Venous thromboembolism (VTE) is a significant health problem in the general population but especially in cancer patients. In this review, we discuss the epidemiology and burden of the disease, the ...pathophysiology of cancer-associated VTE, and the clinical treatment options for both primary prevention and acute treatment. Overall, the development of VTE in cancer patients is related to increases in morbidity, mortality, and medical costs. However, the incidence of cancer-associated VTE varies due to patient-related factors (e.g. thrombophilia, comorbidities, performance status, history of venous diseases), tumour-related factors (e.g. cancer site, stage, grade), and treatment-related factors (e.g. surgery, chemotherapy, anti-angiogenesis treatment, hormonal and supportive treatment). Furthermore, blood count parameters (e.g. platelets and leukocytes) and biomarkers (e.g. soluble P-selectin and D-dimer) are predictive markers for the risk of VTE in cancer patients and have been used to enhance risk stratification. Evidence suggests that cancer itself is associated with a state of hypercoagulability, driven in part by the release of procoagulant factors, such as tissue factor, from malignant tissue as well as by inflammation-driven activation of endothelial cells, platelets, and leukocytes. In general, low-molecular-weight heparin (LWMH) monotherapy is the standard of care for the management of cancer-associated VTE, as vitamin K antagonists are less effective in cancer patients. Direct oral anticoagulants (DOACs) offer a potentially promising treatment option for cancer patients with VTE, but recommendations concerning the routine use of DOACs should await head-to-head studies with LMWH.
Venous thromboembolism (VTE) is frequently observed in patients with coronavirus disease 2019 (COVID‐19). However, reported VTE rates differ substantially.
We aimed at evaluating available data and ...estimating the prevalence of VTE in patients with COVID‐19.
We conducted a systematic literature search (MEDLINE, EMBASE, World Health Organization COVID‐19 database) to identify studies reporting VTE rates in patients with COVID‐19. Studies with suspected high risk of bias were excluded from quantitative synthesis. Pooled outcome rates were obtained within a random effects meta‐analysis. Subgroup analyses were performed for different settings (intensive care unit ICU vs non‐ICU hospitalization and screening vs no screening) and the association of d‐dimer levels and VTE risk was explored.
Eighty‐six studies (33,970 patients) were identified and 66 (28,173 patients, mean age: 62.6 years, 60.1% men, 19.4% ICU patients) were included in quantitative analysis. The overall VTE prevalence estimate was 14.1% (95% confidence interval CI, 11.6‐16.9), 40.3% (95% CI, 27.0‐54.3) with ultrasound screening and 9.5% (95% CI, 7.5‐11.7) without screening. Subgroup analysis revealed high heterogeneity, with a VTE prevalence of 7.9% (95% CI, 5.1‐11.2) in non‐ICU and 22.7% (95% CI, 18.1‐27.6) in ICU patients. Prevalence of pulmonary embolism (PE) in non‐ICU and ICU patients was 3.5% (95% CI, 2.2‐5.1) and 13.7% (95% CI, 10.0‐17.9). Patients developing VTE had higher d‐dimer levels (weighted mean difference, 3.26 µg/mL; 95% CI, 2.76‐3.77) than non‐VTE patients.
VTE occurs in 22.7% of patients with COVID‐19 in the ICU, but VTE risk is also increased in non‐ICU hospitalized patients. Patients developing VTE had higher d‐dimer levels. Studies evaluating thromboprophylaxis strategies in patients with COVID‐19 are needed to improve prevention of VTE.
Cancer patients are at increased risk of deep vein thrombosis and pulmonary embolism. The incidence among different groups of cancer patients varies considerably depending on clinical factors, the ...most important being tumor entity and stage. Biomarkers have been specifically investigated for their capacity of predicting venous thromboembolism (VTE) during the course of disease. Parameters of blood count analysis (elevated leukocyte and platelet count and decreased hemoglobin) have turned out to be useful in risk prediction. Associations between elevated levels and future VTE have been found for d-dimer, prothrombin fragment 1+2, and soluble P-selectin and also for clotting factor VIII and the thrombin generation potential. The results for tissue factor–bearing microparticles are heterogeneous: an association with occurrence of VTE in pancreatic cancer might be present, whereas in other cancer entities, such as glioblastoma, colorectal, or gastric carcinoma, this could not be confirmed. Risk assessment models were developed that include clinical and laboratory markers. In the high-risk categories, patient groups with up to a >20% VTE rate within 6 months can be identified. A further improvement in risk stratification would allow better identification of patients for primary VTE prevention using indirect or novel direct anticoagulants.
Biomarkers and venous thromboembolism Pabinger, Ingrid; Ay, Cihan
Arteriosclerosis, thrombosis, and vascular biology
29, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Venous thromboembolism (VTE) represents a significant health concern because of its high morbidity and mortality and is moreover characterized by high rates of recurrence. It would be useful to know ...biomarkers that enable early identification of patients at high or low risk of primary and recurrent VTE. Various established and novel biomarkers associated with VTE have been investigated with regard to their potential for predicting primary or recurrent VTE, for facilitating the diagnosis and for optimizing the clinical management of VTE. In this review, data on selected biomarkers (D-Dimer, soluble P-selectin, coagulation factor VIII, inflammatory markers and thrombin generation) having procoagulant properties or reflecting a prothrombotic state are summarized, and their role in clinical application is discussed.
Summary Venous thromboembolism (VTE) is the second leading cause of death in patients with cancer. These patients are at an increased risk of developing VTE and are more likely to have a recurrence ...of VTE and bleeding while taking anticoagulants. Management of VTE in patients with cancer is a major therapeutic challenge and remains suboptimal worldwide. In 2013, the International Initiative on Thrombosis and Cancer (ITAC-CME), established to reduce the global burden of VTE in patients with cancer, published international guidelines for the treatment and prophylaxis of VTE and central venous catheter-associated thrombosis. The rapid global adoption of direct oral anticoagulants for management of VTE in patients with cancer is an emerging treatment trend that needs to be addressed based on the current level of evidence. In this Review, we provide an update of the ITAC-CME consensus recommendations based on a systematic review of the literature ranked according to the Grading of Recommendations Assessment, Development, and Evaluation scale. These guidelines aim to address in-hospital and outpatient cancer-associated VTE in specific subgroups of patients with cancer.
Cancer-associated thrombosis (including venous thromboembolism (VTE) and arterial events) is highly consequential for patients with cancer and is associated with worsened survival. Despite ...substantial improvements in cancer treatment, the risk of VTE has increased in recent years; VTE rates additionally depend on the type of cancer (with pancreas, stomach and primary brain tumours having the highest risk) as well as on individual patient's and cancer treatment factors. Multiple cancer-specific mechanisms of VTE have been identified and can be classified as mechanisms in which the tumour expresses proteins that alter host systems, such as levels of platelets and leukocytes, and in which the tumour expresses procoagulant proteins released into the circulation that directly activate the coagulation cascade or platelets, such as tissue factor and podoplanin, respectively. As signs and symptoms of VTE may be non-specific, diagnosis requires clinical assessment, evaluation of pre-test probability, and objective diagnostic testing with ultrasonography or CT. Risk assessment tools have been validated to identify patients at risk of VTE. Primary prevention of VTE (thromboprophylaxis) has long been recommended in the inpatient and post-surgical settings, and is now an option in the outpatient setting for individuals with high-risk cancer. Anticoagulant therapy is the cornerstone of therapy, with low molecular weight heparin or newer options such as direct oral anticoagulants. Personalized treatment incorporating risk of bleeding and patient preferences is essential, especially as a diagnosis of VTE is often considered by patients even more distressing than their cancer diagnosis, and can severely affect the quality of life. Future research should focus on current knowledge gaps including optimizing risk assessment tools, biomarker discovery, next-generation anticoagulant development and implementation science.
The risk of venous thromboembolism (VTE) is increased in cancer patients. To improve prediction of VTE in cancer patients, we performed a prospective and observational cohort study of patients with ...newly diagnosed cancer or progression of disease after remission. A previously developed risk scoring model for prediction of VTE that included clinical (tumor entity and body mass index) and laboratory (hemoglobin level and thrombocyte and leukocyte count) parameters was expanded by incorporating 2 biomarkers, soluble P-selectin, and D-Dimer. Of 819 patients 61 (7.4%) experienced VTE during a median follow-up of 656 days. The cumulative VTE probability in the original risk model after 6 months was 17.7% in patients with the highest risk score (≥ 3, n = 93), 9.6% in those with score 2 (n = 221), 3.8% in those with score 1 (n = 229), and 1.5% in those with score 0 (n = 276). In the expanded risk model, the cumulative VTE probability after 6 months in patients with the highest score (≥ 5, n = 30) was 35.0% and 10.3% in those with an intermediate score (score 3, n = 130) as opposed to only 1.0% in patients with score 0 (n = 200); the hazard ratio of patients with the highest compared with those with the lowest score was 25.9 (8.0-84.6). Clinical and standard laboratory parameters with addition of biomarkers enable prediction of VTE and allow identification of cancer patients at high or low risk of VTE.
Cases of unusual thrombosis and thrombocytopenia after administration of the ChAdOx1 nCoV‐19 vaccine (AstraZeneca) have been reported. The term vaccine‐induced prothrombotic immune thrombocytopenia ...(VIPIT) was coined to reflect this new phenomenon. In vitro experiments with VIPIT patient sera indicated that high‐dose intravenous immunoglobulins (IVIG) competitively inhibit the platelet‐activating properties of ChAdOx1 nCoV‐19 vaccine induced antibodies. Here, we report a case of a 62‐year‐old woman who had received this vaccine and developed VIPIT. She visited the emergency ward because of petechiae and hematomas. In the laboratory work‐up, thrombocytopenia, low fibrinogen, elevated D‐dimer, and positivity in the platelet factor 4/heparin‐enzyme‐immunoassay were present. Signs and symptoms of thrombosis were absent. Upon immediate therapy with non‐heparin anticoagulation, high‐dose IVIG, and prednisolone, laboratory parameters steadily improved and the patient was discharged from hospital without thrombotic complications. We conclude that early initiation of VIPIT treatment results in a swift response without thrombotic complications.
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