Risk of a permanent work-related disability pension after incident venous thromboembolism in Denmark: A population-based cohort study.

BACKGROUND: Long-term complications of venous thromboembolism (VTE) hamper physical function and impair quality of life; still, it remains unclear whether VTE is associated with risk of permanent work-related disability. We aimed to assess the association between VTE and the risk of receiving a permanent work-related disability pension and to assess whether this association was explained by comorbidities such as cancer and arterial cardiovascular disease. METHODS AND FINDINGS: A Danish nationwide population-based cohort study consisting of 43,769 individuals aged 25 to 66 years with incident VTE during 1995 to 2016 and 218,845 birth year-, sex-, and calendar year-matched individuals from the general population, among whom 45.9% (N = 120,540) were women, was established using Danish national registries. The cohorts were followed throughout 2016, with permanent work-related disability pension as the outcome. Hazard ratios (HRs) with 95% confidence intervals (CIs) for disability pension were computed and stratified by sex and age groups (25 to 34, 35 to 44, 45 to 54, and 55 to 66 years of age) and adjusted for comorbidities and socioeconomic variables. Permanent work-related disability pensions were granted to 4,415 individuals with VTE and 9,237 comparison cohort members (incidence rates = 17.8 and 6.2 per 1,000 person-years, respectively). VTE was associated with a 3-fold (HR 3.0, 95% CI: 2.8 to 3.1) higher risk of receiving a disability pension. Adjustments for socioeconomic status and comorbidities such as cancer and cardiovascular diseases reduced the estimate (HR 2.3, 95% CI: 2.2 to 2.4). The risk of disability pension receipt was slightly higher in men than in women (HR 2.5, 95% CI: 2.3 to 2.6 versus HR 2.1, 95% CI: 2.0 to 2.3). As this study is based on medical and administrative registers, information on post-VTE care, individual health behavior, and workplace factors linked to disability pension in the general population are lacking. Furthermore, as disability pension schemes vary, our results might not be directly generalizable to other countries or time periods. CONCLUSIONS: In this study, incident VTE was associated with increased risk of subsequent permanent work-related disability, and this association was still observed after accounting for comorbidities such as cancer and cardiovascular diseases. Our results emphasize the social consequences of VTE and may help occupational and healthcare professionals to identify vulnerable individuals at risk of permanent exclusion from the labor market after a VTE event.

Definitions, adjudication, and reporting of pulmonary embolism-related death in clinical studies: A systematic review.

BACKGROUND: Pulmonary embolism (PE)-related death is a component of the primary outcome in many venous thromboembolism (VTE) studies. The absence of a standardized definition for PE-related death hampers study outcome evaluation and between-study comparisons. OBJECTIVES: To summarize definitions for PE-related death used in recent VTE studies and to assess the PE-related death rate. PATIENTS/METHODS: A systematic literature search was conducted on 26 April 2018 from 1 January 2014 up to the search date in MEDLINE, Embase, and CENTRAL. Cohort studies and randomized trials in which PE-related death was included in the primary outcome were eligible. Screening of titles, abstracts, and full-text articles, and data extraction were independently performed in duplicate by two authors. Study outcomes included the definition for PE-related death, VTE case-fatality rate, and death due to PE rate. Descriptive statistics were used to analyze the data. RESULTS: Of the 6807 identified citations, 83 studies were included of which 27% were randomized trials, 31% were prospective, and 42% retrospective cohort studies. Thirty-five studies (42%) had a central adjudication committee. Thirty-eight (46%) reported a definition for PE-related death of which the most frequently used components were "autopsy-confirmed PE" (50%), "objectively confirmed PE before death" (55%), and "unexplained death" (58%). Median VTE case-fatality rate was 1.8% (interquartile range, 0.0-13). CONCLUSIONS: Only half of the included studies reported definitions for PE-related death, which were very heterogeneous. Case-fatality rate of VTE events varied widely across studies. Standardization of the definition and guidance on adjudication and reporting of PE-related death is needed.

Who should get long-term anticoagulant therapy for venous thromboembolism and with what?

After an initial 3 to 6 months of anticoagulation for venous thromboembolism (VTE), clinicians and patients face an important question: "Do we stop anticoagulants or continue them indefinitely?" The decision is easy in some scenarios (eg, stop in VTE provoked by major surgery). In most scenarios, which are faced on a day-to-day basis in routine practice, it is a challenging decision because of uncertainty in estimates in the long-term risks (principally major bleeding) and benefits (reducing recurrent VTE) and the tight trade-offs between them. Once the decision is made to continue, the next question to tackle is "Which anticoagulant?" Here again, it is a difficult decision because of the uncertainty with regard to estimates of efficacy and the safety of anticoagulant options and the tight trade-offs between choices. We conclude with the approach that we take in our clinical practice.

Epidemiology, Pathophysiology, Stratification, and Natural History of Pulmonary Embolism.

Pulmonary embolism (PE) is a common and potentially fatal form of venous thromboembolism that can be challenging to diagnose and manage. PE occurs when there is obstruction of the pulmonary vasculature and is a common cause of morbidity and mortality in the United States. A combination of acquired and inherited factors may contribute to the development of this disease and should be considered, since they have implications for both susceptibility to PE and treatment. Patients with suspected PE should be evaluated efficiently to diagnose and administer therapy as soon as possible, but the presentation of PE is variable and nonspecific so diagnosis is challenging. PE can range from small, asymptomatic blood clots to large emboli that can occlude the pulmonary arteries causing sudden cardiovascular collapse and death. Thus, risk stratification is critical to both the prognosis and management of acute PE. In this review, we discuss the epidemiology, risk factors, pathophysiology, and natural history of PE and deep vein thrombosis.

Profilaxia de tromboembolismo venoso na gestação / Venous thromboembolism prophylaxis in pregnancy

Resumo O tromboembolismo venoso é importante causa de morbidade e mortalidade obstétrica. Durante a gestação, o risco de sua ocorrência aumenta entre cinco e dez vezes quando comparado ao de mulheres não gestantes de mesma idade. Associado a esse fato, a gestante apresenta algumas limitações para o diagnóstico clínico (alta frequência de dor e edema nos membros inferiores), ecográfico (menor sensibilidade e especificidade no diagnóstico de trombose venosa de ilíaca com a evolução da gestação) e laboratorial (o D-dímero apresenta aumento progressivo no decorrer da gravidez). Uma estratificação criteriosa de risco de tromboembolismo venoso de cada mulher antes da gestação pode diminuir a incidência dessa doença, frequente e de difícil diagnóstico na gravidez, e suas complicações.

Abstract Venous thromboembolism is a major cause of obstetric morbidity and mortality. During pregnancy, the risk of occurrence increases between five and ten times when compared to women of the same age who are not pregnant. Compounding this is the fact that pregnant women present certain characteristics that make diagnosis more difficult using clinical signs (high frequency of pain and swelling in the lower limbs), echographic examination (lower sensitivity and specificity for diagnosis of iliac vein thrombosis as pregnancy progresses), and laboratory findings (D-dimer levels progressively increase throughout pregnancy). Conducting careful stratification of women’s venous thromboembolism risk before pregnancy could reduce the incidence of this disease, which is frequent and difficult to diagnose during pregnancy, and of its complications.

ICD-9 Code-Based Venous Thromboembolism Performance Targets Fail to Measure Up.

Venous thromboembolism (VTE) is a common complication among hospitalized patients. Suboptimal prevention practices have prompted payers to consider hospital-associated VTE as a potentially preventable condition for which financial incentives or penalties exist to drive practice improvement. The authors reviewed all cases of hospital-associated VTE at the Johns Hopkins Hospital between July 1, 2010, and June 30, 2011, that were identified by ICD-9 codes used by a state-run pay-for-performance quality improvement program. Of 157 patients identified as having developed hospital-associated, potentially preventable VTE, only 92 (58.6%) patients developed radiographically confirmed VTE that were potentially preventable. This misclassification of VTE overestimates the marginal additional treatment cost by more than $860 000 and amounts to nearly $200 000 in lost reward in one year alone. ICD-9 codes alone have extremely low positive predictive value to identify true VTE events. The authors recommend linking provision of risk-appropriate prophylaxis to VTE outcomes as a better target for performance improvement.

The validity of ICD codes coupled with imaging procedure codes for identifying acute venous thromboembolism using administrative data.

The purpose of this study was to evaluate the accuracy of using a combination of International Classification of Diseases (ICD) diagnostic codes and imaging procedure codes for identifying deep vein thrombosis (DVT) and pulmonary embolism (PE) within administrative databases. Information from the Alberta Health (AH) inpatients and ambulatory care administrative databases in Alberta, Canada was obtained for subjects with a documented imaging study result performed at a large teaching hospital in Alberta to exclude venous thromboembolism (VTE) between 2000 and 2010. In 1361 randomly-selected patients, the proportion of patients correctly classified by AH administrative data, using both ICD diagnostic codes and procedure codes, was determined for DVT and PE using diagnoses documented in patient charts as the gold standard. Of the 1361 patients, 712 had suspected PE and 649 had suspected DVT. The sensitivities for identifying patients with PE or DVT using administrative data were 74.83% (95% confidence interval [CI]: 67.01-81.62) and 75.24% (95% CI: 65.86-83.14), respectively. The specificities for PE or DVT were 91.86% (95% CI: 89.29-93.98) and 95.77% (95% CI: 93.72-97.30), respectively. In conclusion, when coupled with relevant imaging codes, VTE diagnostic codes obtained from administrative data provide a relatively sensitive and very specific method to ascertain acute VTE.

Improving accuracy of International Classification of Diseases codes for venous thromboembolism in administrative data.

BACKGROUND: Increasingly, clinicians and researchers are using administrative data for clinical and outcomes research. However, they continue to question the accuracy of using International Classification of Diseases 9th Revision (ICD-9) codes alone to capture diagnoses, especially venous thromboembolism (VTE), in administrative data. OBJECTIVES: We tested the hypothesis that incorporation of treatment data and/or common procedural terminology (CPT) codes could improve accuracy of administrative data in detecting VTE. Research Design Using the Veterans Affairs Central Cancer Registry, we compared three competing algorithms by performing three cross-sectional studies. Algorithm 1 identified patients by ICD-9 codes alone. Algorithm 2 required VTE treatment in addition to ICD-9 codes. Algorithm 3 required a VTE diagnostic CPT code in addition to treatment and ICD-9 criteria. RESULTS: The accuracy of ICD-9 codes alone for detection of VTE was marginal, with a PPV of 72%. The PPV was improved to 91% after addition of treatment data (algorithm 2). As compared to algorithm 2, addition of CPT codes (algorithm 3) did not significantly increase the accuracy of detecting VTE (PPV 92%), but decreased sensitivity from 72% to 67%. CONCLUSIONS: Accuracy of VTE detection significantly improved with addition of treatment data to ICD-9 codes. This approach should facilitate use of administrative data to assess the incidence, epidemiology, and outcomes of VTE.

Hyperglycemia, assessed according to HbA1c , and future risk of venous thromboembolism: the Tromsø study.

BACKGROUND: HbA1c , a marker of average plasma glucose level during the previous 8-12 weeks, is associated with the future risk of cardiovascular disease and all-cause mortality. OBJECTIVES: To examine the association between hyperglycemia, assessed according to HbA1c , and the future risk of venous thromboembolism (VTE) in a population-based cohort. METHODS: HbA1c was measured in 16 156 unique subjects (25-87 years) who participated in one or more surveys of the Tromsø study (Tromsø 4, 1994-1995; Tromsø 5, 2001-2002; and Tromsø 6, 2007-2008). All subjects were followed, and incident VTE events were recorded up to 31 December 2010. RESULTS: There were 333 validated first VTE events, of which 137 were unprovoked, during a median follow-up of 7.1 years. HbA1c was not associated with the future risk of VTE in analyses treating HbA1c as a continuous variable, or in categorized analyses. The risk of VTE increased by 5% per one standard deviation (0.7%) increase in HbA1c (multivariable-adjusted hazard ratio [HR] 1.05; 95% confidence interval [CI] 0.97-1.14), and subjects with HbA1c  ≥ 6.5% had a 27% higher risk than those with HbA1c  < 5.7% (multivariable-adjusted HR 1.27; 95% CI 0.72-2.26). There was no significant linear trend for an increased risk of VTE across categories of HbA1c (P = 0.27). CONCLUSIONS: Serum levels of HbA1c were not associated with the future risk of VTE in multivariable analysis. Our findings suggest that hyperglycemia does not play an important role in the pathogenesis of VTE.

Venous thromboembolism: prophylactic and therapeutic practice guideline.

BACKGROUND: Pharmacological prophylactic anticoagulation in many countries, including South Africa, is under-prescribed. This has resulted in unacceptable rates of morbidity and mortality. METHOD: The Southern African Society of Thrombosis and Haemostasis held a meeting to update the previous guideline and review new literature including guidelines from other societies. The following specialties were represented on the committees: anaesthetics, cardiology, clinical haematology, critical care, obstetrics and gynaecology, haematopathology, internal medicine, neurology, orthopaedic surgery and pulmonology. A draft document was presented at the meeting, which was then revised by consensus agreement. To avoid local bias, the guideline was adjudicated by recognised international external experts. RESULTS AND CONCLUSION: A concise, practical updated guideline for thromboprophylaxis and treatment in medical and surgical patients has been produced for South African conditions. It is hoped that this guideline will continue to improve anticoagulation practice in this country, which we believe will directly benefit patient outcomes.

Symptoms and clinical relevance: a dilemma for clinical trials on prevention of venous thromboembolism.

The outcomes of thromboprophylactic trials have been debated for decades. Recently, the 9th edition of the American College of Chest Physicians (ACCP) evidence-based clinical practice guidelines based their strong recommendations only on patient-important outcomes. Practically, symptoms were considered the crucial element. Consequently, studies that primarily aimed at reducing venographic thrombi were considered less pertinent than studies that focused on symptomatic thrombosis. In the present viewpoint, we challenge the argument that "symptomatic" and "clinically relevant" are interchangeable. In particular, the case is made that asymptomatic events may be clinically relevant and that asymptomatic venographically detected thrombosis is a clinically relevant surrogate outcome for fatal pulmonary embolism.

Determining venous thromboembolic risk assessment for patients with trauma: the Trauma Embolic Scoring System.

BACKGROUND: This study aimed to determine the relative "weight" of risk factors known to be associated with venous thromboembolism (VTE) for patients with trauma based on injuries and comorbidities. METHODS: A retrospective review of 16,608 consecutive admissions to a trauma center was performed. Patients were separated into those who developed VTE (n = 141) versus those who did not (16,467). Univariate analysis was performed for each risk factor reported in the trauma literature. Risk factors that were shown to be significant (p < 0.05) by univariate analysis underwent multivariate analysis to develop odds ratios for VTE. The Trauma Embolic Scoring System (TESS) was derived from the multivariate coefficients. The resulting TESS was compared with a data set from the National Trauma Data Bank (2002-2006) to determine its ability to predict VTE. RESULTS: The multivariate analysis demonstrated that age, Injury Severity Score, obesity, ventilator use for more than 3 days, and lower-extremity trauma were significant predictors of VTE in our patient population. The TESS was from 0 to 14, with the best prediction for those patients with a score of more than 6 (sensitivity, 81.6%; specificity, 84%). Overall, the model had excellent discrimination in predicting VTE with a receiver operating characteristic curve of 0.89. The VTE rates for TESS in the National Trauma Data Bank data set were similar for all integers except for 3 and 4, in which the VTE rates were significantly higher (3, 0.2% vs. 0.6%; 4, 0.4% vs. 1.0%). CONCLUSION: The TESS provides an objective measure of classifying VTE risk for patients with trauma. The TESS could allow informed decision making regarding prophylaxis strategies in patients with trauma.

Identifying in-hospital venous thromboembolism (VTE): a comparison of claims-based approaches with the Rochester Epidemiology Project VTE cohort.

BACKGROUND: Efforts to identify hospital-acquired complications from claims data by applying exclusion rules to discharge diagnosis codes exhibit low positive predictive value (PPV). The PPV improves when a variable is added to each secondary diagnosis to indicate whether the condition was "present-on-admission" (POA) or "hospital-acquired". Such indicator variables will soon be required for Medicare reimbursement. No estimates are available, however, of the proportion of hospital-acquired complications that are missed (sensitivity) using either exclusion rules or indicator variables. We estimated sensitivity, specificity, PPV, and negative predictive value (NPV) of claims-based approaches using the Rochester Epidemiology Project (REP) venous thromboembolism (VTE) cohort as a "gold standard." METHODS: All inpatient encounters by Olmsted County, Minnesota, residents at Mayo Clinic-affiliated hospitals 1995-1998 constituted the at-risk-population. REP-identified hospital-acquired VTE consisted of all objectively-diagnosed VTE among County residents 1995-1998, whose onset of symptoms occurred during inpatient stays at these hospitals, as confirmed by detailed review of County residents' provider-linked medical records. Claims-based approaches used billing data from these hospitals. RESULTS: Of 37,845 inpatient encounters, 98 had REP-identified hospital-acquired VTE; 47 (48%) were medical encounters. NPV and specificity were >99% for both claims-based approaches. Although indicator variables provided higher PPV (74%) compared with exclusion rules (35%), the sensitivity for exclusion rules was 74% compared with only 38% for indicator variables. Misclassification was greater for medical than surgical encounters. CONCLUSIONS: Utility and accuracy of claims data for identifying hospital-acquired conditions, including POA indicator variables, requires close attention be paid by clinicians and coders to what is being recorded.