Warfarin-associated coagulopathy is a frequent clinical complication. We aimed to assess whether treatment with vitamin K is safe and more effective than placebo in rapidly lowering the international ...normalised ratio (INR) into the therapeutic range in over anticoagulated patients receiving warfarin.
We did a multicentre, double-blind, placebo-controlled, randomised trial in five tertiary care hospitals. In this study, patients receiving warfarin who had an INR value between 4·5 and 10·0, and who did not have an indication for the immediate normalisation of their INR, had their warfarin withheld, and were randomly allocated to receive either 1 mg of vitamin K or placebo orally. The primary outcome measure was the INR value on the day after treatment. Secondary outcome measures included INR values on subsequent days, and the risk of haemorrhage and recurrent thrombosis over a 3 month follow-up period.
Patients given vitamin K had a more rapid decrease in the INR than those given placebo (25 of 45 56% vs nine of 44 20% patients with INR values of 1·8–3·2 on the day after treatment, respectively, p=0·001; odds ratio OR 0·21, 95% CI 0·07–0·57). Fewer patients given vitamin K had bleeding episodes during the follow-up period than those given placebo (two 4% vs eight 17% patients, respectively, p=0·050; OR 0·87, 95% CI 0·019–0·999).
Low dose oral vitamin K is more effective than placebo for the rapid lowering of raised INR values in patients taking warfarin.
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DOBA, GEOZS, IJS, IMTLJ, IZUM, KILJ, KISLJ, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SIK, UILJ, UKNU, UL, UM, UPCLJ, UPUK, VSZLJ
Acute venous thromboembolism is usually treated with a five-to-seven-day course of unfractionated or low-molecular-weight heparin, followed by a three-month course of oral anticoagulant therapy.
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...Subgroup analyses of the results of a number of recent studies suggest that, after anticoagulant therapy is stopped, the risk of recurrent venous thromboembolism is greater among patients who have a persistent risk factor for thrombosis and those whose initial episode of thrombosis occurred in the absence of an apparent risk factor than it is among patients in whom thrombosis develops in association with a transient risk factor, such as surgery.
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On the basis of . . .
Abstract
Background
The PeriOperative ISchemia Evaluation-2 (POISE-2) trial compared aspirin with placebo after noncardiac surgery.
Methods
The authors randomly assigned 10,010 patients undergoing ...noncardiac surgery to receive 200 mg aspirin or placebo 2 to 4 h before surgery and then 100 mg aspirin daily or placebo daily for up to 30 days after surgery. Herein, the authors report the effect of aspirin on venous thromboembolism (VTE), including deep vein thrombosis and pulmonary embolism, as well as an updated pooled analysis of randomized trials of antiplatelet therapy for VTE prevention in noncardiac surgery patients.
Results
Six thousand five hundred forty-eight patients (65.4%) received anticoagulant prophylaxis. VTE occurred in 53 patients (1.1%) allocated to aspirin and in 60 patients (1.2%) allocated to placebo (hazard ratio, 0.89; 95% CI, 0.61 to 1.28). Major or life-threatening bleeding occurred in 312 patients (6.3%) allocated to aspirin and in 256 patients (5.1%) allocated to placebo (hazard ratio, 1.22; 95% CI, 1.04 to 1.44). Concomitant use of anticoagulant prophylaxis did not modify the effect of aspirin on VTE or bleeding. Pooled analysis of the POISE-2 and Pulmonary Embolism Prevention trials demonstrated that symptomatic VTE occurred in 173 (1.3%) of 13,724 patients allocated to aspirin and in 246 (1.8%) of 13,730 patients allocated to placebo (odds ratio, 0.71; 95% CI, 0.56 to 0.89; heterogeneity P = 0.27; I2 = 17%); the impact of aspirin was very similar in those who did and did not receive pharmacologic prophylaxis. Pooled estimates for symptomatic VTE were similar to the pooled estimates for any deep vein thrombosis and pulmonary embolism from the POISE-2 trial, Pulmonary Embolism Prevention trial, and the Antiplatelet Trialists’ Collaboration meta-analysis.
Conclusions
Aspirin in the POISE-2 trial did not reduce VTE, but two thirds of patients received anticoagulant prophylaxis, there were few VTE events, and results were consistent with a wide range of aspirin effects. A pooled analysis of the randomized trials demonstrates evidence for the efficacy of aspirin for VTE prevention in hospitalized surgical patients.
The risk of major bleeding in association with perioperative management of vitamin K antagonists is about 3% according to systematic reviews. We performed this study to evaluate the safety of ...perioperative management of dabigatran using a specified protocol.
Patients at least 18 years old, treated with dabigatran and planned for an invasive procedure were eligible for inclusion. The last dose of dabigatran before the procedure was at 24 h (creatinine clearance CrCl > 50 mL/min and standard bleeding risk), 48 h (CrCl 31-50 mL/h or increased bleeding risk) or 96 h (CrCl 31-50 mL/h and increased bleeding risk). Resumption was in the evening of the procedure with the first dose of 75 mg (hemostasis secured and low bleeding risk), postop day 1, 2 or 3, depending on the complexity of the surgery and consequences of a bleeding complication; all prespecified. Patients were followed for 30 days for major bleeding (primary outcome), minor bleeding, arterial thromboembolism and death and an independent committee adjudicated these events by. We calculated a sample size of 283 cases to exclude a doubling of major bleeding compared to historical warfarin with heparin bridging. The study was funded by Heart and Stroke Foundation Canada.
We included 286 patients, mean age of 70.6 years (standard deviation, 11.7), 44 (15%) patients had CrCl 31-50 mL/min and 2 (0.7%) had 30 mL/min or less. The planned procedure was considered as “increased bleeding risk” in 102 (36%) patients. The last dose of dabigatran was at 24, 48 and 96 h before surgery in 160, 103 and 23 patients, respectively. Resumption with 75 mg the same day was in 139 patients. Major bleeding occurred in 3 patients (1.05%; 2 adjudicated so far); a 70-year-old male underwent ultrasound-guided drainage of abdomen and was readmitted after 17 days due to rectal bleeding and light headedness; the second patient, an 81-year-old male bled more than expected during the procedure of wide resection of myxosarcoma with free flap rotation and received blood transfusions during surgery, and a 69-year-old male bled 1200 mL during hip revision arthroplasty and received 3 units of red cells. Minor bleeding was observed in 9 adjudicated cases and reported in 10 additional, so far not adjudicated, cases. There were no strokes, systemic emboli, transient ischemic attacks, venous thromboembolic events or deaths. Three serious adverse events were reported (chest pain, congestive heart failure, wound infection)
With our protocol for perioperative management of dabigatran the risk of major bleeding compares favorably with historical data on vitamin K antagonists.
Schulman:Bayer Healthcare: Consultancy, Honoraria, Research Funding; Boehringer Ingelheim: Consultancy, Honoraria, Research Funding. Off Label Use: Dabigatran etexilate is an oral direct thrombin inhibitor approved for the prevention of stroke in patients with atrial fibrillation and (outside the US) for prevention of venous thromboembolism in patients undergoing total hip or knee replacement. This presentation includes discussion of the following off-label use of dabigatran: treatment of venous thromboembolism. Douketis:Boehringer Ingelheim: Consultancy, Honoraria. Lee:Boehringer Ingelheim: Honoraria. Heddle:CIHR: Research Funding; Canadian Blood Services: Membership on an entity's Board of Directors or advisory committees, Research Funding; Health Canada: Research Funding.
Procedures performedNAbdominal (bowel resection, etc.)6Urogenital9Vascular (by-pass, EVAR)6Heart surgery, major2Thoracic (lung, pleura)3Brain surgery or biopsy2Orthopedic (arthroplasty, spine, wrist)10Tumor resection, large3Eye surgery11Dental surgery4Skin surgery2Endoscopies (gastroduodeno-, colon-, hystero-)37Biopsies, centesis, epidural injections9Pacemaker/defibrillator insertion43Cardiac catheterization66Ablation for atrial fibrillation68Neck surgery, rhizotomy5
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
BACKGROUND Our objective was to systematically review the incidence of deep vein thrombosis (DVT) and the efficacy of thromboprophylaxis in critically ill adults, including patients admitted to ...intensive care units and following trauma, neurosurgery, or spinal cord injury. METHODS Two authors independently searched MEDLINE, EMBASE, abstract databases, and the Cochrane database. Data were extracted independently in triplicate. RESULTS Ten percent to 30% of medical and surgical intensive care unit patients develop DVT within the first week of intensive care unit admission. The use of subcutaneous low-dose heparin reduced the rate by 50% compared with no prophylaxis. Approximately 60% of trauma patients developed DVT within the first 2 weeks of admission. Use of unfractionated heparin appears to decrease the incidence of DVT by only 20%, whereas low-molecular-weight heparin decreases the incidence by a further 30%. The estimated prevalence of DVT in neurosurgical patients not given prophylaxis is 22% to 35%. Mechanical prophylaxis is efficacious, with a pooled odds ratio in 5 randomized trials of 0.28. Use of low-molecular-weight heparin has been investigated as an adjunct to mechanical prophylaxis with a pooled odds ratio of 0.59 compared with graduated compression stockings alone. The incidence of DVT without prophylaxis in acute spinal cord injury patients is likely in excess of 50% to 80%. Studies of prophylaxis in these patients are too sparse to come to any definitive conclusion. CONCLUSIONS Critically ill patients commonly develop DVT, with rates that vary from 22% to almost 80%, depending on patient characteristics. Methods of prophylaxis proven in one group do not necessarily generalize to other critically ill patient groups. More potent prophylactic regimens other than unfractionated or low-molecular-weight heparins alone may be needed with higher-risk groups.Arch Intern Med. 2001;161:1268-1279-->
...ultrasound will also inaccurately diagnose some patients with DVT who do not have DVT by venogram, highlighting the false-positive rate of CUS. ...Robinson et al 21 performed CUS and venography in ...a large group of asymptomatic patients at high risk of VTE at the time of hospital discharge; in this study, 6 of 19 positive CUSs were not confirmed by venography. ...we have recently demonstrated in a cohort of 261 critically ill patients that none of 6 commercial d-dimer assays were able to reliably predict DVT developing in critically ill patients undergoing serial monitoring with compression ultrasonography 39.4 Summary There is no diagnostic test for DVT that is both highly accurate and feasible in medical-surgical ICU patients.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Patients with mechanical heart valves (MHV) require temporary interruption of warfarin when undergoing invasive procedures. Current guidelines addressing this subject are discordant because there is ...no high quality evidence to support any single management strategy. We tested the hypothesis that there is significant practice variation amongst clinicians caring for patients with MHV who require temporary cessation of their warfarin therapy.
A survey describing 4 hypothetical patients with mechanical heart valves was distributed to all clinicians attending an anticoagulation specialty meeting. For each scenario, the attendee was given several choices for preoperative and postoperative anticoagulation management. Information about each respondent's profession, specialty and the frequency with which they make perioperative anticoagulation recommendations was also collected.
Three hundred twenty-four of 650 surveys were returned. In each of the case scenarios, a majority of respondents selected subcutaneous low molecular weight heparin (LMWH) or subcutaneous unfractionated heparin (UH) as the preferred pre- and postoperative anticoagulant. Significant variation in practice was noted: for none of the questions was a single strategy selected by greater than 80% of respondents.
Expert clinicians differ in their perioperative management strategies for patients with MHV who require interruption of warfarin. Although subcutaneous LMWH/UH was the treatment of choice in all scenarios, the lack of consensus found in our survey highlights the need for randomized controlled clinical trials of peri-procedural anticoagulant therapy. This survey of anticoagulation experts reveals that there is significant practice variation in scenarios where temporary interruption of warfarin is necessary in patients with mechanical heart valves. Despite discordant guidelines and a lack of high-quality data to support any strategy, a majority of the respondents surveyed would use low molecular weight heparin (or subcutaneous unfractionated heparin) to anticoagulate patients with mechanical heart valves during the peri-operative period.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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