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1.
CMAJ ; 193(2): E38-E46, 2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33431544

RESUMO

BACKGROUND: Evidence-based guidelines advise excluding pulmonary embolism (PE) diagnosis using d-dimer in patients with a lower probability of PE. Emergency physicians frequently order computed tomography (CT) pulmonary angiography without d-dimer testing or when d-dimer is negative, which exposes patients to more risk than benefit. Our objective was to develop a conceptual framework explaining emergency physicians' test choices for PE. METHODS: We conducted a qualitative study using in-depth interviews of emergency physicians in Canada. A nonmedical researcher conducted in-person interviews. Participants described how they would test simulated patients with symptoms of possible PE, answered a knowledge test and were interviewed on barriers to using evidence-based PE tests. RESULTS: We interviewed 63 emergency physicians from 9 hospitals in 5 cities, across 3 provinces. We identified 8 domains: anxiety with PE, barriers to using the evidence (time, knowledge and patient), divergent views on evidence-based PE testing, inherent Wells score problems, the drive to obtain CT rather than to diagnose PE, gestalt estimation artificially inflating PE probability, subjective reasoning and cognitive biases supporting deviation from evidence-based tests and use of evidence-based testing to rule out PE in patients who are very unlikely to have PE. Choices for PE testing were influenced by the disease, environment, test qualities, physician and probability of PE. INTERPRETATION: Analysis of structured interviews with emergency physicians provided a conceptual framework to explain how these physicians use tests for suspected PE. The data suggest 8 domains to address when implementing an evidence-based protocol to investigate PE.

2.
Semin Thromb Hemost ; 46(8): 977-985, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33368114

RESUMO

The role of rivaroxaban in the treatment of leg superficial venous thrombosis (SVT) is uncertain. This article aims to determine if rivaroxaban is an effective and safe treatment for leg SVT. Patients with symptomatic leg SVT of at least 5 cm length were randomized to 45 days of rivaroxaban 10 mg daily or to placebo, and followed for a total of 90 days. Treatment failure (required a nonstudy anticoagulant; had proximal deep vein thrombosis or pulmonary embolism; or had surgery for SVT) at 90 days was the primary efficacy outcome. Secondary efficacy outcomes included leg pain severity, and venous disease-specific and general health-related quality of life over 90 days. Major bleeding at 90 days was the primary safety outcome. Poor enrollment led to the trial being stopped after 85 of the planned 600 patients were randomized to rivaroxaban (n = 43) or placebo (n = 42). One rivaroxaban and five placebo patients had a treatment failure by 90 days (absolute risk reduction = 9.0%, 95% confidence interval: -22 to 5.9%). Leg pain improvement did not differ at 7 (p = 0.16) or 45 days (p = 0.89), but was greater with rivaroxaban at 90 days (p = 0.011). There was no difference in venous disease-specific (p = 0.99) or general health-related (p = 0.37) quality of life over 45 days. There were no major bleeds or deaths in either group. There were no identifiable differences in efficacy or safety between rivaroxaban and placebo in patients with symptomatic SVT but comparisons were undermined by a much smaller than planned sample size (NCT1499953).

3.
J Vasc Interv Radiol ; 31(10): 1517-1528.e2, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32948386

RESUMO

PURPOSE: To evaluate relationships between immediate venographic results and clinical outcomes of pharmacomechanical catheter-directed thrombolysis (PCDT). MATERIALS AND METHODS: Venograms from 317 patients with acute proximal deep vein thrombosis (DVT) who received PCDT in a multicenter randomized trial were reviewed. Quantitative thrombus resolution was assessed by independent readers using a modified Marder scale. The physician operators recorded their visual assessments of thrombus regression and venous flow. These immediate post-procedure results were correlated with patient outcomes at 1, 12, and 24 months. RESULTS: PCDT produced substantial thrombus removal (P < .001 for pre-PCDT vs. post-PCDT thrombus scores in all segments). At procedure end, spontaneous venous flow was present in 99% of iliofemoral venous segments and in 89% of femoral-popliteal venous segments. For the overall proximal DVT population, and for the femoral-popliteal DVT subgroup, post-PCDT thrombus volume did not correlate with 1-month or 24-month outcomes. For the iliofemoral DVT subgroup, over 1 and 24 months, symptom severity scores were higher (worse), and venous disease-specific quality of life (QOL) scores were lower (worse) in patients with greater post-PCDT thrombus volume, with the difference reaching statistical significance for the 24-month Villalta post-thrombotic syndrome (PTS) severity score (P = .0098). Post-PCDT thrombus volume did not correlate with 12-month valvular reflux. CONCLUSIONS: PCDT successfully removes thrombus in acute proximal DVT. However, the residual thrombus burden at procedure end does not correlate with the occurrence of PTS during the subsequent 24 months. In iliofemoral DVT, lower residual thrombus burden correlates with reduced PTS severity and possibly also with improved venous QOL and fewer early symptoms.


Assuntos
Veia Femoral , Fibrinolíticos/administração & dosagem , Veia Ilíaca , Veia Poplítea , Terapia Trombolítica , Ativador de Plasminogênio Tecidual/administração & dosagem , Trombose Venosa/terapia , Adolescente , Adulto , Idoso , Feminino , Veia Femoral/diagnóstico por imagem , Fibrinolíticos/efeitos adversos , Humanos , Veia Ilíaca/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Flebografia , Veia Poplítea/diagnóstico por imagem , Síndrome Pós-Trombótica/etiologia , Terapia Trombolítica/efeitos adversos , Fatores de Tempo , Ativador de Plasminogênio Tecidual/efeitos adversos , Resultado do Tratamento , Estados Unidos , Trombose Venosa/complicações , Trombose Venosa/diagnóstico por imagem , Adulto Jovem
4.
Br J Anaesth ; 2020 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-32768179

RESUMO

BACKGROUND: We aimed to establish diagnostic criteria for bleeding independently associated with mortality after noncardiac surgery (BIMS) defined as bleeding during or within 30 days after noncardiac surgery that is independently associated with mortality within 30 days of surgery, and to estimate the proportion of 30-day postoperative mortality potentially attributable to BIMS. METHODS: This was a prospective cohort study of participants ≥45 yr old having inpatient noncardiac surgery at 12 academic hospitals in eight countries between 2007 and 2011. Cox proportional hazards models evaluated the adjusted relationship between candidate diagnostic criteria for BIMS and all-cause mortality within 30 days of surgery. RESULTS: Of 16 079 participants, 2.0% (315) died and 36.1% (5810) met predefined screening criteria for bleeding. Based on independent association with 30-day mortality, BIMS was identified as bleeding leading to a postoperative haemoglobin <70 g L-1, transfusion of ≥1 unit of red blood cells, or that was judged to be the cause of death. Bleeding independently associated with mortality after noncardiac surgery occurred in 17.3% of patients (2782). Death occurred in 5.8% of patients with BIMS (161/2782), 1.3% (39/3028) who met bleeding screening criteria but not BIMS criteria, and 1.1% (115/10 269) without bleeding. BIMS was associated with mortality (adjusted hazard ratio: 1.87; 95% confidence interval: 1.42-2.47). We estimated the proportion of 30-day postoperative deaths potentially attributable to BIMS to be 20.1-31.9%. CONCLUSIONS: Bleeding independently associated with mortality after noncardiac surgery (BIMS), defined as bleeding that leads to a postoperative haemoglobin <70 g L-1, blood transfusion, or that is judged to be the cause of death, is common and may account for a quarter of deaths after noncardiac surgery. CLINICAL TRIAL REGISTRATION: NCT00512109.

5.
Br J Anaesth ; 2020 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-32718723

RESUMO

BACKGROUND: Diagnostic criteria for Bleeding Independently associated with Mortality after noncardiac Surgery (BIMS) have been defined as bleeding that leads to a postoperative haemoglobin <70 g L-1, leads to blood transfusion, or is judged to be the direct cause of death. Preoperative prediction guides for BIMS can facilitate informed consent and planning of perioperative care. METHODS: In a prospective cohort study of 16 079 participants aged ≥45 yr having inpatient noncardiac surgery at 12 academic hospitals in eight countries between 2007 and 2011, 17.3% (2782) experienced BIMS. An electronic risk calculator for BIMS was developed and internally validated by logistic regression with bootstrapping, and further simplified to a risk index. Decision curve analysis assessed the potential utility of each prediction guide compared with a strategy of identifying risk of BIMS based on preoperative haemoglobin <120 g L-1. RESULTS: With information about the type of surgery, preoperative haemoglobin, age, sex, functional status, kidney function, history of high-risk coronary artery disease, and active cancer, the risk calculator accurately predicted BIMS (bias-corrected C-statistic, 0.84; 95% confidence interval, 0.837-0.852). A simplified index based on preoperative haemoglobin <120 g L-1, open surgery, and high-risk surgery also predicted BIMS, but less accurately (C-statistic, 0.787; 95% confidence interval, 0.779-0.796). Both prediction guides could improve decision making compared with knowledge of haemoglobin <120 g L-1 alone. CONCLUSIONS: BIMS, defined as bleeding that leads to a postoperative haemoglobin <70 g L-1, leads to blood transfusion, or that is judged to be the direct cause of death, can be predicted by a simple risk index before surgery. CLINICAL TRIAL REGISTRATION: NCT00512109.

6.
Pilot Feasibility Stud ; 6: 104, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32699643

RESUMO

Background: Surgical bleeding is associated with postoperative cardiovascular complications. The efficacy and safety of tranexamic acid (TXA) in noncardiac surgery are still uncertain. Statins may prevent perioperative cardiovascular complications. We conducted a pilot to assess the feasibility of a perioperative trial of TXA and rosuvastatin. Methods: Using a factorial design, we randomized patients at cardiovascular risk undergoing noncardiac surgery to intravenous TXA (1 g at the start and end of surgery) or placebo, and oral rosuvastatin (40 mg before and 20 mg daily for 30 days after surgery) or placebo. Feasibility outcomes included recruitment rates, follow-up, and compliance to interventions. Clinical outcomes were secondarily explored. Results: After 3 months, we changed the design to a partial factorial due to the difficult recruitment of statin-naive patients. Over 6 months, 100 patients were randomized in the TXA trial (49 TXA, 51 placebo), 34 in the rosuvastatin trial (18 rosuvastatin, 16 placebo). Ninety-two percent (95% CI 80-98) of TXA and 86% (95% CI 74-94) of TXA-placebo patients received the 2 study doses. Thirty-three percent (95% CI 13-59) of rosuvastatin patients and 37% (95% CI 15-65) of rosuvastatin-placebo patients discontinued the study drug. A major cardiovascular complication occurred at 30 days in 1 TXA and 6 TXA-placebo patients, and 1 rosuvastatin and no rosuvastatin-placebo patients. Conclusions: Our pilot study supports the feasibility of a perioperative TXA trial in noncardiac surgery. Feasibility of a perioperative rosuvastatin trial is uncertain because of a high prevalence of statin use in the target population and concerns about compliance. Trial registration: ClinicalTrials.govNCT02546648.

7.
J Thromb Haemost ; 18(9): 2245-2252, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32433797

RESUMO

BACKGROUND: A previous individual participant data (IPD) meta-analysis showed that the Wells rule and D-dimer testing cannot exclude suspected deep vein thrombosis (DVT) in cancer patients. OBJECTIVES: To explore reasons for this reduced diagnostic accuracy and to optimize the diagnostic pathway for cancer patients suspected of DVT. PATIENTS AND METHODS: Using IPD from 13 studies in patients with suspected DVT, DVT prevalence and the predictive value of the Wells rule items and D-dimer testing were compared between patients with and without cancer. Next, we developed a prediction model with five variables selected from all available diagnostic predictors. RESULTS: Among the 10 002 suspected DVT patients, there were 834 patients with cancer. The median prevalence of DVT in these patients with cancer was 37.5% (interquartile range [IQR], 30.8-45.5), whereas it was 15.1% (IQR, 11.5-16.7) in patients without cancer. Diagnostic performance of individual Wells rule items and D-dimer testing was similar across patients with and without cancer, except "immobility" and "history of DVT." The newly developed rule showed a pooled c-statistic 0.80 (95% confidence interval [CI], 0.75-0.83) and good calibration. However, using this model, still only 4.3% (95% CI, 3.0-5.7) of the suspected patients with cancer could be identified with a predicted DVT posttest probability of <2%. CONCLUSIONS: Likely because of the high prevalence of DVT, clinical models followed by D-dimer testing fail to rule out DVT efficiently in cancer patients suspected of DVT. Direct referral for compression ultrasonography appears to be the preferred approach for diagnosis of suspected DVT in cancer patients.

8.
Blood ; 136(5): 533-541, 2020 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-32457982

RESUMO

Deep vein thrombosis and pulmonary embolism, collectively defined as venous thromboembolism (VTE), are the third leading cause of cardiovascular death in the United States. Common genetic variants conferring increased varying degrees of VTE risk have been identified by genome-wide association studies (GWAS). Rare mutations in the anticoagulant genes PROC, PROS1 and SERPINC1 result in perinatal lethal thrombosis in homozygotes and markedly increased VTE risk in heterozygotes. However, currently described VTE variants account for an insufficient portion of risk to be routinely used for clinical decision making. To identify new rare VTE risk variants, we performed a whole-exome study of 393 individuals with unprovoked VTE and 6114 controls. This study identified 4 genes harboring an excess number of rare damaging variants in patients with VTE: PROS1, STAB2, PROC, and SERPINC1. At STAB2, 7.8% of VTE cases and 2.4% of controls had a qualifying rare variant. In cell culture, VTE-associated variants of STAB2 had a reduced surface expression compared with reference STAB2. Common variants in STAB2 have been previously associated with plasma von Willebrand factor and coagulation factor VIII levels in GWAS, suggesting that haploinsufficiency of stabilin-2 may increase VTE risk through elevated levels of these procoagulants. In an independent cohort, we found higher von Willebrand factor levels and equivalent propeptide levels in individuals with rare STAB2 variants compared with controls. Taken together, this study demonstrates the utility of gene-based collapsing analyses to identify loci harboring an excess of rare variants with functional connections to a complex thrombotic disease.

10.
J Thromb Haemost ; 18(6): 1381-1389, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32145144

RESUMO

BACKGROUND: Using data from the SOX Trial, we recently developed a clinical prediction model for occurrence of the postthrombotic syndrome (PTS) after proximal deep vein thrombosis (DVT), termed the SOX-PTS score. The score includes anatomical extent of DVT; body mass index; and baseline Villalta score. OBJECTIVE: To externally validate the SOX-PTS score. METHODS: Logistic regression analysis of data from the ATTRACT Trial that evaluated pharmacomechanical catheter directed thrombolysis in patients with proximal DVT. The primary outcome was the occurrence of PTS (defined as Villalta score ≥ 5) from 6 to 24 months after DVT. Secondary outcomes included moderate-severe PTS (Villalta scale ≥ 10) and severe PTS (Villalta scale ≥ 14). Predictive performance was assessed by discrimination and calibration. An updated score was evaluated in an exploratory analysis. RESULTS: Six hundred and ninety-one ATTRACT patients were included, of whom 328 (47%) developed PTS. The c-statistic was 0.63; 95% confidence interval (CI) 0.59-0.67 for PTS. The model's performance appeared to be better for the outcomes moderate to severe PTS and severe PTS (c-statistic 0.67; 95% CI 0.62-0.72 for moderate-severe PTS and 0.70; 0.64-0.77 for severe PTS). An updated model with age as an additional variable performed similarly to the original model. CONCLUSION: We externally validated the SOX-PTS score for estimating the risk of developing PTS, moderate to severe PTS, and severe PTS, in patients with proximal DVT. The score may be useful to predict PTS at the time of DVT diagnosis. Further external validation in different patient cohorts is required.

11.
J Am Geriatr Soc ; 68(5): 970-976, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32010977

RESUMO

OBJECTIVES: Emergency department (ED) visits among older adults are frequently instigated by a fall at home. Some of these patients develop intracranial bleeding. The aim of this study was to identify the incidence of intracranial bleeding and the associated clinical features in older adults who present to the ED after falling. DESIGN: Prospective cohort study. SETTING: Three Canadian EDs. PARTICIPANTS: A total of 2 176 patients age 65 years or older who presented to the ED with a fall were assessed, and 1753 were included. Inclusion criteria were a fall on level ground, off a bed, chair, or toilet, or from one or two steps within 48 hours. MEASUREMENTS: Emergency physicians recorded predefined clinical findings on initial assessment. The primary outcome was intracranial bleeding, diagnosed either by computed tomography at the index visit or within 42 days. Associations between baseline clinical findings and the presence of intracranial bleeding were assessed with multivariable logistic regression. RESULTS: A total of 1753 patients (median age = 82 y) were enrolled, of whom 39% were male, 35% were on antiplatelet therapy, and 25% were on an anticoagulant. The incidence of intracranial bleeding was 5.0% (95% confidence interval [CI] = 4.1-6.1). Overall, 76 patients were diagnosed at the index ED visit, and 12 were diagnosed during follow-up. Multivariable regression identified four clinical variables that were independently associated with intracranial bleeding: new abnormalities on neurologic examination (odds ratio [OR] = 4.4; 95% CI = 2.4-8.1), bruise or laceration on the head (OR = 4.3; 95% CI = 2.7-7.0), chronic kidney disease (OR = 2.4; 95% CI = 1.3-4.6), and reduced Glasgow Coma Scale from normal (OR = 1.9; 95% CI = 1.0-3.4). CONCLUSION: The incidence of intracranial bleeding in our study was 5.0%. We found significant associations between intracranial bleeding and four simple clinical variables. We did not find significant associations between intracranial bleeding and antiplatelet or anticoagulant use. J Am Geriatr Soc 68:970-976, 2020.

12.
Blood ; 135(5): 317-325, 2020 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-31917402

RESUMO

The most important decision in the long-term treatment of venous thromboembolism (VTE) is how long to anticoagulate. VTE provoked by a reversible risk factor, or a first unprovoked isolated distal deep vein thrombosis (DVT), generally should be treated for 3 months. VTE provoked by a persistent or progressive risk factor (eg, cancer), or a second unprovoked proximal DVT or PE, is generally treated indefinitely. First unprovoked proximal DVT or PE may be treated for 3 to 6 months or indefinitely. Male sex, presentation as PE (particularly if concomitant proximal DVT), a positive d-dimer test after stopping anticoagulation, an antiphospholipid antibody, low risk of bleeding, and patient preference favor indefinite anticoagulation. The type of indefinite anticoagulation is of secondary importance. Low-dose oral Xa inhibitors are convenient and are thought to have a lower risk of bleeding; they are less suitable if there is a higher risk for recurrence. For cancer-associated VTE, we now prefer full-dose oral Xa inhibitors over low-molecular-weight heparin, with gastrointestinal lesions being a relative contraindication. Graduated compression stockings are not routinely indicated after DVT, but are encouraged if there is persistent leg swelling or if a trial of stockings improves symptoms. Medications have a limited role in the treatment of postthrombotic syndrome. After PE, patients should have clinical surveillance for chronic thromboembolic pulmonary hypertension (CTEPH), with ventilation-perfusion scanning and echocardiography being the initial diagnostic tests if CTEPH is a concern. Patients with CTEPH and other symptomatic patients with extensive residual perfusion defects should be evaluated for endarterectomy, balloon pulmonary angioplasty, or vasodilator therapies.


Assuntos
Tromboembolia Venosa/tratamento farmacológico , Anticoagulantes/uso terapêutico , Humanos , Síndrome Pós-Trombótica/etiologia , Recidiva , Fatores de Risco , Fatores de Tempo , Tromboembolia Venosa/complicações
13.
J Vasc Surg Venous Lymphat Disord ; 8(1): 8-23.e18, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31843251

RESUMO

BACKGROUND: After deep venous thrombosis (DVT), many patients have impaired quality of life (QOL). We aimed to assess whether pharmacomechanical catheter-directed thrombolysis (PCDT) improves short-term or long-term QOL in patients with proximal DVT and whether QOL is related to extent of DVT. METHODS: The Acute Venous Thrombosis: Thrombus Removal with Adjunctive Catheter-Directed Thrombolysis (ATTRACT) trial was an assessor-blinded randomized trial that compared PCDT with no PCDT in patients with DVT of the femoral, common femoral, or iliac veins. QOL was assessed at baseline and 1 month, 6 months, 12 months, 18 months, and 24 months using the Venous Insufficiency Epidemiological and Economic Study on Quality of Life/Symptoms (VEINES-QOL/Sym) disease-specific QOL measure and the 36-Item Short Form Health Survey (SF-36) physical component summary (PCS) and mental component summary general QOL measures. Change in QOL scores from baseline to assessment time were compared in the PCDT and no PCDT treatment groups overall and in the iliofemoral DVT and femoral-popliteal DVT subgroups. RESULTS: Of 692 ATTRACT patients, 691 were analyzed (mean age, 53 years; 62% male; 57% iliofemoral DVT). VEINES-QOL change scores were greater (ie, better) in PCDT vs no PCDT from baseline to 1 month (difference, 5.7; P = .0006) and from baseline to 6 months (5.1; P = .0029) but not for other intervals. SF-36 PCS change scores were greater in PCDT vs no PCDT from baseline to 1 month (difference, 2.4; P = .01) but not for other intervals. Among iliofemoral DVT patients, VEINES-QOL change scores from baseline to all assessments were greater in the PCDT vs no PCDT group; this was statistically significant in the intention-to-treat analysis at 1 month (difference, 10.0; P < .0001) and 6 months (8.8; P < .0001) and in the per-protocol analysis at 18 months (difference, 5.8; P = .0086) and 24 months (difference, 6.6; P = .0067). SF-36 PCS change scores were greater in PCDT vs no PCDT from baseline to 1 month (difference, 3.2; P = .0010) but not for other intervals. In contrast, in femoral-popliteal DVT patients, change scores from baseline to all assessments were similar in the PCDT and no PCDT groups. CONCLUSIONS: Among patients with proximal DVT, PCDT leads to greater improvement in disease-specific QOL than no PCDT at 1 month and 6 months but not later. In patients with iliofemoral DVT, PCDT led to greater improvement in disease-specific QOL during 24 months.


Assuntos
Veia Femoral , Fibrinolíticos/administração & dosagem , Veia Ilíaca , Trombólise Mecânica , Qualidade de Vida , Terapia Trombolítica , Trombose Venosa/terapia , Adulto , Feminino , Veia Femoral/fisiopatologia , Fibrinolíticos/efeitos adversos , Humanos , Veia Ilíaca/fisiopatologia , Masculino , Trombólise Mecânica/efeitos adversos , Pessoa de Meia-Idade , Inquéritos e Questionários , Terapia Trombolítica/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Estados Unidos , Trombose Venosa/diagnóstico , Trombose Venosa/fisiopatologia
14.
Thromb Res ; 186: 13-19, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31838139

RESUMO

INTRODUCTION: Cell-free DNA (CFDNA) is the major structural component of neutrophil extracellular traps (NETs). CFDNA contributes to the prothrombotic potential of NETs by promoting thrombin generation and inhibiting fibrinolysis. Patients with venous thromboembolism (VTE) have elevated circulating nucleosomes (i.e. DNA-histone complexes). In this study, we investigated if CFDNA contributes to a procoagulant and an antifibrinolytic state in patients with unprovoked VTE. MATERIALS AND METHODS: Plasma samples from patients with a first episode of unprovoked VTE were obtained from the D-Dimer Optimal Duration Study (DODS). We measured CFDNA plasma levels in 263 patients while on warfarin and 1-month after stopping. Thrombin generation assays and clot lysis assays were measured in patients after stopping warfarin. Comparisons were made with healthy controls. RESULTS: CFDNA levels in VTE patients who stopped warfarin (5.53 µg/mL; 95%CI: 5.34-5.72) were higher than during warfarin therapy (3.11 µg/mL; 95%CI: 2.98-3.25; p < .001), and higher than in healthy controls (2.77 µg/mL; 95%CI: 2.42-3.11; p < .001). VTE patients had a procoagulant state as evidenced by a shorter lag time (30.8 min; 95%CI: 29.2-32.4) compared to controls (48.2 min; 95%CI :41.0-55.5; p < .001) and a greater endogenous thrombin potential (2656 nM∗min; 95%CI: 2479-2836) compared to healthy controls (1198 nM ∗ min; 95%CI: 793-1603). There was a higher proportion of clots generated from patient plasma that were resistant to lysis (43.7%) compared to healthy controls (46.3%; p < .05). CFDNA levels were not associated with enhanced thrombin generation or impaired fibrinolysis in VTE patients. CONCLUSION: CFDNA levels are elevated in patients with unprovoked VTE but do not correlate with the procoagulant or anti-fibrinolytic properties of patient plasma. This study suggests that additional factors in addition to CFDNA may contribute to the pathogenesis of VTE.

15.
J Thromb Haemost ; 18(3): 669-675, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31869505

RESUMO

BACKGROUND: To increase the clinical usefulness of the D-dimer test in diagnosis of deep vein thrombosis (DVT), two strategies have been proposed: the age-adjusted, and the clinical pre-test probability (CPTP) adjusted interpretation. However, it is not known which of these strategies is superior. OBJECTIVE: To conduct an individual patient data (IPD) meta-analysis that compares the sensitivity, specificity, negative predictive value (NPV), and utility (the proportion of all patients who have a negative D-dimer test) when the two strategies are used to interpret D-dimer results. METHODS: Using an established IPD database, we conducted a meta-analysis to compare the two strategies. A bivariate random effects regression model was used to estimate and compare the pooled sensitivity and specificity simultaneously. The pooled NPV and utility of the two strategies was compared using a univariate random effects model. RESULTS: Four studies were eligible for this analysis, with a total of 2554 patients. Overall prevalence of DVT was 12% with substantial heterogeneity between studies (P value < .001). Both strategies have high pooled NPVs (99.8%) with a difference of 0% (95% confidence interval [CI]: -0.1, 0.1). The difference between the pooled specificity of the CPTP-adjusted strategy (57.3%) and the age-adjusted strategy (54.7%) was 2.6% (95% CI: -7.7, 12.8). The CPTP-adjusted strategy (49.4%) has a marginally greater pooled utility compared with the age-adjusted approach (47.4%), with a pooled difference of 1.9% (95% CI: -0.1, 3.9). CONCLUSIONS: Both D-dimer interpretation strategies were associated with a high and similar NPV, and similar utility.

16.
N Engl J Med ; 381(22): 2125-2134, 2019 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-31774957

RESUMO

BACKGROUND: Retrospective analyses suggest that pulmonary embolism is ruled out by a d-dimer level of less than 1000 ng per milliliter in patients with a low clinical pretest probability (C-PTP) and by a d-dimer level of less than 500 ng per milliliter in patients with a moderate C-PTP. METHODS: We performed a prospective study in which pulmonary embolism was considered to be ruled out without further testing in outpatients with a low C-PTP and a d-dimer level of less than 1000 ng per milliliter or with a moderate C-PTP and a d-dimer level of less than 500 ng per milliliter. All other patients underwent chest imaging (usually computed tomographic pulmonary angiography). If pulmonary embolism was not diagnosed, patients did not receive anticoagulant therapy. All patients were followed for 3 months to detect venous thromboembolism. RESULTS: A total of 2017 patients were enrolled and evaluated, of whom 7.4% had pulmonary embolism on initial diagnostic testing. Of the 1325 patients who had a low C-PTP (1285 patients) or moderate C-PTP (40 patients) and a negative d-dimer test (i.e., <1000 or <500 ng per milliliter, respectively), none had venous thromboembolism during follow-up (95% confidence interval [CI], 0.00 to 0.29%). These included 315 patients who had a low C-PTP and a d-dimer level of 500 to 999 ng per milliliter (95% CI, 0.00 to 1.20%). Of all 1863 patients who did not receive a diagnosis of pulmonary embolism initially and did not receive anticoagulant therapy, 1 patient (0.05%; 95% CI, 0.01 to 0.30) had venous thromboembolism. Our diagnostic strategy resulted in the use of chest imaging in 34.3% of patients, whereas a strategy in which pulmonary embolism is considered to be ruled out with a low C-PTP and a d-dimer level of less than 500 ng per milliliter would result in the use of chest imaging in 51.9% (difference, -17.6 percentage points; 95% CI, -19.2 to -15.9). CONCLUSIONS: A combination of a low C-PTP and a d-dimer level of less than 1000 ng per milliliter identified a group of patients at low risk for pulmonary embolism during follow-up. (Funded by the Canadian Institutes of Health Research and others; PEGeD ClinicalTrials.gov number, NCT02483442.).


Assuntos
Regras de Decisão Clínica , Angiografia por Tomografia Computadorizada , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Embolia Pulmonar/sangue , Embolia Pulmonar/diagnóstico , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Probabilidade , Estudos Prospectivos , Embolia Pulmonar/diagnóstico por imagem
17.
Circ Cardiovasc Qual Outcomes ; 12(10): e005659, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31592728

RESUMO

BACKGROUND: In patients with acute deep vein thrombosis (DVT), pharmacomechanical catheter-directed thrombolysis (PCDT) in conjunction with anticoagulation therapy is increasingly used with the goal of preventing postthrombotic syndrome. Long-term costs and cost-effectiveness of these 2 treatment strategies from the perspective of the US healthcare system have not been compared. METHODS AND RESULTS: Between 2009 and 2014, the ATTRACT trial (Acute Venous Thrombosis: Thrombus Removal With Adjunctive Catheter-Directed Thrombolysis) randomized 692 patients with acute proximal DVT to PCDT plus anticoagulation (n=337) or standard treatment with anticoagulation alone (n=355). Costs (2017 US dollars) were assessed over a 24-month follow-up period using a combination of resource-based costing, hospital bills, Medicare reimbursement rates, and the Drug Topics Red Book. Health state utilities were obtained from the Short Form-36. In-trial results and US life tables were used to develop a Markov cohort model to evaluate lifetime cost-effectiveness. For the PCDT group, mean costs of the initial procedure were $13 600; per-patient costs associated with the index hospitalization were $21 509 for PCDT and $3877 for standard care (difference=$17 632; 95% CI, $16 117-$19 243). The 24-month difference in costs was $20 045 (95% CI, $16 093-$24 120). Utility scores increased significantly between baseline and 6 months for both groups, with no significant differences between groups at any follow-up time point. Projected differences in lifetime costs of $16 740 and quality-adjusted life years (QALYs) of 0.08, yield an incremental cost-effectiveness ratio for PCDT of $222 041/QALY gained. In probabilistic sensitivity analysis, the probability that PCDT would achieve a lifetime incremental cost-effectiveness ratio <$50 000/QALY or <$150 000/QALY was 1% and 25%, respectively. For iliofemoral DVT, QALY gains with PCDT were greater, yielding an incremental cost-effectiveness ratio of $137 526/QALY; for femoral-popliteal DVT, standard therapy was an economically dominant strategy. CONCLUSIONS: With an incremental cost-effectiveness ratio >$200 000/QALY gained, PCDT is not an economically attractive treatment for proximal DVT. PCDT may be of intermediate value in patients with iliofemoral DVT. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT00790335.


Assuntos
Assistência Ambulatorial/economia , Anticoagulantes/administração & dosagem , Anticoagulantes/economia , Custos de Medicamentos , Fibrinolíticos/administração & dosagem , Fibrinolíticos/economia , Custos Hospitalares , Terapia Trombolítica/economia , Trombose Venosa/tratamento farmacológico , Trombose Venosa/economia , Administração Oral , Anticoagulantes/efeitos adversos , Redução de Custos , Análise Custo-Benefício , Fibrinolíticos/efeitos adversos , Humanos , Cadeias de Markov , Modelos Econômicos , Qualidade de Vida , Anos de Vida Ajustados por Qualidade de Vida , Terapia Trombolítica/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Estados Unidos , Trombose Venosa/diagnóstico
18.
Circulation ; 140(20): e774-e801, 2019 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-31585051

RESUMO

Pulmonary embolism (PE) represents the third leading cause of cardiovascular mortality. The technological landscape for management of acute intermediate- and high-risk PE is rapidly evolving. Two interventional devices using pharmacomechanical means to recanalize the pulmonary arteries have recently been cleared by the US Food and Drug Administration for marketing, and several others are in various stages of development. The purpose of this document is to clarify the current state of endovascular interventional therapy for acute PE and to provide considerations for evidence development for new devices that will define which patients with PE would derive the greatest net benefit from their use in various clinical settings. First, definitions and limitations of commonly used risk stratification tools for PE are reviewed. An adjudication of risks and benefits of available interventional therapies for PE follows. Next, considerations for optimal future evidence development in this field are presented in the context of the current US regulatory framework. Finally, the document concludes with a discussion of the pros and cons of the rapidly expanding PE response team model of care delivery.


Assuntos
Embolectomia/normas , Procedimentos Endovasculares/normas , Embolia Pulmonar/terapia , Terapia Trombolítica/normas , American Heart Association , Tomada de Decisão Clínica , Consenso , Técnicas de Apoio para a Decisão , Embolectomia/efeitos adversos , Embolectomia/instrumentação , Embolectomia/mortalidade , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/instrumentação , Procedimentos Endovasculares/mortalidade , Humanos , Seleção de Pacientes , Embolia Pulmonar/diagnóstico por imagem , Embolia Pulmonar/mortalidade , Embolia Pulmonar/fisiopatologia , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Terapia Trombolítica/efeitos adversos , Terapia Trombolítica/instrumentação , Terapia Trombolítica/mortalidade , Resultado do Tratamento , Estados Unidos
19.
BMJ ; 366: l4363, 2019 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-31340984

RESUMO

OBJECTIVES: To determine the rate of a first recurrent venous thromboembolism (VTE) event after discontinuation of anticoagulant treatment in patients with a first episode of unprovoked VTE, and the cumulative incidence for recurrent VTE up to 10 years. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Medline, Embase, and the Cochrane Central Register of Controlled Trials (from inception to 15 March 2019). STUDY SELECTION: Randomised controlled trials and prospective cohort studies reporting symptomatic recurrent VTE after discontinuation of anticoagulant treatment in patients with a first unprovoked VTE event who had completed at least three months of treatment. DATA EXTRACTION AND SYNTHESIS: Two investigators independently screened studies, extracted data, and appraised risk of bias. Data clarifications were sought from authors of eligible studies. Recurrent VTE events and person years of follow-up after discontinuation of anticoagulant treatment were used to calculate rates for individual studies, and data were pooled using random effects meta-analysis. Sex and site of initial VTE were investigated as potential sources of between study heterogeneity. RESULTS: 18 studies involving 7515 patients were included in the analysis. The pooled rate of recurrent VTE per 100 person years after discontinuation of anticoagulant treatment was 10.3 events (95% confidence interval 8.6 to 12.1) in the first year, 6.3 (5.1 to 7.7) in the second year, 3.8 events/year (95% confidence interval 3.2 to 4.5) in years 3-5, and 3.1 events/year (1.7 to 4.9) in years 6-10. The cumulative incidence for recurrent VTE was 16% (95% confidence interval 13% to 19%) at 2 years, 25% (21% to 29%) at 5 years, and 36% (28% to 45%) at 10 years. The pooled rate of recurrent VTE per 100 person years in the first year was 11.9 events (9.6 to 14.4) for men and 8.9 events (6.8 to 11.3) for women, with a cumulative incidence for recurrent VTE of 41% (28% to 56%) and 29% (20% to 38%), respectively, at 10 years. Compared to patients with isolated pulmonary embolism, the rate of recurrent VTE was higher in patients with proximal deep vein thrombosis (rate ratio 1.4, 95% confidence interval 1.1 to 1.7) and in patients with pulmonary embolism plus deep vein thrombosis (1.5, 1.1 to 1.9). In patients with distal deep vein thrombosis, the pooled rate of recurrent VTE per 100 person years was 1.9 events (95% confidence interval 0.5 to 4.3) in the first year after anticoagulation had stopped. The case fatality rate for recurrent VTE was 4% (95% confidence interval 2% to 6%). CONCLUSIONS: In patients with a first episode of unprovoked VTE who completed at least three months of anticoagulant treatment, the risk of recurrent VTE was 10% in the first year after treatment, 16% at two years, 25% at five years, and 36% at 10 years, with 4% of recurrent VTE events resulting in death. These estimates should inform clinical practice guidelines, enhance confidence in counselling patients of their prognosis, and help guide decision making about long term management of unprovoked VTE. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42017056309.


Assuntos
Anticoagulantes/uso terapêutico , Medição de Risco/métodos , Tromboembolia Venosa , Suspensão de Tratamento , Humanos , Recidiva , Tempo , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/fisiopatologia
20.
Vasc Med ; 24(5): 442-451, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31354089

RESUMO

Few studies have documented relationships between endovascular therapy, duplex ultrasonography (DUS), post-thrombotic syndrome (PTS), and quality of life (QOL). The Acute Venous Thrombosis: Thrombus Removal with Adjunctive Catheter-Directed Thrombolysis (ATTRACT) trial randomized 692 patients with acute proximal deep vein thrombosis (DVT) to receive anticoagulation or anticoagulation plus pharmacomechanical catheter-directed thrombolysis (PCDT). Compression DUS was obtained at baseline, 1 month and 12 months. Reflux DUS was obtained at 12 months in a subset of 126 patients. Clinical outcomes were collected over 24 months. At 1 month, patients who received PCDT had less residual thrombus compared to Control patients, evidenced by non-compressible common femoral vein (CFV) (21% vs 35%, p < 0.0001), femoral vein (51% vs 70%, p < 0.0001), and popliteal vein (61% vs 74%, p < 0.0001). At 12 months, in the ultrasound substudy, valvular reflux prevalence was similar between groups (85% vs 91%, p = 0.35). CFV non-compressibility at 1 month was associated with higher rates of any PTS (61% vs 46%, p < 0.001), a higher incidence of moderate-or-severe PTS (30% vs 19%, p = 0.003), and worse QOL (difference 8.2 VEINES-QOL (VEnous INsufficiency Epidemiological and Economic Study on Quality of Life) points; p = 0.004) at 24 months. Valvular reflux at 12 months was associated with moderate-or-severe PTS at 24 months (30% vs 0%, p = 0.01). In summary, PCDT results in less residual thrombus but does not reduce venous valvular reflux. CFV non-compressibility at 1 month is associated with more PTS, more severe PTS, and worse QOL at 24 months. Valvular reflux may predispose to moderate-or-severe PTS. ClinicalTrials.gov Identifier NCT00790335.


Assuntos
Cateterismo Periférico , Fibrinolíticos/administração & dosagem , Terapia Trombolítica , Ultrassonografia Doppler Dupla , Trombose Venosa/terapia , Administração Intravenosa , Adulto , Cateterismo Periférico/efeitos adversos , Feminino , Fibrinolíticos/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , América do Norte , Síndrome Pós-Trombótica/diagnóstico por imagem , Síndrome Pós-Trombótica/etiologia , Síndrome Pós-Trombótica/fisiopatologia , Valor Preditivo dos Testes , Qualidade de Vida , Fatores de Risco , Índice de Gravidade de Doença , Terapia Trombolítica/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/fisiopatologia
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