Novel Insights in Venous Thromboembolism Risk Assessment Methods in Ambulatory Cancer Patients: From the Guidelines to Clinical Practice.

Many cancer patients will experience venous thromboembolism (VTE) at some stage, with the highest rate in the initial period following diagnosis. Novel cancer therapies may further enhance the risk. VTE in a cancer setting is associated with poor prognostic, a decreased quality of life, and high healthcare costs. If thromboprophylaxis in hospitalized cancer patients and perioperative settings is widely accepted in clinical practice and supported by the guidelines, it is not the same situation in ambulatory cancer patient settings. The guidelines do not recommend primary thromboprophylaxis, except in high-risk cases. However, nowadays, risk stratification is still challenging, although many tools have been developed. The Khrorana score remains the most used method, but it has many limits. This narrative review aims to present the current relevant knowledge of VTE risk assessment in ambulatory cancer patients, starting from the guideline recommendations and continuing with the specific risk assessment methods and machine learning models approaches. Biomarkers, genetic, and clinical features were tested alone or in groups. Old and new models used in VTE risk assessment are exposed, underlining their clinical utility. Imaging and biomolecular approaches to VTE screening of outpatients with cancer are also presented, which could help clinical decisions.

Thrombosis risk assessment in patients with congenital thrombophilia during COVID - 19 infection.

BACKGROUND: Coagulation dysfunction represents a serious complication in patients during the COVID-19 infection, while fulminant thrombotic complications emerge as critical issues in individuals with severe COVID-19. In addition to a severe clinical presentation, comorbidities and age significantly contribute to the development of thrombotic complications in this disease. However, there is very little data on association of congenital thrombophilia and thrombotic events in the setting of COVID-19. Our study aimed to evaluate the risk of COVID-19 associated thrombosis in patients with congenital thrombophilia. METHODS: This prospective, case-control study included patients with confirmed COVID-19 infection, followed 6 months post-confirmation. The final outcome was a symptomatic thrombotic event. In total, 90 COVID-19 patients, 30 with known congenital thrombophilia and 60 patients without thrombophilia within the period July 2020-November 2021, were included in the study. Evaluation of hemostatic parameters including FVIII activity and D-dimer was performed for all patients at 1 month, 3 months and 6 months post-COVID-19 diagnosis. RESULTS: Symptomatic thrombotic events were observed in 7 out of 30 (23 %) COVID-19 patients with thrombophilia, and 12 out of 60 (20 %) without thrombophilia, P = 0.715. In addition, the two patient groups had comparable localization of thrombotic events, time to thrombotic event, effect of antithrombotic treatment and changes in FVIII activity, while D-dimer level were significantly increased in patients without thrombophilia. CONCLUSION: Our findings suggest that patients with congenital thrombophilia, irrespective of their age, a mild clinical picture and absence of comorbidities, should receive anticoagulant prophylaxis, adjusted based on the specific genetic defect.

The risk of venous thromboembolism in early pregnancy loss: Review of the literature and current guidelines and the need for guidance - Communication from the SSC on Women's Health Issues for thrombosis and haemostasis.

BACKGROUND: Thromboembolic disease is one of the major causes of mortality and morbidity in pregnancy and the puerperium, with 1 death per 100 000 births attributed to venous thromboembolism (VTE). Factors associated with development of thrombosis are all present in pregnancy, with some of these changes seen from conception. OBJECTIVE: Given how common early pregnancy loss is, the aim of this review is to evaluate the uncertainty surrounding the risk of VTE following early pregnancy loss and termination of pregnancy. METHODS: A structured literature search was conducted to identify existing evidence as well as international pregnancy-specific guidelines regarding assessment and prevention of VTE risk in pregnant women. This review was reviewed, critiqued, and approved by all members of the International Society on Thrombosis and Haemostasis subcommittee for Women's Health Issues in Thrombosis and Haemostasis. RESULTS: Four published original research studies, one clinical comment paper, and six guidelines were reviewed. Despite clear evidence of the increased risk of VTE in pregnancy, there is a lack of guidance regarding evaluation and management after early pregnancy loss. CONCLUSION: International collaborative research to determine the risk of VTE and its prevention in women undergoing surgical termination of pregnancy or following surgical management of early pregnancy loss is urgently needed. Pregnancy-specific risk assessment taking into account preexisting risk factors is advocated. Education of health care professionals involved in early pregnancy care and guidance on management, albeit based on limited existing evidence, are necessary to highlight the need for individualized care.

Validation of the Khorana Venous Thromboembolism Risk Score in Japanese Cancer Patients.

Background: Although the Khorana venous thromboembolism (VTE) risk score (KRS) is well recognized as a simple VTE risk assessment method in patients with cancer, whether it is suitable for Asian populations is unclear. Objectives: This study validated KRS for the prediction of VTE and investigated the value of the KRS in predicting mortality in Japanese patients with cancer. Methods: A body mass index value of 25 kg/m2 or more was defined as obesity according to World Health Organization consensus. A total of 27,687 patients with cancer were subdivided into low- (0), intermediate- (1-2), and high-score (3) groups by the KRS. The primary and secondary endpoints were VTE and all-cause mortality, respectively. Results: The prevalence of VTE was 1.7%, 7.3%, and 11.0% for low-, intermediate-, and high-score patients, respectively. Receiver operating characteristic (ROC) analysis showed that the KRS significantly predicted VTE (area under the curve, 0.679; 95% confidence interval [CI] 0.666-0.692; P < 0.001). The cutoff value for the KRS was 1.0. Logistic regression analysis demonstrated that the KRS was an independent predictor of VTE (odds ratio 1.766; 95% CI 1.673-1.865; P < 0.01). The cutoff value of the KRS for all-cause mortality determined by ROC analysis was 2.0. Kaplan-Meier analysis demonstrated a significantly higher incidence of mortality in the KRS ≥2 group than in the KRS 0-1 group (log-rank: P < 0.01). Conclusions: The KRS was useful in Japanese patients with cancer and might be a potentially useful marker for the prediction of mortality. Establishing optimal scores for Japanese subjects is mandatory because of its low diagnostic ability. (KUMAMON Cancer registry; UMIN000047554).

Two pulmonary emboli in a psych pod.

BACKGROUND: A female patient known to have schizoaffective disorder self-presented to an emergency department in a state of acute agitation and paranoia shortly after a 35-day inpatient stay at a psychiatric facility. CASE REPORT: The patient exhibited no signs or complaints of dyspnea or hypoxia, but later collapsed and became hypoxic after sleeping comfortably with sedation for 12 h in the psychiatric unit. She was intubated and a computed tomography angiogram revealed bilateral lobar pulmonary emboli and right heart strain. CONCLUSION: Psychiatric hospitalizations, medications, diagnoses and relevant sequelae increase venous thromboembolism risk more than many realize.

Evaluation of risk factors and assessment models for predicting venous thromboembolism in lung cancer patients.

The aim of the study was to investigate the prognostic significance of selected risk assessment models (RAMs) for predicting venous thromboembolism (VTE) events in patients undergoing outpatient chemotherapy for lung cancer. We evaluated the following VTE-risk assessment tools: Khorana risk score (KRS), PROTECHT score, CONKO score and COMPASS-cancer-associated thrombosis score (COMPASS-CAT). Retrospective analyses were performed on 118 patients with lung cancer, 20 of whom developed VTE with a median of 2.5 months from diagnosis. Patients receiving gemcitabine-based regimen (25%), patients with a history of atrial fibrillation (AF) and patients with chronic kidney disease developed VTE more often than other patients. In the multivariate analysis, high COMPASS-CAT score (OR 8.73; 95% CI 1.01-75.22, P = 0.049), gemcitabine chemotherapy (OR 3.37; 95% CI 1.09-10.39, P = 0.035) and AF (OR 7.19; 95% CI 1.89-27.33, P = 0.004) were all significantly associated with VTE development. VTE occurred in; 13% (n = 2) of the KRS high-risk group, 17.7% (n = 11) of the PROTECHT high-risk group, 15% (n = 4) of the CONKO high-risk group and 23.8% (n = 20) of the COMPASS-CAT high-risk group (n = 84). Only the COMPASS-CAT score was able to identify 100% of patients who developed VTE, and best discriminated between patients with high and low risk of VTE development (C statistic 0.89). The ROC analysis indicated a cutoff value of 11 points (95% CI 0.821-0.962) for COMPASS-CAT for VTE development in patients with lung cancer. In conclusion, in our study of all the VTE-RAMs analyzed, the COMPASS-CAT model was the most accurate predictor of VTE development in patients with lung cancer.

Evaluation of the ThroLy score for the prediction of venous thromboembolism in newly diagnosed patients treated for lymphoid malignancies in clinical practice.

The utility in clinical practice of a recently developed and validated predictive model for venous thromboembolism (VTE) events in lymphoma patients, known as the thrombosis lymphoma (ThroLy) score, is unknown. We evaluated the association of ThroLy with VTE in patients treated for diffuse large B-cell lymphoma (DLBCL) or Hodgkin lymphoma (HL) undergoing ambulatory first-line chemotherapy. Retrospective analyses were performed on 428 patients (median age 50), 241 were newly diagnosed DLBCL, and 187 had HL. During initial chemotherapy, 64 (15%) patients developed VTE. According to the ThroLy, 322 (75.2%) patients were considered low risk, 88 (20.6%) patients had intermediate risk and 18 (4.2%) patients high risk for VTE development. Patients with DLBCL were more often in the high-risk ThroLy group and had more VTE events than HL. VTE occurred in; 38.9% (n = 7) high-risk patients, 29.5% (n = 26) intermediate risk, and 9.6% (n = 31) low risk according to the ThroLy score. However, in multivariate analysis, high ThroLy (OR 5.13; 95% CI: 1.83-14.36, P = .002), intermediate ThroLy (OR 3.96; 95% CI: 2.19-7.17, P < .001), and aggressive lymphoma-DLBCL (OR 1.91; 95% CI: 1.05-3.47, P = .034) were all significantly associated with development of VTE, 48% of the VTE events occurred in the low-risk ThroLy score group (the ROC AUC (95% CI) 0.40-0.70 and C statistic-0.55). In our study, the ThroLy score was not a suitably accurate model for predicting VTE events in patients at higher risk of VTE. Further research should be conducted to identify new biomarkers that will predict these events and to establish a new VTE risk assessment model.

Concordance among venous thromboembolism risk assessment models. / Concordancia entre las escalas de predicción de riesgo de tromboembolia venosa.

BACKGROUND AND OBJECTIVES: There are a lot of venous thromboembolism risk assessment models with the aim of predicting the individual risk of venous thromboembolism (VTE), although most have not been externally validated. The objective of our study was to analyse the concordance among the Padua, PRETEMED, IMPROVE and MEDENOX scores. PATIENTS AND METHODS: Observational cohort study with 602 patients admitted to Medical Services of the Hospital Universitario Santa Lucía. Concordance was calculated using the kappa index (KI) between the four risk prediction scales and the VTE occurring within 90 days of hospitalisation. RESULTS: Patients considered were those with a high risk of VTE, 78%, 56%, 69% and 59% according to Padua, PRETEMED, IMPROVE and MEDENOX scores respectively. A KI=0.60 was observed among Padua-IMPROVE scores; KI=0.44 among IMPROVE-PRETEMED, KI=0.43 among PRETEMED-MEDENOX, KI=0.33 among Padua-PRETEMED, KI=0.27 among IMPROVE-MEDENOX and a KI=0.24 among Padua-MEDENOX. During follow-up, nine cases of VTE (1.5%) were observed. CONCLUSIONS: The highest degree of agreement was observed among the Padua and IMPROVE scores. There is no good agreement between any of the predictive risk scales for VTE in medical patients. The Padua score was the best predictor of VTE episodes at 90 days among high risk patients.

Thrombin Generation Assay in Hospitalized Nonsurgical Patients: A New Tool to Assess Venous Thromboembolism Risk?

BACKGROUND: Assessment of venous thromboembolism (VTE) risk is important to determine optimal primary prophylaxis in hospitalized patients. The Padua score helps to recognize patients with high VTE risk, but quantifying a VTE risk is often challenging in medical patients. Thrombin generation assay (TGA) reflects the pro-/anticoagulant balance and thus could help to better quantify VTE risk in medical hospitalized patients. AIM: To analyze the relation between TGA and VTE risk according to Padua score in medical hospitalized patients. METHODS: Between May and October 2013, 105 patients were included in an unselected cohort group of patients admitted to an internal medicine department in a large, university hospital. Within the 36 hours after admission and before any anticoagulant therapy, Padua score was calculated and sample for TGA was collected for each patient. Thrombin generation assay (velocity, peak, and endogenous thrombin potential [ETP]) was performed with 1 and 5 picomol/l (pM) tissue factor (TF) reagent. RESULTS: In patients with high Padua score (n = 29), velocity, peak, and ETP differed from patients with low Padua score. This difference was present at 1 and 5 pM TF, in ETP (P < .0001 and P = .003 respectively), in peak (P < .0001 in both conditions), and in velocity (P < .0001). According to multivariate analysis, myeloid disorders, older age, higher body mass index, myocardial infarction, C-reactive protein >5 mg/L, reduced mobility with bed rest significantly increased velocity 1 pM TF value. CONCLUSION: Single thrombin generation measurement could help to identify patients at risk of VTE in medical hospitalized patients.

Risk Factors, Prophylaxis, and Treatment of Venous Thromboembolism in Congenital Heart Disease Patients.

Congenital heart disease (CHD) is a common condition in the pediatric population, affecting up to 1% of all live births (i.e., around 40,000 newborns/year in the United States). Although CHD does have a wide range of severity, by the age of 5 years approximately 80% of patients will require at least one surgical intervention to achieve a complete/palliative cardiac repair. Today, in light of their much-improved surgical survival, the care of these patients focuses on morbidity prevention and/or treatment. One such morbidity has been the increased frequency of thrombotic occlusions [e.g., cardioembolic arterial ischemic strokes; arterial, cardiac, and/or newly created shunt thrombosis; venous thromboembolism (VTE)]. Patients with CHD are at high risk of developing thrombosis due to the disruption of blood flow, CHD-related coagulopathy, inflammation, and/or platelet activation secondary to extracorporeal circulation support required during open-heart surgery or as a bridge to recovery, which can increase thrombus formation. In this article, we will discuss how the coagulation system is altered in patients with CHD in regard to the patient's anatomy, procedures they undergo to correct their congenital heart defect, and other risk factors that may increase their thrombotic risk, focusing on VTE. We will also discuss the most recently published reports pertaining to guidelines on prophylaxis and treatment of VTE in this population. Finally, we will briefly address the long-term VTE outcomes for patients with CHD.

Estratificação do risco de tromboembolismo venoso em pacientes vítimas de traumas ortopédicos / Risk stratification of venous thromboembolism in orthopedic traumas patients / Estratificación del riesgo de tromboembolismo venoso en pacientes con traumas ortopédicos

Objetivo: identificar a estratificação de risco para tromboembolismo venoso em pacientes de traumas ortopédicos. Método: estudo de abordagem quantitativa, descritivo, do tipo transversal, com dados coletados de março a agosto de 2021 e risco de tromboembolismo venoso baseado na escala de Pádua e na escala de Caprini. Resultados: a amostra do estudo foi de 216 pacientes, composta pela maioria do sexo masculino, com a mediana de idade de 37 anos. Em relação a gravidade do paciente, 60,19% foram classificados como atendimento de urgência e o tipo de acidente mais frequente foi o motociclístico. A região mais acometida em decorrência do trauma foi a perna e a coxa, sendo descritos os principais determinantes para a elevação da escala. Conclusão: o tromboembolismo venoso é um evento passível de atenção e cuidados para a prevenção. Por isso, a avaliação para estratificação de risco deve ser realizada para todos os pacientes vítimas de traumas ortopédicos.

Objective: to identify stratification of venous thromboembolism risk in orthopedic trauma patients. Method: in this quantitative, descriptive, cross-sectional study, data were collected from March to August 2021 and risk of venous thromboembolism based on the Padua and Caprini scales. Results: the study sample of 216, mostly male, patients were of median age 37 years. The patients were classified, by severity, as 60.19% emergency care and motorcycle accidents were the most frequent type. Leg and thigh were the region most affected by trauma and the main determinants for raising the scale were described. Conclusion: venous thromboembolism is an event amenable to preventive attention and care. Risk stratification assessment should thus be performed for all orthopedic trauma patients.

Objetivo: identificar la estratificación del riesgo de tromboembolismo venoso en pacientes de traumas ortopédicos. Método: estudio de enfoque cuantitativo, descriptivo, transversal, con datos recolectados de marzo a agosto de 2021 y riesgo de tromboembolismo venoso con base en la escala de Padua y la escala de Caprini. Resultados: la muestra del estudio estuvo constituida por 216 pacientes, en su mayoría del sexo masculino, con un promedio de edad de 37 años. En cuanto a la gravedad del paciente, el 60,19% se clasificó como atención de urgencia y el tipo de accidente más frecuente fue el de motocicleta. La región más afectada a consecuencia del traumatismo fue la pierna y el muslo, y se describieron los principales determinantes para la elevación de la escala. Conclusión: el tromboembolismo venoso es un evento que requiere atención y cuidados para su prevención. Por lo tanto, se debe realizar una evaluación de la estratificación del riesgo para todos los pacientes víctimas de traumas ortopédicos.

Integrin beta-3 genetic variants and risk of venous thromboembolism in colorectal cancer patients.

BACKGROUND: Integrin ß3 is involved in tumor and endothelial cell biology as well as in platelet aggregation. Herein, we evaluated the predictive potential of three germline single nucleotide polymorphisms (SNPs) in the integrin ß3 gene (rs3809865, rs5918 and rs4642) to predict the risk of venous thromboembolism (VTE) in colorectal cancer (CRC) patients, which is one of the leading causes of death among cancer patients. METHODS: 112 patients diagnosed with CRC enrolled in the prospective Vienna Cancer and Thrombosis Study (CATS) were assessed with a median follow-up of 46 months. DNA was isolated from venous blood samples and SNPs were analyzed by the PCR-RFLP method. RESULTS: VTE occurred in 12% (n=13) of all patients. The SNPs rs5918 and rs4642 were not associated with VTE risk. For rs3809565, 23% (n=11) of patients had the A/A genotype, 4% (n=2) had the A/T genotype, but none (0%) had the T/T genotype. In the univariate analysis, patients with the A/A genotype had a significantly higher risk to develop VTE compared to the other polymorphisms (P=0.0005 after Fine and Gray). In the multivariable analysis, the predictive value remained significant. CONCLUSIONS: This study identified the rs3809865 A/A genotype as an independent risk factor for VTE in CRC patients. Our findings would help identify high risk patients and would be essential for tailored anticoagulant prophylaxis.

External validation of a risk assessment model for venous thromboembolism in the hospitalised acutely-ill medical patient (VTE-VALOURR).

Venous thromboembolic (VTE) risk assessment remains an important issue in hospitalised, acutely-ill medical patients, and several VTE risk assessment models (RAM) have been proposed. The purpose of this large retrospective cohort study was to externally validate the IMPROVE RAM using a large database of three acute care hospitals. We studied 41,486 hospitalisations (28,744 unique patients) with 1,240 VTE hospitalisations (1,135 unique patients) in the VTE cohort and 40,246 VTE-free hospitalisations (27,609 unique patients) in the control cohort. After chart review, 139 unique VTE patients were identified and 278 randomly-selected matched patients in the control cohort. Seven independent VTE risk factors as part of the RAM in the derivation cohort were identified. In the validation cohort, the incidence of VTE was 0.20%; 95% confidence interval (CI) 0.18-0.22, 1.04%; 95%CI 0.88-1.25, and 4.15%; 95%CI 2.79-8.12 in the low, moderate, and high VTE risk groups, respectively, which compared to rates of 0.45%, 1.3%, and 4.74% in the three risk categories of the derivation cohort. For the derivation and validation cohorts, the total percentage of patients in low, moderate and high VTE risk occurred in 68.6% vs 63.3%, 24.8% vs 31.1%, and 6.5% vs 5.5%, respectively. Overall, the area under the receiver-operator characteristics curve for the validation cohort was 0.7731. In conclusion, the IMPROVE RAM can accurately identify medical patients at low, moderate, and high VTE risk. This will tailor future thromboprophylactic strategies in this population as well as identify particularly high VTE risk patients in whom multimodal or more intensive prophylaxis may be beneficial.