scholarly journals Low-Molecular-Weight Heparin in Arterial Reconstructive Surgery: A Double-Blind, Randomized Dose-Finding Trial

2002 ◽  
Vol 8 (4) ◽  
pp. 337-345 ◽  
Author(s):  
Peter Kujath ◽  
Christian Eckmann ◽  
Frank Misselwitz

Periprocedural and postprocedural anticoagulation during arterial reconstructive surgery (ARS) with intravenous heparin is standard of care. The general use and correct dosage of low-molecular-weight heparin, however, are still under debate. A prospective, randomized, double-blind trial was performed with a parallel group comparison of four dose regimen of a low-molecular-weight heparin, reviparin sodium, in patients undergoing major ARS. Sixty-five patients were randomly allocated to receive twice-daily subcutaneous injections of reviparin, 3500 (group A, n=17), 4200 (group B, n= 16), 5950 (group C, n= 16), and 7000 (group D, n= 16) anti-Xa IU per day. Patients were eligible for the trial if they had angiographically proven peripheral arterial obstructive disease with a planned arterial reconstruction of the infrarenal aorta, iliaca artery, or femoralis artery. Fifty-nine patients completed the trial. The goal was to determine the optimal dose of the low-molecular-weight heparin to achieve a minimum of early vascular events (less than 12%) with a minimum of major bleeding events (less than 10%) during a shortterm follow-up of up to 8 postoperative days. There was no reocclusion in the entire population. Patients randomized into the two lower dose groups (A and B), however, experienced a relatively high incidence of restenosis, whereas patients enrolled in group D, receiving the highest dose of reviparin, experienced an unacceptably high rate of bleeding events (all bleeds, 43%; major bleeding, 14.3%). Thus, the optimal dose of reviparin sodium to be administered in patients undergoing major ARS is half the therapeutic dose:5950 to 6300 anti Xa IU (75-85 anti Xa IU/kg body weight per day). Patients included in group C had no major bleeding event (95% confidence interval, 0% to 6.6%), a significant improvement of the doppler anklebrachial systolic pressure index (difference of 0.46 ± 0.29, P=.017), and a higher rate of responders with regard to the puls status measured at the tibialis posterior arteries (66.7%) compared to groups A and B (46.7% and 54.5%, respectively, P=.086). The efficacy and safety of this dosage regimen in comparison to standard of care should be further substantiated in larger trials.

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4277-4277
Author(s):  
Mariasanta Napolitano ◽  
Giorgia Saccullo ◽  
Simona Raso ◽  
Salvatrice Mancuso ◽  
Alessandra Casuccio ◽  
...  

Abstract Introduction. The optimal duration of Low Molecular Weight Heparin (LMWH) after cancer associated deep vein thrombosis (DVT) is unknown; current guidelines suggest to prolong anticoagulation until cancer is active. We have recently demonstrated, in a randomized trial, that detection of Residual Vein Thrombosis (RVT) after 6 months of LMWH identify patients who require or not extension of therapy with anticoagulants (JCO in press). Now we present data of a prospective study evaluating a RVT-based management of patients with cancer-associated DVT, in whom LMWH has been extended up to 2 years in patients considered at high-risk for recurrent DVT because of persistence of RVT. Material and Methods. Patients were included at the time of a first diagnosis of cancer-associated DVT of the lower limbs. All received LMWH at therapeutic dosage for the first month (approximately 100 UI anti-FXa b.i.d.) then reduced at 75% for the following months. After 6 months of heparin, the presence of RVT was detected: those without RVT (no-RVT group) suspended treatment, while those with RVT (RVT group) continued LMWH for up to 2 years. Recurrent thrombosis and/or bleeding events were recorded during treatment and one year after LMWH withdrawal. Baseline differences between groups were assessed by the chi-square test (Yates’ correction) for categorical variables and ANOVA test or Kruskal-Wallis test for parametric and nonparametric analyses. Relative risks (RRs) and 95% confidence intervals (CIs) were evaluated. Results. Between January 2009 and April 2011, 211 cancer patients were enrolled; RVT was detected in 129 patients (61.1%). Recurrent VTE occurred in 19 (14.7%); 4 episodes (3.1%) occurred while on heparin. Among patients without RVT (82), 3 (3.6%) developed recurrent VTE (after LMWH therapy). Adjusted HR for RVT vs no-RVT group was 5.8 (95% CI, 1.9 to 19.2; p 0.0003). Three major bleeding events occurred in RVT group and one in no-RVT group (during LMWH administration). The HR for major bleeding (RVT vs no-RVT group) was 2.58 (95% CI, 0.66 to 12.43;p 0.103). Overall, 44 patients (20.8%) died during follow-up as a result of cancer progression. Conclusions. These results indicate that in patients without RVT, a short period of treatment with a LMWH is sufficient; in those with persistent RVT, treatment extended to 2 years substantially reduces, but does not eliminate, the risk of recurrent thrombosis. However, when still on LMWH, the risk for recurrent VTE is low. Disclosures No relevant conflicts of interest to declare.


2021 ◽  
Vol 10 (Supplement_1) ◽  
Author(s):  
A Abdul Razzack ◽  
N Hussain ◽  
S Adeel Hassan ◽  
S Mandava ◽  
F Yasmin ◽  
...  

Abstract Funding Acknowledgements Type of funding sources: None. Background- Low molecular weight heparin (LMWH) and direct oral anticoagulants (DOACs) have been proven to be more effective in the management of venous thromboembolism (MVTE). The efficacy and safety of LMWH or DOACs in treatment of recurrent or malignancy induced VTE is not studied in literature. Objective To compare the efficacy and safety of LMWH and  DOACs in the management of malignancy induced  VTE Methods- Electronic databases ( PubMed, Embase, Scopus, Cochrane) were searched from inception to November  28th, 2020. Dichotomous data was extracted for prevention of VTE and risk of major bleeding in patients taking either LMWH or DOACs. Unadjusted odds ratios (OR) were calculated from dichotomous data using Mantel Haenszel (M-H) random-effects with statistical significance to be considered if the confidence interval excludes 1 and p < 0.05.  Results- Three studies with 2607 patients (DOACs n = 1301 ; LMWH n = 1306) were included in analysis. All the study population had active cancer of any kind diagnosed within the past 6 months. Average follow-up period for each trial was 6 months. Patients receiving DOACs have a lower odds of recurrence of MVTE as compared to LMWH( OR 1.56; 95% CI 1.17-2.09; P = 0.003, I2 = 0). There was no significant difference in major bleeding among patients receiving LMWH or DOACs  (OR-0.71, 95%CI 0.46-1.10, P = 0.13, I2 = 22%) (Figure 1). We had no publication bias in our results (Egger’s regression p > 0.05). Conclusion- DOACs are superior to LMWH in prevention of MVTE and have similar major bleeding risk as that of LMWH. Abstract Figure. A)VTE Recurrence B)Major Bleeding events


2018 ◽  
Vol 25 (4) ◽  
pp. 793-800 ◽  
Author(s):  
Megan K Phelps ◽  
Tracy E Wiczer ◽  
H Paige Erdeljac ◽  
Kelsey R Van Deusen ◽  
Kyle Porter ◽  
...  

Introduction Low-molecular-weight heparins are the standard treatment for cancer-associated thrombosis. Recently, direct oral anticoagulants are a new option for thrombosis treatment; however, data supporting the use of direct oral anticoagulants for cancer-associated thrombosis are limited. Objectives The primary objective of this study was to determine the rate of recurrent cancer-associated thrombosis and major bleeding within 6 months of starting either low-molecular-weight heparin or direct oral anticoagulant for treatment of cancer-associated thrombosis. Secondary objectives were to determine the rates of clinically relevant-non-major bleeding and all-cause mortality. Patients/methods This is a retrospective cohort study including adults with cancer-associated thrombosis treated with low-molecular-weight heparin or direct oral anticoagulant between 2010 and 2016 at the Ohio State University. Medical records were reviewed for 6 months after initiation of anticoagulation or until the occurrence of recurrent cancer-associated thrombosis, major bleeding, cessation of anticoagulation of interest, or death, whichever occurred first. Results Four hundred and eighty patients were included (290 low-molecular-weight heparin and 190 direct oral anticoagulant). Patients treated with direct oral anticoagulant were found to carry “lower risk” features including cancer with lower VTE risk and lower rate of metastatic disease. After adjustment for baseline differences, there was no significant difference in the rate of recurrent cancer-associated thrombosis (7.2% low-molecular-weight heparin vs 6.3% direct oral anticoagulant, p = 0.71) or major bleeding (7.6% low-molecular-weight heparin vs 2.6% direct oral anticoagulant, p = 0.08). Conclusions Our study demonstrates that in a select population of cancer patients with VTE, direct oral anticoagulant use can be as effective and safe compared to the standard therapy with low-molecular-weight heparin.


1987 ◽  

The efficacy and safety of a low molecular weight heparin (Kabi 2165) in preventing postoperative deep vein thrombosis (D.V.T.), was assessed in a double blind randomly allocated multicenter trial. 385 patients were included and analysed on a intention to treat basis. Kabi 2165 was given S.C. 24 hourly in 2 500 anti-factor Xa units and compared with standard low dose calcium heparin 5 000 i.u. S.C. 12 hourly in patients undergoing major abdominal or gynaecological surgery. The first dose was administered two hours before operation in both groups. The relevant characteristics of the patients in the two treatment groups were similar. The two groups were well matched for risk factors which could predispose to D.V.T.DVT was detected by the radioactive fibrinogen test. Venography was performed whenever a positive scan developed in a patient. Six (3,1 96) of 195 patients receiving Kabi 2165 and seven (3,7 96) of 190 patients in the standard heparin group developed D.V.T. No pulmonary embolism we re detected during the prophylactic regimens. There was no significant difference between the two groups in terms of blood loss during surgery, postoperative drainage, blood transfusion, wound haematoma. Mean hemoglobin levels and mean hematocrit values preoperatively and postoperatively (day 1 and 6) were :There were no statistically significant differences in both groups. No thrombocytopenia was reported in this study. The antifactor Xa activity was significantly higher in the Kabi 2165 group.In conclusion, Kabi 2165 once daily is as effective and safe as standard heparin twice daily in preventing postoperative D.V.T. in general surgery.


2003 ◽  
Vol 99 (6) ◽  
pp. 953-959 ◽  
Author(s):  
Jari Siironen ◽  
Seppo Juvela ◽  
Joona Varis ◽  
Matti Porras ◽  
Kristiina Poussa ◽  
...  

Object. From the moment an intracranial aneurysm ruptures, cerebral blood flow is impaired, and this impairment mainly determines the outcome in patients who survive after the initial bleeding. The exact mechanism of impairment is unknown, but activation of coagulation and fibrinolysis correlate with clinical condition and outcome after aneurysmal subarachnoid hemorrhage (SAH). The purpose of this study was to determine whether enoxaparin, a low-molecular-weight heparin, which is a well-known anticoagulating agent, has any effect on the outcome of aneurysmal SAH postoperatively. Methods. In this randomized, double-blind, single-center clinical trial, 170 patients (85 per group) with aneurysmal SAH were randomly assigned to receive either enoxaparin (40 mg subcutaneously once daily) or a placebo, starting within 24 hours after occlusion of the aneurysm and continuing for 10 days. Analysis was done on an intention-to-treat basis. Outcome was assessed at 3 months on both the Glasgow Outcome and modified Rankin Scales. Patients were eligible for the study if surgery was performed within 48 hours post-SAH, and no intracerebral hemorrhage was larger than 20 mm in diameter on the first postoperative computerized tomography scan. At 3 months, there were no significant differences in outcome by treatment group. Of the 170 patients, 11 (6%) died, and only 95 (56%) had a good outcome. Principal causes of unfavorable outcome were poor initial condition, delayed cerebral ischemia, and surgical complications. There were four patients with additional intracranial bleeding in the group receiving enoxaparin. The bleeding was not necessarily associated with the treatment itself, nor did it require treatment, and there were no such patients in the placebo group. Conclusions. Enoxaparin seemed to have no effect on the outcome of aneurysmal SAH in patients who had already received routine nimodipine and who had received triple-H therapy when needed. Routine use of low-molecular-weight heparin should be avoided during the early postoperative period in patients with SAH, because this agent seems to increase intracranial bleeding complications slightly, with no beneficial effect on neurological outcome.


2019 ◽  
Vol 26 (2) ◽  
pp. 351-360 ◽  
Author(s):  
Stephanie Kim ◽  
Jennifer Namba ◽  
Aaron M Goodman ◽  
Thi Nguyen ◽  
Ila M Saunders

Purpose Low-molecular-weight heparins are currently the recommended antithrombotic therapy for treatment and prevention of malignancy-related venous thromboembolism. Currently, the evidence evaluating direct oral anticoagulants versus low-molecular-weight heparins or a vitamin K antagonist in cancer patients with hematologic malignancies is limited. We evaluated the safety and efficacy of direct oral anticoagulants for venous thromboembolism treatment or stroke prevention for non-valvular atrial fibrillation in patients with hematologic malignancies. Methods This was a retrospective evaluation of adult patients with hematologic malignancies who received at least one dose of the Food and Drug Administration-approved direct oral anticoagulant for venous thromboembolism treatment or stroke prevention. We determined the frequency of major bleeding events, non-major bleeding events, stroke, systemic embolism, appropriateness of initial direct oral anticoagulant doses, holding practices prior to procedures, and the rate of all-cause mortality. An analysis was also performed to compare the incidence of bleeding between patients with a history of hematopoietic stem cell transplant to non-transplant patients. Results A total of 103 patients were identified, with the majority of patients receiving rivaroxaban for venous thromboembolism treatment. Major bleeding events occurred in four patients and no fatal bleeding events occurred. Non-major bleeding occurred in 29 patients, most commonly epistaxis and bruising. Two patients experienced a systemic embolism while on direct oral anticoagulant therapy. Conclusion Direct oral anticoagulants may be a safe and effective alternative for anticoagulation therapy in patients with hematologic malignancies. However, larger prospective studies comparing direct oral anticoagulants to low-molecular-weight heparins or vitamin K antagonists are warranted to compare efficacy and safety outcomes in this patient population.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 593-593 ◽  
Author(s):  
Daniel Durant Myers ◽  
Shirely K. Wrobleski ◽  
Krus Kelsey ◽  
Diana Farris ◽  
Diaz A. Jose ◽  
...  

Abstract Background: Previous studies have shown that inhibition of E-selectin can decrease thrombus formation and associated inflammation. E-selectin (CD-62E) is a cell adhesion molecule that is expressed on activated endothelial cells and plays an important role in leukocyte recruitment to the site of vascular injury. GMI-1271 is designed to mimic the bioactive conformation of the sialyl-Lex carbohydrate binding domain of E-selectin and is a specific E-selectin inhibitor. There remains an unmet medical need for a translatable therapeutic that can treat VT in combination with lower, safer levels of low molecular weight heparin (LMWH) anticoagulation. We hypothesize that E-selectin inhibition combined with LMWH will permit lower doses of therapeutic LMWH for the treatment of VT without increasing adverse bleeding events. Methods: Male C57BL/6J mice, 10 weeks old (23-28 grams, n5), underwent our electrolytic IVC model (EIM) to produce a non-occlusive thrombosis, via electrical free radical stimulation (250 µAmp) for 15 minutes. Experimental groups included non-treated controls (CTR-No Tx), animals given LMWH (3-6 mg/kg, SQ, once daily (qd), the E-selectin inhibitor GMI-1271 20/kg intraperitoneal (IP) twice daily (BID), and a combination of the agents. The dose range of LMWH that produced anti-Xa levels in the therapeutic range (0.5-1.0IU/mL) and significantly decreased thrombus weight in this mouse VT model was 5 and 6 mg/kg. Treated mouse groups received the first dose of experimental therapy immediately following thrombus induction and through day 2. Animals were euthanized 2 days post-thrombosis for tissue harvest and blood collection for the following evaluations: thrombus weight (grams), anti-Xa testing, and tail vein bleeding time (seconds). Results: GMI-1271 Works in Combination with LMWH to Decreases Venous Thrombosis : LMWH dosed at 6mg/kg and 5mg/kg alone, significantly decreased venous thrombus weight at 2 days, versus non-treated controls (73.0±7.5, 62.8±1.9 vs. 186.8±63.9 x10-4 grams, P<0.01). Notably, the combination of GMI-1271 20 mg/kg + LMWH 4mg/kg (33% dose decrease from LMWH 6 mg/kg), and GMI-1271 20 mg/kg + LMWH 3mg/kg (50% dose decrease from LMWH 6 mg/kg dose), significantly decreased thrombus weight, versus non-treated controls (75.6±17.1, 73.0±14.8 vs. 186.8±63.9 x10-4 grams, P<0.01), equivalent to the results of higher doses of LMWH alone (FIGURE 1 A). GMI-1271 Does not Increase Bleeding Potential: GMI-1271 administration did not significantly elevate tail bleeding times, versus non-treated control mice (67.00±44 vs. 53.8±7.5 seconds). LMWH dosed at 5mg/kg and 6 mg/kg, elevated tail bleeding times in mice with the 5 mg/kg LMWH group significant versus non-treated controls (87±25 vs. 53.8±7.5 seconds, P<0.005). Both animal groups treated with GMI-1271, in combination with lower dose LMWH therapy, had tail bleeding times comparable to non-treated control animals (FIGURE 1 B). Conclusion: We report, for the first time, that GMI-1271 works in combination with LMWH to significantly reduce acute VT without increasing bleeding times and by inference, bleeding potential. These preliminary studies suggest that E-selectin inhibition with GMI-1271 may be used to treat VT alone, or in combination with lower and safer levels of LMWH anticoagulation. Figure 1 Figure 1. Disclosures Magnani: GlycoMimetics Inc.: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees.


Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 746-746 ◽  
Author(s):  
Nathan T. Connell ◽  
Gregory A. Abel ◽  
Jean M. Connors

Introduction: Patients with active malignancy who develop venous thromboembolism (VTE) have historically been anticoagulated with a vitamin K antagonist (VKA) such as warfarin. The CLOT study (Lee et al., NEJM, 2003) demonstrated that injection with the low-molecular weight heparin (LMWH) dalteparin was better than warfarin at preventing recurrence of VTE in cancer patients, which changed clinical practice in the United States; however, a subsequent competing risks analysis (Parpia et al., Contemp Clin Trials, 2011) suggested the magnitude of this benefit may be less than previously believed. Neither patient-focused measures of utility nor the cost of each strategy have been evaluated in the current treatment era. We aimed to characterize the effectiveness and costs associated with these two management strategies for malignancy-associated VTE. Methods: We constructed a Markov state transition model to compare the cost-effectiveness of LMWH to VKA therapy for treatment of malignancy-associated thrombosis from a societal perspective. The model had 4 health states: initial anticoagulation, extended anticoagulation, no anticoagulation, and deceased. Cycle-length was 6 months with a lifetime horizon. Potential events in each cycle included recurrent VTE and death from recurrent VTE, major bleeding and death from major bleeding, minor bleeding, and death from other causes. Model inputs for event probabilities, costs, and utility were obtained from previously published literature (e.g., the ONCENOX, Main-LITE, CLOT, CANTHANOX, and CATCH trials); while no specific data exist for the utility of each strategy for treatment of malignancy-associated VTE, we assumed they would be similar to utilities previously published for non-malignant VTE, and performed sensitivity analysis to assess the robustness of our results. Microsimulation of 1000 trials was performed to calculate mean quality-adjusted life-years (QALYs) and costs associated with the two anticoagulation strategies. Results: Using a fixed effects model, the meta-analytic estimates of the odds ratio for major bleeding from LMWH as compared to VKA therapy was 0.99 (95% CI 0.65 - 1.50). The odds ratio for recurrent VTE while on LMWH as compared to VKA was 0.55 (95% CI 0.40 - 0.75) in favor of LMWH. The mean cost of the VKA strategy was $6,383.39 (±$5174.56) and for the LMWH strategy it was $64,975.83 (±$3,4743.63). The mean effectiveness of the VKA strategy was 1.19 QALYs (range 0.20 - 7.51); for the LMWH strategy it was 1.46 QALYs (range 0.20 - 9.03), resulting in a mean increase of 0.27 QALYs (Figure). The incremental cost-effectiveness ratio (ICER) was thus $221,281.83 per QALY. One-way sensitivity analysis evaluating the utility of the LMWH strategy from 0 - 1 revealed that VKA was always the preferred strategy at a willingness to pay (WTP) threshold of $100,000 per QALY. Conclusions: While LMWH is an effective treatment for malignancy-associated VTE, we found that it offers only a small gain in QALYs compared to VKAs, and that this gain is associated with a significant increase in cost. Our data suggest that LMWH is not a cost-effective strategy when applied to all patients with malignancy-associated VTE and that VKAs may be a reasonable alternative to LMWH. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.


Phlebologie ◽  
2015 ◽  
Vol 44 (05) ◽  
pp. 256-260
Author(s):  
A. Matzdorff

SummaryIn December 2014 the CATCH study was presented at the annual meeting of the American Society of Hematology. CATCH is a randomized controlled trial comparing the low molecular weight heparin tinzaparin with warfarin for 6 months extended treatment (=secondary prophylaxis) of cancer-associated venous thromboembolism (VTE). 6.9 % of patients in the tanzaparin arm experienced recurrent symptomatic and asymptomatic VTE compared with 10 % in the warfarin arm, this difference was statistically not significant. The difference became significant when only symptomatic VTEs were compared. There was no difference in the incidence of major bleeding events, but significantly fewer patients experienced clinically relevant non-major bleeding with tinzaparin than warfarin. The CATCH study is so far the largest study on extended treatment of cancer-associated VTE. It supports the guideline recommendation that low molecular weight heparins should be preferred to vitamin K antagonists for anticoagulation of cancer-associated VTE.


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