Coagulation and cancer: biological and clinical aspects.
01 Feb 2013-Journal of Thrombosis and Haemostasis (Blackwell Publishing Ltd)-Vol. 11, Iss: 2, pp 223-233
TL;DR: This review provides an overview of the hemostatic complications in cancer, together with new insights into the interaction between hemostasis and cancer biology.
About: This article is published in Journal of Thrombosis and Haemostasis.The article was published on 2013-02-01. It has received 353 citations till now. The article focuses on the topics: Cancer.
Citations
More filters
TL;DR: A mathematical model is developed to guide the optimal use of vascular normalization and stress-alleviation to improve tumor perfusion and delivery of drugs and reveals an optimal perfusion region when vessels are uncompressed, but not very leaky.
Abstract: Blood perfusion in tumors can be significantly lower than that in the surrounding normal tissue owing to the leakiness and/or compression of tumor blood vessels. Impaired perfusion reduces oxygen supply and results in a hypoxic microenvironment. Hypoxia promotes tumor progression and immunosuppression, and enhances the invasive and metastatic potential of cancer cells. Furthermore, poor perfusion lowers the delivery of systemically administered drugs. Therapeutic strategies to improve perfusion include reduction in vascular permeability by vascular normalization and vascular decompression by alleviating physical forces (solid stress) inside tumors. Both strategies have shown promise, but guidelines on how to use these strategies optimally are lacking. To this end, we developed a mathematical model to guide the optimal use of these strategies. The model accounts for vascular, transvascular, and interstitial fluid and drug transport as well as the diameter and permeability of tumor vessels. Model simulations reveal an optimal perfusion region when vessels are uncompressed, but not very leaky. Within this region, intratumoral distribution of drugs is optimized, particularly for drugs 10 nm in diameter or smaller and of low binding affinity. Therefore, treatments should modify vessel diameter and/or permeability such that perfusion is optimal. Vascular normalization is more effective for hyperpermeable but largely uncompressed vessels (e.g., glioblastomas), whereas solid stress alleviation is more beneficial for compressed but less-permeable vessels (e.g., pancreatic ductal adenocarcinomas). In the case of tumors with hyperpermeable and compressed vessels (e.g., subset of mammary carcinomas), the two strategies need to be combined for improved treatment outcomes.
348 citations
Cites background from "Coagulation and cancer: biological ..."
...Finally, apart from vessel compression and hyperpermeability, other causes of decreased blood flow in tumors include heterogeneous distribution of blood vessels, intravascular coagulation/ thrombosis, and formation of vascular shunts (65, 66)....
[...]
02 Jun 2016
TL;DR: An updated overview of the pathophysiology, diagnosis and management of Disseminated intravascular coagulation is provided and the future directions of basic and clinical research in this field are discussed.
Abstract: Disseminated intravascular coagulation (DIC) is an acquired syndrome characterized by widespread intravascular activation of coagulation that can be caused by infectious insults (such as sepsis) and non-infectious insults (such as trauma). The main pathophysiological mechanisms of DIC are inflammatory cytokine-initiated activation of tissue factor-dependent coagulation, insufficient control of anticoagulant pathways and plasminogen activator inhibitor 1-mediated suppression of fibrinolysis. Together, these changes give rise to endothelial dysfunction and microvascular thrombosis, which can cause organ dysfunction and seriously affect patient prognosis. Recent observations have pointed to an important role for extracellular DNA and DNA-binding proteins, such as histones, in the pathogenesis of DIC. The International Society on Thrombosis and Haemostasis (ISTH) established a DIC diagnostic scoring system consisting of global haemostatic test parameters. This scoring system has now been well validated in diverse clinical settings. The theoretical cornerstone of DIC management is the specific and vigorous treatment of the underlying conditions, and DIC should be simultaneously managed to improve patient outcomes. The ISTH guidance for the treatment of DIC recommends treatment strategies that are based on current evidence. In this Primer, we provide an updated overview of the pathophysiology, diagnosis and management of DIC and discuss the future directions of basic and clinical research in this field.
348 citations
Medical Products Agency1, European Medicines Agency2, Paul Ehrlich Institute3, Translational Centre for Regenerative Medicine4, Medicines and Healthcare Products Regulatory Agency5, Leiden University Medical Center6, Curie Institute7, Lithuanian University of Health Sciences8, French Institute of Health and Medical Research9, University of Paris-Sud10
TL;DR: This meeting elucidated the risk of potential tumorigenicity related to MSC-based therapies from two angles: the scientific perspective and the regulatory point of view, leading to a clearer way forward for the development of such products.
291 citations
TL;DR: A better understanding of the pathways that increase VTE in cancer patients may lead to the development of new therapies to reduce the morbidity and mortality associated with thrombosis.
229 citations
TL;DR: In patients with major bleeding or at risk for hemorrhagic complications, administration of platelet concentrates, plasma, or coagulation factor concentrates should be considered.
180 citations
References
More filters
TL;DR: For the treatment of acute venous thromboembolism, a fixed dose of dabigatran is as effective as warfarin, has a safety profile that is similar to that of warfar in, and does not require laboratory monitoring.
Abstract: A total of 30 of the 1274 patients randomly assigned to receive dabigatran (2.4%), as compared with 27 of the 1265 patients randomly assigned to warfarin (2.1%), had recurrent venous thromboembolism; the difference in risk was 0.4 percentage points (95% confidence interval [CI], −0.8 to 1.5; P<0.001 for the prespecified noninferiority margin). The hazard ratio with dabigatran was 1.10 (95% CI, 0.65 to 1.84). Major bleeding episodes occurred in 20 patients assigned to dabigatran (1.6%) and in 24 patients assigned to warfarin (1.9%) (hazard ratio with dabigatran, 0.82; 95% CI, 0.45 to 1.48), and episodes of any bleeding were observed in 205 patients assigned to dabigatran (16.1%) and 277 patients assigned to warfarin (21.9%; hazard ratio with dabigatran, 0.71; 95% CI, 0.59 to 0.85). The numbers of deaths, acute coronary syndromes, and abnormal liver-function tests were similar in the two groups. Adverse events leading to discontinuation of the study drug occurred in 9.0% of patients assigned to dabigatran and in 6.8% of patients assigned to warfarin (P = 0.05). Conclusions For the treatment of acute venous thromboembolism, a fixed dose of dabigatran is as effective as warfarin, has a safety profile that is similar to that of warfarin, and does not require laboratory monitoring. (ClinicalTrials.gov number, NCT00291330.)
2,363 citations
TL;DR: In patients with cancer and acute venous thromboembolism, dalteparin was more effective than an oral anticoagulant in reducing the risk of recurrent thrombosis without increasing therisk of bleeding.
Abstract: Background Patients with cancer have a substantial risk of recurrent thrombosis despite the use of oral anticoagulant therapy. We compared the efficacy of a low-molecular-weight heparin with that of an oral anticoagulant agent in preventing recurrent thrombosis in patients with cancer. Methods Patients with cancer who had acute, symptomatic proximal deep-vein thrombosis, pulmonary embolism, or both were randomly assigned to receive low-molecular-weight heparin (dalteparin) at a dose of 200 IU per kilogram of body weight subcutaneously once daily for five to seven days and a coumarin derivative for six months (target international normalized ratio, 2.5) or dalteparin alone for six months (200 IU per kilogram once daily for one month, followed by a daily dose of approximately 150 IU per kilogram for five months). Results During the six-month study period, 27 of 336 patients in the dalteparin group had recurrent venous thromboembolism, as compared with 53 of 336 patients in the oral-anticoagulant group (haza...
2,224 citations
TL;DR: Hospital or nursing home confinement, surgery, trauma, malignant neoplasm, chemotherapy, neurologic disease with paresis, central venous catheter or pacemaker, varicose veins, and superficial vein thrombosis are independent and important risk factors for VTE.
Abstract: Background Reported risk factors for venous thromboembolism (VTE) vary widely, and the magnitude and independence of each are uncertain Objectives To identify independent risk factors for deep vein thrombosis and pulmonary embolism and to estimate the magnitude of risk for each Patients and Methods We performed a population-based, nested, case-control study of 625 Olmsted County, Minnesota, patients with a first lifetime VTE diagnosed during the 15-year period from January 1, 1976, through December 31, 1990, and 625 Olmsted County patients without VTE The 2 groups were matched on age, sex, calendar year, and medical record number Results Independent risk factors for VTE included surgery (odds ratio [OR], 217; 95% confidence interval [CI], 94-499), trauma (OR, 127; 95% CI, 41-397), hospital or nursing home confinement (OR, 80; 95% CI, 45-142), malignant neoplasm with (OR, 65; 95% CI, 21-202) or without (OR, 41; 95% CI, 19-85) chemotherapy, central venous catheter or pacemaker (OR, 56; 95% CI, 16-196), superficial vein thrombosis (OR, 43; 95% CI, 18-106), and neurological disease with extremity paresis (OR, 30; 95% CI, 13-74) The risk associated with varicose veins diminished with age (for age 45 years: OR, 42; 95% CI, 16-113; for age 60 years: OR, 19; 95% CI, 10-36; for age 75 years: OR, 09; 95% CI, 06-14), while patients with liver disease had a reduced risk (OR, 01; 95% CI, 00-07) Conclusion Hospital or nursing home confinement, surgery, trauma, malignant neoplasm, chemotherapy, neurologic disease with paresis, central venous catheter or pacemaker, varicose veins, and superficial vein thrombosis are independent and important risk factors for VTE
2,069 citations
TL;DR: It is shown that patients with symptomatic proximal DVT may benefit from fitted compression stockings for at least 3 months to reduce the incidence of the postthrombotic syndrome, and patients with VTE who receive adequate anticoagulation generally do not die of recurrent disease.
2,049 citations
TL;DR: This chapter about treatment for venous thromboembolic disease is part of the American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition) and indicates that the benefits do or do not outweigh risks, burden, and costs.
1,985 citations