Lessons from VTE registries: the RIETE experience

doi:10.1016/j.beha.2008.12.003

Best Practice & Research Clinical Haematology

Volume 22, Issue 1, March 2009, Pages 25-33

https://doi.org/10.1016/j.beha.2008.12.003 Get rights and content

Patients with venous thromboembolism (VTE) and active cancer are often excluded from clinical trials of anticoagulant therapy because of short life expectancy, inability or unwillingness to attend for regular laboratory monitoring during vitamin K antagonist therapy, or contraindications to therapy. As such, treatment regimens based on the results from clinical trials might not be suitable for many VTE patients with cancer. ‘Registro Informatizado de la Enfermedad TromboEmbólica’ (RIETE) was initiated in March 2001 to prospectively record the current clinical management of patients with symptomatic, objectively confirmed, acute VTE in Spanish hospitals. This chapter will summarize the most important findings published to date regarding the association between VTE and cancer.

Section snippets

RIETE

Current guidelines from the American College of Chest Physicians (ACCP), based on evidence from clinical trials, recommend that patients with venous thromboembolism (VTE) should be treated initially with heparin, followed by long-term treatment with a vitamin K antagonist (VKA) [1]. However, patients with active cancer are often excluded from clinical trials of anticoagulant therapy because of short life expectancy, inability or unwillingness to attend for regular laboratory monitoring during

Prediction of fatal pulmonary embolism and fatal bleeding [2]

In cancer patients who develop VTE, the risk of death is more than three-fold higher than that in patients without cancer who have VTE *[3], [4], [5], and in patients with cancer but no VTE [6]. The high mortality rate in cancer patients with VTE is probably due to both VTE and the fact that malignancies associated with VTE are usually at later stages, and appear to follow a more aggressive course [6]. Identifying clinical characteristics that put cancer patients with VTE at increased risk of

Hidden cancer in patients with VTE [8]

Although usually developing in advanced stages of cancer, VTE may also appear before the cancer has become symptomatic and may lead to an earlier diagnosis of cancer. This association is greatest within the first few months after VTE, thus suggesting that these cancers are present at the time of diagnosis. In the last three decades, increasing attention has been given to this relationship, and some doubts have been clarified. First, in patients with clinically suspected VTE, the development of

Predicting VTE recurrence or major bleeding [23]

As discussed above, cancer patients with VTE have an increased incidence of VTE recurrence and anticoagulant-related bleeding complications compared with patients without cancer [24], *[25], [26], [27]. Reliable information on factors determining the risk of VTE recurrence or major bleeding complications may facilitate better use of therapy by improving the selection of patients in whom its benefit will likely outweigh the risk, and by identifying those who may benefit from careful management.

Elevated white blood cell count and outcome [29]

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 VTE has not been explored [30], [31], [32], [33]. A study was undertaken to compare the 3-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

Long-term therapy with VKA [38]

As discussed above, international guidelines recommend the use of subtherapeutic doses of LMWH for the long-term prevention of recurrent VTE in all cancer patients. However, in clinical practice, many clinicians still administer VKA to their cancer patients, especially to those with limited disease and longer life expectancy.

The risk of recurrent VTE and major bleeding was determined in a large number of patients with and without cancer who were recruited in RIETE, had an initial treatment with

Summary

Analysis of data from RIETE reveal that: (1) cancer patients with VTE who had recently been immobilized had a higher rate of both fatal PE and fatal bleeding; (2) VTE patients with hidden cancer had an increased incidence of recurrence, major bleeding or death during the first 3 months of therapy, and early identification of occult malignancies by screening may be guided by easily obtainable variables at the diagnosis of VTE, with a direct effect on treatment; (3) cancer patients could be

Conflict of interest statement

The authors declare that they have no conflicts of interest.

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Cited by (15)

Venous thromboembolism in hospital emergency room. A retrospective study on climatic effect
2021, Environmental Research
Citation Excerpt :
We want to draw attention on early diagnosis and management in individuals admitted to the HER at the time of the VTE occurrence are crucial for their good outcome and also in reducing the mortality risk (Llojd et al., 2008; Kakkar et al., 2011). There is a large body of evidence on the efficacy of anti-thrombotic drugs to lower VTE mortality and counter its progression (Lilly et al., 2014; Bustos et al., 2017; Conti et al., 2018; Gussoni et al., 2013; Monreal et al., 2009). Coagulation factors are known to be crucial in causing the venous thromboembolism and some genes that code for hemostatic factors such as the FVII, FVII, and FVII.
Several cardiovascular conditions exhibit seasonality in frequency and mortality, but little is known about the seasonality of Venous ThromboEmbolism (VTE), a very relevant medical condition, and seasonal influences are still conflicting. Patients having co-morbidities, individual suffered from dyspnea, swelling, edema of lower limb, pain (chest, lower limbs) are admitted frequently to the hospital emergency room (HER), particularly. Both mark a potential risk for VTE, that can be increased also by seasonality. A four years retrospective analysis (2016–2019) was carried out in individuals and patients admitted to the HER of the Hospital of Catania (a Mediterranean city of Sicily, Italy) to evaluate the VTE frequency and its seasonal differences, common symptoms, potential usage of some common laboratory tests. Dyspnea, swelling, edema of lower limb and pain (chest, lower limbs) were considered to suspect pulmonary embolism (PE) or for deep vein thrombosis of lower limb (DVT). Platelet count, platelet volume, fibrinogen, C-reactive protein, and D-dimer were considered. VTE frequency per year was 2.9/10,000 (2016), 4.9/10,000 (2017) 3.6/10,000 (2018), and 5.1/10,000 (2019) respectively. Dyspnea was highly frequent for PE, edema and lower limb pain were frequent in DVT patients. Fibrinogen, C reactive protein, and D-dimer values were found raised in all the VTE patients. Platelet volume was found higher in DVT than PE VTE events that occurred in warm periods were modestly greater (57 VTE: 38 DVT, 19 PE) compared to cold months (52 VTE: 34 DVT, 18 PE). Our results could be explained by the increased sweating due to the high temperatures, which in turn, can affect both on plasma concentration and on hematocrit value coupled to the reduction in atmospheric pressure determining both a hyper-coagulative condition. Climate seasonal characteristics, and environmental conditions in Catania city (Sicily) may be as reasonable items in expecting on different VTE rates in warm period compared to cold. This study highlights no specific symptoms, and confirms the common lab tests for individuals and patients admitted to HER as simple and helpful tools in initiating none or mini-invasive diagnostic strategy for the VTE. Finally, the climate/seasonality coupled with latitude can have a direct influence on the incidence of DVT.
Treating pulmonary embolism in Pacific Asia with direct oral anticoagulants
2015, Thrombosis Research
Citation Excerpt :
Rates of VTE recurrence as PE were similar in patients with PE or isolated DVT, in contrast to reports that PE is more likely following an initial PE compared with DVT [37]. The Spanish RIETE registry, documented significantly higher rates of fatal PE in patients with renal insufficiency, cancer, recent bleeding (major or minor), thrombocytopaenia, or who were pregnant [30,38,39]. VTE patients with comorbidities were also more likely than those without to have bleeding complications following anticoagulant therapy, with clinically-overt PE, age > 75 years, cancer, recent bleeding, anaemia and renal insufficiency, independently predicting major bleeding [40,41].
Pulmonary embolism (PE) is the principal preventable cause of in-hospital deaths. Prevalence of PE in Asians is uncertain but undoubtedly underestimated. Asians and Caucasians have similar non-genetic risk factors for PE, and there is mounting evidence that PE affects Asians much more commonly than previously supposed; incidence, especially among high-risk patients, may approach that in Caucasians. Furthermore, PE incidence in Asia is increasing, due to both increased ascertainment, and also population ageing and growing numbers of patients with predisposing risk factors. Despite being warranted, thromboprophylaxis for high-risk patients is not routine in Pacific Asian countries/regions. There also appears to be scope to implement venous thromboembolism (VTE) management guidelines more assiduously.
Anticoagulants, primarily heparins and warfarin, have been the mainstays of VTE management for years; however, these agents have limitations that complicate routine use. The complexity of current guidelines has been another barrier to applying evidence-based recommendations in everyday practice. Updated management approaches have considerable potential to improve outcomes. New oral anticoagulants that are easier to administer, require no, or much less, monitoring or dose-adjustment and have a favourable risk/benefit profile compared with conventional modalities, may offer an alternative with the potential to simplify VTE management. However, more information is required on practical management and the occurrence and treatment of bleeding complications.
Increasing recognition of the burden of PE and new therapeutic modalities are altering the VTE management landscape in Pacific Asia. Consequently, there is a need to further raise awareness and bridge gaps between the latest evidence and clinical practice.
Physicians' management approach to an incidental pulmonary embolism: An international survey
2013, Journal of Thrombosis and Haemostasis
Three-month mortality rate and clinical predictors in patients with venous thromboembolism and cancer. Findings from the RIETE registry
2013, Thrombosis Research
Citation Excerpt :
Further, specific attention was paid to potential predictors of both all-cause and PE-related death. The RIETE registry is an ongoing, international, multicenter, prospective cohort of consecutive patients presenting with symptomatic venous thromboembolism (deep vein thrombosis - DVT, PE, or both) confirmed by objective tests [26,27]. Patients are excluded if they are currently participating in a therapeutic clinical trial with a blind medication, or if they will not be available for a 3-month follow-up.
Patients with venous thromboembolism (VTE), and particularly those with cancer, are at increased risk of recurrences, major bleeding, and short- / medium-term mortality.
Data from 35,539 patients (6,075 of these with cancer), presenting with symptomatic VTE in the previous three months and enrolled in the worldwide RIETE registry, were evaluated to assess overall and pulmonary embolism (PE)-related mortality, and their potential predictors, with particular focus on patients with cancer.
Overall 3-month mortality in the total RIETE population was 7.9%, and death was considered PE-related in 1.4%. Significantly more patients died among those with cancer (26.4%, vs 4.1% in no-cancer group, p < 0.001). In 3.0% of cancer patients death was considered PE-related, compared to 1.0% in no-cancer group (p < 0.001). Cancer was the strongest independent risk factor for both all-cause and PE-related mortality, and in the subgroup of cancer patients those with advanced disease, reduced mobility, chronic pulmonary disease, and those experiencing PE (vs isolated deep vein thrombosis) were at increased risk of PE-related death.
According to the findings of our very large, real-world registry, in the three months following an acute episode VTE remains a substantial cause of mortality. Cancer patients are at particular high risk of VTE-related death. Clinical factors predicting a fatal PE identified in this study (cancer, immobility, comorbidities, increasing age, PE at presentation), could be considered for risk stratification scheme for secondary prophylaxis in daily practice.
Clinical epidemiology of venous thromboembolic disease: An institutional registry
2022, Frontiers in Cardiovascular Medicine
Occult cancer-related first venous thromboembolism is associated with an increased risk of recurrent venous thromboembolism
2017, Journal of Thrombosis and Haemostasis

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3Lessons from VTE registries: the RIETE experience

Section snippets

RIETE

Prediction of fatal pulmonary embolism and fatal bleeding [2]

Hidden cancer in patients with VTE [8]

Predicting VTE recurrence or major bleeding [23]

Elevated white blood cell count and outcome [29]

Long-term therapy with VKA [38]

Summary

Conflict of interest statement

J Thromb Haemost

Chest

Chest

J Thromb Haemost

Lancet

J Thromb Haemost

J Thromb Haemost

Blood

Rates of initial and recurrent thromboembolic disease among patients with malignancy versus those without malignancy. Risk analysis using Medicare claims data

Medicine

The clinical course of pulmonary embolism

N Engl J Med

The long-term clinical course of acute deep venous thrombosis

Ann Intern Med

Prognosis of cancers associated with venous thromboembolism

N Engl J Med

Occult cancer in patients with acute pulmonary embolism

Ann Intern Med

Occult malignant neoplasm in patients with deep venous thrombosis

Arch Intern Med

The risk of a diagnosis of cancer after primary deep venous thrombosis or pulmonary embolism

N Engl J Med

Deep-vein thrombosis and the incidence of subsequent symptomatic cancer

N Engl J Med

Venous thromboembolism as first manifestation of cancer

Acta Haematol

Prognosis of cancer associated with venous thromboembolism

N Engl J Med

Occult cancer in patients with venous thromboembolism: which patients, which cancers

Thromb Haemost

3
Lessons from VTE registries: the RIETE experience