Use of Therapeutic Dose Low Molecular Weight Heparin in Patients with Renal Insufficiency: Analysis of Anti-Xa Levels and Creatinine Clearance.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 884-884
Author(s):  
Wendy Lim ◽  
Manasa Sridhara ◽  
Luqi Wang ◽  
Krystyna Kinnon ◽  
James Douketis ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Renal Function ◽  
Renal Insufficiency ◽  
Creatinine Clearance ◽  
Therapeutic Dose ◽  
Low Molecular Weight Heparin ◽  
Dose Adjustment ◽  
Low Molecular Weight ◽  
Recurrent Vte ◽  
Dependent Patient

Abstract Low molecular weight heparin (LMWH) is predominantly eliminated by the kidneys. In patients with severe renal impairment, use of therapeutic dose LMWH may be associated with accumulation and a resultant bleeding risk. Tinzaparin may be less dependent on renal clearance due to its higher molecular mass and greater negative charge compared to other LMWHs. The objective of this prospective cohort study was to serially measure the anti-Xa anticoagulant effect of therapeutic dose tinzaparin over 5–7 days, used for the initial treatment of venous thromboembolism (VTE) in patients with varying degrees of renal insufficiency. We present the anti-Xa results from the first 78 patients enrolled in the study, correlated with renal function. In this study, consecutive in- and outpatients with objectively confirmed VTE requiring anticoagulation were enrolled and stratified into 4 groups based on the calculated Cockcroft-Gault creatinine clearance (CrCl): > 60 mL/min, 30–60 mL/min, ≤ 30 mL/min and hemodialysis-dependent. Tinzaparin 175 IU/kg was administered subcutaneously once daily for 5–7 days or until the INR ≥ 2.0 with warfarin therapy. Trough anti-Xa levels were measured prior to the 3rd, 5th and/or 7th tinzaparin doses. Patients with anti-Xa level > 0.5 IU/mL received tinzaparin dose adjustment using a standardized nomogram. Bleeding and recurrent VTE events were recorded. The relationship between anti-Xa levels and CrCl is shown in Figure 1. Based on our predefined anti-Xa threshold of 0.5 IU/mL, 5 of 78 patients (6.4%) required dose adjustment; 1 hemodialysis dependent patient, 2 patients with CrCl < 30 mL/min, 1 patient each with CrCl 30–60 and > 60 mL/min, respectively. None of these patients developed bleeding or recurrent VTE. Among all 78 patients, 1 hemodialysis-dependent patient developed a hematoma following a traumatic line insertion, and no patients developed recurrent VTE. In conclusion, in a cohort of 78 patients with differing degrees of renal function including patients requiring hemodialysis, use of therapeutic-dose tinzaparin for the initial treatment of VTE resulted in accumulation (defined by trough anti-Xa > 0.5 IU/mL) in 6% of patients. There appears to be a weak inverse relationship between renal function and trough anti-Xa levels, but does not result in clinically significant accumulation when tinzaparin is used for up to 7 days. Further evaluation of tinzaparin in patients with severe renal insufficiency is required. Figure Figure

Anti-Xa Levels and Renal Function: Analysis of the First 32 Patients in the Tinzaparin in Renal Insufficiency for Venous Thromboembolism Study.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 906-906
Author(s):  
Wendy Lim ◽  
James Douketis ◽  
Luqi Wang ◽  
Karen Woods ◽  
Terri Schnurr ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Renal Function ◽  
Venous Thromboembolism ◽  
Renal Insufficiency ◽  
Therapeutic Dose ◽  
Dose Adjustment ◽  
Function Analysis ◽  
Bleeding Event ◽  
Renal Elimination ◽  
Minor Bleeding

Abstract Background: Low-molecular-weight heparin (LMWH) is renally eliminated; its use in patients with renal insufficiency may be associated with accumulation and an increased bleeding risk. Due to its higher molecular weight and greater negative charge, tinzaparin may be less dependent on renal elimination compared to other LMWHs. As a result, tinzaparin may be less prone to accumulate in patients with renal insufficiency. Purpose: To measure the anticoagulant effect of a 5-day course of therapeutic-dose tinzaparin used for the initial treatment of venous thromboembolism (VTE) in patients with varying degrees of renal insufficiency. We present the anti-Xa results of the first 32 patients enrolled in the study, correlated with renal function. Design: Prospective cohort study. Methods: In- and out-patients requiring therapeutic dose anticoagulation were enrolled and stratified into 4 groups based on creatinine clearance (CrCl): > 60 ml/min, 30–60 ml/min, ≤ 30 ml/min and hemodialysis-dependent. Tinzaparin 175 IU/kg was administered once daily for 5 days or until the INR was ≥ 2.0 with warfarin therapy. Trough anti-Xa levels were measured prior to the 3rd (day 3) and 5th (day 5) tinzaparin doses. Patients with an anti-Xa level > 0.5 IU/mL received tinzaparin dose adjustment using a standardized nomogram. Results: The relationship between anti-Xa levels and CrCl is shown in figure 1. One patient with a CrCl of 47 ml/min had a day 3 anti-Xa level of 0.62 IU/ml and required dose adjustment, resulting in a day 5 anti-Xa of 0.22 IU/ml. There has been one minor bleeding event (hematoma) following a traumatic intravenous catheter insertion. No major bleeding or recurrent VTE events have occurred. Conclusions: In a cohort of 32 patients with differing degrees of renal function including patients requiring hemodialysis, use of therapeutic-dose tinzaparin for 5 days does not appear to result in accumulation of the anticoagulant effects. There is no apparent correlation between anti-Xa level and renal function. Our results support ongoing evaluation of tinzaparin in patients with severe renal insufficiency. Figure 1. Anti-Xa levels an renal function Figure 1. Anti-Xa levels an renal function

Pharmacodynamics and Tolerance of Two Nadroparin Formulations (10,250 and 20,500 Anti Xa IU·ml-1) Delivered for 10 Days at Therapeutic Dose

1998 ◽  
Vol 79 (02) ◽  
pp. 338-341 ◽  
Author(s):  
C. Navarro ◽  
J. P. Cambus ◽  
H. Caplain ◽  
P. d’Azemar ◽  
J. Necciari ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Venous Thromboembolism ◽  
Healthy Volunteers ◽  
Total Dose ◽  
Therapeutic Dose ◽  
Low Molecular Weight Heparin ◽  
Dose Effect ◽  
Low Molecular Weight ◽  
High Dose ◽  
Circadian Effect

SummaryVenous thromboembolism may be efficiently treated by once-a-day (o.d.) administration of a high dose of low molecular weight heparin (LMWH) instead of administration of the same total dose in two injections a day (b.i. d.). To reduce the volume of the subcutaneous (s.c.) injection, a more concentrated form of the drug is advisable. This study was designed to compare the bioavailability of 2 formulations of nadroparin containing 10,250 and 20,500 anti-Xa IU·ml-1 respectively. This was an open, randomized, cross-over study where 12 healthy volunteers (age 18-35) were enrolled. They received either 90 anti-Xa IU·kg-1 b.i. d. of the 10,250 IU preparation (treatment A), or 180 anti-Xa IU·kg-1 o.d. of the 20,500 IU preparation (treatment B) for 10 days. On day 1, the subjects were sampled between 0 and 12 h (treatment A) or between 0 and 24 h (treatment B). On day 10, they were sampled between 0 and 12 h and between 12 and 24 h (treatment A) or between 0 and 24 h (treatment B). Anti-Xa and anti-IIa activities were determined by specific chromogenic assays. The main result of the study was that the bioavailability of the anti-Xa activity of the 2 nadroparin formulations was equivalent, as shown by the comparison of the AUC0-12 h plus AUC12-24 h (treatment A) and the AUC0-24 h (treatment B), calculated on day 10. This study also allowed a number of interesting observations to be made. 1) Between day 1 and day 10, there was an accumulation of the anti-Xa activity for treatment A but not for treatment B (accumulation factors: 1.6 and 1.1 respectively); 2) On day 10, the AUC0-12 h were slightly but significantly lower than the AUC12-24 h suggesting a circadian effect for anti-Xa and anti-IIa activities; 3) the clearance of the anti-Xa activity was comparable at the 2-dose regimens, while that of the anti-IIa activity was lower in treatment B than in treatment A, indicating a significant dose effect for the pharmacodynamics of the longer heparin chains; 4) On average, the clearance of the anti-IIa activity was twice as high as that of the anti-Xa activity; 5) For treatment B, significant APTT prolongations were noticed at Tmax (prolongation factor: 1.7 ± 0.25), in relation with the anti-IIa activity (0.3 ± 0.1 IU·ml–1).

Cost-Effectiveness Analysis of Warfarin Versus Low-Molecular Weight Heparin for the Treatment of Malignancy-Associated Venous Thromboembolism

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 746-746 ◽  
Author(s):  
Nathan T. Connell ◽  
Gregory A. Abel ◽  
Jean M. Connors
Keyword(s):  
Molecular Weight ◽  
Sensitivity Analysis ◽  
Cost Effectiveness ◽  
Major Bleeding ◽  
Odds Ratio ◽  
Low Molecular Weight Heparin ◽  
Low Molecular Weight ◽  
The Mean ◽  
Recurrent Vte ◽  
The Cost

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.

scholarly journals The anti-factor Xa range for low molecular weight heparin thromboprophylaxis

2015 ◽  
Vol 7 (4) ◽  
Author(s):  
Matthew Y. Wei ◽  
Salena M. Ward
Keyword(s):  
Molecular Weight ◽  
Low Molecular Weight Heparin ◽  
Dose Adjustment ◽  
Factor Xa ◽  
Research Data ◽  
Target Range ◽  
Low Molecular Weight ◽  
Low Molecular Weight Heparins ◽  
Therapeutic Doses ◽  
Venous Thromboses

Low molecular weight heparins (LMWHs) are now the mainstay option in the prevention and treatment of venous thromboembolism. In some patients receiving therapeutic doses of LMWH, activity can be measured by quantifying the presence of Anti-factor Xa (AFXa) for dose adjustment. However, currently there are no guidelines for LMWH monitoring in patients on thromboprophylactic, doses, despite certain patient populations may be at risk of suboptimal dosing. This review found that while the AFXa ranges for therapeutic levels of LMWHs are relatively well defined in the literature, prophylactic ranges are much less clear, thus making it difficult to interpret current research data. From the studies published to date, we concluded that a reasonable AFXa target range for LMWH deep venous thromboses prophylaxis might be 0.2-0.5 IU/mL.

scholarly journals Recurrent Venous Thromboembolism (VTE), Major Bleeding (MB), and Associated Cost of Treatment with Low Molecular Weight Heparin (LMWH) or Direct Oral Anticoagulant (DOAC) in High Risk Patients with Gastrointestinal (GI) Malignancies: Retrospective Real-World Analysis at a Comprehensive Cancer Center

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5057-5057 ◽  
Author(s):  
Alejandro Recio Boiles ◽  
Ali McBride ◽  
Hani M. Babiker ◽  
Nimer Alsaid ◽  
Ivo Abraham ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Venous Thromboembolism ◽  
High Risk ◽  
Adverse Events ◽  
Healthcare Costs ◽  
Low Molecular Weight Heparin ◽  
Low Molecular Weight ◽  
Major Bleed ◽  
Recurrent Vte ◽  
Event Rates

Abstract Introduction: Cancer patients who experienced a venous thromboembolism (VTE) are at high risk for poor clinical outcomes; hence VTE recurrence prevention is salient. Low molecular weight heparin (LMWH) has been the preferred treatment for cancer-related VTE; however, direct oral anticoagulants (DOACs) have been prescribed empirically in cancer due to patient convenience. Although the recent HOKUSAI and SELECT-D trials have confirmed the non-inferiority of DOACs to LMWH in the management of recurrent VTE in cancer patients, there remain a continued safety concern for major bleeds (MB). Recurrent VTE and MB complications during anticoagulation treatment of GI cancer (GICA) patients are increased as compared to other cancer types. The incremental health care costs associated with VTE recurrences and MB episodes are significant and steadily increasing. In this retrospective analysis, we aimed (1) to evaluate for differences in the VTE recurrence rate and MB events based on anticoagulation therapy (LMWH or DOAC) prescribed with a prior VTE and (2) to calculate the associated healthcare costs for six months of treatment. Methods: We reviewed the medical records of patients with biopsy-proven GICA and imaging documented VTE treated with DOAC or LMWH from November 2013 to February 2017. Patients were excluded if anticoagulation was given for another treatment indication or cancer diagnosis. Adverse events of recurrent VTE and MB criteria were defined per the Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Costs of LMWH and DOAC t was sourced from Medicare Reimbursement 2018. Hospital admission and adjusted 6-month ambulatory cots were sourced from Economic Evaluations of Anticoagulation Outcomes in the U.S. by Amin et al 2015. Costs were inflation-adjusted to 2018 cost levels using the Medical Care component of the Consumer Price Index. The Chi-squared test was used for overall and the Fisher exact test for pairwise comparisons of the proportions of patients experiencing VTE and MB events. Results: Our analysis included 106 patients on enoxaparin (N=40), rivaroxaban (N=37) and apixaban (N=29). Recurrent VTE outcomes at 6 months were 3 (7.5%) for enoxaparin, 1 (2.7%) for rivaroxaban, and 2 (6.8%), for apixaban (all p=n.s.) (Table 1). Major bleeding events at 6 months were 2 (5%) for enoxaparin, 2 (6.8%) for apixaban, and a significantly higher 8 (21.6%) for rivaroxaban (overall p=0.048; v. LMWH pairwise p=0.042; all other p=n.s.). The estimated composite costs associated with the observed recurrent VTE event rates were $173,130 for enoxaparin, $57,710 for rivaroxaban, and $115,420 for apixaban. The estimated composite costs associated with the observed MB event rates were $117,146 for enoxaparin and apixaban, versus $468,558 for rivaroxaban. The estimated total 6-months healthcare costs for recurrent VTE, MB and prescriptions were $293,784 for enoxaparin, $529,336 for rivaroxaban, and $235,634 for apixaban. Conclusion: Our real-world retrospective analysis corroborates a non-inferiority of DOACs to LMWH in preventing recurrent VTE in GICA patients at 6 months but a higher incidence of MB in rivaroxaban v. LMWH treated patients. The higher MB rate for rivaroxaban mainly accounts for the higher overall costs of this DOAC v. LMWH and apixaban. In absolute total costs, apixaban prevails over LMWH and rivaroxaban, and LMWH prevails over rivaroxaban in cost-efficiency in this analysis of anticoagulation in selected high-risk GICA patients. Rivaroxaban significantly increases medical costs, mainly driven by the total number of major bleed adverse events in GICA patients, confirming previously published evidence. The subpopulation of GICA patients at high risk of VTE/MB warrants an additional prospective clinical trial for primary safety major bleed outcomes of DOACs with an accompanying cost-effectiveness analysis. This may eventually reduce the healthcare economic burden. Disclosures Abraham: Sandoz: Consultancy.

scholarly journals Low Molecular Weight Heparin Protects Lung, Renal and Microcirculation Function in Patients with Covid-19 Pneumonia

2020 ◽  
Author(s):  
Li Ma ◽  
Yigang Zeng ◽  
Bing Zhao ◽  
LiLi Xu ◽  
Jian Li ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Renal Function ◽  
Lactic Acid ◽  
Acid Content ◽  
Low Molecular Weight Heparin ◽  
Arterial Oxygen ◽  
Control Group ◽  
Low Molecular Weight ◽  
Arterial Blood ◽  
Lactic Acid Content

Abstract BackgroundCoronavirus disease 2019 (Covid-19) remains a serious health threat worldwide. It is crucial to explore effective treatment measures that reduce mortality. Our aim was to investigate whether low molecular weight heparin (LMWH) can reduce organ injury in patients with Covid-19 pneumonia.MethodsA retrospective study was conducted at the Shanghai Public Health Clinical Center. We initiated a LMWH protocol from January 18th 2020. LMWH was injected subcutaneously at 4100U per day until the D-dimer(DD) level returned to normal, or 5-7 days after admission, whichever occurred first. Admitted patients who received LMWH between January 18th and February 17th 2020 were assigned to the LMWH group. Patients admitted between January 18th and February 17th who did not receive LMWH anticoagulant therapy were the control group. All patients in both groups were aged >18 years, were not pregnant, had no tumors and were in accordance with the following inclusion criteria: 1) DD increased on admission; 2) Body mass index(BMI) >30; 3) History of diabetes. The exclusion criteria were: 1) Platelets <30x109/L or fibrinogen <150 mg/dL; 2) Pregnancy and lactation; 3) Presence of blood system diseases; 4) Immunosuppression; 5) Diseases with a potential risk of bleeding; 6) Receiving anticoagulant drugs or antiplatelet drugs during treatment. General clinical information, indicators for renal function, arterial blood gas analyses and blood lactic acid content were recorded in the two groups 0 (Day 0), 3 (Day 3), 7 (Day 7), and 11 (Day 11) and 15 (Day 15) days after admission.ResultsThere were 48 patients in the LMWH group and 74 patients in the control group. General information, including age, gender, co-existing diseases and onset-to-admission time in both groups was similar. Compared to the control group, LMWH treatment improved the estimated glomerular filtration rate (eGFR) reduced the serum creatinine level (Scr), blood urea nitrogen (BUN)，arterial blood carbon dioxide partial pressure (PaCO2) and arterial blood lactic acid content. However, LMWH treatment reduced arterial oxygen partial pressure (PaO2) and arterial oxygen saturation (SaO2).ConclusionLMWH might be beneficial to improve renal function, CO2 discharge and microcirculation during the early phase of Covid-19 patients . Further randomized controlled trials(RCTs) are warranted in order to further investigate this issue.Trial registrationChiCTR, ChiCTR2000034796. Registered 19 July 2020 - Retrospectively registered, http:// www. chictr.org.cn/listbycreater.aspx.

Sign in / Sign up

Export Citation Format

Share Document