Differences in Major Bleeding Events in Elderly Surgical Patients Receiving Low Molecular Weight Heparin (LMWH) Versus LLow-dose Unfractionated Heparin (LDUH)

2012 ◽  
Vol 172 (2) ◽  
pp. 321
Author(s):  
J.C. Roberts ◽  
R. Jones ◽  
R. Rentea ◽  
D. Helbling ◽  
K.J. Brasel
Keyword(s):  
Molecular Weight ◽  
Unfractionated Heparin ◽  
Major Bleeding ◽  
Low Molecular Weight Heparin ◽  
Surgical Patients ◽  
Low Molecular Weight ◽  
Bleeding Events ◽  
Major Bleeding Events

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
Keyword(s):  
Molecular Weight ◽  
Major Bleeding ◽  
Reconstructive Surgery ◽  
Low Molecular Weight Heparin ◽  
Standard Of Care ◽  
Optimal Dose ◽  
Low Molecular Weight ◽  
Bleeding Events ◽  
Double Blind ◽  
Group D

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.

scholarly journals Cancer-Associated Deep Vein Thrombosis: The Role of Residual Vein Thrombosis for Assessing the Duration of Low Molecular Weight Heparin (the EXTENDED Cancer-DACUS)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4277-4277
Author(s):  
Mariasanta Napolitano ◽  
Giorgia Saccullo ◽  
Simona Raso ◽  
Salvatrice Mancuso ◽  
Alessandra Casuccio ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Deep Vein Thrombosis ◽  
Major Bleeding ◽  
Low Molecular Weight Heparin ◽  
Low Molecular Weight ◽  
Recurrent Thrombosis ◽  
Bleeding Events ◽  
Vein Thrombosis ◽  
Recurrent Vte ◽  
Deep Vein

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.

scholarly journals Tinzaparin in Pregnancy, Cancer and Renal Impairment: A Systematic Review Focusing on Safety

2020 ◽  
Author(s):  
Ioannis Vathiotis ◽  
Nikolaos Syrigos ◽  
Evangelos Dimakakos
Keyword(s):  
Molecular Weight ◽  
Renal Impairment ◽  
Creatinine Clearance ◽  
Pregnant Women ◽  
Cancer Patients ◽  
Major Bleeding ◽  
Dose Adjustment ◽  
Low Molecular Weight ◽  
Bleeding Events ◽  
Major Bleeding Events

Abstract Background: Low-molecular-weight heparins are approved for primary and secondary venous thromboembolism prevention. Tinzaparin (Innohep®) is the low-molecular-weight heparin with the highest average molecular weight. The purpose of this study is to provide an update regarding the safety profile of tinzaparin sodium, prescribed either as a prophylactic or as a therapeutic regimen for VTE, in pregnant women, cancer patients and individuals suffering from renal impairment. Methods: We identified clinical trials reporting safety outcomes for pregnant women, cancer patients and individuals with renal impairment receiving either prophylactic or therapeutic doses of tinzaparin. We extracted predefined, clinically relevant outcomes of patients on tinzaparin.Results: For pregnant women on tinzaparin bleeding rates ranged from 9.7% to 10.3%; reported rates of major bleeding events, allergic reactions and thrombocytopenia were low. No maternal deaths or neonatal hemorrhages were recorded. Prophylactic administration of tinzaparin also showed promising results in pregnant women with recurrent unexpected pregnancy loss. In patients with cancer bleeding rates fluctuated between 0.8% and 27%; there was a trend showing that patients on tinzaparin exhibited fewer bleeding events than those on vitamin K antagonists. Bioaccumulation of tinzaparin was not correlated with age, body weight or creatinine clearance. Therapeutic administration of tinzaparin did not produce significant increase in the rates of clinically relevant or major bleeding events in patients with renal impairment. Periodic administration of tinzaparin did not result in bioaccumulation and tinzaparin is safe and can be used without dose adjustment in patients with severe renal impairment and creatinine clearance < 20 ml/min.Conclusions: Tinzaparin represents a thoroughly studied and safe choice for special populations that are at increased risk for both thrombosis and bleeding. Tinzaparin is safe for pregnant women. Current literature supports the use of tinzaparin without dose adjustment in patients with renal impairment and creatinine clearance < 20ml/min.

Markers of Hemostatic System Activation in Acute Deep Venous Thrombosis-Evolution during the First Days of Heparin Treatment

1993 ◽  
Vol 70 (06) ◽  
pp. 0909-0914 ◽  
Author(s):  
Keyword(s):  
Molecular Weight ◽  
Venous Thrombosis ◽  
Deep Venous Thrombosis ◽  
Unfractionated Heparin ◽  
Low Molecular Weight Heparin ◽  
Factor Xa ◽  
Low Molecular Weight ◽  
Dose Adaptation ◽  
Heparin Treatment ◽  
Lung Scan

SummaryFibrin D-Dimer (D-Di), prothrombin activation fragment (F 1+2) and thrombin-antithrombin III complexes (TAT) were measured using ELISA procedures in the plasma of patients with an acute deep venous thrombosis (DVT), at presentation and on days 2, 6 and 10 after initiation of heparin treatment. Patients were randomly allocated into two treatment groups: 44 patients received adapted doses of continuous intravenous unfractionated heparin (UH) whereas 47 received 1 mg/kg every twelve hours of a low molecular weight heparin (enoxaparin) subcutaneously. A phlebography and a perfusion lung scan were performed before inclusion and on day 10. Failure of therapy (n = 9) was defined by venogram worsening or confirmed pulmonary embolism. Improvement (n = 44) or stationary state (n = 38) were defined by venogram evolution in the absence of new leg scan defects.At presentation, D-Di, F 1 + 2 and TAT were above cut-off values in 97, 66 and 89% of patients respectively. D-Di levels correlated with the extent of venous thrombosis whereas TAT and F 1 + 2 did not. Mean levels of D-Di decreased sharply during the first days of treatment but were still abnormal on day 10. A secondary increase of D-Di on days 6 or 10 by more than 3 μg/ml occurred in 4 of the 9 patients who developed a thromboembolic recurrence but in none of the 72 patients who had a more favorable outcome. F 1 + 2 and TAT time-courses were not related to clinical evolution. In the Enoxaparin group, there was no relationship between antifactor Xa activities and any biological markers. TAT and F 1 + 2 levels fell on day 2 and remained stable until day 10. In contrast, in the UH group, TAT and F 1 + 2 did not significantly decrease on day 2, probably due to a delay in dose adaptation, but they declined slowly until day 10.In conclusion, D-Di displays a higher sensitivity than F 1 + 2 or TAT for the diagnosis of D\T. D-Di, but not TAT or F 1 + 2, follow-up seems to be of potential value for early detection of recurrency. Hemostatic activation is controlled earlier by fixed doses of a low molecular weight heparin, irrespective of the plasma anti-factor Xa activities, than by unfractionated heparin at adapted doses.

Effects of Unfractionated and Low Molecular Weight Heparins on Platelet Thromboxane Biosynthesis “In Vivo”

1994 ◽  
Vol 72 (06) ◽  
pp. 942-946 ◽  
Author(s):  
Raffaele Landolfi ◽  
Erica De Candia ◽  
Bianca Rocca ◽  
Giovanni Ciabattoni ◽  
Armando Antinori ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Unfractionated Heparin ◽  
Low Molecular Weight Heparin ◽  
Primary Source ◽  
In Vivo Studies ◽  
Low Molecular Weight ◽  
Heparin Administration ◽  
To Receive

SummarySeveral “in vitro” and “in vivo” studies indicate that heparin administration may affect platelet function. In this study we investigated the effects of prophylactic heparin on thromboxane (Tx)A2 biosynthesis “in vivo”, as assessed by the urinary excretion of major enzymatic metabolites 11-dehydro-TxB2 and 2,3-dinor-TxB2. Twenty-four patients who were candidates for cholecystectomy because of uncomplicated lithiasis were randomly assigned to receive placebo, unfractionated heparin, low molecular weight heparin or unfractionaed heparin plus 100 mg aspirin. Measurements of daily excretion of Tx metabolites were performed before and during the treatment. In the groups assigned to placebo and to low molecular weight heparin there was no statistically significant modification of Tx metabolite excretion while patients receiving unfractionated heparin had a significant increase of both metabolites (11-dehydro-TxB2: 3844 ± 1388 vs 2092 ±777, p <0.05; 2,3-dinor-TxB2: 2737 ± 808 vs 1535 ± 771 pg/mg creatinine, p <0.05). In patients randomized to receive low-dose aspirin plus unfractionated heparin the excretion of the two metabolites was largely suppressed thus suggesting that platelets are the primary source of enhanced thromboxane biosynthesis associated with heparin administration. These data indicate that unfractionated heparin causes platelet activation “in vivo” and suggest that the use of low molecular weight heparin may avoid this complication.

Comparison of the Non-Specific Binding of Unfractionated Heparin and Low Molecular Weight Heparin (Enoxaparin) to Plasma Proteins

1993 ◽  
Vol 70 (04) ◽  
pp. 625-630 ◽  
Author(s):  
Edward Young ◽  
Benilde Cosmi ◽  
Jeffrey Weitz ◽  
Jack Hirsh
Keyword(s):  
Molecular Weight ◽  
Unfractionated Heparin ◽  
Plasma Proteins ◽  
Low Molecular Weight Heparin ◽  
Specific Binding ◽  
Anticoagulant Activity ◽  
Factor Xa ◽  
Low Molecular Weight ◽  
Heparin Binding ◽  
Fixed Amount

SummaryThe non-specific binding of anticoagulantly-active heparin to plasma proteins may influence its anticoagulant effect. We used low affinity heparin (LAH) essentially devoid of anti-factor Xa activity to investigate the extent and possible mechanism of this non-specific binding. The addition of excess LAH to platelet-poor plasma containing a fixed amount of unfractionated heparin doubled the anti-factor Xa activity presumably because it displaces anticoagulantly-active heparin from plasma proteins. Although dextran sulfates of varying molecular weights also increased the anti-factor Xa activity, less sulfated heparin-like polysaccharides had no effect. These findings suggest that the ability to displace active heparin from plasma protein binding sites is related to charge and may be independent of molecular size. In contrast to its effect in plasma containing unfractionated heparin, there was little augmentation in anti-factor Xa activity when LAH was added to plasma containing low molecular weight heparin (LMWH), indicating that LMWH binds less to plasma proteins than unfractionated heparin. This concept is supported by studies comparing the anticoagulant activity of unfractionated heparin and LMWH in plasma with that in buffer containing antithrombin III. The anti-factor Xa activity of unfractionated heparin was 2-fold less in plasma than in the purified system. In contrast, LMWH had identical anti-factor Xa activity in both plasma and buffer, respectively. These findings may be clinically relevant because the recovered anti-factor Xa activity of unfractionated heparin was 33% lower in plasma from patients with suspected venous thrombosis than in plasma from healthy volunteers. The reduced heparin recovery in patient plasma reflects increased heparin binding to plasma proteins because the addition of LAH augmented the anti-factor Xa activity. In contrast to unfractionated heparin, there was complete recovery of LMWH added to patient plasma and little increase of anti-factor Xa activity after the addition of LAH. These findings may explain why LMWH gives a more predictable dose response than unfractionated heparin.

scholarly journals Safety and efficacy of direct oral anticoagulants (DOACs) vs low molecular weight heparin (LMWH) in malignancy induced venous thromboembolism-a systematic review and meta analysis

2021 ◽  
Vol 10 (Supplement_1) ◽  
Author(s):  
A Abdul Razzack ◽  
N Hussain ◽  
S Adeel Hassan ◽  
S Mandava ◽  
F Yasmin ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Venous Thromboembolism ◽  
Major Bleeding ◽  
Low Molecular Weight Heparin ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Low Molecular Weight ◽  
Efficacy And Safety ◽  
Dichotomous Data ◽  
Significant Difference

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 &lt; 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 &gt; 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

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