Low-Dose Warfarin for Prevention of Symptomatic Thromboembolism after Orthopedic Surgery

2005 ◽  
Vol 39 (6) ◽  
pp. 1002-1007 ◽  
Author(s):  
Jeremy J Enyart ◽  
Ronald J Jones
Keyword(s):  
Low Dose ◽  
Weighted Average ◽  
International Normalized Ratio ◽  
Odds Ratios ◽  
Vte Prophylaxis ◽  
Dose Warfarin ◽  
Total Knee ◽  
Observational Design ◽  
Warfarin Dosing ◽  
Event Rates

BACKGROUND: Warfarin dosing with a target international normalized ratio (INR) range of 1.5–2.5 has not been reported as adequate for venous thromboembolism (VTE) prophylaxis after total knee (TKR) and total hip replacement (THR) surgery. OBJECTIVE: To evaluate the rate of symptomatic VTE after TKR and THR surgery using a low-dose (INR 1.5–2.5) warfarin protocol started the evening before surgery compared with a literature cohort treated with enoxaparin. METHODS: TKR/THR patients treated with a 21-day low-dose warfarin protocol were followed via a consecutive observational design. Main outcome measures were symptomatic VTE and pulmonary embolism (PE), with major bleeds and death as secondary outcomes. Low-dose warfarin was compared with a literature cohort of patients treated with enoxaparin who received enoxaparin for a similar length of time and was evaluated for the same outcomes. Cohort event rates were derived as a weighted average using the DerSimonian model. RESULTS: VTE, PE, bleeds, and deaths in the low-dose warfarin group were 8 (1.04%), 4 (0.52%), 8 (1.04%), and 4 (0.52%), respectively. The cohort weighted average values were 35 (1.33%), 19 (0.72%), 65 (2.46%), and 18 (0.67%), respectively. Odds ratios for low-dose warfarin for VTE, PE, and VTE plus PE were 0.778 (95% CI 0.36 to 1.68), 0.717 (0.24 to 2.11), and 0.754 (0.41 to 1.42), respectively, all nonsignificant. Odds ratios for bleeds and death were 0.420 (0.20 to 0.87; p = 0.02) and 0.756 (0.26 to 2.24; NS), respectively. CONCLUSIONS: For this evaluation, low-dose warfarin was comparable to the enoxaparin cohort for development of VTE, PE, and VTE+PE. Incidences of bleeds in the enoxaparin cohort were significantly higher than in patients receiving low-dose warfarin.

Evaluation of dosing and safety outcomes of low-dose prophylactic warfarin in children after cardiothoracic surgery

2020 ◽  
Vol 77 (13) ◽  
pp. 1018-1025
Author(s):  
Maura Harkin ◽  
Brittany Powers Shaddix ◽  
Stephen B Neely ◽  
Leigh A Peek ◽  
Katy Stephens ◽  
...  
Keyword(s):  
Low Dose ◽  
Warfarin Dose ◽  
International Normalized Ratio ◽  
Primary Objective ◽  
Cardiothoracic Surgery ◽  
Entire Study Period ◽  
Entire Study ◽  
Frequent Monitoring ◽  
Safety Outcomes ◽  
Warfarin Dosing

Abstract Purpose Prophylactic warfarin with an International Normalized Ratio (INR) goal of 1.5 to 2.0 is one antithrombotic therapy utilized in children after cardiothoracic surgery (CTS); published sources suggest a dose of 0.1 mg/kg per day to achieve this goal. However, few studies have evaluated dosing in this population. The purpose of this study was to evaluate dosing and safety outcomes in children receiving warfarin after CTS. Methods A descriptive, retrospective review was conducted to evaluate warfarin dosing and INR outcomes in patients 18 years of age or younger who underwent CTS and received prophylactic warfarin with an INR goal of 1.5 to 2.0 from January 2014 through December 2018. The primary objective was to determine the median initial warfarin dose. Secondary objectives included identifying the percentage of documented INR values that were outside the therapeutic range, the percentage of patients with therapeutic INRs at discharge, and the 30-day readmission rate. Results Twenty-six patients were included in the review. The median initial warfarin dosage was 0.07 mg/kg/d (interquartile range [IQR], 0.05-0.10 mg/kg/d). Of the total of 177 INR values collected during the entire study period, 67 (37.9%) were therapeutic, 64 (36.2%) were subtherapeutic, and 46 (26.0%) were supratherapeutic. Eighteen patients (69.2%) had at least 1 supratherapeutic INR at any point during the study period, most frequently on days 2 through 4 of therapy. At discharge, 11 patients (42.3%) had therapeutic INRs. Four patients (15.4%) were readmitted within 30 days, with bleeding documented in 2 patients during their readmission. Conclusion The majority of patients received an initial warfarin dose less than that specified in published recommendations but still had a supratherapeutic INR at least once during the study period. When initiating warfarin after CTS, a dosage of <0.1 mg/kg per day and frequent monitoring may be needed to achieve an INR goal of 1.5 to 2.0.

Meta-Analyses of Randomised Controlled Trials (RCT) of Warfarin and Low Molecular Weight Heparin (LMWH) for the Prevention of Venous Thromboembolism (VTE) and Death in Cancer Patients.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 909-909 ◽  
Author(s):  
Keith Wheatley ◽  
Laura E. Gross ◽  
Robert K. Hills ◽  
Annie M. Young
Keyword(s):  
Cancer Patients ◽  
Survival Data ◽  
Low Dose ◽  
Meta Analysis ◽  
Oral Anticoagulants ◽  
Clinical Problem ◽  
Vte Prophylaxis ◽  
Dose Warfarin ◽  
Randomised Controlled ◽  
Meta Analyses

Abstract VTE is a common clinical problem in cancer patients. Uncertainty remains as to whether prophylactic treatment of oral anticoagulants (mainly warfarin) or LMWHs, given by subcutaneous injection, is beneficial and practice varies widely. It has been proposed that anticoagulant therapy may also improve survival in cancer patients. The largest trial of VTE prophylaxis in cancer patients with central venous catheters (CVCs), WARP, has just been completed and showed no apparent benefit for low dose warfarin - among 811 patients randomised to low dose warfarin versus not, the VTE rate was 5% in both arms (odds ratio [OR]=1.04, 95% confidence interval [CI]=0.56–1.92, p=1.0) and mortality was not reduced (OR=1.02, CI=0.74–1.4, p=0.8) (Young et al., ASCO, 2005, LBA8004). This result needs to be put in the context of other RCTs of prophylaxis with anticoagulants, so we performed a meta-analysis to evaluate the effect of warfarin and LMWH on VTE rates and cancer mortality. Computerized searches for trials were performed, including MedLine, Embase, NCI trials register, ASCO and ASH meeting abstracts. Standard meta-analysis methods were used and the results presented as ORs and CIs, with heterogeneity of treatment effect between trials examined using tests for interaction. In 5 trials (n=1355 patients) of warfarin v. not, there was no clear evidence of a decrease in VTEs (OR=0.68, CI=0.46–1.01, p=0.06). An additional 3 trials (n=2034 for all 8 trials) had survival data and there was no clear evidence of a decrease in mortality (OR=0.88, CI=0.77–1.01, p=0.06). In 5 trials (n=793) of LMWH v. not, VTE rate was reduced (OR=0.53, CI=0.32–0.87, p=0.01). 6 trials (n=1295) contained survival data and mortality was reduced with LMWH (OR=0.79, CI=0.67–0.92, p=0.003). In 3 trials (n=985) of LMWH v. oral anti-coagulation (mainly with warfarin), VTE rates were lower with LMWH (OR=0.46, CI=0.32–0.67, p<0.0001) but no mortality benefit was observed (OR=0.89, CI=0.72–1.1, p=0.3). The results of these preliminary meta-analyses suggest that LMWH is the preferred form of prophylaxis for VTE in cancer patients and that overall, there may be an anti-tumour effect, leading to a survival benefit.

Incidence of venous thromboembolic (VTE) in chronic lymphocytic leukemia (CLL) patients (pts) treated with immunomodulating agents (IMiDs)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 8625-8625
Author(s):  
D. Depaolo ◽  
K. Miller ◽  
L. Musial ◽  
P. Marshall ◽  
J. Coignet ◽  
...  
Keyword(s):  
Low Dose ◽  
Dose Range ◽  
Single Agent ◽  
Lymphocytic Leukemia ◽  
Clinical Activity ◽  
Vte Prophylaxis ◽  
Dose Warfarin ◽  
Venous Thromboembolic ◽  
Baseline Incidence ◽  
Available Information

8625 Introduction: We recently reported the clinical activity of IMiDs (both thalidomide (T) and lenalidomide (L)) in pts with CLL. VTE is a commonly reported complication of these agents requiring prophylaxis. Most available information is in pts treated for multiple myeloma (MM), a disease with a high baseline incidence of VTE. To determine whether the incidence of IMiDs associated VTE is similar in CLL pts we reviewed all CLL pts treated with IMiDs at our institute. Method: All CLL pts treated at our institute with T or L either alone or in combination with other antileukemic agents such as rituximab (R) or fludarabine (F)) were evaluable for this analysis. All pts were treated on IRB approved clinical trials and signed informed consent. Prophylaxis for VTE was recorded. Dose range for T was 100–300mg/day, while that of L was 5–25mg/day. Results: To date a total of 55 pts (35 on L and 20 on T) are treated with IMiDs at our center. All pts treated with L received single agent L while those treated with T received concurrent F (FT). All T treated pts also received low-dose warfarin (1 or 2 mg for body weight ≤ or > than 70 kg respectively) for VTE prophylaxis. No prophylaxis was given to L treated pts. VTE was noted in 2 (6%) pts on L and 2 (10%) on FT. Thus the cumulative incidence of IMiDs associated VTE in CLL pts at our center was 7% (4/55). Conclusion: VTE is a known side effect of IMiDs. Its incidence in CLL treated pts is unknown. Our experience with both T and L in CLL pts suggest that VTE remains a concern in this pt population as well though the incidence may be lower. Three other studies investigated T either alone (n=28)1, with F (n=18)2 or with dexamethasone/cyclophosphamide (n=3)3. Only 1 episode of VTE was reported in these studies.3 Our current analysis failed to reveal any apparent risk factors for VTE in CLL pts treated with IMiDs. Several pts on the L clinical trial continue to be on therapy. Updated results with prolonged L treatment will be presented at the meeting. 1. Kay N et al: ASH 2003 2. Furman RR et al: ASCO 2005 3. Trompeter S et al: IWCLL 2005 [Table: see text]

scholarly journals Continuous use of low-dose warfarin for gastric endoscopic submucosal dissection: a prospective study

2017 ◽  
Vol 05 (05) ◽  
pp. E348-E353 ◽  
Author(s):  
Hideaki Harada ◽  
Satoshi Suehiro ◽  
Daisuke Murakami ◽  
Takanori Shimizu ◽  
Ryotaro Nakahara ◽  
...  
Keyword(s):  
Endoscopic Submucosal Dissection ◽  
Low Dose ◽  
Postoperative Bleeding ◽  
Warfarin Dose ◽  
International Normalized Ratio ◽  
Safety And Efficacy ◽  
Submucosal Dissection ◽  
Day Range ◽  
Dose Warfarin ◽  
Significant Difference

Abstract Background and study aims Patients who receive warfarin usually require heparin bridge therapy (HBT) to prevent thromboembolic events during endoscopic submucosal dissection (ESD); however, clinical evidence demonstrating the safety and efficacy of HBT during gastric ESD is limited. Conversely, warfarin can be continuously used as a substitute for HBT to endoscopic procedures which have a low risk of bleeding. This study aimed to clarify the safety and efficacy of continuous low-dose warfarin (LDW) for gastric ESD. Patients and methods This was a prospective observational study at a single institution. A total of 22 patients who received warfarin between December 2014 and January 2016 were enrolled. The patients were treated with gastric ESD with a low dose of warfarin ( ≤ 4 mg) at approximately 1.6 – 2.6 of the international normalized ratio (INR) levels. Furthermore, we analyzed a total of 23 patients with HBT who underwent gastric ESD between January 2011 and November 2014. Results The average of warfarin dose and the INR level on the day of gastric ESD in the continuous LDW group were 2.3 mg/day (range 0.5 – 4.0) and 1.87 (range 1.41 – 2.75), respectively. Two of the 22 patients (9.1 %) in the continuous LDW group and 5 of the 23 patients (21.7 %) in the HBT group had postoperative bleeding after gastric ESD. Although the postoperative bleeding rate in the continuous LDW group was lower than that in the HBT group, no significant difference was observed between the 2 groups (P = 0.414). Conclusions Gastric ESD with continuous LDW as a substitute for HBT was feasible and may be acceptable.

Weight Adjusted Low-Dose Warfarin Decreases the Incidence of Thalidomide (T) Associated Venous Thromboembolism (VTE) in Patients (pts) with Multiple Myeloma (MM) and Waldenstroms Macroglobulinemia (WM).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4101-4101
Author(s):  
Kena C. Miller ◽  
Rami Manochakian ◽  
Swaminathan Padmanabhan ◽  
Jean-Gabriel Coignet ◽  
Laurie Musial ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Low Dose ◽  
Bleeding Complications ◽  
Actual Body Weight ◽  
Not Given ◽  
Vte Prophylaxis ◽  
Dose Warfarin ◽  
Is Development ◽  
First Time

Abstract Introduction: T is an effective antimyeloma therapy. An important and problematic side effect of T is development of VTE. The underlying etiology of T associated VTE remains unknown, though a definite rise in its incidence is recorded when combined with other antimyeloma therapies such as dexamethasone (15%) and doxorubicin (26%). Defining an optimal way to prevent T associated VTE is important to improve patient’s quality of life and safety of T. We prospectively investigated the use of weight-adjusted, low-dose warfarin to decrease the incidence of VTE among pts treated with T based regimens. Methods: All pts treated with T-based therapies, at our institute were given VTE prophylaxis with 1 vs. 2mg warfarin for actual body weight &lt;70 kg vs. ≥ 70 kg, respectively. Concurrent aspirin or other anticoagulants were not given. Pts with underlying pre-existing hypercoaguable disorders were fully anticoagulated with warfarin and were excluded from this analysis. Warfarin was continued throughout the duration of T therapy. Results: A total of 80 pts, 60 years (range 43–82), 35M and 45F are included in this analysis. Sixty three had stage III and 14 had ≤ stage II MM while 3 pts had WM. T was given with dex in 58 (72%) with dox in 57(71%) and with bortezomib in 32 (40%). Table 1 outlines the T based regimens used. IgG MM was noted in 39, IgA in 20 and 31 had other types of MM. Median T dose was 200 mg (range 50–300) and the median duration 4 months (range 1–6 months). Thirty two pts received 1mg and 48 received 2mg warfarin. Overall incidence of VTE was 6.25% (n=5). There were no bleeding complications noted with the use of warfarin in this pt population. Conclusion: Our study demonstrates for the first time that a weight adjusted low-dose warfarin approach in MM pts decreases the incidence of T associated VTE and can be safely instituted in pts treated with this important anti-myeloma therapy. Interestingly, none of the pts who received T with Doxil experienced any episode of VTE. Regimen No. of Patients Thalidomide Alone 1 Dexamethasone + Thalidomide 28 Bortezomib + Doxil + Thalidomide 24 VAD + Thalidomide 22 Bortezomib + Cyclophosphmaide + Dexamethasone + Thalidomide 5

Low-dose warfarin prophylaxis to prevent symptomatic pulmonary embolism after total knee arthroplasty

1997 ◽  
Vol 12 (2) ◽  
pp. 180-184 ◽  
Author(s):  
Jay R. Lieberman ◽  
Roger Sung ◽  
Frederick Dorey ◽  
Bert J. Thomas ◽  
Douglas J. Kilgus ◽  
...  
Keyword(s):  
Pulmonary Embolism ◽  
Total Knee Arthroplasty ◽  
Knee Arthroplasty ◽  
Low Dose ◽  
Symptomatic Pulmonary Embolism ◽  
Dose Warfarin ◽  
Total Knee

Venous thromboembolism in a general hospital. An update with low molecular weight heparin prophylaxis

VASA ◽  
2007 ◽  
Vol 36 (1) ◽  
pp. 17-22
Author(s):  
Schulz ◽  
Kesselring ◽  
Seeberger ◽  
Andresen
Keyword(s):  
Molecular Weight ◽  
Pulmonary Embolism ◽  
Venous Thromboembolism ◽  
Low Molecular Weight ◽  
Trauma Patients ◽  
Vte Prophylaxis ◽  
Vein Thrombosis ◽  
Patients At Risk ◽  
Hospital Stays ◽  
Event Rates

Background: Patients admitted to hospital for surgery or acute medical illnesses have a high risk for venous thromboembolism (VTE). Today’s widespread use of low molecular weight heparins (LMWH) for VTE prophylaxis is supposed to have reduced VTE rates substantially. However, data concerning the overall effectiveness of LMWH prophylaxis is sparse. Patients and methods: We prospectively studied all patients with symptomatic and objectively confirmed VTE seen in our hospital over a three year period. Event rates in different wards were analysed and compared. VTE prophylaxis with Enoxaparin was given to all patients at risk during their hospital stay. Results: A total of 50 464 inpatients were treated during the study period. 461 examinations were carried out for symptoms suggestive of VTE and yielded 89 positive results in 85 patients. Seventy eight patients were found to have deep vein thrombosis, 7 had pulmonary embolism, and 4 had both deep venous thrombosis and pulmonary embolism. The overall in hospital VTE event rate was 0.17%. The rate decreased during the study period from 0.22 in year one to 0,16 in year two and 0.13 % in year three. It ranged highest in neurologic and trauma patients (0.32%) and lowest (0.08%) in gynecology-obstetrics. Conclusions: With a simple and strictly applied regimen of prophylaxis with LMWH the overall rate of symptomatic VTE was very low in our hospitalized patients. Beside LMWH prophylaxis, shortening hospital stays and substantial improvements in surgical and anasthesia techniques achieved during the last decades probably play an essential role in decreasing VTE rates.

Relationship Between Total Prothrombin, Native Prothrombin and the International Normalized Ratio (INR)

1992 ◽  
Vol 68 (02) ◽  
pp. 160-164 ◽  
Author(s):  
P J Braun ◽  
K M Szewczyk
Keyword(s):  
Anticoagulant Therapy ◽  
Oral Anticoagulant ◽  
Inverse Relationship ◽  
Low Dose ◽  
Oral Anticoagulant Therapy ◽  
International Normalized Ratio ◽  
Antigen Assay ◽  
Dose Oral ◽  
Anticoagulated Patients ◽  
Sensitive Method

SummaryPlasma levels of total prothrombin and fully-carboxylated (native) prothrombin were compared with results of prothrombin time (PT) assays for patients undergoing oral anticoagulant therapy. Mean concentrations of total and native prothrombin in non-anticoagulated patients were 119 ± 13 µg/ml and 118 ± 22 µg/ml, respectively. In anticoagulated patients, INR values ranged as high as 9, and levels of total prothrombin and native prothrombin decreased with increasing INR to minimum values of 40 µg/ml and 5 µg/ml, respectively. Des-carboxy-prothrombin increased with INR, to a maximum of 60 µg/ml. The strongest correlation was observed between native prothrombin and the reciprocal of the INR (1/INR) (r = 0.89, slope = 122 µg/ml, n = 200). These results indicated that native prothrombin varied over a wider range and was more closely related to INR values than either total or des-carboxy-prothrombin. Levels of native prothrombin were decreased 2-fold from normal levels at INR = 2, indicating that the native prothrombin antigen assay may be a sensitive method for monitoring low-dose oral anticoagulant therapy. The inverse relationship between concentration of native prothrombin and INR may help in identification of appropriate therapeutic ranges for oral anticoagulant therapy.

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