Definite Venous Thromboembolism Research Articles

Venous thromboembolism and COVID-19: a single center experience from an academic tertiary referral hospital of Northern Italy

Preliminary evidence supports the notion that COVID-19 patients may have an increased susceptibility to develop venous thromboembolism (VTE). However, the magnitude of this association still needs to be defined. Furthermore, clinical predictors of thrombogenesis, and the relationship with the inflammatory status are currently unknown. On this basis, we conducted a retrospective, observational study on 259 consecutive COVID-19 patients admitted to an academic tertiary referral hospital in Northern Italy between March 19th and April 6th, 2020. Records of COVID-19 patients with a definite VTE event were reviewed for demographic information, co-morbidities, risk factors for VTE, laboratory tests, and anticoagulation treatment. Twenty-five cases among 259 COVID-19 patients developed VTE (9.6%), all of them having a Padua score > 4, although being under standard anticoagulation prophylaxis since hospital admission. In the VTE subcohort, we found a significant positive correlation between platelet count (PLT) and either C reactive protein (CRP) (p < 0.0001) or lactate dehydrogenase (LDH) (p = 0.0013), while a significant inverse correlation was observed between PLT and mean platelet volume (p < 0.0001). Platelet-to-lymphocyte ratio significantly correlated with CRP (p < 0.0001). The majority of VTE patients was male and younger compared to non-VTE patients (p = 0.002 and p = 0.005, respectively). No significant difference was found in d-dimer levels between VTE and non VTE patients, while significantly higher levels of LDH (p = 0.04) and IL-6 (p = 0.04) were observed in VTE patients in comparison to non-VTE patients. In conclusion, our findings showed a quite high prevalence of VTE in COVID-19 patients. Raised inflammatory indexes and increased serum levels of pro-inflammatory cytokines should raise the clinical suspicion of VTE.

Incidence of venous thromboembolism in care homes: a prospective cohort study.

Care home residents have venous thromboembolism (VTE) risk profiles similar to medical inpatients; however, the epidemiology of VTE in care homes is unclear. To determine the incidence of VTE in care homes. Observational cohort study of 45 care homes in Birmingham and Oxford, UK. A consecutive sample of care home residents was enrolled and followed up for 12 months. Data were collected via case note reviews of care home and GP records; mortality information was supplemented with Health and Social Care Information Centre (now called NHS Digital) cause of death data. All potential VTE events were adjudicated by an independent committee according to three measures of diagnostic certainty: definite VTE (radiological evidence), probable VTE (high clinical indication but no radiological evidence), or possible VTE (VTE cannot be ruled out). (Study registration number: ISTCTN80889792.) RESULTS: There were 1011 participants enrolled, and the mean follow-up period was 312 days (standard deviation 98 days). The incidence rate was 0.71 per 100 person years of observation (95% confidence interval [CI] = 0.26 to 1.54) for definite VTE, 0.83 per 100 person years (95% CI = 0.33 to 1.70) for definite and probable VTE, and 2.48 per 100 person years (95% CI = 1.53 to 3.79) for definite, probable, and possible VTE. The incidence of VTE in care homes in this study (0.71-2.48 per 100 person years) is substantial compared with that in the community (0.117 per 100 person years) and in people aged ≥70 years (0.44 per 100 person years). Further research regarding risk stratification and VTE prophylaxis in this population is needed.

Treatment patterns of venous thromboembolism in a real-world population: The Q-VTE study cohort

BackgroundFew studies have assessed treatment patterns of acute venous thromboembolism (VTE) in a real-world population. We aimed to describe anticoagulant treatment patterns for acute VTE using healthcare databases of Québec, Canada. MethodsWe used linked healthcare databases of the province of Québec, Canada to identify all incident cases of deep vein thrombosis (DVT) and pulmonary embolism (PE) between 2000 and 2009. We formed two patient cohorts, one with definite cases (definite VTE cohort, N=40,776) and the other including cases with definite or probable VTE (any VTE cohort, N=54,803) that were followed until death, end of health coverage, or end of study (December 31, 2009). ResultsIn the definite cohort, 73.6% of subjects were dispensed an anticoagulant following the diagnosis of VTE. Of those who were dispensed a vitamin K antagonist (VKA), median duration of use was 61days (interquartile range 89). VKA initiation was more likely in patients with pulmonary embolism than deep vein thrombosis alone (HR 1.62, 95% CI (1.58-1.66)). Among outpatients, those managed initially in the outpatient setting were less likely to initiate VKA therapy (HR 0.75, 95% CI (0.68-0.77)), while those requiring admission to hospital for VTE management were more likely to initiate (HR 1.81, 95% CI (1.76-1.87)). Findings were similar in the any VTE cohort. ConclusionOur study describes VTE treatment patterns in a real-world setting and suggests that there may be important gaps. These may include significant numbers of patients who did not initiate oral anticoagulant therapy, particularly in the outpatient setting, and shorter duration of oral anticoagulant use than recommended.

Case fatality of bleeding and recurrent venous thromboembolism during, initial therapy with direct oral anticoagulants: A systematic review

IntroductionThe frequency and case fatality of venous thromboembolism (VTE) and major bleeding during the initial 3months of therapy in those treated for symptomatic VTE with either direct oral anticoagulants (DOACs) or vitamin K antagonists (VKA) are important clinically relevant outcomes. We sought to measure it during the initial months of anticoagulation for symptomatic VTE. Material and MethodsWe searched MEDLINE, EMBASE, and CENTRAL to identify studies that enrolled patients with acute symptomatic VTE treated with DOACs or VKA and reported data on bleeding, VTE recurrence and death. Studies were evaluated according to a priori inclusion criteria and critically appraised using established internal validity criteria. Single-proportion random-effects models were used to pool estimates. ResultsOf the 2453 citations retrieved, 5 RCTs that enrolled 24,507 patients were included. The rate of major bleeding was 1.8 (95% CI: 1.3-2.5) and 3.1 (95% CI: 2.4-3.9) per 100 patient-years in DOAC and VKA arms, respectively. The rate of VTE recurrence was 3.7 (95% CI: 2.7-4.7) and 4.1 (95% CI: 3.0-5.4) per 100 patient-years of DOAC and VKA, respectively. The case fatality rate of bleeding was significantly higher in the VKA arms 10.4% (95% CI: 6.6-15.4) compared to DOACs 6.1% (95% CI: 2.7-11.7; p value for difference=0.029) with no statistical difference between the case fatalities for recurrent VTE. The rate of death from either definite major bleeding or definite recurrent VTE was 0.27 (95% CI: 0.16-0.40) and 0.46 (95% CI: 0.32-0.63) per 100 patient-years for DOACs and VKAs respectively, resulting in a number needed to treat of 875 for DOACs to prevent one death. ConclusionDOACs are attractive alternatives to VKAs for initial treatment of symptomatic VTE, with lower frequency and case fatality for major bleeding. However, the incremental safety benefit of DOACs over VKAs is small, with large numbers needed to treat.

Oral Anticoagulation Treatment and Persistence After Venous Thromboembolism In a Real World Population: The Q-VTE Study Cohort

BackgroundFor patients who are diagnosed with venous thromboembolism (VTE) provoked by transient risk factors, clinical guidelines typically recommend 3 months of oral anticoagulation, with longer treatment considered for unprovoked VTE. Describing treatment patterns of VTE in a real world population may identify remedial gaps in patient care. AimWe aimed to characterize oral anticoagulant treatment with vitamin K antagonists (VKA) following incident VTE and assess persistence of VKA therapy in patients with provoked vs. unprovoked VTE in a real world setting. MethodsWe used the linked administrative healthcare databases of the province of Québec, Canada, including the hospitalization, universal healthcare services, and out-patient prescription databases. We identified all beneficiaries with an incident DVT or PE between 2000 and 2009, which we classified as definite or probable VTE using a priori determined diagnostic algorithms based on ICD-9-CM or ICD-10-CA diagnosis codes. We formed two patient cohorts, one with definite and the other including definite or probable first-time VTE, that were followed until death or end of study (December 31, 2009). Anticoagulant out-patient prescription patterns were analyzed for both patient cohorts. ResultsFrom 245,452 Québec residents between 2000 and 2009 with at least 1 VTE diagnosis in RAMQ or MED-ÉCHO, we formed the definite VTE cohort including 40,776 definite cases and the any VTE cohort consisting of 54,803 definite or probable cases. From the 40,776 patients with a first definite VTE, there were 24,860 patients with DVT alone (61%) and 15,916 with PE with or without DVT (39%). Furthermore, there were 78% of patients over the age of 60 and 58.3% of patients were women. In all, 8,998 (22.1%) patients had an unprovoked VTE event while 19,010 (46.6%) patients had a provoked non-cancer event. Similar findings were found in the any VTE cohort.Among definite VTE cohort patients with a provoked non-cancer VTE, 68.6% of patients received anticoagulation after the VTE event. Most were dispensed VKA (64.9%) and 23.9% received a prescription for low molecular weight heparin (LMWH). Among patients with an unprovoked VTE, 86.3% of patients were prescribed anticoagulation (84.5% used VKA and 39.9% used LMWH). Overall, a greater number of patients received anticoagulation following PE (85.2%) than DVT alone (66.2%). Results were similar in the any VTE cohort.Persistence with VKA therapy among patients with provoked VTE was 86.9% at 90 days, 59.5% at 180 days and 19.9% at 365 days. Treatment persistence for patients with unprovoked non-cancer VTE was 88.8%, 66.8% and 22.9% for 90, 180 and 365 days, respectively. Similar findings were found in the any VTE cohort. ConclusionsOur study provides useful information on VTE management in a real world population. Treatment persistence was similar for patients with provoked and unprovoked VTE. VKA therapy duration after provoked VTE was longer than the recommended 3 months, whereas treatment was shorter than suggested in patients with unprovoked VTE. Further investigation is needed to determine reasons for non-adherence to clinical guidelines. Disclosures:No relevant conflicts of interest to declare.

High Mortality After Venous Thromboembolism: A Population-Based Cohort Study

AbstractAbstract 1140 Background:Current estimates on mortality after venous thromboembolism (VTE) are limited and are based largely on randomized clinical studies with select populations of relatively health patient groups. Objectives:We estimated the mortality following a first VTE event in the general population, and compared survival rates among patients with idiopathic, cancer-associated, and secondary non-cancer associated VTE. Methods:This retrospective, observational study used the linked administrative healthcare databases of the province of Québec, Canada, including the province-wide hospitalization database (MED-ÉCHO), the healthcare services database of RAMQ which is a governmental agency that administers the Québec universal healthcare program and oversees all physician reimbursement claims, and the vital statistics database of the Institut de la Statistique du Québec (ISQ). From a source population of all RAMQ beneficiaries with a physician visit or a hospitalization associated with an ICD-9-CM or ICD-10-CA diagnosis code for deep vein thrombosis (DVT) or pulmonary embolism (PE) recorded between January 1, 2000 and December 31, 2009 and without a DVT or PE code prior to January 1, 2000, we identified a cohort of Québec residents with definite incident VTE and a cohort with definite or probable incident VTE. We used a priori determined diagnostic algorithms using RAMQ and MED-ÉCHO data to identify definite and probable cases of VTE. Subjects were followed forward in time from fist-time VTE occurrence until the earliest of either death or end of study period (December 31, 2009). Death was identified from MED-ÉCHO and ISQ. Thirty-day and 1-year case-fatality rates and associated 95% confidence intervals (CI) for VTE, DVT alone, and PE with or without DVT were calculated using all-cause deaths as the numerator and the number of patients with VTE as the denominator. Kaplan Meier curves were used to represent crude survival following a VTE episode, stratified by VTE risk factor group (idiopathic, cancer-associated, and secondary). The log-rank test was used to determine the significance of differences in the survival curves. Results:From the 245 452 Québec residents between 2000 and 2009 with at least 1 VTE diagnosis in RAMQ or MED-ÉCHO, we identified 67 410 cases with definite VTE, and an additional 35 123 cases with probable VTE. The cohort of definite VTE included 56% women, 46.5% patients aged 70 years or older, and 28.3% idiopathic VTE cases. The cohort of definite or probable VTE also included 56% women, 42.3% patients aged 70 years or older, and 34% idiopathic VTE cases. In the year following the VTE event, 14 407 (30%) deaths occurred in the definite VTE cohort, and 15 395 (25%) in the definite or probable VTE cohort. Among definite VTE cases, the 30-day case fatality rate was 14.1% (95% CI: 13.9–14.4), and the 1-year case fatality rate was 29.2% (95% CI: 28.9–29.6). The corresponding rates in the definite or probable VTE cohort were lower with a 30-day and 1-year case-fatality rate of 10.61% (95% CI: 10.41–10.81) and 23.04% (95% CI: 22.77–23.31), respectively. The 30-day case fatality was almost 2-fold higher in patients with PE with or without DVT vs. patients with DVT alone (RR 1.92, 95% CI: 1.85–1.99), and this difference in mortality was less at 1 year (RR 1.20, 95% CI: 1.17–1.23). The Kaplan-Meier overall survival plot showed a 1-year survival rate of 42% (95% CI: 41–43%) among definite VTE cases with cancer (Figure 1). The 1-year survival rates following definite VTE in patients with idiopathic and secondary VTE were different (90% vs. 81%, respectively; p<0.0001). Similar survival rates were observed in the definite or probable VTE cohort. Conclusion:In a large unselected general population, VTE is associated with a high mortality and patients with PE are at a higher risk of death than patients with DVT alone. Among cancer patients with VTE, long-term survival remains poor. The observed lower survival in patients with secondary VTE as opposed to idiopathic VTE may be explained by the advanced age of our patient population. These data highlight the need for optimization of current VTE treatment strategies, especially in cancer patients. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

The Economic Burden of Acute Venous Thromboembolism During One Year Following Diagnosis: A Population-Based Cohort Study

AbstractAbstract 1152 Background:Although venous thromboembolism (VTE) is the third most common cardiovascular condition after myocardial infarct and stroke, few data exist on the economic burden associated with this condition. Objective:We aimed to quantify the economic burden of acute VTE in direct medical costs in the general population. Methods:Using the linked administrative healthcare databases of the province of Québec, Canada, including the provincial hospitalization database (MED-ÉCHO) and the healthcare claims databases of RAMQ which is a government agency that administers the provincial universal healthcare program, we determined a source population of all RAMQ beneficiaries with a physician visit or a hospitalization associated with an ICD-9-CM or ICD-10-CA diagnosis code for deep vein thrombosis (DVT) or pulmonary embolism (PE) between January 1, 2000 and December 31, 2009 and without a DVT or PE code prior to January 1, 2000. From the source population, we identified a cohort of Québec residents with a definite VTE and a cohort with a definite or probable VTE. We used a priori determined diagnostic algorithms using RAMQ and MED-ÉCHO data to identify definite and probable VTE cases. Subjects were followed forward in time from first VTE until the earliest of either death or end of study period (December 31, 2009). We determined the total direct cost per year for VTE by applying unit costs to the patient resource use profile in the year after diagnosis of VTE. Resource costs included hospitalizations, physician visits, and prescription medications. Resources were valued by the use of individual patient-level information from RAMQ and MED-ÉCHO. All costs were standardized to the 2009–2010 fiscal year costs, and are reported in Canadian dollars (year 2010 average US exchange rate 1.04). The RAMQ Manuel de Facturation and Manuel des Services de laboratoire en établissement was used to determine fees physician acts associated with a VTE diagnosis. The RAMQ List des médicaments contains information on drugs covered by the provincial drug insurance plan and was used to determine VTE-related drug costs. Because hospital costs are not available in Québec, we used the Ontario Case Costing Initiative to obtain hospital cost data. Hospitalizations for VTE–related outcomes were identified. The mean cost per person-years of follow-up was calculated as the sum of all costs during the year after VTE diagnosis divided by the total person-time of follow-up during that year. Results:From the 245 452 Québec residents between 2000 and 2009 with at least 1 VTE diagnosis in RAMQ or MED-ÉCHO, we identified 40 776 cases with definite VTE, and 14 027 cases with probable VTE. The average direct cost per person-year for VTE is $4,449.13 in the year following a definite VTE (Table 1) and $3,418.83 in the year following a definite or probable VTE. In both cohorts, the majority of cost was incurred by hospitalization for the initial VTE, and average cost after PE was higher than cost following DVT. Conclusions:The economic burden of VTE is large, and is mainly due to the initial VTE hospitalization. Use of measures favouring the safe out-patient treatment of VTE and the development of management strategies to identify patients with acute PE who can safely be treated in the ambulatory setting have the potential to decrease cost.Table 1Cost per person-year of resource use in the year following VTE diagnosis (definite cohort)VTEDVTPESubjects, N40,77624,86015,916Person-years31,79719,27612,521Cost per person-yearInitial VTE hospitalization2,863.361,454.835,031.68Follow-up resource use:1,585.771,426.481,831.00Diagnostic procedures:208.10213.58199.66VTE-related176.00180.40169.22Bleeding-related32.1033.1830.44Hospitalizations:573.86513.83666.28VTE recurrence265.19212.50346.31Bleeding276.37278.65272.86Post thrombotic syndrome12.0213.349.98CTEPH20.289.3437.14Treatments:490.21431.25580.98VTE Medications486.18428.06575.65Insertion of intravenous filter4.043.195.33Physician billed medical acts313.59267.81384.07Total cost (Canadian dollars)4,449.132,881.316,862.6Abbreviations: VTE, venous thromboembolism; DVT, deep vein thrombosis; PE, pulmonary embolism; CTEPH, chronic thromboembolic pulmonary hypertension. Disclosures:No relevant conflicts of interest to declare.

Contemporary Estimates of the Incidence of Venous Thromboembolism: A Population-Based Cohort Study

AbstractAbstract 1143 Background:Venous thromboembolism (VTE) is a growing public health problem due largely to the aging population and the increasing prevalence of known risk factors such as surgery and cancer-related treatments. As a result, the true burden of VTE is not fully known and more contemporary estimates of incidence are needed. Objectives:We estimated the incidence of a first VTE event in a general population. Methods:This retrospective, observational study used the linked administrative healthcare databases of the province of Québec, Canada, including the province-wide hospitalization database (MED-ÉCHO) and the healthcare services database of RAMQ which oversees all physician reimbursement claims for services provided to Québec residents. From a source population of all RAMQ beneficiaries with a physician visit or a hospitalization associated with an ICD-9-CM or ICD-10-CA diagnosis code for deep vein thrombosis (DVT) or pulmonary embolism (PE) recorded between January 1, 2000 and December 31, 2009 and without a DVT or PE code prior to January 1, 2000, we identified a cohort of Québec residents with definite incident VTE and a cohort with definite or probable incident VTE. We used a priori determined diagnostic algorithms using RAMQ and MED-ÉCHO data to identify definite and probable cases of VTE. Subjects were followed forward in time from first-time VTE occurrence until the earliest of either death or end of study period (December 31, 2009). Incidence rates of first VTE, DVT alone, and PE with or without DVT were calculated by dividing the number of new cases by the total person-years at risk in the population of Québec residents eligible for RAMQ between 2000 and 2009. Age-specific incidence rates and associated 95% confidence intervals (CI) were calculated using achieved age during follow-up, and as a result patients contributed person-time in different age categories while aging during follow-up. Crude and age-adjusted incidence rate ratios (IRR) were reported comparing rates among women and men. Results:From the 245 452 Québec residents between 2000 and 2009 with at least 1 VTE diagnosis in RAMQ or MED-ÉCHO (source population), we identified 67 410 cases with definite VTE and 35 123 cases with probable VTE. The incidence rate of definite VTE was 0.91 per 1000 person-years (95% CI: 0.90–0.91). For DVT alone, the incidence was 0.53 per 1000 person-years (95% CI: 0.52–0.52) and for PE with or without DVT it was 0.38 per 1000 person-years (95% CI: 0.38–0.38). The incidence rates increased with age, and rates in patients 70 years of age and older were more than 4 times higher than rates in patients who were 40–69 years of age (Table 1). The VTE incidence rate was 0.99 per 1000 person-years (95% CI: 0.98–1.00) in women as compared to 0.82 per 1000 person-years (95% CI: 0.81–0.83) in men. The IRR was 1.19 (95% CI: 1.17–1.22) but this sex difference was no longer seen when adjusted for age (IRR 0.98; 95% CI: 0.96–1.01). The corresponding VTE, DVT alone, and PE incidence rates per 1000 person-years for definite or probable VTE were 1.24 (95% CI: 1.23–1.24), 0.79 (95% CI: 0.78–0.79), and 0.45 (95% CI: 0.45–0.46), respectively. Conclusion:Our study provides real-world contemporary estimates of VTE incidence. The risk in the general population is about 0.9 to 1.2 per 1000 person-years and is highest in the elderly. These data may help inform public healthcare planning and future research.Table 1VTE Incidence Rates per 1000 person-yearsAge (Years)Person-YearsVTEDVT alonePE with or without DVTnIR (95% CI)nIR (95% CI)nIR (95% CI)0–1917,300,8507700.04 (0.04 – 0.05)5720.03 (0.03 – 0.04)1980.01 (0.01 – 0.01)20–299,391,3492,0700.22 (0.21 – 0.23)1,1710.12 (0.12 – 0.13)8990.10 (0.09 – 0.10)30–3910,360,5233,3850.33 (0.32 – 0.34)1,9930.19 (0.18 – 0.20)1,3920.13 (0.13 – 0.14)40–4912,421,7966,2530.50 (0.49 – 0.52)3,5500.29 (0.28 – 0.30)2,7030.22 (0.21 – 0.23)50–5910,585,38310,1040.95 (0.94 – 0.97)5,7870.55 (0.53 – 0.56)4,3170.41 (0.40 – 0.42)60–697,035,33613,4511.91 (1.88 – 1.94)7,8771.12 (1.10 – 1.14)5,5740.79 (0.77 – 0.81)70–794,700,61416,7213.56 (3.50 – 3.61)9,7262.07 (2.03 – 2.11)6,9951.49 (1.45 – 1.52)>=802,501,91314,6565.86 (5.76 – 5.95)8,4983.40 (3.33 – 3.47)6,1582.46 (2.40 – 2.52)Total74,297,76467,4100.91 (0.90 – 0.91)39,1740.53 (0.52 – 0.53)28,2360.38 (0.38 – 0.38)VTE, venous thromboembolism; DVT, deep vein thrombosis; PE, pulmonary embolism; IR, incidence rate; CI, confidence interval. Disclosures:No relevant conflicts of interest to declare.

A Negative D-dimer Excludes Recurrent Deep Vein Thrombosis: Results of a Multicentre Management Study.

The high frequency of residual radiologic abnormalities after initial deep vein thrombosis (DVT) makes management of patients with suspected recurrence difficult. D-dimer (DD) and serial compression ultrasonography (CUS) of the proximal veins have a high sensitivity and negative predictive value (NPV) in suspected first DVT. We hypothesized that it would be safe to withhold anticoagulation in patients with suspected recurrence who had a negative sensitive DD or negative serial CUS when DD testing was positive. In a multicentre prospective cohort study, patients underwent DD testing with an immunoturbidometric assay (MDA DD). If the DD was negative (<0.5 ug fibrinogen equivalent units [FEU]/mL), patients had no further testing. If the DD was positive, CUS was performed and, if normal, repeated after 1–3 and 7–10 days. Patients with a positive DD and abnormal CUS at presentation were managed as per their treating physician. Patients were followed for 3 months to detect venous thromboembolism (VTE) and suspected VTE were adjudicated centrally. Of the 504 patients enrolled in this study, 14 were subsequently deemed ineligible and 2 patients were lost to follow-up. The overall prevalence of confirmed recurrent DVT at presentation or during follow-up was 17%. 230 patients had a negative DD at presentation and, of the 227 evaluable patients, 4 had definite confirmed VTE (NPV of DD = 98%; 95% Confidence Interval [CI], 96–99%). Of the 135 patients with a positive DD and normal initial CUS, serial CUS was negative in 129 cases. Of these patients, 3 had definite VTE during follow-up (NPV of serial CUS in patients with positive DD = 98%; 95% CI, 93–99%). These results suggest that a negative MDA DD result excludes clinically significant recurrent DVT and that anticoagulants can also be safely withheld in patients with negative serial CUS, even if their DD is positive. This simple diagnostic approach can be used to safely manage approximately 70% of patients with suspected recurrent DVT.