Venous Thromboembolism In Elderly Patients Research Articles

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

Data on the relationship between aging, chemotherapy, and risk for venous thromboembolism (VTE) are controversial. We sought to evaluate the risk of chemotherapy-associated VTE in young to middle-aged (YMA) and elderly cancer patients and to analyze the VTE-free survival time in both groups. Patients with histologically confirmed diagnosis of solid malignancy receiving any type of systemic chemotherapy, no clinical diagnosis of VTE before chemotherapy initiation, and Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤2 were enrolled in this study. Of the 486 consecutive patients included in the study, 380 (78%) were classified as YMA (≤70 years of age) and 106 (22%) as elderly (>70 years of age). At a median follow-up of 1 year, the incidence of VTE events was almost two-fold greater in elderly than in YMA (11% vs. 6%). Age (≤70 years vs. >70 years (hazard ratio [HR], 2.42; 95% confidence interval [CI] 1.15-5.06; p=0.020), ECOG-PS (HR, 6.54; 95% CI 3.10-13.8; p<0.0001), and platinum-based chemotherapy (HR, 2.46; 95% CI 1.06-5.69; p=0.035) were independent risk factors for VTE. In the elderly subset, a trend toward an increased risk of VTE in patients receiving a platinum-based chemotherapy when compared with a non-platinum-containing regimen was observed (15% vs. 9.1%). The Kaplan-Meier analysis showed that elderly patients had a significantly shorter VTE-free survival time compared with younger cancer patients (log-rank test=2.0; p=0.045). Our study reports an increase incidence of VTE in elderly cancer patients treated with chemotherapy compared with the younger group, suggesting that aging is one of the most important risk factors for VTE. On the basis of the results of this study, we believe that a validated predictive model including age, ECOG-PS, and type of chemotherapy (platinum- vs. non-platinum containing regimen) would enable clinicians to target thromboprophylaxis to those patients considered to be at greatest risk.

Risk factors for venous thromboembolism in elderly patients with glioblastoma.

e13031 Background: Venous thromboembolism (VTE) is a common complication in glioblastoma (GBM) patients. Physicians are reluctant to administer anticoagulants to GBM patients with VTE, particularly to the elderly patients. Methods: After obtaining IRB approval, the Cleveland Clinic Brain Tumor and Neuro-Oncology Center’s database was used to identify patients with histologically confirmed GBM who were diagnosed with VTE and were ≥65 years of age at the time of diagnosis of GBM. Bivariate comparison of demographic and clinical features was performed by occurrence of DVT, using t-test for continuous data and fishers exact test for categorical variables. Multivariate proportional hazard model was developed adjusting for number of comorbidities (none, 1, 2-3, &gt;3), Karnofsky Performance Status (KPS) at presentation (&gt;70, ≤70), age (&gt;75, ≤75), race, treatment (chemotherapy, radiation therapy, tumor resection). All p-values were 2-sided and were considered significant when &lt;0.005. Results: Chart records of 517 patients diagnosed between 1990 and 2010 were included for analysis. Among 517 cases, 99 patients (54% male, median age at presentation 72 years, range 65-92 years) developed VTE. Median follow-up was 6.58 ± 9.58 months. Eighty-nine (90.8%) cases were diagnosed within 3 months of craniotomy. On univariable analysis, risk factors for VTE included lower KPS (HR 0.98, CI 0.96– 0.99, p = 0.001), thalamic tumors (HR 3.11, CI 1.14– 8.50, p = 0.027), and lower extremity paresis (HR 2.24, CI 1.46-3.46, p &lt; 0.0001). Caucasian patients had a lower trend for developing VTE, however this was not statistically significant. On multivariable analysis, lower KPS was found to be related with higher incidence of VTE (HR 0.35, CI 0.18 – 0.66, p = 0.001). Conclusions: Lower KPS is associated with higher incidence of VTE. Further studies are needed to determine risk stratification and whether the use of medical prophylaxis after neurosurgical intervention can lead to decrease in the rates of VTE in elderly GBM patients.

Prophylaxis of venous thromboembolism in elderly patients with multimorbidity

Pharmacological thromboprophylaxis (TP) is known to reduce venous thromboembolism (VTE) in medical inpatients, but the criteria for risk-driven prescription, safety and impact on mortality are still debated. We analyze data on elderly patients with multimorbidities admitted in the year 2010 to the Italian internal medicine wards participating in the REPOSI registry to investigate the rate of TP during the hospital stay, and analyze the factors that are related to its prescription. Multivariate logistic regression, area under the ROC curve and CART analysis were performed to look for independent predictors of TP prescription. Association between TP and VTE, bleeding and death in hospital and during the 3-month post-discharge follow-up were explored by logistic regression and propensity score analysis. Among the 1,380 patients enrolled, 171 (15.2 %) were on TP during the hospital stay (162 on low molecular weight heparins, 9 on fondaparinux). The disability Barthel index was the main independent predictor of TP prescription. Rate of fatal and non-fatal VTE and bleeding during and after hospitalization did not differ between TP and non-TP patients. In-hospital and post-discharge mortality was significantly higher in patients on TP, that however was not an independent predictor of mortality. Among elderly medical patients there was a relatively low rate of TP, that was more frequently prescribed to patients with a higher degree of disability and who had an overall higher mortality.

Abstract 498: Age-adjusted Cut-off Levels Improve Test Performance in the Diagnosis Strategy of Venous Thromboembolism in Elderly Patients With a Non-high Pre-test Probability

Background D-dimer levels below a well defined cut-off level enable to safely rule out VTE in patients with non-high PTP. Ageing is associated with higher levels of D-dimer. To address the issue of their usefulness in elderly patients, we firstly managed data from 644 out-patients with non-high PTP included in a multicenter management study of a D-dimer assay (C.Legnani et al. 2010). We then validated our results in a cohort of 1,042 consecutive patients investigated using another assay. Results In the first part, D-dimer level, evaluated using the HemosIL D-dimer HS500 assay (Instrumentation Laboratory), was above the cut-off level (500 ng/ml) in all 88 patients with VTE and in 299 of those without (53.8%). Test negative predictive value (NPV) and sensitivity were 100%. Overall test specificity was 46.2%, but decreased in an age-dependent manner over 70 y. ROC-analysis of test results obtained in patients classified according to age allowed us to propose an age- adjustment of the cut-off level calculated by increasing its level by 100 ng/ml per 10 y-increments in patients aged over 59 y e.g. 600 ng/ml between 60 et 69 y, 700 ng/ml between 70 et 79 y. Using those age-adjusted cut-off levels yielded to significantly improve test specificity (56.1%), particularly in old patients. If an 84 y old patient (D-dimer=625 ng/ml) was missed, NPV remained high (99.6%). That strategy was then validated by evaluating data from 1,042 consecutive out-patients, investigated using the Vidas D-dimer assay (BioMérieux). When applied, that age- adjusted cut-off levels leaded to improve test specificity 62.2% vs. 55.1% using the fixed cut-off level. 3 additional patients, with D-dimer &gt;500 ng/ml but below age- adjusted cut-off level, were missed but overall NPV remained high 99.0% vs. 99.4%. Conclusions Age-adjusted cut-off levels for D-dimer, calculated by increasing the traditional cut- off level (500 ng/ml) by 100 ng/ml per 10 y-increments in patients aged over 59 y, significantly increased the test specificity. Correlatively, NPV and sensitivity were slightly decreased, as some patients, with D-dimer above 500 ng/ml but below the age-adjusted cut-off level, could be misdiagnosed. However such a strategy was safe, as NPV remained above 99% in our studied populations.

Symptomatic venous thromboembolism in elderly patients following major orthopedic surgery of the lower limb is associated with elevated vitamin B12 serum levels

BackgroundElevated vitamin B12 serum levels are associated with systemic inflammation and mortality. Since venous thromboembolism (VTE) is associated with systemic inflammation and mortality as well, we have hypothesized that it is also associated with elevated vitamin B12 serum levels in elderly patients following major orthopedic surgery of the lower limb. MethodsThis is a retrospective study. Medical charts of consecutive elderly (≥65years) patients admitted for rehabilitation following major orthopedic surgery of the lower limb during 2007–2009 were reviewed. The study group included symptomatic VTE patients. The control group included patients in whom VTE was excluded. Demographics, co-morbidities, VTE risk factors, vitamin B12 serum levels, and 1-year mortality were studied. ResultsThe cohort included 197 elderly patients (median age: 82years): 140 (71.1%) women and 57 (28.9%) men. Overall, 20 (10.2%) patients had VTE (study group) and in 177 (89.8%) patients VTE was excluded (control group). Vitamin B12 serum levels were higher in the study group compared with the control group (median: 634 vs. 409pg/dL, p=0.024). The incidence of elevated vitamin B12 serum levels (≥500pg/dL) was higher in the study group compared with the control group (odds ratio 3.1, p=0.031). Elevated vitamin B12 serum levels were associated with VTE (odds ratio 5.3, p=0.011) and with 1-year mortality (odds ratio 6.6, p=0.015) independent of demographics, co-morbidities, and VTE risk factors. ConclusionsSymptomatic VTE is associated with elevated vitamin B12 serum levels in elderly patients following major orthopedic surgery of the lower limb.

Impact of Venous Thromboembolism on Mortality of Elderly Medicare Patients with Stage III Colon Cancer

The improvement in survival rates for patients with colon cancer has shifted the focus from examining cancer-specific mortality to exploring all-cause mortality. Adverse events such as venous thromboembolism (VTE) affect overall survival times and the net clinical benefit of cancer management strategies. This retrospective study used Surveillance, Epidemiology and End Results (SEER) Medicare data to examine VTE incidence and mortality rates for elderly patients with stage III colon cancer who were diagnosed in 2004 or 2005 and followed through 2007. The impact of VTE on mortality was estimated using multivariable Cox proportional hazards regression. In all, 20.7% of 4,985 elderly patients with stage III colon cancer had clinically diagnosed VTE following diagnosis. All-cause mortality risk was higher for patients with a VTE diagnosis (hazard ratio [HR]: 1.15, 95% confidence interval [CI]: 1.04-1.27), greater comorbidity burden, more advanced tumor depth and nodal involvement within stage III, advanced age, and male sex; the risk was lower for patients treated with chemotherapy. VTE was associated with higher mortality hazards (HR: 1.41, 95% CI: 1.21-1.64) for patients treated with adjuvant chemotherapy but not for untreated patients. A new diagnosis of VTE significantly reduced survival rates for elderly patients with stage III colon cancer and further reduced survival rates for patients treated with chemotherapy. Improved prevention and management of VTE for elderly patients with stage III colon cancer who are at risk for VTE is warranted, particularly for patients treated with chemotherapy.

Systematic screening for occult cancer in elderly patients with venous thromboembolism: a prospective study

Cancer is an established risk factor for venous thromboembolism (VTE) and the incidence of cancer increases in the elderly. The benefit of screening for occult cancers in this population is still not clear. To evaluate a systematic screening programme for cancer in elderly patients with VTE. This was a prospective study with a 12-month follow-up period. It was conducted in a single centre in consecutive patients over the age of 70 years who had a confirmed diagnosis of VTE. Predefined non-invasive screening techniques for cancer with clinical, laboratory (including tumour markers) and radiological investigations (abdominal ultrasound, chest X-ray and a thoraco-abdominopelvic computed tomography scan) were evaluated. Fifty patients with a median age of 80 years (range: 70 to 94 years) were included. One patient was diagnosed with chronic lymphocytic leukaemia at inclusion and cancers were found in three other patients during the follow-up period (rectosigmoid adenocarcinoma with hepatic metastases, hepatocellular carcinoma and gastric adenocarcinoma). Only one of the four cancers could have been treated at an earlier stage. The mortality rate of the entire cohort after 12 months was 28%. Two patients died as a direct consequence of cancer. In this study of elderly patients, a non-invasive screening strategy did not detect several cancers that were subsequently overt clinically. A full history, clinical examination and routine laboratory investigations might be the optimal first-line strategy to detect cancer after the diagnosis of VTE in elderly patients, but regular clinical examinations during follow up are warranted.

Antipsychotic Drug Use and the Risk of Venous Thromboembolism in Elderly Patients

Our aim was to investigate the relationship between exposure to antipsychotic drugs and the risk of venous thromboembolism (VTE) in elderly patients. A time-matched case-control analysis nested within a cohort of 111,818 patients with at least 1 antipsychotic drug prescription during 1998 to 2008. Data were used from the PHARMO institute's database, which contains drug dispensing data from community pharmacies and hospital admission data. The index date was for the cases defined as the date of hospital admission for VTE (deep venous thrombosis [DVT] or pulmonary embolism) or, for outpatient cases, the start of therapeutic dose low-molecular weight heparin therapy. For each case, 4 controls matched by age and sex were randomly sampled from the cohort. Two measures were used to evaluate the temporal relationship between antipsychotic drug use and the occurrence of VTE: being a current, recent, or past user and the duration of use up to the index date. The strength of the association was expressed as odds ratios with 95% confidence intervals, taking into account potential confounders. We identified 367 cases of hospital admission for DVT, 342 cases of hospital admission for PE, and 323 cases of outpatient treatment of DVT. Current exposure to antipsychotic drugs was not associated with an increased risk of VTE, compared with nonusers (odds ratio, 0.9; 95% confidence interval, 0.7-1.1). We found no association between dosage, the duration of use, or the type of antipsychotic drug and the risk of VTE. We found no evidence of an increased risk of VTE in elderly patients using antipsychotic drugs.

Primary prevention of venous thromboembolism in elderly medical patients.

Primary prophylaxis with the use of an effective and safe intervention appears the best approach of venous thromboembolism (VTE) management in medical elderly patients, the most affected by VTE. With increasing life expectancy, prevention of VTE, particularly in elderly patients, will arise as a major public health problem. Few well designed clinical trials evaluating thromboprophylaxis in medical settings were conducted in the specific population of geriatric patients. However, among the several pharmacological treatments evaluated, low molecular weight heparins enoxaparin 40 mg daily or dalteparin 5000 IU daily appeared effective and safe in the prevention of VTE in elderly patients. Despite available data, and recommendations for VTE prevention in medical patients, thromboprophylaxis is underused or misused in practice. Heterogeneity of clinical studies, selected populations, concern about bleeding, and lack of a clear clinical benefit are some of the reasons that could explain the gap between theory and practice. In this review, after a brief report of epidemiologic data and specificities of VTE in elderly patients, the authors discuss the available results of VTE primary prevention trials for elderly medical patients, the limitations of these data, and the challenges to improve the practice and to reduce the incidence of this frequent but preventable disease.