Analysis of Partial Thromboplastin Times in Patients With Pulmonary Embolism During the First 48 Hours of Anticoagulation With Unfractionated Heparin.

OBJECTIVE: The objective was to determine the proportion of patients with pulmonary embolism (PE) treated with unfractionated heparin (UFH) who achieved therapeutic activated partial thromboplastin time (aPTT) values within 48 hours of treatment. METHODS: Retrospective analysis of a PE response team (PERT) database was performed at a large, urban, academic teaching hospital. Inclusion criteria were adult patients with acute PE for whom the PERT was consulted and who received anticoagulation (AC) with UFH according to guideline standard dosing. aPTT values during 6-hour time periods during the first 48 hours of AC were collected and analyzed. RESULTS: A total of 505 patients met inclusion criteria. For patients receiving a bolus and infusion of UFH, the proportions (95% confidence interval [CI]) of patients in the therapeutic range were 19.0% (14.2% to 25.0%) at 12 hours, 26.3% (26.3% to 33.1%) at 24 hours, 28.3% (22.0% to 35.4%) at 36 hours, and 28.4% (20.8% to 37.5%) at 48 hours. For titrated infusion only, the proportions (95% CIs) of patients were 23.3% (16.2% to 32.3%) at 12 hours, 41.4% (31.6% to 51.9%) at 24 hours, 37.0% (26.8% to 48.5%) at 36 hours, and 42.1% (30.2% to 55.0%) at 48 hours. No patient had all therapeutic aPTT values. CONCLUSIONS: The majority of patients with acute PE spend most of their first 48 hours outside of the therapeutic range of AC when treated with guideline standard dosing of UFH. Over half of the patients fail to achieve any therapeutic PTT level within 24 hours of UFH initiation, and no patient had all therapeutic aPTTs. Future research should focus on identifying factors associated with achieving therapeutic AC with UFH.

Multicenter Implementation of a Novel Management Protocol Increases the Outpatient Treatment of Pulmonary Embolism and Deep Vein Thrombosis.

OBJECTIVE: The objective was to determine whether a protocol combining risk stratification, treatment with the direct-acting oral anticoagulant rivaroxaban, and defined follow-up is associated with a greater proportion of patients with venous thromboembolism (VTE) treated as outpatients, without hospital admission. METHODS: We performed a multicenter study of patients diagnosed with VTE (pulmonary embolism [PE] or deep vein thrombosis [DVT]) in two urban EDs, 18 months before and 18 months after implementation of an outpatient VTE treatment protocol. Patients with radiographically confirmed acute VTE were eligible. Our primary outcome was the proportion of VTE patients discharged from the ED or observation unit (i.e., without hospital admission). We performed subgroup analyses according to hospital, DVT and PE, and low-risk PE. We also assessed 7- and 30-day mortality, major bleeding, and returns to the ED. We compared proportions using chi-square and Fisher's exact tests. RESULTS: We enrolled 2,212 patients, 1,081 (49%) before protocol and 1,131 (51%) after protocol. Mean age (59 years vs. 60 years), female sex (49% vs. 49%), other demographics, comorbid illness, and PE risk stratification were similar before and after. After protocol, more VTE (35% from 26%, p < 0.001), PE (18% from 12%, p = 0.002), low-risk PE (28% from 18%, p < 0.001), and DVT (60% from 49%, p = 0.002) patients were treated as outpatients. Mortality, bleeding, and returns to ED were rare and did not increase after protocol. CONCLUSIONS: A treatment protocol combining risk-stratification, rivaroxaban treatment and defined follow-up is associated with an increase in PE and DVT patients treated as outpatients, with no increase in adverse outcomes.

International, multicenter evaluation of a new D-dimer assay for the exclusion of venous thromboembolism using standard and age-adjusted cut-offs.

INTRODUCTION: We sought to determine the test characteristics of an automated INNOVANCE D-dimer assay for the exclusion of pulmonary embolism (PE) and deep venous thrombosis (DVT) in emergency department (ED) patients using standard and age-adjusted cut-offs. METHODS: Cross-sectional, international, multicenter study of consecutive patients with suspected DVT or PE in 24 centers (18 USA, 6 Europe). Evaluated patients had low or intermediate Wells PE or DVT scores. For the standard cut-off, a D-dimer result <500 ng/ml was negative. For the age adjusted cut-off, we used the formula: Age (years) ∗ 10. The diagnostic standard was imaging demonstrating PE or DVT within 3 months. We calculated test characteristics using standard methods. We also explored modifications of the age adjustment multiplier. RESULTS: We included 3837 patients and excluded 251. The mean age of patients evaluated for PE (n = 1834) was 48 ±â€¯16 years, with 676 (37%) male, and 1081 (59%) white. The mean age of evaluated for DVT (n = 1752) was 53 ±â€¯16 years, with 710 (41%) male, and 1172 (67%) white. D-dimer test characteristics for PE were: sensitivity 98.0%, specificity 55.4%, negative predictive value (NPV) 99.8%, positive predictive value (PPV) 11.4%, and for DVT were: sensitivity 92.0%, specificity 44.8%, NPV 98.8%, PPV 10.3%. Age adjustment increased specificity (59.6% [PE], 51.1% [DVT]), but increasing the age-adjustment multiplier decreased sensitivity without increasing specificity. CONCLUSIONS: INNOVANCE D-dimer is highly sensitive and can exclude PE and DVT in ED patients with low- and intermediate- pre-test probability. Age-adjustment increases specificity, without increasing false negatives.

The creation and implementation of an outpatient pulmonary embolism treatment protocol.

The ability to rapidly and accurately risk-stratify patients with venous thromboembolism (VTE), and the availability of direct acting oral anticoagulants have reduced the need for intravenous anticoagulation for patients with deep vein thrombosis (DVT) and pulmonary embolism (PE). Emergency physicians are generally reluctant to discharge patients with VTE without defined and reliable follow up in place, and VTE patients treated with anticoagulants can be at risk for complications related to recurrent VTE and bleeding. In addition, screening for associated diseases (e.g. cancer, hypercoagulable states) may be indicated. Therefore, the outpatient treatment of low risk VTE requires coordinated effort and reliable follow up. By leveraging detailed outcome data and collaborative relationships, we have created a protocol for the safe outpatient treatment of patients with low risk DVT and PE. Our protocol is data driven and designed to address barriers to outpatient VTE management. We expect our protocol to result in improved patient satisfaction, more efficient emergency department (ED) throughput, and decreased cost. Applied nationally, the outpatient treatment of select patients with DVT and PE could have major public health and economic impact.

Comparison of Emergency Department Patients to Inpatients Receiving a Pulmonary Embolism Response Team (PERT) Activation.

OBJECTIVES: The development of pulmonary embolism response teams (PERTs) has been widely adopted nationally with the goal of providing multidisciplinary care to patients with high-risk PE. Most PERT activations originate from the emergency department (ED), while others are from the intensive care unit (ICU) or inpatient floors. It is unclear if ED PERT activations differ from non-ED PERT activation in terms of presentation, management, and outcome. METHODS: We enrolled a consecutive cohort of patients for whom PERT was activated at an urban academic medical center. We compared three groups of PERT activations based on whether the activation originated from the ED, ICU, or a non-ICU inpatient floor. We compared these groups in terms of the proportion of PERT activations that occurred during day, evening, or weekend hours and the proportion of confirmed PE. We also compared PE severity, treatment, and outcomes across locations. We tested differences using chi-square tests, with a two-tailed p-value of <0.05 considered statistically significant. RESULTS: We enrolled 561 patients, of whom 449 (79.5%) had confirmed PE. The mean ± SD age of patients with confirmed PE was 61 ± 17 years, and 300 (53.5%) were male. Activations from the ED (n = 283, 88.4%) or floor (n = 100, 74.6%) were more likely to be for confirmed PE than activations from the ICU (n = 63, 58.9%; p < 0.0001). There was a statistical difference in the time of day of PERT activation with the ED having more activations during night hours than the ICU or floors (p = 0.004). Most activations for confirmed, massive PE originated from the ICU (n = 41, 65.1%), followed by the ED (n = 82, 29%) and inpatient floors (n = 22, 22%; p < 0.0001). Most activations from the ED (n = 155, 54.8%) and floors (n = 55, 55%) were for submassive PE. The use of thrombolysis or thrombectomy was more common among ICU patients (n = 18, 33.3%), followed by ED patients (n = 53, 19.6%) and then floor patients (n = 8, 8.2%). Mortality and major bleeding events were most common among ICU patients and similar among ED and floor patients. CONCLUSIONS: Pulmonary embolism response team activations from different clinical locations differ in terms of patient presentation, PE confirmation, treatments, and outcomes. PERTs should be customized to support the different needs of each clinical area.