Elevated white blood cell count and outcome in cancer patients with venous thromboembolism. Findings from the RIETE Registry

A significant association between elevated white blood cell (WBC) count and mortality in patients with cancer has been reported, but the predictive value of elevated WBC on mortality in cancer patients with acute venous thromboembolism (VTE) has not been explored. RIETE is an ongoing registry of consecutive patients with acute VTE. We compared the three-month outcome of cancer patients with acute VTE according to their WBC count at baseline. As of May 2007, 3805 patients with active cancer and acute VTE had been enrolled in RIETE. Of them, 215 (5.7%) had low- (<4,000 cells/microl), 2,403 (63%) normal- (4,000-11,000 cells/microl), 1,187 (31%) elevated (>11,000 cells/microl) WBC count. During the study period 190 patients (5.0%) had recurrent VTE, 156 (4.1%) major bleeding, 889 (23%) died (399 of disseminated cancer, 113 of PE, 46 of bleeding. Patients with elevated WBC count at baseline had an increased incidence of recurrent VTE (odds ratio [OR]: 1.6; 95% confidence interval [CI]: 1.2-2.2), major bleeding (OR: 1.5; 95% CI: 1.1-2.1) or death (OR: 2.7; 95% CI: 2.3-3.2). Most of the reported causes of death were significantly more frequent in patients with elevated WBC count. Multivariate analysis confirmed that elevated WBC count was independently associated with an increased incidence of all three complications. In conclusion, cancer patients with acute VTE and elevated WBC count had an increased incidence of VTE recurrences, major bleeding or death. This worse outcome was consistent among all subgroups and persisted after multivariate adjustment.     

Long-term anticoagulation treatment for acute venous thromboembolism in patients with and without cancer. The SWIss Venous ThromboEmbolism Registry (SWIVTER) II

In patients with acute cancer-associated thrombosis, current consensus guidelines recommend anticoagulation therapy for an indefinite duration or until the cancer is resolved. Among 1,247 patients with acute venous thromboembolism (VTE) enrolled in the prospective Swiss Venous Thromboembolism Registry (SWIVTER) II from 18 hospitals, 315 (25%) had cancer of whom 179 (57%) had metastatic disease, 159 (50%) ongoing or recent chemotherapy, 83 (26%) prior cancer surgery, and 63 (20%) recurrent VTE. Long-term anticoagulation treatment for >12 months was more often planned in patients with versus without cancer (47% vs. 19%; p<0.001), with recurrent cancer-associated versus first cancer-associated VTE (70% vs. 41%; p<0.001), and with metastatic versus non-metastatic cancer (59% vs. 31%; p<0.001). In patients with cancer, recurrent VTE (OR 3.46; 95%CI 1.83-6.53), metastatic disease (OR 3.04; 95%CI 1.86-4.97), and the absence of an acute infection (OR 3.55; 95%CI 1.65-7.65) were independently associated with the intention to maintain anticoagulation for >12 months. In conclusion, long-term anticoagulation treatment for more than 12 months was planned in less than half of the cancer patients with acute VTE. The low rates of long-term anticoagulation in cancer patients with a first episode of VTE and in patients with non-metastatic cancer require particular attention.     

Disease burden and unmet needs for prevention of venous thromboembolism in medically ill patients in Europe show underutilisation of preventive therapies

It was the aim of this review to assess the incidence of venous thromboembolism (VTE) and current practice patterns for VTE prophylaxis among medical patients with acute illness in Europe. A literature search was conducted on the epidemiology and prophylaxis practices of VTE prevention among adult patients treated in-hospital for major medical conditions. A total of 21 studies with European information published between 1999 and April 2010 were retrieved. Among patients hospitalised for an acute medical illness, the incidence of VTE varied between 3.65% (symptomatic only over 10.9 days) and 14.9% (asymptomatic and symptomatic over 14 days). While clinical guidelines recommend pharmacologic VTE prophylaxis for patients admitted to hospital with an acute medical illness who are bedridden, clear identification of specific risk groups who would benefit from VTE prophylaxis is lacking. In the majority of studies retrieved, prophylaxis was under-used among medical inpatients; 21% to 62% of all patients admitted to the hospital for acute medical illnesses did not receive VTE prophylaxis. Furthermore, among patients who did receive prophylaxis, a considerable proportion received medication that was not in accord with guidelines due to short duration, suboptimal dose, or inappropriate type of prophylaxis. In most cases, the duration of VTE prophylaxis did not exceed hospital stay, the mean duration of which varied between 5 and 11 days. In conclusion, despite demonstrated efficacy and established guidelines supporting VTE prophylaxis, utilisation rates and treatment duration remain suboptimal, leaving medical patients at continued risk for VTE. Improved guideline adherence and effective care delivery among the medically ill are stressed.     

Long-term death and recurrence in patients with acute venous thromboembolism: The MASTER registry

BACKGROUND: The long-term clinical outcome of VTE has been essentially assessed in cohorts of selected patients. The aim of this multicenter registry was to prospectively assess the long-term clinical outcome in a cohort of unselected patients with objectively confirmed acute VTE. MATERIALS AND METHODS: Death and VTE recurrence at 24months were the main study outcomes. Univariate and multivariate survival analyses were performed according to the Kaplan-Meyer and Cox proportional hazard model, respectively. RESULTS: 2119 patients with acute VTE were included in the registry: 1541 (72.7%) with deep vein thrombosis, 206 (9.7%) with pulmonary embolism and 372 (17.6%) with both. Information about death was available in 2021 patients (95.4%) and about recurrence in 1988 patients (93.8%). 167 patients (4.55% patient-year) died during follow-up. After adjusting for age, cancer (Hazard ratio [HR]: 7.2; 95%CI 4.8-10.8), long-term heparin treatment (HR: 2.5; 95%CI 1.8-3.5), in-hospital management of VTE (HR: 2.0; 95%CI 1.3-3.0), and ileo-caval thrombosis (HR: 1.7; 95%CI 1.2-2.4) were found to be independent predictors of death. 124 (3.63% patient-year) patients had a VTE recurrence during follow-up. In-hospital management of VTE (HR: 1.8; 95%CI 1.2-2.9), male gender (HR: 1.7; 95%CI 1.2-2.4) were independent risk factors for recurrent VTE. Cancer (HR: 1.6; 95%CI 1.0-2.8) showed a trend for increased risk of VTE recurrence (p=0.056). The reported rate of major bleeding was 2.5%. CONCLUSIONS: In a large cohort of unselected VTE patients, cancer, ileo-caval thrombosis, long-term heparin treatment and in-hospital management were associated with increased mortality during long-term follow-up. In-hospital management, male gender were associated with an increased risk of VTE recurrence.     

Incidence of venous thromboembolism in first-degree relatives of patients with venous thromboembolism who have factor V Leiden

The factor V Leiden (FVL) mutation, a genetic abnormality with an autosomal mode of inheritance, is associated with an increased risk of venous thromboembolism (VTE). We aimed to determine the annual incidence of VTE in first-degree relatives of patients with VTE and FVL and to identify factors in patients and the relatives that influence this incidence. In this retrospective and prospective cohort study, the incidence of objectively diagnosed first episodes of VTE was assessed in 553 first-degree relatives of 161 patients with acute VTE and FVL. The annual incidence of VTE was 0.43% (95% CI, 0.3 to 0.56) with FVL and 0.17% (95% CI, 0.07 to 0.27) without FVL (relative risk of 2.5,95% CI, 1.3 to 4.7). A majority (70%) of episodes of VTE were provoked, and this proportion was similar with and without FVL. A larger proportion of VTE was provoked in women (83%) that in men (33%), with the difference accounted for by pregnancy and use of oral contraceptives. The proportion of pregnancies complicated by VTE was 3.9% (95% CI, 2.0-5.8) with FVL and 1.4% (95% CI, 0.04-2.7) without FVL. FVL is associated with a two- to threefold increase in VTE in first-degree relatives of patients with VTE. No subgroup of relatives was identified who require more than routine prophylaxis because of a particularly high risk of VTE.     

Venous thromboembolism risk assessment and thromboprophylaxis among hospitalized acute medical patients in China - the RAMP study

Background

In developed countries, hospitalized patients with acute medical conditions are at significant risk for venous thromboembolism (VTE). Little is known about VTE risk and prophylaxis practices in China.

Objective

To determine the VTE risk and the frequency of recommended VTE prophylaxis in hospitalized Chinese patients with acute medical conditions.

Methods

Multi-center, cross-sectional, observational study. Eligibility criteria: ≥ 30 years, admitted to an intensive care unit (ICU)/coronary care unit (CCU) for acute medical illness, had ≥ 1 VTE risk factor/1 disease that predisposes to VTE, and provided informed consent. We used 2004 American College of Chest Physicians (ACCP) evidence-based consensus guidelines to assess VTE risk and the frequency of recommended VTE prophylaxis.

Results

1247 patients from 19 hospitals in 11 cities across 11 provinces of China were enrolled from July 2007 to June 2008. 57.3% patients had > 2 VTE risk factors. Only 20.2% received ACCP-recommended VTE prophylaxis (CCU patients: 22.7%, ICU patients: 16.9%, p = 0.0117).

Limitations

Excluding some patients with VTE risk factors did not allow assessment of the prevalence of VTE risk in the acute hospital-care setting. We could not determine whether the duration of prophylaxis complied with the ACCP recommendations. Our results may not be representative of hospitals in small cities/rural areas in China.

Conclusions

The prevalence of VTE risk factors in Chinese patients was similar to that in developed countries; however, only a small proportion of eligible patients received the recommended VTE prophylaxis. Our findings highlight the need for dissemination and implementation of appropriate VTE prophylaxis guidelines in China.     

Metabolic syndrome as a risk factor for deep vein thrombosis after acute cardiac conditions

The metabolic syndrome (MS), a cluster of cardiovascular risk factors known to be associated with type II diabetes and arterial disease, has been recently reported to be associated with venous thromboembolism (VTE). In this case-control study MS was tested as a potential risk factor for deep vein thrombosis (DVT) after acute coronary syndromes (ACS) and acute heart failure (AHF).Globally, 86 patients with objectively diagnosed DVT during cardiac rehabilitation after ACS and AHF were compared with a sex and age-matched population of cardiac patients without objectively confirmed DVT. MS was significantly associated to the presence of DVT (OR 2.38; 95% CI 1.64, 3.12), independent from type of cardiac event, prolonged hospitalization, and obesity. Among single determinants of MS, only hypertriglyceridemia was significantly associated with VTE.The presence of MS could increase the risk of VTE after acute cardiac events, thus affecting morbidity and mortality in this patient population.     

Direct oral anticoagulants in the treatment of acute venous thromboembolism: A systematic review and meta-analysis

Introduction

Acute venous thromboembolism (VTE) is a common disease associated to significant morbidity and mortality.

Materials and methods

We systematically reviewed and meta-analysed clinical outcomes with direct oral anticoagulants (DOAC: dabigatran, rivaroxaban, apixaban or edoxaban) for treatment of acute VTE. We used MEDLINE and CENTRAL, clinical trials registers, conference proceedings, and websites of regulatory agencies to identify randomised clinical trials of DOAC compared with conventional treatment [parenteral anticoagulant followed by a vitamin K antagonist (VKA)] for acute VTE. Two investigators independently extracted data. Relative risk of recurrent VTE, bleeding events, deaths and a net clinical endpoint (composite of recurrent VTE, major bleeding, and death) were estimated using a random effect meta-analysis (RevMan software).

Results

Six trials including 27,127 patients were selected. The risk of recurrent VTE was similar with the DOAC and standard treatment (relative risk 0.91, 95% confidence interval 0.79 to 1.06). The DOAC reduced the risk of major bleeding in comparison with standard treatment (0.62, 0.45 to 0.85) (absolute risk difference, − 0.6%; 95% confidence interval − 1.0% to − 0.3%), but there was heterogeneity across trials in the relative risk of bleeding. No between treatment differences were found in the relative risk of all-cause mortality (0.98, 0.84 to 1.14). The DOAC and conventional treatment differed on the net clinical endpoint (0.85, 0.75 to 0.97). Subgroup analyses in relevant subgroups (index pulmonary embolism, heparin lead-in, age, gender, renal function, presence of cancer), as well as sensitivity analyses, were consistent with the main analysis.

Conclusions

The DOAC seem as effective as, and probably safer than standard treatment of acute VTE. The relative efficacy and safety of the DOAC was consistent across a wide range of patients.     

Prolonged travel and venous thromboembolism findings from the RIETE registry

There is a lack of information on clinical risk factors for venous thromboembolism (VTE) development following prolonged traveling. Clinical characteristics and additional risk factors for VTE in travelers were analyzed in RIETE, an ongoing registry of patients with symptomatic, confirmed acute VTE. Of 26,172 patients enrolled in RIETE as of May 2009, 2% developed VTE in association with recent traveling. Travelers were ten years younger, had significantly more previous VTE events (20% vs. 16%; OR: 1.4; 95%CI: 1.1-1.7) and their body mass index (BMI) was 28.4 ± 5.1 vs. 27.7 ± 5.2 in other patients from the registry (P = 0.004). 115 (20%) of recent travelers had previous VTE compared to 16% among others patients (OR: 1.4; 95%CI: 1.1-1.7). Recent travelers used hormones significantly more frequently (8.7% vs. 3.7%; OR: 2.5; 95% CI: 1.8-3.3) and more often had a positive thrombophilia test (16% vs. 8.7%; OR: 2; 95%CI: 1.6-2.6). Travelers used LMWH prophylaxis significantly less frequently than other patients in the registry (2.4% vs. 13%; OR 0.2; 95%CI: 0.1-0.3). There were differences in VTE risk in professional drivers compared to passengers. The current study demonstrates four risk factors for VTE development after long traveling: high BMI, previous VTE, hormone use and thrombophilia. Studies of prophylactic antithrombotic therapy in high risk travelers are warranted.     

Venous thromboembolism during pregnancy or postpartum: findings from the RIETE Registry

Venous thromboembolism (VTE) occurs infrequently during pregnancy, and issues concerning its natural history, prevention and therapy remain unresolved. RIETE is an ongoing registry of consecutive patients with objectively confirmed, symptomatic acute VTE. In this analysis, we compared the clinical characteristics and outcome for all enrolled pregnant and postpartum women with acute VTE, and all non-pregnant women in the same age range. Up to May 2005, 11,630 patients were enrolled in RIETE, of whom 848 (7.3%) were women aged <47 years. Of them, 72 (8.5%) were pregnant, 64 (7.5%) postpartum. Pregnant women presented less often with symptomatic pulmonary embolism (11%) than non-pregnant women (39%). VTE developed during the first trimester in 29 (40%) pregnant patients; in the second in 13; in the third in 30. Thrombophilia tests were more often positive in women who had VTE during the first trimester (odds ratio [OR]: 4.4; 95% CI: 0.9-2.4; p=0.037). Most patients in all three groups were initially treated with low-molecular-weight heparin (LMWH). As for long-term therapy, 75% of pregnant women received LMWH until delivery. There were no maternal deaths, and no pregnant patient had recurrence or bled before delivery. However, after delivery one patient (1.4%) developed recurrent thrombosis, four (5.6%) had major bleeding. In conclusion, VTE developed during the first trimester in 40% of the pregnant women, thus suggesting that thromboprophylaxis, when indicated during pregnancy, should start in the first trimester. No patient showed recurrence or bled before delivery, but after delivery the risk of bleeding exceeded the risk of recurrences.     

Management and adherence to VTE treatment guidelines in a national prospective cohort study in the Canadian outpatient setting. The Recovery Study

Documenting patterns and outcomes of venous thromboembolism (VTE) management and degree of adherence by clinicians to treatment guidelines could help identify remediable gaps in patient care. Prospective, clinical practice-based data from Canadian outpatient settings on management of VTE, degree of adherence with treatment guidelines and frequency of recurrent VTE and bleeding during follow-up was obtained in a multicentre, prospective observational study. From 12 Canadian centres, we assessed 868 outpatients with acute symptomatic VTE who received the low-molecular-weight heparin (LMWH) enoxaparin alone or with vitamin K antagonists (VKA), at baseline and at six months (or at the end of treatment, whichever came first). Index VTE was limb deep venous thrombosis (DVT) in 583 (67.2%) patients, pulmonary embolism (PE) with or without DVT in 262 (30.2%) patients, and unusual site DVT in 23 (2.6%) patients. VTE was unprovoked in 399 (46.0%) patients, associated with cancer in 74 (8.5%) patients, transient risk factors in 327 (37.7%) patients and hormonal factors in 68 (7.8%) patients.With regard to guideline adherence, 58 (7.3%) patients received <5 days LMWH and 114 (14.5%) had overlap <1 day. Among patients with cancer-related VTE, 59.5% were prescribed LMWH monotherapy and 43.2% received such treatment for >3 months. Only 38.1% of patients with transient VTE risk factors had received thromboprophylaxis. Our study provides useful information on clinical presentation, management and related outcomes in Canadian outpatients with VTE. Our results suggest there may be important gaps in use of thromboprophylaxis to prevent VTE and use of LMWH monotherapy to treat cancer-related VTE.     

The use of rivaroxaban for short- and long-term treatment of venous thromboembolism

Venous thromboembolism (VTE) is a major healthcare concern and affects more than 1.6 million individuals each year worldwide. Long-term complications include recurrent VTE, chronic thromboembolic pulmonary hypertension and post-thrombotic syndrome. Rivaroxaban is an oral, direct factor Xa inhibitor that has advantages over traditional VTE therapies, including minimal drug and food interactions and no requirement for routine coagulation monitoring. It is currently approved for VTE prevention in adult patients undergoing elective hip or knee replacement surgery. This review evaluates the potential clinical implications of the multicentre, randomised EINSTEIN studies (EINSTEIN DVT and EINSTEIN EXT), which investigated rivaroxaban for the treatment and prevention of recurrent VTE. In EINSTEIN DVT, rivaroxaban was non-inferior to the standard of care (enoxaparin plus a vitamin K antagonist) for recurrent VTE in patients with acute deep-vein thrombosis (DVT) without pulmonary embolism (PE). In EINSTEIN EXT, extended-duration rivaroxaban had superior efficacy to placebo in patients with confirmed DVT or PE who had received 6-12 months of prior VTE treatment. Rivaroxaban was associated with an acceptable safety profile in both studies. The net clinical benefit (efficacy and safety endpoints combined) of rivaroxaban was significantly greater than its comparators. The EINSTEIN studies are the first demonstration that a single drug--rivaroxaban--can be effective for both the initial treatment of DVT and prevention of recurrent VTE. Moreover, the simple, once-daily oral administration of rivaroxaban could potentially improve adherence to extended-duration VTE treatment compared with the current standard of care in individuals with confirmed DVT or PE.     

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

Background

Few 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.

Methods

We 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).

Results

In 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 61 days (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.

Conclusion

Our 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.     

Initial treatment of venous thromboembolism

Immediate anticoagulant treatment is essential to reduce morbidity and mortality in patients with acute venous thromboembolism (VTE). Currently, rapid anticoagulation can only be achieved with parenteral anticoagulants, such as heparin or low-molecular-weight heparin (LMWH). Weight-adjusted LMWH is the treatment of choice, because it produces predictable anticoagulation and does not require coagulation monitoring. If heparin is used, the activated partial thromboplastin time must be monitored and the heparin dose adjusted to ensure a therapeutic level of anticoagulation. Heparin is recommended for patients with renal impairment and for those at high risk of bleeding. The selective factor Xa inhibitor fondaparinux is a recently introduced alternative to heparin or LMWH for initial VTE treatment. Heparin, LMWH, or fondaparinux should be given for at least five to seven days. Vitamin K antagonists should be initiated on the first day, or as soon as possible, in patients who are candidates for an oral anticoagulant. An oral anticoagulant agent to be used without laboratory monitoring for both acute and long-term treatment of VTE remains an unsolved clinical need in the treatment of VTE.     

Comparison of the two-year outcomes and costs of prophylaxis in medical patients at risk of venous thromboembolism

A decision-analytic model incorporating a Markov process to assess the incremental cost and effectiveness of venous thromboembolism (VTE) prevention strategies was used. Modeling was carried out using a hypothetical cohort of medical patients at risk of VTE. The model compared clinical effectiveness (primary and recurrent VTE, death), safety (adverse events), and direct medical costs between patients receiving enoxaparin prophylaxis, unfractionated heparin (UFH) prophylaxis, and no prophylaxis (n = 10,000 for each arm). Monte Carlo simulation was performed to identify changes in inputs that would affect the results. The estimated incidence ofVTE at two years (including recurrent VTE) was 6.8% with enoxaparin prophylaxis, 7.9% with UFH prophylaxis, and 17.9% with no prophylaxis. Two-year mortality occurred in 15.7% of enoxaparin patients and 16.0% of UFH patients, with the incidences of major bleeding in these groups being 0.7% and 1.2%, respectively. However, both enoxaparin and UFH prophylaxis were associated with higher rates of major bleeds than no prophylaxis (0.6%). Total average costs per patient were (US dollars) $1,264 (for enoxaparin prophylaxis, $1,585 for UFH prophylaxis, and $2,245 for no prophylaxis). No realistic parameter changes resulted in enoxaparin prophylaxis being more costly than UFH prophylaxis. For the healthcare payer, considering all direct medical costs associated with VTE up to two years after an admission for acute illness, prophylaxis with enoxaparin was more effective and less costly than UFH. This identifies enoxaparin as a potentially favorable VTE prophylaxis regimen compared with UFH and no prophylaxis in at-risk medical patients.     

Clinical outcome of patients with major bleeding after venous thromboembolism. Findings from the RIETE Registry

The natural history of patients with venous thromboembolism (VTE) who develop a major bleeding complication while on anticoagulant therapy is not well known. RIETE is a prospective registry of consecutive patients with symptomatic, objectively confirmed, acute VTE. The clinical characteristics, treatment decisions and outcome of all VTE patients who had major bleeding during the first three months of anticoagulant therapy were retrospectively studied. As of January 2007, 17, 368 patients were included in RIETE. Of these, 407 (2.3%) had major bleeding during the study period: 144 gastrointestinal, 119 haematoma, 51 intracranial, 43 genitourinary, 50 other. In 286 (69%) patients anticoagulant therapy was discontinued, in 74 (18%) not modified, in 38 (9.1%) a vena cava filter was inserted. During the first 30 days after bleeding, 24 (5.9%) patients re-bled, 20 (4.9%) had recurrent VTE, 133 (33%) died. Of these, 75 died of bleeding, 12 of recurrent pulmonary embolism. Most deaths occurred shortly after the bleeding episode (median: 1 day). On multivariate analysis, insertion of a vena cava filter was the only variable independently associated with a lower incidence of fatal bleeding (odds ratio [OR]: 0.10; 95% confidence interval [CI]: 0.01-0.79) and all-cause mortality (OR: 0.21; 95% CI: 0.07-0.63). In conclusion, the occurrence of major bleeding in patients with VTE is outstanding in terms of overall mortality (33% within 30 days), fatal bleeding (18%) or re-bleeding (5.9%). However, these patients also have an increased incidence of recurrent VTE (4.9%) and fatal pulmonary embolism (1.2%).     

Association of elevated NTproBNP with recurrent thromboembolic events after acute pulmonary embolism

Introduction

N-Terminal Pro-Brain Natriuretic Peptide (NTproBNP) is a predictor of adverse short-term clinical outcomes in patients with acute pulmonary embolism (APE), but its long-term prognostic value remains largely undefined. The aim of this study was to assess the value of plasma NTproBNP with regard to recurrent venous thromboembolism (VTE).

Materials and Methods

NTproBNP levels were measured in 224 consecutive patients with the first episode of acute pulmonary embolism occurring from January 2005 through October 2010. Patients were categorized into two groups by NTproBNP reference range. Follow-ups were performed at 3, 6, and 12 months and yearly thereafter. The primary end point was symptomatic, recurrent fatal or nonfatal VTE.

Results

NTproBNP was elevated in 158 (70.5%) patients and not elevated in 66 (29.5%) patients. After a mean follow-up period of 31.0 ± 19.4 months, patients with elevated NTproBNP showed an increased risk of recurrent VTE (20 patients, 12.7%) compared to those without elevated NTproBNP (only 1 patient, 1.5%) (P = 0.009). Of the 7 deaths related to pulmonary embolism, 6 occurred in patients with elevated NTproBNP compared to patients with normal NTproBNP (1 of 7 deaths). In a multivariate analysis stratified by oral anticoagulant treatment duration, elevated NTproBNP was an independent predictor of recurrent VTE (hazard ratio, 9.32; P = 0.02).

Conclusions

Elevated NTproBNP is associated with recurrent VTE in acute pulmonary embolism patients.     

Recurrent venous thromboembolism after pregnancy-associated versus unprovoked thromboembolism

It is not known whether women who develop venous thromboembolism (VTE) during pregnancy have a higher or lower incidence of recurrent VTE than women with unprovoked VTE. The aim of the study was to compare the risk of recurrent VTE among women with pregnancy-associated VTE to women with unprovoked VTE. Hospital discharge data identified women age 18-46 years old with pregnancy-associated or unprovoked index VTE between 1994 and 2005. Risk of recurrent VTE was compared between six and 60 months after the index event using both age-matched comparison of disease-free survival and proportional hazard modelling, adjusting for age and other risk factors. The Kaplan-Meier incidence of recurrent VTE in 1085 women with pregnancy-associated VTE was 5.8% versus 10.4% in 7625 women with unprovoked VTE (p = 0.02). Twelve of 34 (35%) recurrent events in the pregnancy-associated group occurred during a subsequent pregnancy compared with 29 of 331 (8.7%) events in the unprovoked group (p < 0.001). In the risk-adjusted multivariate model, women with pregnancy-associated VTE had a significantly lower risk of recurrent VTE (HR = 0.6, 95%CI = 0.4-0.9). Overall, the incidence of recurrent VTE during subsequent pregnancies was higher in the pregnancy group, 21 of 465 (4.5%), than in the unprovoked group, 37 of 1353 (2.7%, RR = 1.7, CI: 1.0-2.8). Compared to women with unprovoked VTE, women with pregnancy-associated VTE had a significantly lower long-term risk of recurrent VTE but a higher risk of recurrent VTE during a subsequent pregnancy. These findings should be considered when decisions are made about VTE prophylaxis in women with a history of pregnancy-associated VTE.     

Venous thromboembolism in acutely ill hospitalized medical patients

Background

Acute and chronic illness, immobility, and procedural and pharmacologic interventions may predispose patients in the Internal Medicine Wards to venous thromboembolic disease (VTE). The purpose of this study was to determine the incidence of VTE in these patients.

Materials and Methods

A retrospective chart review of cohort of consecutive patients admitted to Internal Medicine wards in Spain between January 1st 2005 and December 31st 2007 was performed. For each patient, demographic data, risk factors for VTE and the diagnosis of VTE during hospitalization was recorded.

Results

We analyzed 1,567,659 patients, excluding 28,226 patients who had DVT or PE before admission, and 196,555 who were discharged in the first 48 hours. We identify 12,458 new diagnosed VTE events among 1,344,959 patients (incidence 0.93%) hospitalized more than two days. Hospitalized-acquired VTE risk factors were feminine gender (odds ratio [OR] 1.31; CI95% 1.26-1.35), age > 70 (OR 1.08 CI95% 1.04-1.13), acute infectious disease (OR 1.27 CI95% 1.17-1.38), acute respiratory disease (OR 1.23 CI95% 1.17-1.28), dementia (OR 1.22 CI95% 1.14-1.31), neoplasic disease (OR 2.29, CI95% 2.19-2.49), and hemiplegia (OR 1.49, CI95% 1.31-1.69).

Conclusions

The number of patients with VTE in an Internal Medicine ward is higher than expected. Several independent risk factors for VTE were identified. Based on the large number of patients who developed a VTE during hospitalization, our data add strength to the argument that VTE prevention should be high on the list of priorities when health care policies are being formed.     

Risk of Venous Thromboembolism in Hospitalized Patients with Acute Ischemic Stroke Versus Other Neurological Conditions

BackgroundThe mechanism of increased risk of venous thromboembolism (VTE) after acute ischemic stroke (AIS) is unclear. In this study, we aimed to evaluate the risk of VTE in hospitalizations due to AIS as compared to those due to non-vascular neurological conditions. We also aimed to assess any potential association between VTE risk and the use of intravenous thrombolysis (rtPA) among hospitalizations with AIS.Materials and methodsIn this case-control study, data were obtained from the Nationwide Inpatient Sample 2016-2018. Propensity score matching was used to adjust for the baseline differences between the groups. Logistic regression analysis was used to compare the risk of VTE.ResultsWe identified 1,541,685 hospitalizations due to AIS and 1,453,520 hospitalizations due to non-vascular neurological diagnoses that served as controls. After propensity score matching, 640,560 cases with AIS and corresponding well-matched controls were obtained. Hospitalizations due to AIS had higher odds of VTE as compared to the controls [odds ratio (OR) 1.50, 95% confidence interval (CI) 1.40-1.60, P<0.001]. Among hospitalizations with AIS, 184,065 (11.9%) got rtPA. The odds of VTE were lower among the AIS hospitalizations that received rtPA as compared to those that did not (OR 0.89, 95% CI 0.79-0.99, P0.035).ConclusionHospitalizations due to AIS have a higher risk of VTE as compared to the non-vascular neurological controls. Among AIS cases, the risk of VTE is lower among patients treated with rtPA. These epidemiological findings support the hypothesis that the risk of VTE after AIS might be partly mediated by an intrinsic pro-coagulant state.