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Concept: Deep vein thrombosis

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Effective treatment of venous thromboembolism (VTE) strikes a balance between prevention of recurrence and bleeding complications. The current standard of care is heparin followed by a vitamin K antagonist such as warfarin. However, this option is not without its limitations, as the anticoagulant effect of warfarin is associated with high inter- and intra-patient variability and patients must be regularly monitored to ensure that anticoagulation is within the narrow target therapeutic range. Several novel oral anticoagulant agents are in the advanced stages of development for VTE treatment, some of which are given after an initial period of heparin treatment, in line with current practice, while others switch from high to low doses after the initial phase of treatment. In this review we assess the critical considerations for treating VTE in light of emerging clinical data for new oral agents and discuss the merits of novel treatment regimens for patients who have experienced an episode of deep vein thrombosis or pulmonary embolism.

Concepts: Stroke, Thrombosis, Pulmonary embolism, Warfarin, Vein, Low molecular weight heparin, Anticoagulant, Deep vein thrombosis

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Clinical guidelines recommend early discharge of patients with low-risk pulmonary embolism (LRPE). This study measured the overall impact of early discharge of LRPE patients on clinical outcomes and costs in the Veterans Health Administration population. Adult patients with ≥1 inpatient diagnosis for pulmonary embolism (PE) (index date) between 10/2011-06/2015, continuous enrollment for ≥12 months pre- and 3 months post-index date were included. PE risk stratification was performed using the simplified Pulmonary Embolism Stratification Index. Propensity score matching (PSM) was used to compare 90-day adverse PE events (APEs) [recurrent venous thromboembolism, major bleed and death], hospital-acquired complications (HACs), healthcare utilization, and costs among short (≤2 days) versus long length of stay (LOS). Net clinical benefit was defined as 1 minus the combined rate of APE and HAC. Among 6,746 PE patients, 95.4% were men, 22.0% were African American, and 1,918 had LRPE. Among LRPE patients, only 688 had a short LOS. After 1:1 PSM, there were no differences in APE, but short LOS had fewer HAC (1.5% vs 13.3%, 95% CI: 3.77-19.94) and bacterial pneumonias (5.9% vs 11.7%, 95% CI: 1.24-3.23), resulting in better net clinical benefit (86.9% vs 78.3%, 95% CI: 0.84-0.96). Among long LOS patients, HACs (52) exceeded APEs (14 recurrent DVT, 5 bleeds). Short LOS incurred lower inpatient ($2,164 vs $5,100, 95% CI: $646.8-$5225.0) and total costs ($9,056 vs $12,544, 95% CI: $636.6-$6337.7). LRPE patients with short LOS had better net clinical outcomes at lower costs than matched LRPE patients with long LOS.

Concepts: Pneumonia, Pulmonary embolism, Hematology, Thrombus, Vein, Ape, Propensity score, Deep vein thrombosis

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Background Venous disease is the most common cause of leg ulceration. Although compression therapy improves venous ulcer healing, it does not treat the underlying causes of venous hypertension. Treatment of superficial venous reflux has been shown to reduce the rate of ulcer recurrence, but the effect of early endovenous ablation of superficial venous reflux on ulcer healing remains unclear. Methods In a trial conducted at 20 centers in the United Kingdom, we randomly assigned 450 patients with venous leg ulcers to receive compression therapy and undergo early endovenous ablation of superficial venous reflux within 2 weeks after randomization (early-intervention group) or to receive compression therapy alone, with consideration of endovenous ablation deferred until after the ulcer was healed or until 6 months after randomization if the ulcer was unhealed (deferred-intervention group). The primary outcome was the time to ulcer healing. Secondary outcomes were the rate of ulcer healing at 24 weeks, the rate of ulcer recurrence, the length of time free from ulcers (ulcer-free time) during the first year after randomization, and patient-reported health-related quality of life. Results Patient and clinical characteristics at baseline were similar in the two treatment groups. The time to ulcer healing was shorter in the early-intervention group than in the deferred-intervention group; more patients had healed ulcers with early intervention (hazard ratio for ulcer healing, 1.38; 95% confidence interval [CI], 1.13 to 1.68; P=0.001). The median time to ulcer healing was 56 days (95% CI, 49 to 66) in the early-intervention group and 82 days (95% CI, 69 to 92) in the deferred-intervention group. The rate of ulcer healing at 24 weeks was 85.6% in the early-intervention group and 76.3% in the deferred-intervention group. The median ulcer-free time during the first year after trial enrollment was 306 days (interquartile range, 240 to 328) in the early-intervention group and 278 days (interquartile range, 175 to 324) in the deferred-intervention group (P=0.002). The most common procedural complications of endovenous ablation were pain and deep-vein thrombosis. Conclusions Early endovenous ablation of superficial venous reflux resulted in faster healing of venous leg ulcers and more time free from ulcers than deferred endovenous ablation. (Funded by the National Institute for Health Research Health Technology Assessment Program; EVRA Current Controlled Trials number, ISRCTN02335796 .).

Concepts: Randomized controlled trial, Median, Interquartile range, Vein, Cardiovascular system, Randomness, Deep vein thrombosis, Venous ulcer

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IMPORTANCE Retrievable inferior vena cava (IVC) filters were designed to provide temporary protection from pulmonary embolism, sparing patients from long-term complications of permanent filters. However, many retrievable IVC filters are left in place indefinitely. OBJECTIVES To review the medical records of patients with IVC filters to determine patient demographics and date of and indication for IVC filter placement, as well as complications, follow-up data, date of IVC filter retrieval, and use of anticoagulant therapy. DESIGN AND SETTING A retrospective review of IVC filter use between August 1, 2003, and February 28, 2011, was conducted at Boston Medical Center, a tertiary referral center with the largest trauma center in New England. PARTICIPANTS In total, 978 patients. Twenty six patients were excluded from the study because of incomplete medical records. INTERVENTION Placement of retrievable IVC filter. MAIN OUTCOME MEASURES In total, 952 medical records were included in the analysis. RESULTS Of 679 retrievable IVC filters that were placed, 58 (8.5%) were successfully removed. Unsuccessful retrieval attempts were made in 13 patients (18.3% of attempts). Seventy-four venous thrombotic events (7.8% of 952 patients included in the study) occurred after IVC filter placement, including 25 pulmonary emboli, all of which occurred with the IVC filter in place. Forty-eight percent of venous thrombotic events were in patients without venous thromboembolism at the time of IVC filter placement, and 89.4% occurred in patients not receiving anticoagulants. Many IVC filters placed after trauma were inserted when the highest bleeding risk had subsided, and anticoagulant therapy may have been appropriate. While many of these filters were placed because of a perceived contraindication to anticoagulants, 237 patients (24.9%) were discharged on a regimen of anticoagulant therapy. CONCLUSION AND RELEVANCE Our research suggests that the use of IVC filters for prophylaxis and treatment of venous thrombotic events, combined with a low retrieval rate and inconsistent use of anticoagulant therapy, results in suboptimal outcomes due to high rates of venous thromboembolism.

Concepts: Stroke, Pulmonary embolism, Warfarin, Low molecular weight heparin, Anticoagulant, Inferior vena cava, Deep vein thrombosis, Inferior vena cava filter

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Objective To prospectively validate the HERDOO2 rule (Hyperpigmentation, Edema, or Redness in either leg; D-dimer level ≥250 μg/L; Obesity with body mass index ≥30; or Older age, ≥65 years), which states that women with none or one of the criteria can safely discontinue anticoagulants after short term treatment.Design Prospective cohort management study.Setting 44 secondary or tertiary care centres in seven countries.Participants Of 3155 consecutive eligible participants with a first unprovoked venous thromboembolism (VTE, proximal leg deep vein thrombosis or pulmonary embolism) who completed 5-12 months of short term anticoagulant treatment, 370 declined to participate, leaving 2785 enrolled participants. 2.3% were lost to follow-up.Interventions Women with none or one of the HERDOO2 criteria were classified as at low risk of recurrent VTE and discontinued anticoagulants (intervention arm), whereas anticoagulant management for high risk women (≥2 HERDOO2 criteria) and men was left to the discretion of the clinicians and patients (observation arm).Main outcome measure Recurrent symptomatic VTE (independently and blindly adjudicated) over one year of follow-up.Results Of 1213 women, 631 (51.3%) were classified as low risk and 591 discontinued oral anticoagulant treatment. In the primary analysis, 17 low risk women who discontinued anticoagulants developed recurrent VTE during 564 patient years of follow-up (3.0% per patient year, 95% confidence interval 1.8% to 4.8%). In 323 high risk women and men who discontinued anticoagulants, 25 had VTE during 309 patient years of follow-up (8.1%, 5.2% to 11.9%), whereas in 1802 high risk women and men who continued anticoagulants 28 had recurrent VTE during 1758 patient years of follow-up (1.6%, 1.1% to 2.3%).Conclusions Women with a first unprovoked VTE event and none or one of the HERDOO2 criteria have a low risk of recurrent VTE and can safely discontinue anticoagulants after completing short term treatment.Trial registration clinicaltrials.gov NCT00967304.

Concepts: Stroke, Thrombosis, Pulmonary embolism, Hematology, Vein, Low molecular weight heparin, Anticoagulant, Deep vein thrombosis

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BACKGROUND: Peripherally inserted central catheters (PICCs) are associated with an increased risk of venous thromboembolism. However, the size of this risk relative to that associated with other central venous catheters (CVCs) is unknown. We did a systematic review and meta-analysis to compare the risk of venous thromboembolism associated with PICCs versus that associated with other CVCs. METHODS: We searched several databases, including Medline, Embase, Biosis, Cochrane Central Register of Controlled Trials, Conference Papers Index, and Scopus. Additional studies were identified through hand searches of bibliographies and internet searches, and we contacted study authors to obtain unpublished data. All human studies published in full text, abstract, or poster form were eligible for inclusion. All studies were of adult patients aged at least 18 years who underwent insertion of a PICC. Studies were assessed with the Newcastle-Ottawa risk of bias scale. In studies without a comparison group, the pooled frequency of venous thromboembolism was calculated for patients receiving PICCs. In studies comparing PICCs with other CVCs, summary odds ratios (ORs) were calculated with a random effects meta-analysis. FINDINGS: Of the 533 citations identified, 64 studies (12 with a comparison group and 52 without) including 29 503 patients met the eligibility criteria. In the non-comparison studies, the weighted frequency of PICC-related deep vein thrombosis was highest in patients who were critically ill (13·91%, 95% CI 7·68-20·14) and those with cancer (6·67%, 4·69-8·64). Our meta-analysis of 11 studies comparing the risk of deep vein thrombosis related to PICCs with that related to CVCs showed that PICCs were associated with an increased risk of deep vein thrombosis (OR 2·55, 1·54-4·23, p<0·0001) but not pulmonary embolism (no events). With the baseline PICC-related deep vein thrombosis rate of 2·7% and pooled OR of 2·55, the number needed to harm relative to CVCs was 26 (95% CI 13-71). INTERPRETATION: PICCs are associated with a higher risk of deep vein thrombosis than are CVCs, especially in patients who are critically ill or those with a malignancy. The decision to insert PICCs should be guided by weighing of the risk of thrombosis against the benefit provided by these devices. FUNDING: None.

Concepts: Blood, Thrombosis, Hematology, Vein, Low molecular weight heparin, Central venous catheter, Deep vein thrombosis, Deep vein

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Purpose: Early detection of deep vein thrombosis (DVT) is critical to prevent clinical pulmonary thromboembolism. However, most conventional methods for diagnosing DVT are functionally limited and complicated. The aim of this study was to evaluate the value of infrared-thermal-imaging (IRTI), a novel imaging detection or screening technique, in diagnosis of DVT in animal models.Methods: DVT model of femoral veins was established in nine New Zealand rabbits. The right hind femoral vein was embolized and the contralateral one served as a nonembolized control. Measurements of IRTI, compression ultrasonography (CPUS), and angiography under ultrasonic observation (AGUO) were performed at three time points: T1 (baseline, 10 min prior to surgery), T2 (2 h after thrombin injection), and T3 (48 h postoperatively). Qualitative pseudocolor analysis and quantitative temperature analysis were performed based on mean area temperature (Tav) and mean curvilinear temperature (Tca) of the region of interest as shown in IRTI. Temperature differences (TD) in Tav (TD(Tav)) and Tca (TD(Tca)) between the DVT and control sides were computed. Comparative statistical analysis was carried out by paired t-test and repeated measure, while multiple comparisons were performed by using Greenhouse-Geisser and Bonferroni approach. Values of P < 0.05 and P < 0.01 were considered statistically significant and highly significant.Results: Modeling of DVT was successful in all rabbits, as confirmed by CPUS and AGUO and immediately detected by IRTI. IRTI qualitative analysis of pseudocolor revealed that the bilateral temperatures were apparently asymmetrical and that there were abnormally high temperature zones on the DVT side where thrombosis formed. The results of paired t-test of Tav and Tca between DVT side and control sides did not reveal statistical difference at T1 (Tav: P = 0.817; Tca: P = 0.983) yet showed statistical differences at both T2 (Tav: P = 0.023; Tca: P = 0.021) and T3 (Tav: P = 0.016; Tca: P = 0.028). Results of repeated measure and multiple comparisons of TD(Tav) and TD(Tca) were highly different and significant differences across the T2 (TD(Tav): P = 0.009; TD(Tav): P = 0.03) and T3 (TD(Tav): P = 0.015; TD(Tav): P = 0.021).Conclusions: IRTI temperature quantitative analysis may help further detection of DVT. Additionally, IRTI could serve as a novel detection and screening tool for DVT due to its convenience, rapid response, and high sensitivity.

Concepts: Scientific method, Statistics, Statistical significance, Vein, Femoral vein, Deep vein thrombosis, Deep vein, Profunda femoris vein

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The exclusion of deep venous thrombosis (DVT) in the elderly is hampered by low specificity in clinical decision of D-dimer assays in older patients. To reduce false-positive results, we evaluated specific fibrin(ogen) degradation product assays for their contribution in the diagnosis of DVT. In a post-hoc study with outpatients suspected for DVT, we evaluated the elastase-specific fibrinogen (fibrinogen elastase degradation product, FgEDP) and D-E-specific fibrin (fibrin degradation product, FbDP) degradation product assays in relation to DVT. Results were combined with five D-dimer assays as ratio, with a specific focus on age-dependency. In 437 patients (DVT prevalence 39%), FgEDP correlated with D-dimer in DVT-negative patients (P < 0.001), but not in DVT-positive patients (P > 0.55). FbDP results correlated with D-dimer in both groups (P < 0.001). The values of the area under the curve of the receiver operating characteristic curve for both assays were lower than D-dimer. Using the ratios, only in the fourth age quartile D-dimer/FgEDP ratios had diagnostic value with lower number needed to test (1.8-12.7) as compared to D-dimer less than 500 μg/l alone (5.4-102). The D-dimer/FbDP ratios in DVT-negative elderly patients increased to a plateau by increasing D-dimer. In DVT-positive patients, these ratios were near constant for increasing values of D-dimer. In elderly patients, the D-dimer/FgEDP ratios may improve the number of patients in whom DVT could be excluded. The D-dimer/FbDP ratios showed differences in composition of fibrin degradation products between DVT-negative and DVT-positive patients and between young and old DVT-negative patients.

Concepts: Hematology, Vein, Receiver operating characteristic, Deep vein thrombosis, Deep vein, D-dimer, Coagulation system, Fibrin degradation product

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Venous thromboembolism is a relatively rare but serious complication of abdominal surgery. This study evaluated the incidence and risk factors for the development of deep venous thrombosis (DVT) after abdominal oncologic surgery using color Doppler ultrasonography (DUS).

Concepts: Medical ultrasound, Stroke, Hematology, Vein, Medical ultrasonography, Low molecular weight heparin, Deep vein thrombosis, Deep vein

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PURPOSE: To evaluate of the medium-term integrity, efficacy, and complication rate associated with the Gunther Tulip vena cava filter. METHODS: A retrospective study was performed of 369 consecutive patients who had infrarenal Gunther Tulip inferior vena cava filters placed over a 5-year period. The mean patient age was 61.8 years, and 59 % were men. Venous thromboembolic disease and a contraindication to or complication of anticoagulation were the indications for filter placement in 86 % of patients; 14 % were placed for prophylaxis in patients with a mean of 2.3 risk factors. Follow-up was obtained by review of medical and radiologic records. RESULTS: Mean clinical follow-up was 780 days. New or recurrent pulmonary embolus occurred in 12 patients (3.3 %). New or recurrent deep-vein thrombosis occurred in 53 patients (14.4 %). There were no symptomatic fractures, migrations, or caval perforations. Imaging follow-up in 287 patients (77.8 %) at a mean of 731 days revealed a single (0.3 %) asymptomatic fracture, migration greater than 2 cm in 36 patients (12.5 %), and no case of embolization. Of 122 patients with CT scans, asymptomatic perforations were identified in 53 patients (43.4 %) at a mean 757 days. CONCLUSION: The Gunther Tulip filter was safe and effective at 2-year follow-up. Complication rates were similar to those reported for permanent inferior vena cava filters.

Concepts: Stroke, Pulmonary embolism, Vein, Low molecular weight heparin, Anticoagulant, Inferior vena cava, Deep vein thrombosis, Inferior vena cava filter