Overview of risk assessment models for venous thromboembolism in ambulatory patients with cancer

A B S T R A C T Important progress has been made in the development of risk assessment models (RAM) for the identification of outpatients on anticancer treatment at risk of venous thromboembolism (VTE). Since the breakthrough publication of the original Khorana risk score (KRS) more than 10 years ago, a new generation of KRS-based scores have been developed, including the Vienna Cancer and Thrombosis Study, PROTECHT, CONKO, ONCOTEV, TicOnco and the CATS/MICA score. Among these the CATS/MICA score showed that a simplified score composed of only two calibrated predictors, the type of cancer and the D-dimer levels, offers a user-friendly tool for the evaluation of cancer-associated thrombosis (CAT) risk. The COMPASS-CAT score is the first that introduced a more synthetic approach of risk evaluation by combining cancer-related predictors with patient comorbidity in a score which is designed for the types of cancer frequently seen in the community (i.e. breast, lung colon or ovarian cancers) and has been externally validated in independent studies. The Throly score is registered as part of the same group as it has a similar structure to the COMPASS-CAT score and is applicable in patients with lymphoma. The incorporation of specific biomarkers of hypercoagulability to the RAM for CAT offers the possibility to perform a precision medicine approach in the prevention of CAT. The improvement of RAM for CAT with artificial intelligence methodologies and deep learning techniques is the challenge in the near future. © 2020 Elsevier Lt

Prospective Assessment of Clinical Risk Factors and Biomarkers of Hypercoagulability for the Identification of Patients with Lung Adenocarcinoma at Risk for Cancer-Associated Thrombosis: The Observational ROADMAP-CAT Study

Background: The aim of this prospective study was to identify the most clinically relevant hypercoagulability biomarkers in lung adenocarcinoma patients for elaboration of an improved risk assessment model (RAM) for venous thromboembolism (VTE). Subjects, Materials, and Methods: One hundred fifty ambulatory patients with lung adenocarcinoma were prospectively enrolled. Thrombin generation, procoagulant phospholipid-dependent clotting time (Procoag-PPL), tissue factor activity (TFa), factor VIIa (FVIIa), factor V (FV), antithrombin, D-Dimers, P-selectin, and heparanase levels were assessed in platelet-poor plasma at inclusion (baseline) and at the end of the third chemotherapy cycle (third chemotherapy). Cox regression analysis was used to identify independent VTE predictors. Results: At baseline, patients had significantly attenuated thrombin generation, shorter Procoag-PPL, higher levels of TFa, D-Dimers, and heparanase, and lower levels of FVIIa and P-selectin, compared with controls. A significant increase in Procoag-PPL, FV, and FVIIa and a decrease of P-selectin levels were observed between baseline and third chemotherapy. Hospitalization within the last 3 months prior to assessment, time since cancer diagnosis less than 6 months, mean rate index (MRI) of thrombin generation, and Procoag-PPL were independently associated with symptomatic VTE. Accordingly, a prediction model including Procoag-PPL and MRI showed significant discriminating capacity (area under the curve: 0.84). Conclusion: Ambulatory patients with lung adenocarcinoma may display pronounced blood hypercoagulability due to decreased Procoag-PPL, increased endothelial cell activation, and increased degradation of fibrin. Incorporation of Procoag-PPL and MRI of thrombin generation may improve the accuracy of a VTE-RAM in the above setting. Implications for Practice: The prospective ROADMAP-CAT study identified two biomarkers of hypercoagulability, the procoagulant phospholipid-dependent clotting time (Procoag-PPL) and the mean rate index (MRI) of the propagation phase of thrombin generation assessed with the Calibrated Automated Thrombinoscope, as being clinically relevant for the classification of ambulatory patients with lung adenocarcinoma receiving a maximum of one cycle of chemotherapy into high and intermediate/low risk for venous thromboembolism. Measurement of Procoag-PPL and MRI within 1 month after the administration of the first chemotherapy cycle provides significant accuracy of the assessment. Association of the Procoag-PPL and MRI with the clinical risk assessment model for cancer-associated thrombosis in ambulatory patients with solid tumors (COMPASS-CAT RAM) further improved its accuracy. © AlphaMed Press 201

Longer procoagulant phospholipid-dependent clotting time, lower endogenous thrombin potential and higher tissue factor pathway inhibitor concentrations are associated with increased VTE occurrence in patients with newly diagnosed multiple myeloma: results of the prospective ROADMAP-MM-CAT study

Venous thromboembolism (VTE) is a common complication in newly diagnosed symptomatic multiple myeloma (NDMM) patients. We explored cellular and plasma hypercoagulability in NDMM patients to identify relevant biomarkers that can be used in combination with clinical factors in the development of a risk assessment model (RAM) for VTE. Untreated patients (n = 144) with NDMM were prospectively enrolled, baseline biomarkers prior to anti-myeloma treatment and thromboprophylaxis initiation were obtained. These were compared against values in a group of healthy individuals with similar age and sex distribution. The primary study end point was symptomatic VTE occurrence. At 12-month follow-up cumulative VTE rate was 10.4%. NDMM patients showed biological signs of cellular and plasma hypercoagulability and endothelial cell activation. Procoagulant phospholipid clotting time (Procoagulant-PPL) was shorter, P-selectin levels lower and thrombin generation attenuated overall compared to healthy subjects. Longer Procoag-PPL ® , lower endogenous thrombin potential (ETP), and higher levels of tissue factor pathway inhibitor (TFPI) were associated with VTE occurrence. Multivariate analysis showed that Procoag-PPL ® and ETP were independent risk factors for VTE. We conclude that Procoag-PPL ® and ETP can be prospectively incorporated into a RAM for VTE in MM in combination with clinical and disease risk factors. © 2018, The Author(s)

Derivation and Validation of a Predictive Score for Disease Worsening in Patients with COVID-19

The prospective observational cohort study COMPASS-COVID-19 aimed to develop a risk assessment model for early identification of hospitalized COVID-19 patients at risk for worsening disease. Patients with confirmed COVID-19 (n = 430) hospitalized between March 18 and April 21, 2020 were divided in derivation (n = 310) and validation (n = 120) cohorts. Two groups became evident: (1) good prognosis group (G-group) with patients hospitalized at the conventional COVID-19 ward and (2) Worsening disease group (W-group) with patients admitted to the intensive care unit (ICU) from the emergency departments. The study end point was disease worsening (acute respiratory failure, shock, myocardial dysfunction, bacterial or viral coinfections, and acute kidney injury) requiring ICU admission. All patients were routinely evaluated for full blood count, prothrombin time, fibrinogen, D-dimers, antithrombin (AT), and protein C activity. Data from the first hospitalization day at the conventional ward or the ICU were analyzed. Cardiovascular risk factors and comorbidities were routinely registered. Obesity, hypertension, diabetes and male gender, increased fibrinogen and D-dimers, thrombocytopenia, AT deficiency, lymphopenia, and an International Society on Thrombosis and Haemostasis (ISTH) score for compensated disseminated intravascular coagulation score (cDIC-ISTH) ≥ 5 were significant risk factors for worsening disease. The COMPASS-COVID-19 score was derived from multivariate analyses and includes obesity, gender, hemoglobin, lymphocyte, and the cDIC-ISTH score (including platelet count, prothrombin time, D-dimers, AT, and protein C levels). The score has a very good discriminating capacity to stratify patients at high and low risk for worsening disease, with an area under the receiver operating characteristic curve value of 0.77, a sensitivity of 81%, and a specificity of 60%. Application of the COMPASS-COVID-19 score at the validation cohort showed 96% sensitivity. The COMPASS-COVID-19 score is an accurate clinical decision-making tool for an easy identification of COVID-19 patients being at high risk for disease worsening. © 2020 Georg Thieme Verlag. All rights reserved

Improved strategies to counter the COVID-19 pandemic: Lockdowns vs. primary and community healthcare

COVID-19 pandemic mitigation strategies are mainly based on social distancing measures and healthcare system reinforcement. However, many countries in Europe and elsewhere implemented strict, horizontal lockdowns because of extensive viral spread in the community which challenges the capacity of the healthcare systems. However, strict lockdowns have various untintended adverse social, economic and health effects, which have yet to be fully elucidated, and have not been considered in models examining the effects of various mitigation measures. Unlike commonly suggested, the dilemma is not about health vs wealth because the economic devastation of long-lasting lockdowns will definitely have adverse health effects in the population. Furthermore, they cannot provide a lasting solution in pandemic containment, potentially resulting in a vicious cycle of consecutive lockdowns with in-between breaks. Hospital preparedness has been the main strategy used by governments. However, a major characteristic of the COVID-19 pandemic is the rapid viral transmission in populations with no immunity. Thus, even the best hospital system could not cope with the demand. Primary, community and home care are the only viable strategies that could achieve the goal of pandemic mitigation. We present the case example of Greece, a country which followed a strategy focused on hospital preparedness but failed to reinforce primary and community care. This, along with strategic mistakes in epidemiological surveillance, resulted in Greece implementing a second strict, horizontal lockdown and having one of the highest COVID-19 death rates in Europe during the second wave. We provide recommendations for measures that will reinstate primary and community care at the forefront in managing the current public health crisis by protecting hospitals from unnecessary admissions, providing primary and secondary prevention services in relation to COVID-19 and maintaining population health through treatment of non−COVID-19 conditions. This, together with more selective social distancing measures (instead of horizontal lockdowns), represents the only viable and realistic long-term strategy for COVID-19 pandemic mitigation. © 2020 The Author

Risk for Venous Thromboembolic Events in Patients With Advanced Urinary Tract Cancer Treated With First-Line Chemotherapy

We identified the incidence and risk factors of venous thromboembolism in 335 chemotherapy-treated patients with urothelial cancer. The Khorana risk score did not accurately predict risk for thromboembolic events; on the contrary, history of vascular events was associated with a 3-fold increase of this risk. The role of prophylaxis in this group should be further studied. © 2020 Elsevier Inc. Background: Venous thromboembolic events (VTEs) frequently occur in cancer patients. Risk assessment models (RAMs) for cancer-associated thrombosis have been proposed. However, advanced urinary tract cancer (aUTC) was not adequately represented in these models. We studied the incidence of VTEs, the risk factors, and the applicability of recently described RAMs. Patients and Methods: Data from 335 patients with aUTC treated with chemotherapy between April 1995 and September 2015 in a single institution were analyzed. Results: A total of 95.2% received platinum-based first-line chemotherapy. Twenty-nine patients (8.7%) experienced VTEs. The 6-, 12-, and 24-month VTE incidence was 7.4% (95% confidence interval [CI], 4.8-10.6), 8.1% (95% CI, 5.4-11.5) and 9.4% (95% CI, 6.4-13.1), respectively. No significant association of VTE incidence with the Khorana risk score was observed. History of vascular event (VTE and/or arterial thromboembolic event) was significantly associated with the development of VTE. Patients with such history had a 6-, 12-, and 24-month VTE incidence of 16.2% (95% CI, 6.6-29.7), 19.2% (95% CI, 8.4-33.3), and 25.2% (95% CI, 12.5-40.1) compared to 6.2% (95% CI, 3.7-9.4), 6.6% (95% CI, 4.1-10), and 7.1% (95% CI, 4.4-10.6) of those who did not. The discriminatory ability of this factor adjusted for leucocyte count, sex, Eastern Cooperative Oncology Group performance status, and type of chemotherapy reached 0.79 (95% CI, 0.71-0.87) compared to the 0.58 (95% CI, 0.49-0.66) for the Khorana risk score. Conclusion: Development of tumor-specific algorithms for the risk of VTEs is advisable. Patients with aUTC and a history of vascular events are at high risk for VTE development, and prophylaxis should be prospectively studied in this group. © 2020 Elsevier Inc

A RAND/UCLA-Modified VAS Study on Telemedicine, Telehealth, and Virtual Care in Daily Clinical Practice of Vascular Medicine

Background: Telemedicine is increasingly used in several fields of healthcare, including vascular medicine. This study aimed to investigate the views of experts and propose clinical practice recommendations on the possible applications of telemedicine in vascular medicine. Methods: A clinical guidance group proposed a set of 67 clinical practice recommendations based on the synthesis of current evidence and expert opinion. The Telemedicine Vascular Medicine Working Group included 32 experts from Europe evaluating the appropriateness of each clinical practice recommendation based on published RAND/UCLA methodology in two rounds. Results: In the first round, 60.9% of clinical practice recommendations were rated as appropriate, 35.9% as uncertain, and 3.1% as inappropriate. The strongest agreement (a median value of 10) was reached on statements regarding the usefulness of telemedicine during the 2019 coronavirus disease (COVID-19) pandemic, its usefulness for geographical areas that are difficult to access, and the superiority of video calls compared to phone calls only. The lowest degree of agreement (a median value of 2) was reported on statements regarding the utility of telemedicine being limited to the COVID-19 pandemic and regarding the applicability of teleconsultation in the diagnosis and management of abdominal aortic aneurysm. In the second round, 11 statements were re-evaluated to reduce variability. Conclusions: This study highlights the levels of agreement and the points that raise concern on the use of telemedicine in vascular medicine. It emphasizes the need for further clarification on various issues, including infrastructure, logistics, and legislation.SCOPUS: ar.jinfo:eu-repo/semantics/publishe