Thromboembolic Complications In Cancer Patients Research Articles

Venous thromboembolitic complications in children and adults with permanent venous access (literature review)

Introduction. Over the past decades, permanent venous access devices, in particular port systems and peripherally implanted central catheters, has been increasingly introduced in adult and pediatric oncology. As far as central catheters and permanent access devices are foreign bodies in basic veins, quite naturally that they are one more risk factor for thrombosis.Material and methods. The authors searched literature data ( in Russian and English) for the period up to May 3, 2022 using public databases (Embase, Medline/PubMed, Researchgate, medrxiv.org, RSCI/eLibrary). The following keywords were used for the search: “port-system”, “peripherally implanted central catheter”, “totally implanted vascular access device”, “venous thromboembolism”, “VTE”, “venous thromboembolic complications”, “VTEC”, “catheter dysfunction”, “device malfunction”. Available preprints, articles with “in press” or “online first” status, and clinical cases were also included in the analysis.Conclusion. This review discusses prevention, diagnostics and treatment of venous thromboembolic complications in cancer patients using similar implantable devices. In patients with catheter-associated thromboses, of practical interest are various diagnostic and curative algorithms, recommendations on the choice of vascular access, medicamentous therapy as well as variants of surgical intervention.

Expanding the possibilities of treatment and prevention of venous thromboembolic complications in cancer patients. The role of oral anticoagulants

Improving the quality of care for patients with oncological diseases due to the improvement of methods of chemoradiotherapy and surgical interventions, accessibility and modernization of diagnostic potential, is accompanied by a steady increase in the frequency of venous thromboembolic complications, which occupy one of the leading places among the causes of death.Patients with oncological diseases are subject to various risk factors for thromboembolic complications, which are caused by the presence of a malignant neoplasm, due to the development of many coagulation abnormalities, initiating not only an increased tendency to thrombosis, but also a tendency to bleeding. Cancer-associated venous thrombosis, growing out of the framework of certain medical specialties, act as comorbid pathological conditions that require an interdisciplinary approach in developing rational methods of prevention and treatment. Improving the understanding of the pathophysiological mechanisms of venous thrombosis in cancer patients contributes to the development of modern methods of prevention and treatment, among which anticoagulant therapy plays a dominant role. The appearance of oral anticoagulants on the pharmaceutical market, the effectiveness and safety of which is confirmed by a series of randomized clinical trials, opens up new prospects for improving the quality of life and long-term survival in patients with malignant neoplasms.

Increased risk of venous thrombosis in breast cancer patients receiving chemotherapy treatment after COVID-19.

e24106 Background: Immune suppression and coagulopathy development in cancer patients receiving chemotherapy determines a high incidence of complications, including venous thrombosis, and mortality from COVID-19 infection. There are still no explicit data on managing cancer patients when anticancer treatment is resumed after coronavirus disease. According to clinical guidelines for the prevention of venous thromboembolic complications in cancer patients receiving chemotherapy, patients with breast cancer are classified as having a low risk of these complications and do not require prophylactic anticoagulation. The purpose of this study was to assess the parameters of the blood coagulation system and the frequency of venous thrombosis in breast cancer patients with chemotherapy resumption after coronavirus disease. Methods: The study included 30 patients receiving anticancer medical therapy for breast cancer after COVID-19. Anticancer treatment was resumed no earlier than 4 weeks after clinical recovery, absence of SARS-CoV-2 RNAs in nasopharyngeal swabs, infiltrative lung damage according to a chest CT scan, exclusion of venous thrombosis by a lower extremity venous ultrasound. Control group included 20 breast cancer patients without a history of COVID-19. Stage I tumors were registered in 26.6% in the main group vs 15% controls; II - 40% vs 60%; III - 20% vs 15%. Some patients were diagnosed with distant metastases (stage IV- 13.3% vs 10%). Results: Initially, before chemotherapy resumption in the main group, half of the patients had elevated levels of fibrinogen and D-dimer compared with the control group (66.7% vs. 35%, p > 0.05). After a cycle of chemotherapy, a significant difference in the coagulation system parameters was noted (73.3% vs 30%). A lower extremity venous ultrasound after the end of the therapy cycle in the main group showed venous thrombosis in 3 patients (catheter-related n = 2, distal vein thrombosis of the lower extremities n = 1), while no venous thrombotic complications were detected in the control group (10% vs. 0%). Conclusions: Breast cancer patients after coronavirus disease 2019 have hemostasis abnormalities and higher risk of venous thrombosis, and the resumption of anticancer treatment increases the incidence of thrombotic complications. COVID-19 should be considered an additional risk factor of venous thrombosis in cancer patients and requires reconsideration of indications for prophylactic anticoagulation when resuming anticancer treatment for patients with breast cancer.

Old is new again: Emergence of thromboembolic complications in cancer patients on immunotherapy

Cancer immunotherapy has emerged as one of the most important new treatments for cancer in many years, moving rapidly to front-line therapy for several cancers. Cancer immunotherapy is based on treatment with immune checkpoint inhibitors (ICI), which are monoclonal antibodies directed toward immunoregulatory proteins including PD-1, PD-L1 and CTLA-4. ICI inhibit interactions between these proteins and their ligands, disabling physiologic immune regulatory networks and enhancing anti-tumor immunity. However, since the immune response cannot be directed specifically to the tumor, ICI are associated with immune-related adverse events (irAEs) resulting from immune-mediated attack of normal tissues. We and others have reported a high incidence of thrombosis in patients treated with ICI, which may approach 20%. Given the rapidly increasing use of ICIs, it is clear that ICI-Associated Thrombosis (IAT) is a major emerging clinical problem. However, there is a remarkable knowledge gap concerning mechanisms of IAT. IAT may be a composite irAE resulting from activation of blood and vascular cells, leading to thromboinflammation. Cancer itself is an inflammatory disorder, and inducing further inflammation through ICI administration may stimulate procoagulant activity by multiple cell types. Moreover, some blood and vascular cells express ICI target proteins. Here, we review the results of several studies describing the clinical manifestations of IAT, as well as our recent studies demonstrating that elevated levels of myeloid derived suppressor cells and inflammatory cytokines may serve as biomarkers of IAT. It is hoped that the concepts reviewed here may stimulate further research into this important clinical problem.

Prevention and treatment of thrombosis in cancer and oncohematological patients

The purpose of the review is to highlight the current possibilities for the prevention and treatment of venous thrombotic complications in patients with cancer.The data of 52 scientific sources published in the Russian and foreign press in 1997–2020 are considered.Cancer patients are at high risk of thrombotic complications, which worsen the outcome of anticancer treatment and are one of the leading causes of death. Thrombosis in an oncological patient increases the risk of death by 30 times, which is associated with fatal thromboembolism and a more aggressive course of the disease. The leading role in the pathogenesis of thrombotic complications is played by disorders in the hemostasis system caused both by the tumor itself and by therapy. Low molecular weight heparins are considered the basis for specific prophylaxis of thromboembolic complications in cancer patients. The use of low molecular weight heparins after surgery and during chemotherapy effectively reduces the incidence of venous thrombosis. Direct oral anticoagulants are promising drugs for oral administration and are indicated as one of the treatment options for patients with tumor-associated thrombosis with a low risk of bleeding and no drug interactions with ongoing systemic chemotherapy.

Management of the risk of thromboembolic complications in oncology

Oncological disease is a hypercoagulable state with an associated increased risk of venous thromboembolism and is associated with high rates of recurrence and mortality. For those reasons, the prevention of cancer-associated thrombosis is of paramount importance. Knowledge of thromboembolic risk factors in oncology is absolutely necessary for the evaluation of the individual risk-benefit ratio of prophylaxis. The aim of this paper is to elucidate the risk factors of thromboembolic complications in cancer patients. In order to achieve the set aim, the medical scientifi c publications from the GoogleSearch database, PubMed, Z-library, NCIB, Medscape, Hinari, were searched for the keywords: „cancer-associated thrombosis”, „cancer”, „risk factor”. The information was systematized, highlighting the risk factors for thromboembolic complications in patients with cancer.

Modern low-molecular-weight heparins in the prevention and treatment of venous thromboembolic complications in oncourologic patients

Oncourologic diseases are accompanied by a risk for subsequent venous thromboembolic complications, which are rated the most dangerous in terms of thrombogenic effect. The article presents a review of the clinical studies of efficacy and safety, and the experience in using of modern low-molecular-weight heparins in clinical practice - drugs of choice for the prevention of venous thromboembolic complications in cancer patients. Particular attention is paid to Bemiparin - a new second-generation low-molecular-weight heparin with a significant antithrombotic effect and improved pharmacological parameters that allow it to be successfully used in patients with impaired renal function in oncourological practice.

Индивидуальный подход к послеоперационной профилактике тромбозов в онкологии

Цель исследования: повысить эффективность профилактики венозных тромбоэмболических осложнений (ВТЭО) у онкологических больных на хирургическом этапе лечения. Материалы и методы. Проанализированы результаты антикоагулянтной профилактики ВТЭО в послеоперационном периоде у 216 больных с высоким риском тромбоза, обусловленным злокачественными новообразованиями (ЗНО) желудочно-кишечного тракта. В динамике сравнивали результаты показателей коагулограммы, нового глобального теста оценки гемостаза и ультразвукового исследования триплексного сканирования венозной системы нижних конечностей в течение 1 месяца. Результаты. Наибольшее количество ВТЭО зарегистрировано в группе без использования медикаментозной профилактики (26,9%) после оперативного вмешательства. Наименьшая частота ВТЭО отмечена в группе с индивидуальным подбором дозы антикоагулянта (4,9%) на основании глобального теста оценки гемостаза. Заключение. Полагаем, что в послеоперационном периоде у больных со ЗНО желудочно-кишечного тракта необходима комплексная оценка состояния свертывающей системы с коррекцией режима антикоагулянтной профилактики на основании динамики показателей гемостаза, что позволяет снизить частоту ВТЭО. Aim: to increase prophylaxis eff ectiveness of venous thromboembolic complications (VTE) in cancer patients under surgery. Materials and methods. We analyzed the results of anticoagulant postoperative VTE prophylaxis in 216 patients with high risk of thrombosis due to malignant neoplasms of gastrointestinal tract. In dynamics we compared coagulogram parameters, the results of new global hemostatic assessment test, and ultrasound triplex scan of lower limbs venous system during 1 month. Results. Most VTE cases were registered in patients without medicamentous prophylaxis (26.9%) after surgery. The lowest VTE frequency was observed in patients with individual anticoagulant dose selection (4.9%) based on the global hemostatic assessment test. Conclusion. We consider that in postoperative period in patients with malignant neoplasms of gastrointestinal tract integrated assessment of coagulation system and correction of anticoagulant prophylaxis regimen based on the dynamics of hemostasis parameters are required that allows to reduce VTE frequency.

Nadroparin in the prophylaxis and treatment of thromboembolic complications in cancer patients

Nadroparin in the prophylaxis and treatment of thromboembolic complications in cancer patients

THROMBOEMBOLISM IN ONCOLOGY. MODERN VIEW ON THE PROBLEM

Patients with malignant neoplasms are characterized by a high risk of thrombotic complications, which could complicate antitumor treatment and worsen the survival rate. Changes in the hemostatic system, caused by both the tumor and the treatment methods have the main role in the pathogenesis of thrombotic complications in cancer patients. Low molecular weight heparins are the basis for specific prevention of thromboembolic complications in cancer patients. The use of low molecular weight heparins before and after surgery and chemotherapy reduces the activation of intravascular coagulation, reduces the incidence of venous thrombosis and prevent fatal pulmonary embolism, which enhances the antitumor treatment and improves the quality of life in cancer patients.

THE ROLE OF PHYSICAL THERAPY IN CANCER TREATMENT

ENWEndNote BIBJabRef, Mendeley RISPapers, Reference Manager, RefWorks, Zotero AMA Sidor M, Jeziorski K. THE ROLE OF PHYSICAL THERAPY IN CANCER TREATMENT. Health Problems of Civilization. 2015;9(1):29-32. doi:10.5114/hpc.2015.57102. APA Sidor, M., & Jeziorski, K. (2015). THE ROLE OF PHYSICAL THERAPY IN CANCER TREATMENT. Health Problems of Civilization, 9(1), 29-32. https://doi.org/10.5114/hpc.2015.57102 Chicago Sidor, Mirosława, and Krzysztof Jeziorski. 2015. "THE ROLE OF PHYSICAL THERAPY IN CANCER TREATMENT". Health Problems of Civilization 9 (1): 29-32. doi:10.5114/hpc.2015.57102. Harvard Sidor, M., and Jeziorski, K. (2015). THE ROLE OF PHYSICAL THERAPY IN CANCER TREATMENT. Health Problems of Civilization, 9(1), pp.29-32. https://doi.org/10.5114/hpc.2015.57102 MLA Sidor, Mirosława et al. "THE ROLE OF PHYSICAL THERAPY IN CANCER TREATMENT." Health Problems of Civilization, vol. 9, no. 1, 2015, pp. 29-32. doi:10.5114/hpc.2015.57102. Vancouver Sidor M, Jeziorski K. THE ROLE OF PHYSICAL THERAPY IN CANCER TREATMENT. Health Problems of Civilization. 2015;9(1):29-32. doi:10.5114/hpc.2015.57102.

Thromboembolic complications in cancer patients.

e21143 Background: Thromboembolic events are frequent and important complications causing mortality and morbidity in cancer patients.To determine the charecteristics of these events can help us to determine the patients who have higher risks for thromboembolism. Methods: Characteristics of clinically or radiologically determined thromboembolic events were retrospectively analayzed from files of cancer patients followed up in the outpatient oncology clinic of Cerrahpasa Medical Faculty of Istanbul University. Results: A total of 267 thromboembolic events were analyzed.Events were encountered mostly in the venous system, only 3% were in the form of arterial embolism.Venous events were in the form of deep vein thrombosis (67%), pulmonary embolism (16.5%), vena cava superior thrombosis (2.6%), superficial migratory thrombophlebitis (0.4%) or two different forms occuring concomitantly(10.5%). Thromboembolism was determined most frequently in patients with gastrointestinal tumors (41.9%), lung cancer (22.1%) and gynecological tumors (12.1%). The most frequent histopathology was adenocarcinoma (72.4%).Thromboembolic complications were mostly in the form of lower extremity deep venous thrombosis in patients with gastointestinal, gynecological and urogenital tumors where as in the form of pulmonary embolism and vena cava superior thrombosis in patients with lung cancer. Nearly half of the patients with pulmonary embolism (%48.%) were asymptomatic and were diagnosed incidentally with radiological imaging. Upper extremity thrombosis were frequently encountered in patients with venous port a-cath system Most of the patients (87.7%) had metastatic cancer and were receiving chemotherapy (65.5% ) when the event occured. Cisplatin, 5–FU and gemcitabine were the most frequently used chemotherapy agents.Thromboembolic events related to cancer surgery occured usually (59%) in the first month after surgery.Recurrent thromboembolic events were determined in 8.9% of patients mostly whom had gastrointestnal primary tumors (54%). Conclusions: Characteristics of thromboembolic events can help to determine the patients who have higher risk for thromboembolism and predict types and time of the event and provide anticoagulation without delay.

Clinical Potential of Targeting Bruton's Tyrosine Kinase

Targeting Bruton's tyrosine kinase (BTK) with a small-molecule inhibitor may be useful in treatment of BTK-expressing malignancies because of the antiapoptotic function of BTK in cancer cells. Furthermore, BTK inhibitors also exhibit antithrombotic properties, which may be desirable in the context of the increased risk of thromboembolic complications in cancer patients. This review will focus on the role of BTK in drug resistance in cancer, thromboembolism, and various pathologic immune responses, such as graft-versus-host disease. The therapeutic potential of targeting BTK is illustrated by discussion of the biologic activity profile of the rationally designed BTK inhibitor LFM-A13.

Brutons Tyrosine Kinase as a New Therapeutic Target

Targeting Bruton's tyrosine kinase (BTK) with a small molecule inhibitor may be useful in treatment of BTK-expressing malignancies because of the anti-apoptotic function of BTK in cancer cells. Furthermore, BTK inhibitors also exhibit anti-thrombotic properties that may be desirable in the context of the increased risk of thromboembolic complications in cancer patients. This review will focus on the role of BTK in drug resistance in cancer, thromboembolism, and various pathologic immune responses, such as graft versus host disease. The therapeutic potential of targeting BTK is illustrated by discussion of the biologic activity profile of the rationally designed BTK inhibitor LFM-A13.

The heparins and cancer: review of clinical trials and biological properties

The association between cancer and thromboembolic disease is a well-known phenomenon and can contribute significantly to the morbidity and mortality of cancer patients. The spectrum of thromboembolic manifestations in cancer patients includes deep vein thrombosis, pulmonary embolism, but also intravascular disseminated coagulation and abnormalities in the clotting system in the absence of clinical manifestations. Unfractionated heparin (UFH) and particularly low molecular weight heparins (LMWH-s) are widely used for the prevention and treatment of thromboembolic manifestations that commonly accompany malignancies. Malignant growth has also been linked to the activity of heparin-like glycosaminoglycans, to neoangiogenesis, to protease activity, to immune function and gene expression. All these factors contribute in the proliferation and dissemination of malignancies. Heparins may play a role in tumour cell growth and in cancer dissemination. The aims of the study are to review the efficiency of heparins in the prevention and treatment of cancer-related thromboembolic complications, and review the biological effects of heparins. Heparins are effective in reducing the frequency of thromboembolic complications in cancer patients. Meta-analyses comparing unfractionated heparins and LMWH-s for the treatment of deep vein thrombosis have shown better outcome with a reduction of major bleeding complications in patients treated with LMWH-s. LMWH have antitumour effects in animal models of malignancy: heparin oligosaccharides containing less than 10 saccharide residues have been found to inhibit the biological activity of basic fibroblast growth factor (bFGF), whereas heparin fragments with less than 18 saccharide residues have been reported to inhibit the binding of vascular endothelial growth factor (VEGF) to its receptors on endothelial cells. It has been shown that LMWH, in contrast with UFH, can hinder the binding of growth factors to their high-affinity receptors as a result of its smaller size. In vitro heparin fragments of less than 18 saccharide residues reduce the activity of VEGF, and fragments of less than 10 saccharide residues inhibit the activity of bFGF. Small molecular heparin fractions have also been shown to inhibit VEGF- and bFGF-mediated angiogenesis in vivo, in contrast with UFH. Moreover, heparin may influence malignant cell growth through other different interrelated mechanisms: inhibition of (1) heparin-binding growth factors that drive malignant cell growth; (2) tumour cell heparinases that mediate tumour cell invasion and metastasis; (3) cell surface selectin-mediated tumour cell metastasis and blood coagulation. The above evidence, together with favourable pharmaco-properties and with a reduction in major bleeding complications, suggests an important role for LMWH-s in thromboprophylaxis and in the therapy of venous thromboembolism in cancer patients. There is sufficient experimental data to suggest that heparins may interfere with various aspects of cancer proliferation, angiogenesis, and metastasis formation. Large-scale clinical trials are required to determine the clinical impact of the above activities on the natural history of the disease.

Modulation of Malignant Growth by the Coagulation Mechanism and Anticoagulants

This issue of Seminars in Thrombosis and Hemostasis reviews the impact of the clotting and fibrinolytic systems as well as anticoagulants on the modulation of malignant growth. The interrelationship between hemostasis and cancer is as yet not widely appreciated, although the propensity for thromboembolic complications in cancer patients appears to be widely accepted. The interrelationship, however, goes beyond thrombosis. Hemostasis is deeply involved in tumor growth, angiogenesis, and metastasis and modulation of these pathways may yield interesting and promising future treatment modalities.

The hypercoagulable state of malignancy: pathogenesis and current debate.

A hypercoagulable or prothrombotic state of malignancy occurs due to the ability of tumor cells to activate the coagulation system. It has been estimated that hypercoagulation accounts for a significant percentage of mortality and morbidity in cancer patients. Prothrombotic factors in cancer include the ability of tumor cells to produce and secrete procoagulant/fibrinolytic substances and inflammatory cytokines, and the physical interaction between tumor cell and blood (monocytes, platelets, neutrophils) or vascular cells. Other mechanisms of thrombus promotion in malignancy include nonspecific factors such as the generation of acute phase reactants and necrosis (i.e., inflammation), abnormal protein metabolism (i.e., paraproteinemia), and hemodynamic compromise (i.e., stasis). In addition, anticancer therapy (i.e., surgery/chemotherapy/hormone therapy) may significantly increase the risk of thromboembolic events by similar mechanisms, e.g., procoagulant release, endothelial damage, or stimulation of tissue factor production by host cells. However, not all of the mechanisms for the production of a hypercoagulable state of cancer are entirely understood. In this review, we attempt to describe what is currently accepted about the pathophysiology of the hypercoagulable state of cancer. We also discuss whether or not to screen patients with idiopathic deep venous thrombosis for an underlying malignancy, and whether this would be beneficial to patients. It is hoped that a better understanding of these mechanisms will ultimately lead to the development of more targeted treatment to prevent thromboembolic complications in cancer patients. It is also hoped that antithrombotic strategies may also have a positive effect on the process of tumor growth and dissemination.

Preventing thromboembolic complications in cancer patients after surgery: a role for prolonged thromboprophylaxis

Patients undergoing major abdominal surgery for malignancy are at particularly high risk of developing VTE. Extra protection against this can be given to patients with cancer by using a higher dose of LMWH than normally used for prophylaxis, with no increase in bleeding complications. Despite thromboprophylaxis with high-dose LMWH for the first postoperative week, the rate of late VTE is estimated to be between 10% and 20%. A meta-analysis of two studies using dalteparin or enoxaparin has shown that prolonging thromboprophylaxis for a further 3 weeks significantly reduces the risk of late occurring VTE by 62%. Thromboprophylaxis with LMWH for at least one month should be considered in patients undergoing surgery for malignant disease.

Pathogenesis of thrombosis in patients with malignancy.

Cancer cells can contribute to activation of the clotting system by their capacity to produce and release procoagulant/fibrinolytic substances and inflammatory cytokines, and by their interaction with host cells (endothelial, monocytes, platelets, and neutrophils). Moreover, anticancer drugs (chemotherapy/hormone therapy) may greatly affect the risk of thromboembolic complications in cancer patients by similar mechanisms, eg, through the release of procoagulants by tumor cells, through endothelial damage, or stimulation of tissue factor production by host cells. The interactions between cancer/metastatic processes and thrombosis have been reviewed here from the pathogenetic viewpoint. We hope that better knowledge of these pathogenetic pathways will lead to the development of more targeted strategies to prevent thromboembolism in cancer patients.

Coagulation and cancer: implications for diagnosis and management.

Coagulation disorders are a common problem in neoplastic patients and many factors contribute to increase the risk of thromboembolic events in these patients. An hypercoagulable state is induced by malignant cells interacting directly with hemostatic system and activating the coagulation cascade. More sensitive tests to assess an hypercoagulable state in cancer patients have been developed; even though these tests are always altered in cancer patients, none of them possess a clinical significance in terms of predictive value for the occurence of thromboembolism and disease prognosis in the individual patient. The most frequent thromboembolic complications in cancer patients are deep vein thrombosis of the lower extremities and pulmonary embolism; therefore, disseminated intravascular coagulation, thrombotic thrombocytopenic purpura or haemolytic uremic syndrome are special manifestations of neoplastic disease. Diagnosis of idiopathic deep vein thrombosis, in the absence of other risk factors, could indicate the presence of occult malignant disease; however, the need for an extensive work-up to detect malignancy is still controversial. Neoplastic patients showing a thromboembolic event should be treated with unfractioned heparin or, alternatively, with low molecular weight heparins. In order to prevent recurrence, the administration of heparin should be associated and followed by an oral anticoagulant drug. In recent years new approaches in anti-aggregation therapy have been studied, such as COX-inhibitors, cicaprost and ReoPro; further studies are needed to determine the usefulness of these molecules in treatment of malignancies.