Capsule Commentary on Leiss et al., Polypharmacy Is Associated with an Increased Risk of Bleeding in Elderly Patients with Venous Thromboembolism

SummaryVitamin K antagonists (VKA) are widely used in atrial fibrillation and venous thromboembolism (VTE). Their efficacy and safety depend on individual time in the therapeutic range (iTTR). Due to the variable dose-response relationship within patients, also patients with initially stable VKA treatment may develop extreme overanticoagulation (EO). EO is associated with an immediate bleeding risk, but it is unknown whether VKA treatment will subsequently restabilise. We evaluated long-term quality of VKA treatment and clinical outcome after EO. EO was defined as international normalized ratio (INR) ≥ 8.0 and/or unscheduled vitamin K supplementation. We included a consecutive cohort of initially stable atrial fibrillation and venous thromboembolism patients. In EO patients, the 90 days pre- and post-period were compared. In addition, patients with EO were compared with patients without EO using a matched 1:2 cohort. Of 14,777 initially stable patients, 800 patients developed EO. The pre-period was characterised by frequent overanticoagulation, and half of EO patients had an inadequate iTTR (< 65 %). After EO, underanticoagulation became more prevalent. Although the mean time between INR-measurements decreased from 18.6 to 13.2 days, after EO inadequate iTTR became more frequent (62 %), p-value < 0.001. A 2.3 times (95 % confidence interval [CI] 2.0–2.5) higher risk for iTTR< 65 % after EO, was accompanied by increased risk of bleeding (hazard ratio [HR] 2.1;CI 1.4–3.2), VKA-related death 17.0 (HR 17.0;CI 2.1–138) and thrombosis (HR 5.7;CI 1.5–22.2), compared to the 1600 controls. In conclusion, patients continuing VKA after EO have long-lasting inferior quality of VKA treatment despite intensified INR-monitoring, and an increased risk of bleeding, thrombosis and VKA-related death.Note: There have been no previous presentations, reports or publications of the complete data that appear in the article. Parts of the data in this article have been presented as a poster at the American Society of Hematology (ASH) congress 2013, New Orleans, United States.

Download Full-text

Modified IMPROVE VTE Risk Score and Elevated D-Dimer Identify a High Venous Thromboembolism Risk in Acutely Ill Medical Population for Extended Thromboprophylaxis

TH Open ◽

10.1055/s-0040-1705137 ◽

2020 ◽

Vol 04 (01) ◽

pp. e59-e65 ◽

Cited By ~ 30

Author(s):

Alex C. Spyropoulos ◽

Concetta Lipardi ◽

Jianfeng Xu ◽

Colleen Peluso ◽

Theodore E. Spiro ◽

...

Keyword(s):

Venous Thromboembolism ◽

High Risk ◽

Risk Score ◽

Lower Risk ◽

Risk Group ◽

High Risk Group ◽

Cutoff Score ◽

Risk Of Bleeding ◽

Increased Risk ◽

D Dimer

AbstractAn individualized approach to identify acutely ill medical patients at increased risk of venous thromboembolism (VTE) and a low risk of bleeding to optimize the benefit and risk of extended thromboprophylaxis (ET) is needed. The International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) VTE risk score has undergone extensive external validation in medically ill patients for in-hospital use and a modified model was used in the MARINER trial of ET also incorporating an elevated D-dimer. The MAGELLAN study demonstrated efficacy with rivaroxaban but had excess bleeding. This retrospective analysis investigated whether the modified IMPROVE VTE model with an elevated D-dimer could identify a high VTE risk subgroup of patients for ET from a subpopulation of the MAGELLAN study, which was previously identified as having a lower risk of bleeding. We incorporated the modified IMPROVE VTE score using a cutoff score of 4 or more or 2 and 3 with an elevated D-dimer (>2 times the upper limit of normal) to the MAGELLAN subpopulation. In total, 56% of the patients met the high-risk criteria. In the placebo group, the total VTE event rate at Day 35 was 7.94% in the high-risk group and 2.83% for patients in the lower-risk group. A reduction in VTE was observed with rivaroxaban in the high-risk group (relative risk [RR]: 0.68, 95% confidence interval [CI]: 0.51–0.91, p = 0.008) and in the lower-risk group (RR: 0.69, 95% CI: 0.40 -1.20, p = 0.187). The modified IMPROVE VTE score with an elevated D-dimer identified a nearly threefold higher VTE risk subpopulation of patients where a significant benefit exists for ET using rivaroxaban.

Download Full-text

External validation of the VTE-BLEED score for predicting major bleeding in stable anticoagulated patients with venous thromboembolism

Thrombosis and Haemostasis ◽

10.1160/th16-10-0810 ◽

2017 ◽

Vol 117 (06) ◽

pp. 1164-1170 ◽

Cited By ~ 33

Author(s):

Frederikus A. Klok ◽

Stefano Barco ◽

Stavros V. Konstantinides

Keyword(s):

Venous Thromboembolism ◽

High Risk ◽

Major Bleeding ◽

External Validation ◽

Chronic Phase ◽

Bleeding Risk ◽

Bleeding Events ◽

Risk Of Bleeding ◽

Increased Risk ◽

Study Population

SummaryOne of the main determinants of establishing the optimal treatment duration of patients with venous thromboembolism (VTE) is the risk of major bleeding during long-term anticoagulant therapy. The 6-variable VTE-BLEED score was recently developed to enable estimation of this bleeding risk. This study aimed at externally validating VTE-BLEED. This was a post-hoc study of the randomised, double-blind, double-dummy, Hokusai-VTE study that compared edoxaban versus warfarin for treatment of VTE. VTE-BLEED was calculated in all 8,240 study patients. The numbers of adjudicated major bleeding events during ‘stable anticoagulation’, i. e. occurring after day 30, in patients with low (total score <2 points) and high risk of bleeding (total score ≥2 points) were compared for the overall study population, patients randomised to edoxaban or warfarin, and for important patient subcategories. During ‘stable’ anticoagulation, major bleeding occurred in 1.02% (40/3,903) and 0.82% (32/3,899) of patients treated with warfarin and edoxaban, respectively. For the overall study population, the risks of bleeding in the low and high risk groups were 0.51% and 2.03%, respectively, for an odds ratio (OR) of 4.04 (95% confidence interval [CI]: 2.51–6.48). ORs were 5.04 (95%CI: 2.62–9.69) and 3.09 (95%CI: 1.54–6.22) for warfarin and edoxaban, respectively. VTE-BLEED was consistently able to identify patients at a 2.5- to 11-fold higher bleeding risk across all the predefined subcategories, as well as for the treatment period between day 30 to day 180, and beyond day 180. In conclusion, patients identified as high risk by VTE-BLEED had a four-fold increased risk of bleeding during the chronic phase of treatment.Supplementary Material to this article is available online at www.thrombosis-online.com.

Download Full-text

Venous Thromboembolism in Patients with Liver Cirrhosis: Findings from the RIETE (Registro Informatizado de la Enfermedad TromboEmbolica) Registry

Seminars in Thrombosis and Hemostasis ◽

10.1055/s-0039-1697682 ◽

2019 ◽

Vol 45 (08) ◽

pp. 793-801 ◽

Cited By ~ 5

Author(s):

Behnood Bikdeli ◽

David Jiménez ◽

Guadalupe Garcia-Tsao ◽

Raquel Barba ◽

Carme Font ◽

...

Keyword(s):

Venous Thromboembolism ◽

Hazard Ratio ◽

Risk Of Bleeding ◽

Fatal Bleeding ◽

Increased Risk ◽

All Cause Mortality ◽

Recurrent Vte ◽

One Year ◽

Related Mortality

AbstractPatients with cirrhosis are not only at an increased risk of bleeding but also at risk of venous thromboembolism (VTE). We sought to determine the clinical characteristics, management, and outcomes after VTE in patients with cirrhosis. We used the data from RIETE (Registro Informatizado de la Enfermedad TromboEmbolica), an international registry of patients with VTE, to compare the outcomes in patients with and without cirrhosis. Main outcomes included all-cause mortality, pulmonary embolism (PE)-related mortality, recurrent VTE, and bleeding. Among 43,611 patients with acute VTE, 187 (0.4%) had cirrhosis. Of these, 184 (98.4%) received anticoagulation for a median of 109 days (interquartile range [IQR]: 43–201 days), most commonly with enoxaparin (median dose: 1.77 [IQR: 1.38–2.00] mg/kg/day). Compared with patients without cirrhosis, those with cirrhosis had a higher rate of all-cause mortality (10.7 vs. 3.4%; odds ratio [OR]: 3.41; 95% confidence interval [CI]: 2.03–5.46) and fatal bleeding (2.1 vs. 0.2%; OR: 13.94; 95% CI: 3.65–37.90) but similar rates of fatal PE (0.5 vs. 0.5%; OR: 1.17; 95% CI: 0.03–6.70). Patients with cirrhosis had a higher rate of all-cause mortality per 100 patient-years of follow-up (58.9 vs. 16.0; hazard ratio [HR]: 3.70; 95% CI: 2.69–4.91). One-year hazard ratio of clinically relevant bleeding (HR: 2.86; 95% CI: 1.91–4.27), fatal bleeding (HR: 8.51; 95% CI: 3.5–20.7), or recurrent VTE (HR: 2.08; 95% CI: 1.00–4.36) was higher in patients with cirrhosis. Cirrhosis is a challenging comorbidity in patients with VTE. Most patients were treated with anticoagulation and had an elevated risk of recurrence, similar risk of fatal PE, and a very high risk of bleeding including fatal bleeds.

Download Full-text

Increased Risk of Chemotherapy-Associated Venous Thromboembolism in Elderly Patients with Cancer

Rejuvenation Research ◽

10.1089/rej.2013.1409 ◽

2013 ◽

Vol 16 (3) ◽

pp. 224-231 ◽

Cited By ~ 11

Author(s):

Matteo Vergati ◽

David Della-Morte ◽

Patrizia Ferroni ◽

Vittore Cereda ◽

Livia Tosetto ◽

...

Keyword(s):

Venous Thromboembolism ◽

Elderly Patients ◽

Patients With Cancer ◽

Increased Risk

Download Full-text

Prophylaxis for venous thromboembolism in liver disease: a narrative literature review

Gastrointestinal Nursing ◽

10.12968/gasn.2021.19.sup10.s24 ◽

2021 ◽

Vol 19 (Sup10) ◽

pp. S24-S31

Author(s):

Alex Hadall

Keyword(s):

Liver Disease ◽

Venous Thromboembolism ◽

Bleeding Risk ◽

Assessment Tools ◽

Decompensated Liver Disease ◽

Vte Prophylaxis ◽

Risk Of Bleeding ◽

Number Of Patients ◽

Increased Risk ◽

Narrative Literature Review

Background: Patients with liver disease have traditionally been regarded as auto-anticoagulated against developing blood clots due to haemorrhage being regarded as the most significant haemostatic complication. More recently, there has been increasing recognition that hypercoagulability is a prominent aspect of cirrhosis, with an increasing number of patients developing thromboembolisms. When prescribing prophylactic low molecular weight heparin for prevention, clinicians are often concerned about the risk of bleeding, including gastrointestinal bleeding, specifically in those with decompensated liver disease and cirrhosis, due to the altered coagulopathy associated with these patients. Aim: The aim of this review was to assess if the use of prophylaxis in patients with liver disease is effective in the prevention of venous thromboembolism (VTE) and whether its use is related to an increase in bleeding episodes. Methods: A review of the literature was conducted to identify the incidence of VTE and bleeding in liver patients when given prophylactic VTE treatment. Results: The majority of evidence was inconclusive; however, the main emerging theme was that administering prophylaxis to patients with decompensated liver disease results in an increased risk of bleeding, while having little effect on reducing the risk of VTE development. Conclusion: The bleeding risk associated with VTE prophylaxis treatment and liver disease remains uncertain. Thus the ideal methods of medical prophylactic VTE prevention and monitoring in this patient population have not yet been determined. It is suggested that additional consideration should be given to serum albumin, platelet count and international normalised ratio, as well as renal function, in conjunction with risk assessment tools, when deciding whether to prescribe VTE prophylaxis or not.

Download Full-text

Derivation and validation of a novel bleeding risk score for elderly patients with venous thromboembolism on extended anticoagulation

Thrombosis and Haemostasis ◽

10.1160/th17-03-0162 ◽

2017 ◽

Vol 117 (10) ◽

pp. 1930-1936 ◽

Cited By ~ 1

Author(s):

Andreas Limacher ◽

Marie Méan ◽

Hans-Jürg Beer ◽

Joseph Osterwalder ◽

Beat Frauchiger ◽

...

Keyword(s):

Venous Thromboembolism ◽

High Risk ◽

Elderly Patients ◽

Major Bleeding ◽

Clinical Score ◽

Low Risk ◽

University Hospital ◽

Moderate Risk ◽

Internal Validation ◽

Risk Of Bleeding

SummaryExisting clinical scores do not perform well in predicting bleeding in elderly patients with acute venous thromboembolism (VTE). We sought to derive an easy-to-use clinical score to help physicians identify elderly patients with VTE who are at high-risk of bleeding during extended anticoagulation (>3 months). Our derivation sample included 743 patients aged ≥65 years with VTE who were enrolled in a prospective multicenter cohort study. All patients received extended anticoagulation with vitamin K antagonists. We derived our score using competing risk regression, with the time to a first major bleeding up to 36 months of extended anticoagulation as the outcome, and 17 candidate variables as predictors. We used bootstrapping methods for internal validation. Sixty-six (9%) patients suffered major bleeding. The clinical score is based on seven clinical factors (previous bleeding, active cancer, low physical activity, anemia, thrombocytopenia, antiplatelet drugs/NSAIDs, and poor INR control). Overall, 48% of patients were classified as low-risk, 37% as moderate-risk, and 15% as high-risk of bleeding. The rate of major bleeding was 1.4 events in low-risk, 5.0 events in moderate-risk, and 12.2 events per 100 patientyears in high-risk patients. The c-statistic was 0.78 at 3 months and 0.71 at 36 months of extended anticoagulation. Model calibration was excellent (p=0.93). Internal validation showed similar results. This simple clinical score accurately identified elderly patients with VTE who are at high risk of major bleeding and who may not benefit from extended anticoagulation. Further validation of the score is important before its implementation into practice. The study is registered to https://clinicaltrials.gov as NCT00973596.This work was carried out at the Department of General Internal Medicine in the Bern University Hospital, Switzerland.

Download Full-text

Increased Risk of Bleeding in Elderly Patients Treated With Oral Anticoagulants and Angiotensin-Converting Enzyme Inhibitors

Canadian Journal of Cardiology ◽

10.1016/j.cjca.2019.02.001 ◽

2019 ◽

Vol 35 (4) ◽

pp. 545.e3-545.e4

Author(s):

Alice Laudisio ◽

Michele Ciaburri ◽

Domenico Gabrielli ◽

Daniele Sticchi ◽

Silvia Giovannini ◽

...

Keyword(s):

Elderly Patients ◽

Angiotensin Converting Enzyme ◽

Enzyme Inhibitors ◽

Oral Anticoagulants ◽

Angiotensin Converting Enzyme Inhibitors ◽

Converting Enzyme ◽

Converting Enzyme Inhibitors ◽

Risk Of Bleeding ◽

Increased Risk

Download Full-text

Epidemiology, Prevention, Diagnosis, and Management of Venous Thromboembolism in Gastrointestinal Cancers

Digestive Disease Interventions ◽

10.1055/s-0040-1716738 ◽

2020 ◽

Vol 04 (03) ◽

pp. 248-259

Author(s):

William J. Chapin ◽

Preeti Sudheendra ◽

Luis Goity ◽

Deepak Sudheendra

Keyword(s):

Venous Thromboembolism ◽

Oral Anticoagulants ◽

Vena Cava ◽

Filter Placement ◽

Diagnosis And Management ◽

Patients With Cancer ◽

Risk Of Bleeding ◽

Catheter Directed Thrombolysis ◽

Increased Risk ◽

Recurrent Vte

AbstractVenous thromboembolism (VTE) is a leading cause of cardiovascular death and is associated with significant morbidity. Patients with cancer, and gastrointestinal (GI) malignancies in particular, are at increased risk of VTE, increased risk of bleeding with VTE treatment, and increased risk of recurrent VTE compared with the general population. VTE has been shown to be a leading cause of death among patients with cancer. This review will discuss special considerations in the prevention, diagnosis, and management of VTE in patients with GI malignancies. Given the increased risk of VTE observed in ambulatory patients with GI malignancies, multiple trials have examined and demonstrated the efficacy of prophylactic anticoagulation in high-risk patients with cancer undergoing chemotherapy, particularly in patients with gastric and pancreatic cancers. Patients with GI malignancies have also played a central role in discussions of the risks and benefits of the use of direct oral anticoagulants in patients with cancers, with first-line anticoagulation options expanding to include low-molecular-weight heparin, rivaroxaban, edoxaban, and apixaban. However, there continue to be concerns regarding an increased risk of bleeding with edoxaban and rivaroxaban in patients with GI malignancies. In addition to anticoagulation, individualized risk and benefit analysis should be undertaken for interventions including inferior vena cava (IVC) filter placement and catheter-directed thrombolysis in the setting of increased risk of bleeding and recurrent VTE for patients with GI malignancies. Several unique scenarios that may be seen with GI malignancies, including incidental VTE, splanchnic vein thrombosis, IVC thrombosis, and iliac vein compression, require individualized decision making.

Download Full-text