Risk Of Venous Thromboembolic Events In Patients Research Articles

Risk Factors of Venous Thromboembolic Disease in Cancer Patients Treated with Immune Checkpoint Inhibitor.

Immune checkpoint inhibitors (ICIs) have revolutionized the management of cancers. The risk factors and pathophysiological mechanisms of venous thromboembolic events (VTEs) of this new therapeutic class are still to be specified. The included patients had to have cancer and should be treated with ICI. Data analyzed included demographic data, biological data, and immune-related adverse events (IRAEs). We studied the prevalence of VTEs and the factors associated with VTEs. Of 374 patients on ICI, over a median follow-up period of 15.2 months, the number of VTE was 50 (13.4%). The majority of patients were treated for metastatic melanoma or nonsmall cell lung cancer. There was no difference in prevalence or survival between cancer types. Patients with combined therapy composed of nivolumab and ipilimumab had higher 1-year cumulative VTE occurrence (29.3% [95% confidence interval [CI]: 9.7; 44.6]) than patients with pembrolizumab (14.9%, [95%CI: 2.5; 25.8], p = 0.03) or nivolumab (9.1%, [95% CI: 5.0; 12.9], p < 0.01). The presence of IRAE was associated with a higher risk of VTE occurrence compared with patients without any IRAE (1-year VTE cumulative incidence: 17.42% [95% CI: 9.5; 24.65] vs. 9.46% [95% CI: 5.18; 13.55], p = 0.04). There was a higher risk of VTE in patients treated with the combination of nivolumab and ipilimumab (adjusted subdistribution hazard ratio [SHR]: 3.71 [95% CI: 1.74; 7.90], p < 0.001) and in patients with IRAE (adjusted SHR: 2.14 [95% CI: 1.22; 3.75], p < 0.01). The prevalence of VTE was 14.2% under ICIs. IRAE and combine treatment of nivolumab and ipilimumab were associated with VTE. The pathophysiological mechanisms are multiple and complex with a possible link to aberrant activation of the immune system.

Abstract #1403021: HIV Status in a Patient on Testosterone Therapy: Confounder or Modifier to Venous Thromboembolism?

The association between venous thromboembolic events (VTE) and testosterone therapy has been controversial. Some studies showed an increased risk of VTE with testosterone use, while few studies showed none. Furthermore, some data suggest HIV can also predispose patients to a hypercoagulable state due to immune dysregulation. A 60-year-old male presented with right leg pain and dyspnea. He was on an aromatase inhibitor and testosterone replacement therapy (TRT) for aromatase excess syndrome, and on bictegravir, emtricitabine and tenofovir alafenamide for HIV infection with normal CD4 count and undetectable viral load. Hospital course revealed right mid-femoral deep vein thrombosis and right-sided pulmonary embolism. He was managed conservatively with IV heparin and eventually discharged on a direct oral anticoagulant. Existing literature on the correlation between VTE and TRT is inconclusive. A case-control study in the USA showed no increased risk of VTE in those on TRT. However, another population-based case-control study in the UK showed that TRT had an increased incidence of VTE compared to general population, with peak risk noted at 6 months. Possible reasons for the higher risk of VTE in patients requiring TRT included increased hematocrit, platelet aggregation, and blood viscosity. A recent case-crossover study that included more VTE-exposed cases showed that TRT patients had greater short-term risk of VTE, especially in the immediate period after initiation of therapy. Another important factor to consider in this patient’s predisposition to VTE is his HIV status which promotes a prothrombotic state and predisposes patients to venous and arterial thromboembolism. Likely due to immune dysregulation secondary to chronic inflammation and immune activation. It usually happens in patients with low CD4 counts and high viral loads. But, in HIV patients with well-controlled viral load and CD4 counts, data suggests that VTE incidence is close to that of general population. In our patient, who was on TRT chronically with no previous VTE, it is hard to assess if his current HIV status was a confounder to his hypercoagulable state or a modifier to an existing risk. With subgroups of TRT-using patients like the transgender population having an increased incidence of HIV, concurrent infection may heighten clinical risk. It is essential to further explore the confounding versus modifying effect that HIV may have on VTE incidence. Currently, there are no large-scale clinical trial data available to identify the true association of VTE with TRT.

Incorporating genetic and clinical data into the prediction of thromboembolism risk in patients with lymphoma.

BackgroundThe incorporation of genetic variables into risk scores for predicting venous thromboembolic events (VTE) could improve their capacity to identify those patients for whom thromboprophylaxis would be most beneficial. Proof‐of‐concept of this is provided by the TiC‐ONCO score for predicting the risk of VTE in patients with solid tumours. Our aim was to develop a similarly improved tool—the TiC‐LYMPHO score—for predicting VTE in patients with lymphoma.MethodsIn a retrospective observational study of 208 patients with lymphoma, 31 (14.9%) were found to have experienced an episode of VTE either at the time of diagnosis or over the next 6 months. Clinical variables associated with VTE, determined via logistic regression analysis, plus the same genetic variables included in the TiC‐ONCO score, were used to build the TiC‐LYMPHO score algorithm. The sensitivity, specificity, predictive values and AUC of the TiC‐LYMPHO, the Khorana and ThroLy scores were compared in the same population.ResultsThe TiC‐LYMPHO score showed a significantly higher AUC, sensitivity and NPV (0.783, 95.35% and 97.98% respectively) than the other scores. The ThroLy score showed a significantly higher specificity (96.43% vs. 54.49%; p < 0.0001) and PPV (37.50% vs. 26.36%; p = 0.0147) than the TiC‐LYMPHO score, whereas its AUC, sensitivity and NPV were significantly lower (0.579, 19.35% and 86.48%, respectively).ConclusionThese results show that by incorporating genetic and clinical data into VTE risk assessment, the TiC‐LYMPHO score can categorize patients with lymphoma better in terms of their risk of VTE and allow individualized thromboprophylaxis to be prescribed.

1776P - High incidence of venous thromboembolic events (VTE) in patients with diffuse large b-cell lymphoma

BackgroundIncidence of venous thromboembolic events (VTE) is higher among cancer patients, especially while on chemotherapy. Diffuse large B-cell lymphoma (DLBL) is the most common lymphoma. Studies that specifically evaluated the risk of VTE in patients with different kinds of lymphomas reported a risk ranged from 1.5% to 14.6%. In this study, we specifically address VTE in a unified lymphoma population. MethodsMedical records and hospital databases were searched for patients with a diagnosis of DLBL and VTE. All patients were diagnosed, treated and followed up at our institution. The Khorana and “Throly” risk assessment models (RAM) were applied on all patients and known risk factors for VTE were studied. ResultsA total of 393 patients (52.4% males), median age: 49 (range: 18-90) years were included. At diagnosis, 163 (41.5%) were stage IV, 116 (29.5%) had bulky disease and 197 (50.1%) had high LDH. All patients were treated on a unified guidelines using R-CHOP chemotherapy; 285 (72.5%) achieved CR while 72 (18.3) had salvage chemotherapy. Venous thromboembolic events were reported in 57 (14.5%) patients. Pulmonary embolism (PE) with or without deep venous thrombosis (DVT) was reported in 24 (42.1%), 8 of them (33.3%) were incidental. Upper extremity DVT were seen in 18 (31.6%); only 4 (22.2%) were associated with a vascular device. Thrombosis was diagnosed in ambulatory sitting in 30 (52.6%) and majority of the VTE occurred while on active chemotherapy; 20 (35.1%) while on initial induction and 15 (26.3%) while on salvage chemotherapy, however, 19 (33.3%) occurred before the initiation of any chemotherapy. Among the 35 patients on active chemotherapy, only 6 (17.1%) had high Khorana risk score. In a multivariate analysis, significantly higher rates of thrombosis were associated with stage-IV disease, high LDH and high International Prognostic Index (IPI). Sex, age, BMI, and the Khorana risk score were not. ConclusionsIncidence of VTE in patients with DLBL is high and majority of such events occurred in ambulatory setting were VTE prophylaxis is not offered. Upper extremity DVT and incidental PE were exceptionally high. Stage at diagnosis, IPI score and LDH are important in predicting the risk for thrombosis. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

Venous Thromboembolic Events in Idiopathic Inflammatory Myopathy: Occurrence and Relation to Disease Onset.

To assess the incidence of venous thromboembolic events (VTEs) in patients with idiopathic inflammatory myopathies (IIMs), to compare the incidence of VTEs in IIM to the incidence in the general population, and to identify patient categories at high risk and investigate the development of risk in relation to a diagnosis of IIM. Using nationwide registers, we identified a cohort of 440 individuals with newly diagnosed IIM and 4,459 individuals from the general population. Patients with IIM were diagnosed between 2005 and 2011. The start of follow-up was the date of IIM diagnosis and the corresponding date in the general population. VTE was defined as hospital care with an International Statistical Classification of Diseases and Related Health Problems, Tenth Revision code indicating VTE, with a filled prescription for anticoagulant medication. Incidence rates including 95% confidence intervals (95% CIs) were calculated, and Cox proportional hazards models were used to compare the risk of VTE in patients with IIM to the risk in the general population. The incidence of VTEs was higher in patients with IIM than in the general population and was highest in patients who previously had cancer, who were ages >71 years when diagnosed with IIM, or who had dermatomyositis. The overall hazard ratio (HR) of VTE comparing the IIM cohort to the general population was 7.81 (95% CI 4.74, 12.85). The HR was highest the first year after IIM diagnosis, with HR 26.6 (95% CI 10.4, 68.0). Patients with IIM are at increased risk of VTE compared to the general population, especially during the first year after the diagnosis. Preventive measures should be focused on patients who previously have had cancer, who are ages >71 years when diagnosed, or who have dermatomyositis.

Risk of Venous Thromboembolism in Patients With Cancer Treated With Cisplatin: A Systematic Review and Meta-Analysis

Several reports suggest that cisplatin is associated with an increased risk of thromboembolism. However, because the excess risk of venous thromboembolic events (VTEs) with cisplatin-based chemotherapy has not been well described, we conducted a systemic review and meta-analysis of randomized controlled trials evaluating the incidence and risk of VTEs associated with cisplatin-based chemotherapy. PubMed was searched for articles published from January 1, 1990, to December 31, 2010. Eligible studies included prospective randomized phase II and III trials evaluating cisplatin-based versus non-cisplatin-based chemotherapy in patients with solid tumors. Data on all-grade VTEs were extracted. Study quality was calculated using Jadad scores. Incidence rates, relative risks (RRs), and 95% CIs were calculated using a random effects model. A total of 8,216 patients with various advanced solid tumors from 38 randomized controlled trials were included. The incidence of VTEs was 1.92% (95% CI, 1.07 to 2.76) in patients treated with cisplatin-based chemotherapy and 0.79% (95% CI, 0.45 to 1.13) in patients treated with non-cisplatin-based regimens. Patients receiving cisplatin-based chemotherapy had a significantly increased risk of VTEs (RR, 1.67; 95% CI, 1.25 to 2.23; P = .01). Exploratory subgroup analysis revealed the highest RR of VTEs in patients receiving a weekly equivalent cisplatin dose > 30 mg/m(2) (2.71; 95% CI, 1.17 to 6.30; P = .02) and in trials reported during 2000 to 2010 (1.72; 95% CI, 1.27 to 2.34; P = .01). Cisplatin is associated with a significant increase in the risk of VTEs in patients with advanced solid tumors when compared with non-cisplatin-based chemotherapy.

Risk of venous thromboembolism in cancer patients treated with cisplatin: A systematic review and meta-analysis.

e21016 Background: Several reports suggest that cisplatin is associated with an increased risk of thromboembolism (TE). However, patients with solid tumors have multiple risk factors for TE and the excess risk of venous thromboembolic events (VTEs) with cisplatin-based chemotherapy as compared with non-cisplatin-based chemotherapy has not been well described. We performed a systemic review and meta-analysis of randomized controlled trials (RCTs) evaluating the incidence and risk of VTE associated with cisplatin-based chemotherapy. Methods: PubMed was searched for articles published from January 1, 1990 until December 31, 2010.The primary aim was to evaluate the association between treatment with cisplatin and VTEs in patients with cancer. Clinical trials that met the following criteria were included in the meta-analysis: (1) prospective randomized phase 2 and 3 trials of patients with cancer; (2) randomization to treatment with cisplatin versus a non-cisplatin containing chemotherapy regimen (3) available data on venous thromboembolic events. Data on all grade venous thromboembolic events was extracted. Study quality was calculated utilizing Jadad scores. Incidence rates, relative risks, and 95% confidence intervals (CIs) were calculated using a random-effects model. Subgroup analyses included the impact of publication year, tumor type, and cisplatin dose. Results: A total of 8216 patients with a variety of advanced solid tumors from 38 RCTs were included for analysis. Among patients treated with cisplatin-based chemotherapy, the summary incidence of VTE was 1.64% (95% CI, 1.06–2.25). Patients treated with cisplatin-based chemotherapy had a significantly increased risk of VTE with a relative risk of 1.65 (95% CI, 1.25–2.18; P = .01) compared with controls. Exploratory subgroup analysis revealed the highest relative risk of VTE in patients receiving a weekly equivalent cisplatin dose &gt;30 mg/m2 (2.64; 95% CI, 1.18–5.77; P = .02) and in studies reported during 2000-2010 (1.70; 95% CI, 1.27–2.28; P = .01). Conclusions: Cisplatin chemotherapy is associated with a significant increase in the risk of VTE in patients with advanced solid tumors compared with non-cisplatin chemotherapy.