Prescribing patterns and outcomes of venous thromboembolism prophylaxis in hospitalized medical and cancer patients: Observations from the Ottawa Hospital.

Guidelines suggest broad use of pharmacologic prophylaxis to prevent venous thromboembolism (VTE) in hospitalized medical patients, however little 'real-world' data exists to support this. Our goal was to describe the use of thromboprophylaxis among general medical and cancer patients admitted to hospital, compare VTE and bleeding outcomes according to use of thromboprophylaxis, and to determine what variables influence prescribing patterns and outcomes. Patients admitted to the general medical and oncology services at The Ottawa Hospital between 2010 and 2015 were retrospectively reviewed and classified according to whether they received initial, delayed, or no pharmacologic thromboprophylaxis during their first hospitalization. Patients with an alternate indication for anticoagulation or those admitted with a bleeding event were excluded from analysis. The primary efficacy outcome was any symptomatic VTE during index hospitalization or within 90 days of discharge, and the primary safety outcome was clinically relevant bleeding during the index hospitalization. 17,262 patients were included in our final analysis. General medical patients selected to receive no, initial, or delayed thromboprophylaxis had 0.4%, 0.7%, and 2.4% rates of VTE; and 0.2%, 0.7%, and 1.5% rates of clinically relevant bleeding complications, respectively. Cancer patients had significantly higher rates of VTE: 3.3%, 3.9%, and 5.0%; and 0.9%, 0.7%, and 3.0% rates of clinically relevant bleeding among those selected to receive no, initial, or delayed thromboprophylaxis, respectively. Overall, our study suggests that broad use of pharmacologic thromboprophylaxis may be unnecessary in select low-risk general medical patients and may be less effective in cancer patients in whom new studies are indicated.

Cognitive and behavioural effects of genetic testing for thrombophilia.

Very few studies have examined the impact of genetic testing for thrombophilia on health behaviours, perceptions of control over risk factors for venous thromboembolism, or health services utilization. Through a postal questionnaire we compared first degree relatives with thrombophilia (carriers) most of whom had received counseling, to those without (non-carriers) with respect to: (a) perceived causes of venous thromboembolism; (b) perceived control; (c) health behaviour changes; and (d) use of health care services. 44/51 for carriers and 26/47 for non-carriers completed questionnaires. Carriers were more likely to believe their risk of venous thromboembolism 'is a little higher' or 'much higher' than average (p < 0.001) but some continued to believe their risk 'is the same as' or 'lower than' average. 16%-32% of carriers did not recognize major risk factors. Stress, worry, or depression, negative attitude, and over-exertion were over-interpreted as risks. 37.2% did not appreciate that thrombophilia increases risk. Behaviour changes were uncommon. There is a need for research on education and strategies to improve knowledge in thrombophilia carriers.

Ruling out pulmonary embolism across different subgroups of patients and healthcare settings: protocol for a systematic review and individual patient data meta-analysis (IPDMA).

BACKGROUND: Diagnosing pulmonary embolism in suspected patients is notoriously difficult as signs and symptoms are non-specific. Different diagnostic strategies have been developed, usually combining clinical probability assessment with D-dimer testing. However, their predictive performance differs across different healthcare settings, patient subgroups, and clinical presentation, which are currently not accounted for in the available diagnostic approaches. METHODS: This is a protocol for a large diagnostic individual patient data meta-analysis (IPDMA) of currently available diagnostic studies in the field of pulmonary embolism. We searched MEDLINE (search date January 1, 1995, till August 25, 2016) to retrieve all primary diagnostic studies that had evaluated diagnostic strategies for pulmonary embolism. Two authors independently screened titles, abstracts, and subsequently full-text articles for eligibility from 3145 individual studies. A total of 40 studies were deemed eligible for inclusion into our IPDMA set, and principal investigators from these studies were invited to participate in a meeting at the 2017 conference from the International Society on Thrombosis and Haemostasis. All authors agreed on data sharing and participation into this project. The process of data collection of available datasets as well as potential identification of additional new datasets based upon personal contacts and an updated search will be finalized early 2018. The aim is to evaluate diagnostic strategies across three research domains: (i) the optimal diagnostic approach for different healthcare settings, (ii) influence of comorbidity on the predictive performance of each diagnostic strategy, and (iii) optimize and tailor the efficiency and safety of ruling out PE across a broad spectrum of patients with a new, patient-tailored clinical decision model that combines clinical items with quantitative D-dimer testing. DISCUSSION: This pre-planned individual patient data meta-analysis aims to contribute in resolving remaining diagnostic challenges of time-efficient diagnosis of pulmonary embolism by tailoring available diagnostic strategies for different healthcare settings and comorbidity. SYSTEMATIC REVIEW REGISTRATION: Prospero trial registration: ID 89366.

Integrated strategies for the diagnosis of venous thromboembolism.

Diagnosis of deep vein thrombosis (DVT) and pulmonary embolism (PE) is an important medical problem because of the high fatality rate from PE and the large number of cases not diagnosed before causing death. Over the last decade, there has been considerable research into the diagnostic process. It is widely accepted that venous ultrasound imaging is an accurate test for the diagnosis of DVT and is the imaging test of choice. For PE, computer tomographic pulmonary angiography (CTPA) is replacing ventilation perfusion lung scanning. Technology for CTPA is rapidly evolving and multi-row detector scans have quite reasonable sensitivity and specificity. Despite the accuracy of imaging tests, the post-test probability of disease is highly dependent on pretest probability. Clinical evaluation tools have developed that enable us to accurately categorize patients' risk prior to diagnostic imaging. One advantage of this characterization is an ability to exclude the diagnosis of DVT or PE if clinical probability is sufficiently low and when the D-dimer is negative. There are now a number of D-dimer assays that have well-defined specificities and sensitivities, which enable use in conjunction with clinical probability. A careful combination of clinical assessment, D-dimer and imaging enables safe PE rule out protocols without imaging, an ability to suspect false positive imaging results, and more accurate determination of true positive imaging. These integration strategies result in safer, more convenient and cost-effective care for patients.

A pilot study of central venous catheter survival in cancer patients using low-molecular-weight heparin (dalteparin) and warfarin without catheter removal for the treatment of upper extremity deep vein thrombosis (The Catheter Study).

BACKGROUND: Central venous catheters in patients with cancer are associated with development of deep vein thrombosis (DVT); however, there is no accepted standard treatment. OBJECTIVES: To assess the safety and effectiveness of a management strategy for central venous catheter-related DVT in cancer patients consisting of dalteparin and warfarin without the need for line removal. PATIENTS/METHODS: Patients older than 18 years of age with an active malignancy and who had symptomatic, acute, objectively documented UEDVT were eligible. Patients were treated with dalteparin 200 IU kg(-1) per day for 5-7 days and warfarin with a target International Normalized Ratio of 2.0-3.0. Patients were followed for 3 months for recurrent venous thromboembolism, major hemorrhage and survival of the central venous catheter. RESULTS: There were 74 patients (48 males). The average age was 58 years. There were no episodes of recurrent venous thromboembolism and three (4%) major bleeds. No lines were removed because of infusion failure or recurrence/extension of DVT. CONCLUSION: Treatment of UEDVTs secondary to central catheters in cancer patients with standard dalteparin/warfarin can allow the central line to remain in situ with little risk of line failure or recurrence/extension of the DVT.

Accuracy of coding for possible warfarin complications in hospital discharge abstracts.

BACKGROUND: Hospital discharge abstracts could be used to identify complications of warfarin if coding for bleeding and thromboembolic events are accurate. OBJECTIVES: To measure the accuracy of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9CM) codes for bleeding and thromboembolic diagnoses. SETTING: University affiliated, tertiary care hospital in Ottawa, Canada. PATIENTS: A random sample of patients discharged between September 1999 and September 2000 with an ICD-9-CM code indicating a bleeding or thromboembolic diagnosis. METHODS: Gold-standard coding was determined by a trained chart abstractor using explicit standard diagnostic criteria for bleeding, major bleeding, and acute thromboembolism. The abstractor was blinded to the original coding. We calculated the sensitivity, specificity, positive, and negative predictive values of the original ICD-9CM codes for bleeding or thromboembolism diagnoses. RESULTS: We reviewed 616 medical records. 361 patients (59%) had a code indicating a bleeding diagnosis, 291 patients (47%) had a code indicating a thromboembolic diagnosis and 36 patients (6%) had a code indicating both. According to the gold standard criteria, 352 patients experienced bleeding, 333 experienced major bleeding, and 188 experienced an acute thromboembolism. For bleeding, the ICD-9CM codes had the following sensitivity, specificity, positive and negative predictive values [95% CI]: 93% [90-96], 88% [83-91], 91% [88-94], and 91% [87-94], respectively. For major bleeding, the ICD-9CM codes had the following sensitivity, specificity, positive and negative predictive values: 94% [91-96], 83% [78-87], 87% [83-90], and 92% [88-95], respectively. For thromboembolism, the ICD-9CM codes had the following sensitivity, specificity, positive and negative predictive values: 97% [94-99], 74% [70-79], 62% [57-68], and 98% [96-99], respectively. By selecting a sub-group of ICD-9CM codes for thromboembolism, the positive predictive value increased to 87%. CONCLUSION: In our centre, the discharge abstract could be used to identify and exclude patients hospitalized with a major bleed or thromboembolism. If coding quality for bleeding is similar in other hospitals, these ICD-9-CM diagnostic codes could be used to study population-based warfarin-associated hemorrhagic complications using administrative databases.

A decision aid for autologous pre-donation in cardiac surgery--a randomized trial.

OBJECTIVES: The objective of this randomized, controlled study was to determine the usefulness of a decision aid on pre-donation of autologous blood before elective open heart surgery. METHODS: The decision aid (DA) group received a tape and booklet which described the options for peri-operative transfusion in detail. The no decision aid (NDA) group received information usually given to patients about autologous donation. RESULTS: A total of 120 patients were randomized. The DA group rated themselves better prepared for decision making and showed significant improvements in knowledge (p = 0.001) and realistic risk perceptions (p = 0.001). In both groups there was an increase in the proportion of patients choosing allogeneic blood between baseline and follow-up (p = 0.001). Patients in the DA group were significantly more satisfied with the amount of information they received, how they were treated and with the decision they made, than patients in the NDA group. CONCLUSION: The decision aid is useful in preparing patients for decision making. PRACTICE IMPLICATIONS: The next stage is to explore strategies to make it available to all appropriate patients.

PO-41 - Rivaroxaban is effective therapy for high risk cancer patients with venous thromboembolic disease.

INTRODUCTION: The standard of care for cancer associated venous thromboembolism (VTE) is generally accepted to be at least six months of therapeutic doses of low molecular weight heparin (LMWH). After six months it is recommended that therapy be continued but no studies have evaluated treatment in this period. Rivaroxaban is a potentially effective therapy given cancer patients were enrolled in the EINSTEIN trial with acceptable safety and efficacy but details on these patients is lacking. AIM: To determine the safety and efficacy of rivaroxaban for the treatment of cancer associated VTE. MATERIALS AND METHODS: We performed a retrospective chart review of all cancer patients seen in our thrombosis program and enrolled patients seen between January 2012 and April 2015. Complete patient identification was accomplished through our hospital data warehouse. We recorded all relevant demographics. Initial diagnoses were all confirmed with objective imaging tests according to standard definitions. Major bleeds, using the ISTH definition, and recurrent VTE events were adjudicated by at least two observers. RESULTS: 237 active cancer patients received treatment with rivaroxaban; 65 (27%) were initiated on rivaroxaban, 30 (12.6%) started between day 8 and 2 months, 75 (32%) started therapy between day 8 and the 6 month point and 97 (41%) started therapy at 6 months or beyond. 26 patients were put on rivaroxaban after failing LMWH. The average duration of rivaroxaban therapy was 297 days; The average age of patients was 61 (SD±13); 41% of patients were male, 59% were female. 47% of patients had metastatic cancer. Of the 65 patients who were initiated on rivaroxaban 24 (37%) had metastatic cancer. Overall 3.8% of patients recurred while on rivaroxaban therapy with no deaths due to PE, and 3 patients had major hemorrhage with 2 deaths. Of the 9 patients who recurred on rivaroxaban, 3 of them were initiated on rivaroxaban, 3 of them were started 8 days-6 months, and 3 of them started after 6 months. The median number of days from initiation of rivaroxaban to VTE recurrence was 113. 26 patients received rivaroxaban after a recurrent event on therapeutic doses of LMWH, none recurred. Of the 65 patients who were initiated on rivaroxaban 3 recurred and of the 97 patients who were started on rivaroxaban after 6 months three recurred 0.580). All patients were treated on an outpatient basis. CONCLUSIONS: Recurrence and major bleeding events on rivaroxaban were low despite the fact almost half the patients had metastatic disease. Rivaroxaban can be considered acceptable therapy for the treatment of cancer associated with venous thromboembolic disease.

Rivaroxaban for treatment of suspected or confirmed heparin-induced thrombocytopenia study.

UNLABELLED: Essentials Heparin-induced thrombocytopenia (HIT) is a thrombogenic condition that is difficult to treat. We evaluated rivaroxaban as a treatment option in patients with suspected or confirmed HIT. One patient had recurrent thrombosis and 9/10 patients with thrombocytopenia had platelet recovery. Rivaroxaban may be an effective and safe treatment option for HIT. SUMMARY: Background Rivaroxaban is a direct oral anti-Xa inhibitor that has the potential to greatly simplify treatment of heparin-induced thrombocytopenia (HIT). Objectives To evaluate the efficacy and safety of rivaroxaban in this patient population, we conducted a multicenter, single-arm, prospective cohort study of patients with suspected or confirmed HIT. Patients/Methods Twenty-two consecutive adults with suspected or confirmed HIT received rivaroxaban 15 mg bid until a local HIT assay result was available. Participants with a positive local assay result continued rivaroxaban 15 mg bid until platelet recovery (or until day 21 if they had acute thrombosis at study entry), then stepped down to rivaroxaban 20 mg daily until day 30. Results and Conclusions The primary outcome measure, incidence of new symptomatic, objectively-confirmed venous and arterial thromboembolism at 30 days, occurred in one HIT-positive participant (4.5%; 95% confidence interval [CI], 0-23.5%) and one HIT-positive participant required limb amputation despite platelet recovery. Platelet recovery was achieved in nine out of 10 HIT-positive patients with thrombocytopenia. Rivaroxaban appears to be effective for treating patients with confirmed HIT, although the small number of patients enrolled limits precision.

Single-arm study of bridging therapy with low-molecular-weight heparin for patients at risk of arterial embolism who require temporary interruption of warfarin.

BACKGROUND: When warfarin is interrupted for surgery, low-molecular-weight heparin is often used as bridging therapy. However, this practice has never been evaluated in a large prospective study. This study was designed to assess the efficacy and safety of bridging therapy with low-molecular-weight heparin initiated out of hospital. METHODS AND RESULTS: This was a prospective, multicenter, single-arm cohort study of patients at high risk of arterial embolism (prosthetic valves and atrial fibrillation with a major risk factor). Warfarin was held for 5 days preoperatively. Low-molecular-weight heparin was given 3 days preoperatively and at least 4 days postoperatively. Patients were followed up for 3 months for thromboembolism and bleeding. Eleven Canadian tertiary care academic centers participated; 224 patients were enrolled. Eight patients (3.6%; 95% CI, 1.8 to 6.9) had an episode of thromboembolism, of which 2 (0.9%; 95% CI, 0.2 to 3.2) were judged to be due to cardioembolism. Of these 8 episodes of thromboembolism, 6 occurred in patients who had warfarin deferred or withdrawn because of bleeding. There were 15 episodes of major bleeding (6.7%; 95% CI, 4.1 to 10.8): 8 occurred intraoperatively or early postoperatively before low-molecular-weight heparin was restarted, 5 occurred in the first postoperative week after low-molecular-weight heparin was restarted, and 2 occurred well after low-molecular-weight heparin was stopped. There were no deaths. CONCLUSIONS: Bridging therapy with subcutaneous low-molecular-weight heparin is feasible; however, the optimal approach for the management of patients who require temporary interruption of warfarin to have invasive procedures is uncertain.

The safety of dosing dalteparin based on actual body weight for the treatment of acute venous thromboembolism in obese patients.

Data evaluating the safety of using weight-based low-molecular-weight heparin in the treatment of obese patients with acute venous thromboembolism are limited. The product monograph of dalteparin suggests the maximum dose should be limited to 18,000 U subcutaneously once daily. There are no specific data regarding the risk of recurrence or bleeding in patients given dalteparin in a weight-based dose of 200 IU kg(-1). We report a retrospective chart review of 193 obese patients who weighed more than 90 kg and who received dalteparin at or near to 200 IU kg(-1) actual body weight for 5-7 days for acute venous thromboembolism with 90 day follow-up information. Of the patients, 77% had idiopathic venous thromboembolism, 16% had an underlying malignancy, and 7% had a transient risk factor. Warfarin was initiated within 2 days with a target International Normalized Ratio range of 2.0-3.0. All patients were followed for 12 weeks post diagnosis. Only two patients had a major hemorrhage, 4 and 8 weeks from diagnosis. This study supports the safety of dosing dalteparin based on actual body weight in obese patients.

Does the type of hormone replacement therapy influence the risk of deep vein thrombosis? A prospective case-control study.

BACKGROUND: Although hormone replacement therapy (HRT) is associated with an increased risk of deep vein thrombosis (DVT), it is not clear if the risk differs in users of combined estrogen-progestin HRT and estrogen-only HRT. METHODS: We prospectively studied postmenopausal women with suspected DVT in whom HRT use status was ascertained and who subsequently had objective diagnostic testing to confirm or exclude DVT. Cases were patients with idiopathic DVT, in whom there were no DVT risk factors, and controls were patients without DVT, in whom there were also no DVT risk factors. The risk of DVT was determined in users of estrogen-progestin HRT and estrogen-only HRT by comparing the prevalence of current HRT use in cases with idiopathic DVT and controls without DVT (reference group). Multivariable regression analysis was done to adjust for factors that might confound an association between HRT use and the risk of DVT. RESULTS: One thousand one hundred and sixty-eight postmenopausal women with suspected DVT were assessed, from whom 95 cases of idiopathic DVT and 610 controls without DVT and no DVT risk factors were identified. Estrogen-only HRT was associated with an increased risk for DVT that was not statistically significant [odds ratio (OR) = 1.22; 95% confidence interval (CI) 0.57, 2.61]. Estrogen-progestin HRT was associated with a greater than 2-fold increased risk for DVT (OR = 2.70; 95% CI 1.44, 5.07). CONCLUSION: The risk of developing DVT may be higher in users of combined estrogen-progestin HRT than in users of estrogen-only HRT.

Graduated compression stockings in the prevention of postoperative venous thromboembolism. A meta-analysis.

BACKGROUND: The effectiveness of graduated compression stockings in prophylaxis of postoperative venous thromboembolism is unclear to many physicians. Surveys show there is considerable variability in their use and their perceived effectiveness. We undertook to establish, by a systematic overview of the literature, the effectiveness of graduated compression stockings in the prophylactic setting of postoperative venous thromboembolism. METHODS: Studies published between 1966 and June 1992 were identified through the MEDLINE database, with a search in all languages, through reviews of Current Contents, and including references cited in identified articles. Articles were selected for initial analysis if they assessed the use of graduated compression stockings for the prophylaxis of venous thromboembolism, and if the stocking group was compared with an untreated or unconfounded control group. Criteria were established a priori, to select only studies with sound methods. On the basis of these criteria, 12 studies were identified for the combined analysis. Each eligible study was independently analyzed for the risk of development of deep venous thrombosis in the control and stocking groups, and this was expressed as an odds ratio. Odds ratios were combined across studies by means of the Mantel-Haenszel chi 2 procedure. The data were analyzed separately for orthopedic surgery because of its high risk for venous thromboembolism. RESULTS: Eleven of the 12 studies were in moderate-risk surgery (abdominal, gynecologic, and neurosurgery); the summary odds ratio was 0.28, which translates into a risk reduction of 68% (95% confidence interval, 53% to 73%), which is statistically significant (P < .0001). In the one study in orthopedic surgery that was eligible for inclusion, the odds ratio was 0.50 (95% confidence interval, 0.19 to 1.29; P = .17). CONCLUSIONS: The use of graduated compression stockings for prophylaxis of venous thromboembolism after moderate-risk surgery results in a significant risk reduction. It is unknown whether the use of graduated compression stockings in combination with other forms of prophylaxis results in further risk reduction. The efficacy of graduated compression stockings in orthopedic surgery has been assessed by only one study that used sound methods, hence no definitive conclusions can be made in these high-risk patients.

Preoperative autologous donation decreases allogeneic transfusion but increases exposure to all red blood cell transfusion: results of a meta-analysis. International Study of Perioperative Transfusion (ISPOT) Investigators.

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.

Reevaluation of the sensitivity of impedance plethysmography for the detection of proximal deep vein thrombosis.

BACKGROUND: To reevaluate the sensitivity of impedance plethysmography (IPG) for proximal deep vein thrombosis (DVT) and to establish a relationship between the location and size of thrombi and the results of IPG. DESIGN: Prospective cohort study. METHODS: One hundred thirty-two consecutive patients with clinically suspected DVT underwent IPG testing and most (n = 118) underwent contrast-enhanced venography; in 14 patients, venous ultrasonography was performed and demonstrated definitive proximal DVT in which the size and extent of the thrombus could be delineated. All patients with dubious or normal ultrasound results underwent contrast-enhanced venography. All tests were performed and test results were interpreted without knowledge of the results of the other tests. Patients were considered to have proximal DVT if this was demonstrated on venography or ultrasound, calf DVT if this was demonstrated on venography, or no DVT if venography yielded normal findings. The sensitivity and specificity of IPG for DVT were calculated. RESULTS: Of the 132 patients, 40 (30%) had proximal DVT, seven (5%) had calf DVT, and 85 (64%) had no DVT. The sensitivity of IPG for proximal DVT was 65% and the specificity was 93%. Of the proximal vein thrombi, IPG detected three (23%) of 13 that involved the popliteal vein but not the superficial femoral vein and 23 (85%) of 27 proximal vein thrombi that involved the superficial femoral vein. CONCLUSIONS: Our study demonstrated that the sensitivity of IPG for proximal DVT at our center is only 65%, a figure that is much lower than those reported in earlier studies from our institution. We hypothesize that because of a change in referral practice, an increased proportion of patients with less severe symptoms are now referred to our center than in the past. These patients have thrombi that are smaller, less likely to be occlusive, and therefore less likely to yield abnormal IPG findings.

Thrombosis in the emergency department: use of a clinical diagnosis model to safely avoid the need for urgent radiological investigation.

CONTEXT: The management of patients presenting to hospital emergency departments with suspected deep vein thrombosis (DVT) is problematic because urgent diagnostic imaging capability is sometimes unavailable. Experienced physicians using clinical skills alone can classify patients with suspected DVT into low-, moderate-, and high-probability categories. OBJECTIVES: To determine the accuracy of an explicit clinical model for the diagnosis of DVT when applied by emergency department physicians and to assess the safety and feasibility of a management strategy based on the clinical pretest probability for patients presenting to the emergency department with suspected DVT outside of regular hospital staff work hours. METHODS: A prospective cohort study was performed in the emergency departments of 2 tertiary care institutions involving 344 patients with suspected DVT. Patient conditions were evaluated by an emergency department physician who determined the pretest probability for DVT to be low, moderate, or high using an explicit clinical model. Patients for whom DVT was considered a low pretest probability were discharged from the emergency department and returned the following day for venous compression ultrasound imaging of the affected leg. Patients for whom DVT was considered a moderate pre-test probability received a single, weight-adjusted dose of subcutaneous unfractionated heparin sodium (between 12 500 and 20 000 U), were discharged from the emergency department, and returned the next morning to undergo ultrasonography. Patients for whom DVT was considered a high pretest probability were admitted to the hospital, administered intravenous unfractionated heparin, and ultrasonography was arranged within 24 hours. Patients with positive ultrasonographic findings were diagnosed with DVT, except for those with low pretest probability for whom confirmatory venography was performed. Patients with DVT excluded in the initial evaluation period did not receive anticoagulant therapy. All patients were followed up for 90 days to monitor development of thromboembolic or bleeding complications. RESULTS: Twenty-four (49.0% [95% confidence interval (CI), 34.5%-63.6%]) of 49 patients in the high-probability category, 15 (14.3% [95% CI, 8.3%-22.4%]) of 105 in the moderate-, and 6 (3.2% [95% CI, 1.2%-6.7%]) of 190 in the low-probability category were confirmed to have DVT. Overall, 45 (13.1%) of 344 patients were confirmed to have DVT. No patient developed pulmonary embolism or major bleeding complications within 48 hours of initial evaluation in the emergency department. Of the 301 patients who had DVT excluded during the initial evaluation period, only 2 (0.7% [95% CI, 0.1%-2.3%]) developed venous thromboembolic complications (calf vein thromboses in both) in the 3-month follow-up period. CONCLUSIONS: Using an explicit clinical model, emergency department physicians can accurately classify patients with suspected DVT into high-, moderate-, and low-probability groups. A management plan based on probability for DVT that avoids the need for urgent diagnostic imaging is safe and feasible in the emergency department setting.

Expanding eligibility for outpatient treatment of deep venous thrombosis and pulmonary embolism with low-molecular-weight heparin: a comparison of patient self-injection with homecare injection.

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.

Inflammation markers and their trajectories after deep vein thrombosis in relation to risk of post-thrombotic syndrome.

BACKGROUND: Post-thrombotic syndrome (PTS) is a frequent chronic complication of deep vein thrombosis (DVT). OBJECTIVE: In the BioSOX study, we investigated whether inflammation markers predict the risk of PTS after DVT. METHODS: We measured C-reactive protein (CRP), ICAM-1, interleukin (IL)-6, and IL-10, at baseline, and 1 month and 6 months after a first proximal DVT, among 803 participants in the SOX trial. Participants were prospectively followed for 24 months for development of PTS. RESULTS: Median CRP levels at 1 month, ICAM-1 levels at baseline, 1 month and 6 months, IL-6 levels at 1 month and 6 months and IL-10 levels at 6 months were higher in patients who developed PTS than in those who did not. Multivariable regression with the median as a cutoff showed risk ratios (RRs) for PTS of 1.23 (95% confidence interval [CI] 1.05-1.45) and 1.25 (95% CI 1.05-1.48) for ICAM-1 at 1 month and 6 months, respectively, and 1.27 (95% CI 1.07-1.51) for IL-10 at 6 months. Quartile-based analysis demonstrated a dose-response association between ICAM-1 and PTS. ICAM-1 and IL-10 were also associated with PTS severity. Analysis of biomarker trajectories after DVT demonstrated an association between the highest-trajectory group of ICAM-1 and PTS. CONCLUSIONS: In this prospective study, ICAM-1 over time was most consistently associated with the risk of PTS. Further study is required to confirm these findings and assess their potential clinical relevance.

Use of elastic compression stockings after deep venous thrombosis: a comparison of practices and perceptions of thrombosis physicians and patients.

Daily long-term use of elastic compression stockings (ECS) by patients with deep venous thrombosis (DVT) may help to prevent the post-thrombotic syndrome (PTS). However, the effectiveness of ECS in clinical practice is difficult to predict, since the practices and perceptions of patients and thrombosis physicians regarding ECS have not been documented. The objectives were to survey DVT patients and thrombosis physicians on their practices and perceptions regarding use of ECS after DVT, and to evaluate whether physician perceptions are supported by patient responses. Two surveys were conducted. The first was sent to 38 Canadian thrombosis physicians. The second was administered to 80 DVT patients attending Thrombosis Clinic at one of two Canadian university-affiliated hospitals. Most physicians believed that ECS were useful in preventing PTS and in managing venous symptoms. However, there was a lack of consensus regarding the optimal timing of initiation of ECS, duration of therapy, and compression strength, and only one-third routinely prescribed ECS to asymptomatic patients to prevent PTS. Most DVT patients who were prescribed ECS purchased them, 87% wore them daily, and most reported that ECS relieved swelling and symptoms. Physicians underestimated the degree of patient compliance with ECS, but correctly identified the main reasons for non-compliance. There is a lack of consensus among thrombosis physicians regarding ECS use after DVT. Patients with DVT are willing to comply with ECS therapy and most find them to be helpful. Our findings suggest that long-term study of the optimal use of ECS after DVT is both necessary and feasible.

Combined use of clinical assessment and d-dimer to improve the management of patients presenting to the emergency department with suspected deep vein thrombosis (the EDITED Study).

Suspected deep vein thrombosis (DVT) is a common problem facing emergency physicians. Timely diagnostic testing must be performed to accurately identify patients with DVT. The purpose of this study was to evaluate the safety and effectiveness of a management strategy that combined consideration of clinical pretest probability and a d-dimer test to evaluate patients presenting to the emergency department with suspected deep vein thrombosis (DVT). A prospective cohort study was performed in the emergency departments of four tertiary care institutions involving 1075 patients with suspected DVT. An emergency physician determined the pretest probability for DVT to be low, moderate, or high using an explicit clinical model. A blood sample was taken for d-dimer testing. Subsequent investigations (compression ultrasound, venography) were performed based upon the pretest probability and the d-dimer result. Patients considered at low pretest probability with negative d-dimer had no further diagnostic testing performed. All patients in whom the diagnosis of DVT was excluded by the algorithm did not receive anticoagulant therapy and were followed up for 90 days for the development of proximal DVT or pulmonary embolism. Overall, 195 (18.1%; 95% CI 15.9% to 20.6%) of 1075 patients were confirmed to have proximal DVT. Of the 882 patients who had proximal DVT excluded during the initial evaluation period using the algorithms, four (0.5%; 95% CI 0.1% to 1.2%) were subsequently diagnosed with proximal DVT in the follow-up period, including three patients in the low pretest probability group (1.0%; 95% CI 0.2% to 2.1%) who had normal d-dimer and no additional diagnostic testing performed. None of the 882 patients (0%: 95% CI 0% to 0.5%) developed pulmonary embolism in the follow-up period. A diagnostic strategy for the evaluation of patients with suspected DVT based on pretest probability and d-dimer is safe and feasible in the emergency department setting.