ABSTRACTPulmonary embolism is a common and potentially fatal cardiovascular disorder that must be promptly diagnosed and treated. The diagnosis, risk assessment, and management of pulmonary embolism ...have evolved with a better understanding of efficient use of diagnostic and therapeutic options. The use of either clinical probability adjusted or age adjusted D-dimer interpretation has led to a reduction in diagnostic imaging to exclude pulmonary embolism. Direct oral anticoagulation therapies are safe, effective, and convenient treatments for most patients with acute venous thromboembolism, with a lower risk of bleeding than vitamin K antagonists. These oral therapeutic options have opened up opportunities for safe outpatient management of pulmonary embolism in selected patients. Recent clinical trials exploring the use of systemic thrombolysis in intermediate to high risk pulmonary embolism suggest that this therapy should be reserved for patients with evidence of hemodynamic compromise. The role of low dose systemic or catheter directed thrombolysis in other patient subgroups is uncertain. After a diagnosis of pulmonary embolism, all patients should be assessed for risk of recurrent venous thromboembolism to guide duration of anticoagulation. Patients with a venous thromboembolism associated with a strong, transient, provoking risk factor can safely discontinue anticoagulation after three months of treatment. Patients with an ongoing strong risk factor, such as cancer, or unprovoked events are at increased risk of recurrent events and should be considered for extended treatment. The use of a risk prediction score can help to identify patients with unprovoked venous thromboembolism who can benefit from extended duration therapy. Despite major advances in the management of pulmonary embolism, up to half of patients report chronic functional limitations. Such patients should be screened for chronic thromboembolic pulmonary hypertension, but only a small proportion will have this as the explanation of their symptoms. In the remaining patients, future studies are needed to understand the pathophysiology and explore interventions to improve quality of life.
Treatment of Venous Thromboembolism Wells, Philip S; Forgie, Melissa A; Rodger, Marc A
JAMA : the journal of the American Medical Association,
02/2014, Letnik:
311, Številka:
7
Journal Article
Recenzirano
IMPORTANCE Venous thromboembolism (VTE), comprising deep vein thrombosis (DVT) and pulmonary embolism (PE), is a common, potentially lethal condition with acute morbidity. OBJECTIVE To review the ...etiology of VTE and the 3 phases of VTE treatment: acute (first 5-10 days), long-term (from end of acute treatment to 3-6 months), and extended (beyond 3-6 months). EVIDENCE REVIEW Cochrane reviews, meta-analyses, and randomized controlled trials, as well as other clinical trials for topics not covered by the former, were reviewed. Literature searches using broad terms were used to find meta-analyses published in the last 15 years. The ninth edition of the American College of Chest Physicians Antithrombotic Therapy Guidelines was used to supplement the literature search. Guidelines from specialty organizations were consulted when relevant. The Canadian Agency for Drugs and Technologies in Health was searched for relevant cost-effectiveness studies. We also searched our own literature database of 8386 articles for relevant research. FINDINGS Low-molecular-weight heparin (LMWH) along with with vitamin K antagonists and the benefits and proven safety of ambulation have allowed for outpatient management of most cases of DVT in the acute phase. Development of new oral anticoagulants further simplifies acute-phase treatment and 2 oral agents can be used as monotherapy, avoiding the need for LMWH. Patients with PE can also be treated in the acute phase as outpatients, a decision dependent on prognosis and severity of PE. Thrombolysis is best reserved for severe VTE; inferior vena cava filters, ideally the retrievable variety, should be used when anticoagulation is contraindicated. In general, DVT and PE patients require 3 months of treatment with anticoagulants, with options including LMWH, vitamin K antagonists, or direct factor Xa or direct factor IIa inhibitors. After this time, decisions for further treatment are based on balancing the risk of VTE recurrence, determined by etiology of the VTE (transient risk factors, unprovoked or malignancy associated), against the risk of major hemorrhage from treatment. Better prediction tools for major hemorrhage are needed. Experience with new oral anticoagulants as acute, long-term, and extended therapy options is limited as yet, but as a class they appear to be safe and effective for all phases of treatment. CONCLUSIONS AND RELEVANCE The mainstay of VTE treatment is anticoagulation, while interventions such as thrombolysis and inferior vena cava filters are reserved for limited circumstances. Multiple therapeutic modes and options exist for VTE treatment with small but nonetheless important differential effects to consider. Anticoagulants will probably always increase bleeding risk, necessitating tailored treatment strategies that must incorporate etiology, risk, benefit, cost, and patient preference. Although great progress has been made, further study to understand individual patient risks is needed to make ideal treatment decisions.
Background Previous studies regarding survival in patients with splanchnic vein thrombosis (SVT) are limited. This study measured overall survival in a large cohort of SVTs through linkage to ...population-based data. Methods and Results Using a previously derived text-search algorithm, we screened the reports of all abdominal ultrasound and contrast-enhanced computed tomography studies at The Ottawa Hospital over 14 years. Screen-positive reports were manually reviewed by at least 2 authors to identify definite SVT cases by consensus. Images of uncertain studies were independently reviewed by 2 radiologists. One thousand five hundred sixty-one adults with SVT (annual incidence ranging from 2.8 to 5.9 cases/10 000 patients) were linked with population-based data sets to measure the presence of concomitant cancer and survival status. Thrombosis involved multiple veins in 314 patients (20.1%), most commonly the portal vein (n=1410, 90.3%). Compared with an age-sex-year matched population, patients with SVT had significantly reduced survival in particular with local cancer (adjusted relative excess risk for recent cases 12.0 95% CI, 9.8-14.6 and for remote cases 9.7 7.7-12.2), distant cancer (relative excess risk for recent cases 5.7 4.5-7.3 and for remote cases 5.4 4.4-6.6), cirrhosis (relative excess risk 8.2 5.3-12.7), and previous venous thromboembolism (relative excess risk 3.8 2.4-6.0). One hundred fifty (23.9%) of patients >65 years of age were anticoagulated within 1 month of diagnosis. Conclusions SVT is more common than expected. Most patients have cancer and the portal vein is by far the most common vein involved. Compared with the general population, patients with SVT had significantly reduced survival, particularly in patients with concomitant cancer, cirrhosis, and previous venous thromboembolic disease. Most elderly patients did not receive anticoagulant therapy.
Therapies for Venous Thromboembolism—Reply Wells, Philip S; Forgie, Melissa A; Rodger, Marc A
JAMA : the journal of the American Medical Association,
06/2014, Letnik:
311, Številka:
24
Journal Article
Summary
The deletion/deletion (D/D) genotype of the angiotensin converting enzyme (ACE) has been purported to be a risk for postoperative thrombosis. This D/D genotype has not been evaluated as a ...risk factor for idiopathic venous thromboembolism (VTE).
The primary objective of the present study was to determine whether the D/D genotype of ACE is independently associated with the occurrence of idiopathic venous thromboembolic disease.
We prospectively enrolled consecutive patients with at least one objectively confirmed idiopathic VTE. Friends of cases were recruited as controls and matched to cases by sex, ethnicity, and age. Patients were tested for the ACE I/D polymorphism in addition to factor V Leiden, prothrombin G20210A, and factor VIII levels.
Three hundred cases and 300 controls were enrolled; 97% were Caucasian. There were 148 females and 152 males in each group with a mean age of 56.21 years (SD=15.33). The ACE D/D genotype was present in 25.3% of cases and 32.4% of controls for an adjusted odds ratio of 0.66 (95% CI = 0.433 to 0.997). We can conclude that the ACE D/D genotype is protective against idiopathic venous thromboembolism.
BACKGROUND Low-molecular-weight heparins (LMWHs) are now standard therapy for the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE). No published trials have compared LMWHs, and few ...studies have examined outpatient therapy for PE. Only tinzaparin sodium has demonstrated superiority to unfractionated heparin in a clinical trial. METHODS We compared 2 LMWH products, tinzaparin and dalteparin sodium, for the treatment of acute DVT and PE in a randomized, controlled clinical trial of consecutive outpatients presenting to a venous thromboembolism service at 4 tertiary-care hospitals. Patients were treated with subcutaneous tinzaparin sodium, 175 IU/kg every 24 hours, or subcutaneous dalteparin sodium, 200 IU/kg every 24 hours, for at least 5 days. Warfarin sodium therapy was started simultaneously and continued for 90 days. The primary end point was efficacy (recurrence of venous thromboembolism); safety (bleeding) was a composite end point. RESULTS Two hundred fifty-four patients received tinzaparin (39 with PE and 215 with DVT) and 251 received dalteparin (51 with PE and 200 with DVT). Most patients had an active malignancy or idiopathic DVT/PE. The outcome events occurred in 11 (4.4%; 95% confidence interval CI, 2.2%-7.7%) and 15 patients (5.9%; 95% CI, 3.3%-9.5%) in the dalteparin and tinzaparin groups, respectively, including 9 and 10 recurrences, respectively, and 2 and 5 major hemorrhages, respectively (P = .44). The 95% CI on the difference of −1.5% was −5.3% to 2.4%. CONCLUSIONS Tinzaparin and dalteparin are safe and effective for the outpatient treatment of DVT or PE. Our finding of no differences between the LMWHs based on major clinical end points means that practical issues can be the deciding factor on which drug to use.Arch Intern Med. 2005;165:733-738-->
BACKGROUND Long-term anticoagulation prevents recurrent thrombosis in patients with idiopathic deep venous thrombosis or pulmonary embolism, but with a risk of clinically important so-called major ...bleeding. Physician- and patient-based decisions on the optimal duration of therapy are sensitive to the bleeding risk. The Outpatient Bleeding Risk Index potentially provides a means of calculating the potential risk of bleeding using easily elicited clinical findings, but, to our knowledge, the authors of the index have provided the only published validation of it. We sought to determine the accuracy of the index in our population of patients. METHODS We prospectively applied the Outpatient Bleeding Risk Index to consecutive patients in our clinic who had been objectively diagnosed as having pulmonary embolism or deep venous thrombosis and who were about to undergo standard therapy. Standard therapy consisted of a minimum of 5 days of low-molecular-weight heparin therapy overlapped with warfarin sodium therapy, and continuation of warfarin therapy for at least 3 months, with a target international normalized ratio of 2.5. Patients were placed in 3 risk groups (low, moderate, or high), as defined by the index. The survival curves of the groups, using major hemorrhages as the events, were then compared by the log-rank test. RESULTS Bleeding rates were lower than expected, but the index did discriminate between low- and moderate-risk groups (P = .03, log-rank test). The rate of major hemorrhage per 100 person-years was 0% (95% confidence interval, 0%-2.8%) in the low-risk group and 4.3% (95% confidence interval, 1.1%-11.1%) in the moderate-risk group. The rate in the high-risk group could not be defined because only 2 patients were at high risk. CONCLUSION The Outpatient Bleeding Risk Index discriminates between low- and moderate-risk patients, and could be used to guide decisions on the optimal duration of anticoagulant therapy.Arch Intern Med. 2003;163:917-920-->
BACKGROUND Concern about risks associated with allogeneic red blood cell transfusion has led to interest in methods of decreasing patient exposure to perioperative transfusion. OBJECTIVE To perform a ...meta-analysis to determine the degree to which predonation of autologous blood reduces patients' exposure to allogeneic blood and all transfusions of red blood cells (allogeneic or autologous). METHODS We searched MEDLINE, EMBASE, bibliographies, annual reports, press releases, newsletters from organizations with interests in the blood system, and personal files for randomized studies and concurrent control cohort studies in which the control groups were patients excluded for nonmedical reasons. RESULTS Patients who predonated autologous blood were less likely to receive allogeneic blood in the 6 randomized studies (n=933) (odds ratio OR, 0.17; 95% confidence interval CI, 0.08-0.32) and in the 9 cohort studies (n=2351) (OR, 0.19; 95% CI, 0.14-0.26). However, autologous donors were more likely to undergo transfusion with allogeneic and/or autologous blood (for randomized studies: OR, 3.03; 95% CI, 1.70-5.39 and for cohort studies: OR, 12.32; 95% CI, 5.90-25.40). Studies that reported use of transfusion protocols found less benefit with preoperative autologous donation, although the difference was not statistically significant. CONCLUSIONS Preoperative autologous donation of blood decreases exposure to allogeneic blood but increases exposure to any transfusion (allogeneic and/or autologous). There is a direct relationship between the transfusion rate in the control group and the benefit derived from preoperative autologous donation. This suggests that other methods of decreasing blood transfusion, such as surgical technique and transfusion protocols, may be as important as preoperative autologous donation of blood.Arch Intern Med. 1998;158:610-616-->
AC proph after OS results in a decrease in the incidence of VTE with an associated increase in the risk of major bleeding (MB). Several AC agents and schedules are used; however the optimal timing of ...initiation has not been determined. It is likely that the proximity to the time of surgery might influence both the efficacy and safety of the AC thus altering their risk-benefit profile. Using a clinical cost-effectiveness approach we compared different AC and timings of VTE proph in patients undergoing OS. A meta-analysis of 55 randomized trials was done to estimate the risk (MB) and benefit (averted VTE) of proph in OS using placebo (plac) or different AC (ximelagatranxim, low molecular weight heparin-LMWH, unfractionated heparin-UFH, warfarin-warf and fondaparinux-fonda) and timings of initiation (defined as preoperative (preop) if the first dose of the AC was administered >2 hrs before surgery, perioperative (periop)if between 2 hrs before or up to 12 hrs after the surgery and postoperative (postop) if starting 12 hrs or more after surgery). Means and variances of the MB and VTE estimates were used to parameterize Monte Carlo simulations for a beta distribution using 1,000 replications. Incremental risk, benefit and risk-benefit ratios (compared to placebo) were calculated from the replications. All AC/timing combinations were compared across a range of benefit-risk tradeoff values (risk acceptance) by calculating the percentage of replications with the highest net clinical benefit (NCB; e.g. incremental benefit - incremental risk · tradeoff) for each AC/timing combination. A higher NCB represents a better risk-benefit profile. In addition all anticoagulants were pooled together according to the initial timing of administration and NCB was calculated using random re-sampling of the replications. Analyses were done separately for major VTE (mVTE; proximal deep vein thrombosis (DVT) + pulmonary embolism), and total VTE (tVTE; mVTE + distal DVT) and a sensitivity analysis was done after excluding xim. The reference tradeoff was estimated from the case-fatality rate-ratios of VTE to MB (mVTE/MB=0.39; tVTE/MB=0.10). At the reference tradeoff value, the AC/timing combination with the highest probability of having the best risk-benefit profile was postop xim analyzed by both mVTE and tVTE (99 and 58%, respectively). After excluding xim the AC/timing combination of choice was postop LMWH if analyzed by mVTE (60%) or preop LMWH if analyzed by tVTE (59%). When all AC were pooled those administered postop had the highest probability of having the best risk-benefit profile analyzed by mVTE (48%) and the choice was indifferent between preop (45%) and postop (40%) if analyzed by tVTE. After excluding xim from the pooled analysis the choice was indifferent between preop (40%) and postop (35%) if analyzed by mVTE and if analyzed by tVTE the choice was preop (55%) followed by postop (27%). Our results suggest that:
1.postop administration of AC proph has the best risk-benefit profile;2.the results are influenced by the event defining benefit (mVTE or tVTE);3.in some analyses preop administration was best, and;4.periop administration always had the worst risk-benefit profile. We conclude that periop AC proph after OS should not be used.
BACKGROUND The outpatient treatment of patients with deep vein thrombosis and pulmonary embolism using low-molecular-weight heparin has the potential to reduce health care costs, but it is unclear if ...most patients with deep vein thrombosis and pulmonary embolism can be treated as outpatients. In the published studies, more than 50% of patients were excluded from outpatient treatment for reasons such as comorbid conditions, short life expectancy, concomitant pulmonary embolism, and previous deep vein thrombosis, and many patients were not treated entirely at home. We sought to determine if expanding patient eligibility for the outpatient treatment of deep vein thrombosis and pulmonary embolism affects the safety and effectiveness of the treatment, and to determine if patient self-injection compared with injections administered by a homecare nurse affected these outcomes. PATIENTS AND METHODS We treated as outpatients all patients with deep vein thrombosis and pulmonary embolism, except for those with massive pulmonary embolism, high risk for major bleeding or an active bleed, phlegmasia, and patients hospitalized for reasons that prevented discharge. We compared 2 models of outpatient care to determine feasibility, safety, and efficacy. Both models involved nurse managers who provided daily patient contact and ongoing treatment; however, in one model the patients were taught to inject themselves and in the other model homecare nurses administered the injections. We expanded the population of patients eligible for outpatient treatment by including many patients not treated at home in previous studies. Most patients in our study were treated with dalteparin sodium, 200 U/kg every 24 hours, for a minimum of 5 days. Therapy with warfarin sodium was started on the day of diagnosis or the following day. Patients were followed up for 3 months to determine rates of recurrent venous thromboembolism, bleeding, and death. RESULTS In this study, 194 (83%) of 233 consecutive patients were deemed eligible and treated as outpatients. Of the 39 patients who did not receive home therapy, 20 had concomitant medical problems responsible for their admission or were already inpatients, 6 had massive pulmonary embolism, 6 refused to pay for the dalteparin therapy, 4 had active bleeding, and 3 had phlegmasia cerulea dolens, which required treatment with intravenous narcotics for pain control. More than 184 (95%) of the 194 patients were treated entirely at home. There was no significant difference (P>.99) in the rate of recurrent venous thromboembolic events between the patients who were injected by homecare nurses (3/95 3.2) and those who injected themselves (4/99 4.0). Combining the 2 models, the overall recurrent event rate was 3.6% (95% confidence interval, 1.5%-7.4%). Similarly, there were no significant differences in rates of major hemorrhage (2/95 vs 2/99; P>.99), minor hemorrhage (8/95 vs 2/99; P=.06), and death (6/95 vs 8/99; P =.63). The overall rate of major hemorrhage was 2.0% (95% confidence interval, 0.6%-5.2%). CONCLUSIONS We demonstrate that more than 80% of patients at our tertiary care hospital could be treated at home using 1 of the 2 models of care we describe. Our results demonstrate that patients can safely and effectively perform home self-injection under the supervision of a hospital-based nurse. Injections at home by a homecare nurse are similarly effective. Our overall rates of recurrent venous thromboembolism, bleeding, and death are at least as favorable as those previously reported despite using 1 dose per day of dalteparin for most patients.Arch Intern Med. 1998;158:1809-1812-->
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