < 0.05). The content of TNF-α decreased significantly only in Group IV, but increased in the other three groups. Targeted microbubbles combined with Low-power focused ultrasound can reduce inflammation, significantly promote thrombolysis, and provide new ideas and methods for the diagnosis and treatment of acute DVT.

New perspectives for prevention of the post-thrombotic syndrome

While on conventional anticoagulation, up to 50% of patients with one or more episodes of proximal deep vein thrombosis (DVT) can develop post-thrombotic (PTS) manifestations. The potential strategies for PTS prevention are the treatment of acute DVT with catheter-directed thrombolysis (CDT), the use of elastic compression stockings (ECS) and that of the direct oral anticoagulants (DOAC) in place of vitamin K antagonists (VKA) for the initial and long-term treatment of DVT. Based on the results of three randomized clinical trials, CDT cannot be recommended on a routine basis because of its invasiveness, the associated risk of major bleedings and the uncertainty about its efficacy. According to the results of a placebo-controlled randomized clinical trial, ECS are no longer recommended for PTS prevention on a routine basis. However, based on the results of a recent subanalysis of a prospective cohort study, patients with residual vein thrombosis and/or popliteal valve reflux at three months are likely to benefit from ECS for at least six months. Finally, following the demonstration that the inadequacy of VKA therapy plays a key role in the PTS development, several retrospective and prospective studies have shown that the use of DOACs for the initial and long-term treatment of DVT in place of VKAs reduces the risk of PTS by approximately 50%. In conclusion, the availability of DOACs and the potential of ECS in selected patients with proximal DVT are expected to play a key role for decreasing the rate and the severity of PTS in the forthcoming years.

Assessment of Quality of Life Between Patients Undergoing Pharmacomechanical Catheter-Directed Thrombolysis Versus Conservative Management with Iliofemoro-Popliteal Deep-Vein Thrombosis

Background: Pharmacomechanical catheter-directed thrombolysis (PCDT) has revolutionized the treatment of acute deep-vein thrombosis (DVT). Assessment and comparison of quality of life (QOL) in patients treated with anticoagulation alone and PCDT need to be elaborated more in the context of better management of patients. The objective of this study was to compare and assess QOL using health-related QOL (HRQOL) which includes short form-36 (SF-36) and VIENES QOL/sym scoring systems in anticoagulation alone group and patients treated with PCDT. Methods: There were 130 consecutive patients presenting to our department with acute iliofemoro-popliteal DVT (IFPDVT) with &lt;2 weeks duration treated between April 2018 and April 2019 were included in the study. Sixty-five patients received anticoagulation alone and the other 65 patients received PCDT along with anticoagulation. Patients were assessed at baseline, the 1st month, and the 6th month in terms of QOL, deep venous patency (DVP), and deep venous reflux (DVR). Results: There was a statistically significant difference between the two groups in terms of QOL at 1st and 6 months. Mean physical component score and mental component score were statistically significantly better in PCDT than the conservative group at 1 and 6 months, respectively (P = 0.001). Mean venous insufficiency epidemiological and economic study (VEINES) QOL and VEINES SYM scores were significantly better in PCDT group than conservative group at 1 and 6 months, respectively (P = 0.001). Conclusion: QOL, DVP, and DVR are significantly better when PCDT is offered as an initial option when compared to anticoagulation alone. HRQOL (SF 36 and VEINESQOL/SYM score) should be considered as an outcome measure in clinical studies on patients with IFPDVT along with other comparison parameters with respect to QOL. However, long-term follow-up is required to establish the superiority of PCDT in IFPDVT patients.

Abstract 16892: Impact of Catheter-Directed Thrombolysis on Hospital Readmission Rates in Patients With Acute Proximal and Caval Deep Vein Thrombosis

Objective: To evaluate the readmission rate and identify the predictors of rehospitalization in patients with acute proximal and caval DVT. Background: Acute Deep Vein Thrombosis (DVT) is a significant cause of mortality and morbidity in the US that affects more than 600,000 patients each year. Catheter-directed thrombolysis (CDT) is a minimally invasive treatment option that improve acute symptoms as well as quality of life of patients with acute DVT. Methods: Patients with index hospitalization for acute proximal and caval DVT between 2016 and 2017 in the U.S. Nationwide Readmission Database were evaluated for the rates, predictors, and costs of unplanned readmission at 30 days. We used Cox proportional hazard model to determine predictors of 30 days readmissions. Results: This analysis included 58,306 patients (age&gt;=18 years) with index hospitalization for acute proximal and caval DVT; 8589 (14.7%) were readmitted within 30 days. The significant predictors for 30 day unplanned readmission were Malignancy (HR 1.60, 1.41-1.81), Charlson comorbidity index &gt; 3 (HR 1.43, 1.30-1.57), Insurance Medicare vs Private(HR 1.39, 1.25-1.57), Length of stay more than 2 days (HR 1.34, 1.24-1.45), and Acute Kidney Injury (HR 1.28, 1.17-1.40), COPD (HR 1.25, 1.13-1.38), Age (HR 0.77,0.70-0.85), Catheter directed thrombolysis ( HR 0.83, 0.76-0.90), and Acute Pulmonary Embolism(HR 0.83, 0.76-0.90)(Figure1). The cost of readmission was higher than index hospitalization ($ 56733 vs $ 47396). Conclusion: The 30 days readmission rate continue to be high in patients with acute DVT. Patient’s characteristics and comorbid conditions are predictors of readmission. Use of Catheter directed thrombolysis for treatment of acute DVT predicts reduced readmission risk.

Post-thrombotic syndrome in patients treated with rivaroxaban or enoxaparin/vitamin K antagonists for acute deep-vein thrombosis. A post-hoc analysis.

Post-thrombotic syndrome (PTS) is a common complication of deep-vein thrombosis (DVT). Poor quality treatment with vitamin K antagonists (VKA) is a risk factor for PTS. We hypothesised that treatment with the direct oral anticoagulant (DOAC) rivaroxaban may lower PTS incidence as compared to enoxaparin/VKA, as DOACs have a more stable pharmacologic profile than VKA. We performed a post-hoc subgroup analysis of the Einstein DVT trial (n=3449). Kaplan-Meier survival analysis was performed to compare the cumulative incidence of PTS between the rivaroxaban and enoxaparin/VKA groups. Hazard ratios (HR) and 95 % confidence intervals (CI) were calculated using Cox proportional hazards models. We included 336 patients with a mean age of 58 ± 16 years and a median follow-up after index DVT of 57 months (interquartile range 48-64). Of these, 162 (48 %) had been treated with rivaroxaban and 174 (52 %) with enoxaparin/VKA. The cumulative PTS incidence at 60 months follow-up was 29 % in the rivaroxaban group and 40 % in the enoxaparin/VKA group. After adjusting for age, gender, body mass index, previous VTE, ipsilateral recurrent DVT, extent of DVT, idiopathic DVT, duration of anticoagulant treatment, compliance to assigned study medication, elastic compression stocking use and active malignancy, the HR of PTS development for rivaroxaban was 0.76 (95 % CI: 0.51-1.13). In conclusion, treatment of acute DVT with rivaroxaban was associated with a numerically lower but statistically non-significant risk of PTS compared to enoxaparin/VKA treatment. The potential effect on reducing PTS deserves evaluation in a large randomised trial.

Bemiparin: a guide to its use in thromboprophylaxis and the treatment of deep vein thrombosis

Subcutaneous bemiparin, a second-generation low-molecular-weight heparin, is an effective and well tolerated option for the prevention of venous thromboembolism (VTE) in surgical and medical patients, the treatment of established deep vein thrombosis (DVT), and the secondary prevention of VTE in at-risk patients following acute treatment of DVT. It is also effective in the prevention of clotting in the extracorporeal circuit during haemodialysis.

Steps toward simplifying the treatment of pulmonary embolism

SUMMARY: Therapeutic strategies for most patients with pulmonary embolism (PE) include the administration of low-molecular-weight heparin, fondaparinux or unfractionated heparin, followed by vitamin K antagonists. Over the last few years, research has focused on the development of new oral anticoagulant drugs that could overcome some of the main limitations of available parenteral anticoagulants or vitamin K antagonists. These drugs (e.g., dabigatran, rivaroxaban, apixaban or edoxaban) have been compared with standard treatment in a number of Phase III clinical trials in different clinical settings, including the treatment of acute deep-vein thrombosis and PE. The results of the completed trials with dabigatran and rivaroxaban suggest that both compounds can at least be as effective and safe as the standard treatment in these patients. Thus, there is now the possibility of greatly simplifying the treatment of PE patients with drugs that are administered orally and do not require laboratory monitoring. Thi...

Management strategies for acute proximal deep vein thrombosis: a Delphi consensus

Deep vein thrombosis (DVT) is a leading cause of cardiovascular disease. We tested the hypothesis that there is a consensus regarding the treatment of acute DVT among clinicians experienced in DVT management. A Delphi consensus approach was used to gather expert opinion regarding attitudes towards the treatment of acute proximal DVT and management of specific cases. Strength of preference for various treatment strategies across a number of case scenarios was quantified. Univariate and multivariate analyses were performed to quantify the influence of various factors on treatment modality selected. Respondents strongly agreed that DVT was a significant health problem and that further research was a priority. A multidisciplinary team approach with access to various treatment strategies was encouraged. Pregnancy and recent surgery independently predicted preference for medical treatment, whereas proximal DVT and May-Thurner syndrome were associated with interventional strategies. Acute proximal DVT is a significant health problem for which a variety of treatments are available. This study demonstrates that no consensus exists as to the optimum strategy for certain patient groups. Trends in opinion based on local experience and case-series exist, but the results of ongoing randomized trials will ultimately inform best practice.

Rivaroxaban

Rivaroxaban is an oral, direct Factor Xa inhibitor, which is at an advanced stage of clinical development for prevention and treatment of thromboembolic disorders. Two phase II studies, ODIXa-DVT and EINSTEIN DVT, assessed the efficacy and safety of oral rivaroxaban (once daily or twice daily) for treatment of acute deep-vein thrombosis (DVT). Population pharmacokinetic and pharmacodynamic analyses of rivaroxaban in patients in these two phase II studies were conducted to characterize the pharmacokinetics/pharmacodynamics of rivaroxaban and the relationship between important patient covariates and model parameters. Exposure simulations in patients with atrial fibrillation (AF) were also performed in order to predict the exposure of rivaroxaban, using modified demographic data reflecting the characteristics of a typical AF population. A population pharmacokinetic model was developed using plasma samples from these patients. Various simulations were conducted to explore the pharmacokinetics of rivaroxaban in patients with DVT and to predict exposure in those with AF. Correlations between plasma rivaroxaban concentrations and the prothrombin time, Factor Xa activity, HepTest® and activated partial thromboplastin time were also described. The pharmacokinetics of rivaroxaban in patients with DVT were found to be consistent and predictable across all doses studied. The area under the plasma concentration-time curve (AUC) increased dose dependently. The same total daily doses given once daily achieved higher maximum plasma concentration (C(max)) values (∼20%) and lower trough (minimum) plasma concentration (C(trough)) values (∼60%) than when given twice daily; however, the 5th-95th percentile ranges for these parameters overlapped. Rivaroxaban clearance was moderately influenced by age and renal function, and the volume of distribution was influenced by age, body weight and sex; the effects were within the observed interindividual variability. Simulations in virtual patient populations with AF showed that a rivaroxaban dose of 15 mg once daily in patients with creatinine clearance of 30-49 mL/min would achieve AUC and C(max) values similar to those observed with 20 mg once daily in patients with normal renal function. The prothrombin time correlated almost linearly with plasma rivaroxaban concentrations (≤500 μg/L). Population analyses of phase II clinical data indicated that the pharmacokinetics and pharmacodynamics of all rivaroxaban doses were predictable and were affected by expected demographic factors in patients with acute DVT.

Differentiation of parenteral anticoagulants in the prevention and treatment of venous thromboembolism.

BackgroundThe prevention of venous thromboembolism has been identified as a leading priority in hospital safety. Recommended parenteral anticoagulant agents with different indications for the prevention and treatment of venous thromboembolism include unfractionated heparin, low-molecular-weight heparins and fondaparinux. Prescribing decisions in venous thromboembolism management may seem complex due to the large range of clinical indications and patient types, and the range of anticoagulants available.MethodsMEDLINE and EMBASE databases were searched to identify relevant original articles.ResultsLow-molecular-weight heparins have nearly replaced unfractionated heparin as the gold standard antithrombotic agent. Low-molecular-weight heparins currently available in the US are enoxaparin, dalteparin, and tinzaparin. Each low-molecular-weight heparin is a distinct pharmacological entity with different licensed indications and available clinical evidence. Enoxaparin is the only low-molecular-weight heparin that is licensed for both venous thromboembolism prophylaxis and treatment. Enoxaparin also has the largest body of clinical evidence supporting its use across the spectrum of venous thromboembolism management and has been used as the reference standard comparator anticoagulant in trials of new anticoagulants. As well as novel oral anticoagulant agents, biosimilar and/or generic low-molecular-weight heparins are now commercially available. Despite similar anticoagulant properties, studies report differences between the branded and biosimilar and/or generic agents and further clinical studies are required to support the use of biosimilar low-molecular-weight heparins. The newer parenteral anticoagulant, fondaparinux, is now also licensed for venous thromboembolism prophylaxis in surgical patients and the treatment of acute deep-vein thrombosis; clinical experience with this anticoagulant is expanding.ConclusionsParenteral anticoagulants should be prescribed in accordance with recommended dose regimens for each clinical indication, based on the available clinical evidence for each agent to assure optimal safety and efficacy.

Clinical Experience with Bemiparin

Subcutaneous bemiparin has been evaluated for the prevention of venous thromboembolism (VTE) in moderate to high-risk patients undergoing surgery, and for the acute and long-term treatment of established VTE. General and orthopaedic surgery is associated with VTE incidence rates of 15-60% in the absence of thromboprophylaxis and this can be reduced by over 70% with appropriate thromboembolic prophylaxis. Bemiparin was as effective as unfractionated heparin (UFH) in the prevention of VTE, when both were initiated preoperatively, but was associated with significantly fewer bleeding episodes than UFH. Bemiparin prophylaxis initiated postoperatively was at least as effective as bemiparin initiated preoperatively and was associated with a lower incidence of bleeding complications than preoperative initiation. In terms of patients with cancer undergoing abdominal or pelvic surgery, preliminary results from a recent study with bemiparin showed that extended prophylaxis for 4 weeks significantly reduced the rate of major VTE, without increasing bleeding risk, compared with prophylaxis for one week. Bemiparin, initiated postoperatively, was as effective as enoxaparin, initiated preoperatively, in the prevention of VTE in patients undergoing total knee replacement. The incidence of bleeding complications was similar between groups, although the incidence of injection site haematoma was significantly higher with enoxaparin than with bemiparin. Postoperative initiation of bemiparin thromboprophylaxis minimized the risk of spinal haematoma in patients using neuraxial anaesthesia (approximately 93% of patients). In addition, postoperative initiation is likely to reduce the total costs, because patients do not need to be admitted to hospital the day before surgery. Bemiparin was more effective than intravenous UFH in the acute treatment of established deep vein thrombosis (DVT) and was as effective as oral warfarin in the subsequent secondary prevention of VTE over 3 months of therapy, while bleeding complications over 3 months of therapy were similarly low. In a European study, acute treatment of DVT with bemiparin for one week followed by 12 weeks' secondary prevention with bemiparin (i.e. bemiparin/bemiparin) was associated with a cost saving of &U20AC;908 per patient compared with UFH/warfarin. Similarly, bemiparin/warfarin produced a cost saving of &U20AC;769 compared with UFH/warfarin. The savings were predominantly the result of reduced hospital stays during acute treatment with bemiparin. Bemiparin was also associated with increased quality-adjusted life expectancy. Observational studies in routine clinical practice demonstrated that outpatient treatment of acute VTE was as effective as inpatient treatment, but with lower costs, and bemiparin was as effective as vitamin K antagonists over 3 months for secondary prevention, with VTE recurrence rates of 0% and 0.3% over 3 months in separate studies. Bemiparin is thus an effective, well tolerated agent for thromboprophylaxis in surgery, and for the acute and long-term treatment of established VTE, having advantages over UFH and particular benefits as a result of initiating therapy postoperatively.

Therapie der postoperativen Thrombose

For the treatment of deep vein thrombosis (DVT), rapid diagnosis and prompt therapy are crucial to minimize the risk of fatal pulmonary embolism and long-term complications, including the postthrombotic syndrome and recurrent thromboembolism. The treatment of acute DVT remains controversial. In this review, treatment options in relation to exposing and predisposing risk factors are discussed. Evidence-based data and recommendations from official guidelines are presented.

Compression therapy in the treatment of acute deep vein thrombosis

Especially in Europe patients with acute deep vein thrombosis (DVT) of the leg are treated with compression therapy. A look at the literature, however, reveals that the exact mechanism of compression therapy in the treatment of acute deep vein thrombosis is not completely understood. Effects on fibrinolysis, resolution of pain and swelling as well as a fixation of the thrombus towards the vessel wall have been discussed. The literature indicates that compression stockings were mostly used in the treatment of DVT although there is some evidence that inelastic compression bandages have a greater impact on resolution of swelling and pain. Large randomised multicenter trials are still not available. Furthermore, evidence-based data providing an advantage of thigh-length compression therapy in the treatment of acute DVT are lacking. Studies have, however, shown that compression therapy is a safe therapy and can reduce the development of postthrombotic syndrome after acute DVT.

Current pharmacotherapeutic options for treating deep vein thrombosis

The treatment of deep vein thrombosis (DVT) has been evolving over the past 50 years. Initially, unfractionated heparin (UFH) given subcutaneously every 6 h, progressed to constant infusion therapy followed by warfarin, which has become the mainstay of therapy. Over the past 12 years, a new therapy, low molecular weight heparin (LMWH), has proven to be at least as effective or more effective than UFH in the acute treatment of DVT. These drugs are administered subcutaneously, are better absorbed and do not require monitoring. LMWHs have changed the paradigm of caring for patients with DVT. Finally a number of studies with thrombolytic agents have attempted to improve the outcome of DVT by reducing clot burden and preventing the sequelae of thrombotic valvular damage. This paper will review the management of DVT from the acute phase to long-term management.

Effectiveness and economic impact associated with a program for outpatient management of acute deep vein thrombosis in a group model health maintenance organization.

Controlled clinical trials have demonstrated that outpatient administration of low-molecular-weight heparin to patients with acute deep vein thrombosis (DVT) provides safety and efficacy equivalent to that of traditional inpatient therapy with unfractionated heparin. Whether favorable results reported in controlled clinical trials are achievable in clinical practice is an important consideration. Appropriate patients with objectively diagnosed DVT were treated as outpatients with low-molecular-weight heparin and warfarin sodium according to an approved guideline. The primary end point for analysis consisted of objectively diagnosed symptomatic recurrent thromboembolism or major bleeding within a 90-day evaluation period. The incremental cost incurred by the organization while using the outpatient DVT treatment guideline was determined. Incremental cost savings of the outpatient DVT treatment program were determined based on the cost that would have accrued had the patient been admitted to the hospital for treatment with unfractionated heparin. We enrolled 391 patients (91.4%) in the outpatient DVT treatment program. Of these, 373 (95.4%) completed 90 days of therapy without reaching the primary end point. The percentage of patients reaching the primary outcome measure (4.6%) fell within the range of patients enrolled in controlled clinical trials (3.5%-9.4%). During the 2-year program evaluation, total cost savings of $1,108,587 were realized. Outpatient treatment of acute DVT can be managed safely and effectively in clinical practice. The potential savings associated with outpatient DVT treatment are substantial. Arch Intern Med. 2000;160:2926-2932