Showing 10 ideas for tag "thrombosis"

Goal 2: Reduce Human Disease

Funding for Hemostasis & Thrombosis Research

Thrombotic disorders, a result of the inappropriate activation of the hemostatic system, remain major causes of morbidity and mortality in the United States. Cancer, cardiovascular disease, trauma, and many of the other causes of death in the U.S. frequently culminate in a fatal thrombotic event. Notably, thromboembolic disease affects 500,000 people annually and leads to 100,000 deaths in the United States alone. Current... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

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Following vascular injury, regulated hemostasis is both rapid and appropriate, thereby quenching hemorrhage. Nonetheless, it is clear that both hemostasis and thrombosis are dynamic processes, characterized by the sequential accumulation and removal of newly activated platelets and fibrin at sites of vascular damage. Over the past 10 years, research in hemostasis and thrombosis has been transformed, broadened and infused with new energy driven by novel technologies and ideas. NHLBI-funded science has revealed new pathways for platelet activation, for platelets in physiologic events outside of the hemostatic response, for coagulation proteases in modulating inflammation and tissue repair after injury, and new mechanistic insights into coagulation. Many tacitly accepted ideas in the field are yielding to these new mechanistic insights that suggest new ways to modulate coagulation leading to therapeutic gain. The NHLBI should continue its strong support of research to understand these mechanisms and should continue to bolster the training that will equip the next generation of scientists and physician-scientists to translate discovery from the lab to the bedside.

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Goal 2: Reduce Human Disease

Understand the Impact of Thrombosis in Children with Cancer

CC: Despite the potential impact that venous thrombotic events (VTE) have on children with cancer, several unresolved issues remain. To date, we are yet to understand:
- incidence/prevalence of VTE according to cancer type/staging
- ideal imaging modalities to diagnose/follow VTE
- thromboprophylaxis according to thrombosis risk stratification (development of VTE predictors)
- efficacy/safety to anticoagulate children... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

Details on the impact of addressing this CQ or CC

Venous thrombotic events (VTE) are now occurring in 1/200 children admitted to a tertiary pediatric facility. In around 70-90% of cases, VTE occurs in children with an underlying condition, amongst which cancer represents up to 1/3 of patients. Within this group of patients, the thrombotic complications are associated with a higher morbidity (e.g. higher recurrence rates, high rate of CNS events in acute leukemia) and mortality. Nevertheless, the clinical challenges highlighted in the itemized Critical Challenge Section illustrate the lack of basic science, translational and clinical research available, as well as the paucity of evidence-based medicine recommendations necessary to acoount for the increasing number of patients with this complication.
On the other hand, pediatric oncology is one of the areas of pediatric care where the medical progresses of the last decades have drastically changed the natural history of cancer in children. In light of much higher survival rates for almost all types of pediatric cancer, the focus has now shifted towards decreasing treatment-related, as well as disease-related morbidities, increasing the quality of life of the many survivors. Because VTE is now recognized as one of the significant remaining complications within this patient population, addressing the list summarized herein would contribute to further improve the care of children with cancer.

Feasibility and challenges of addressing this CQ or CC

The infrastructure that is already in place under the Children's Oncology Group (COG), where almost any new clinical and/or translational idea related to the care of children with cancer becomes part of a clinical trial, could be rolled over to explore many of the items listed under the CC Section.
As a principle, VTE in children with cancer develop due to: a) host-related factors; b) chemotherapy/treatment-related factors; and c) disease-related issues. Therefore, protocol- and disease-specific studies could address, under the auspices of COG, the prevalence of VTE according to cancer type in a prospective manner. Similarly, high risk groups for VTE could be submitted to standardized imaging and/or biomarker investigation prospectivelly, in addition to collection of outcome data related to VTE and to anticoagulation protocols. Furthermore, tumor specimens/genetic markers could be evaluated and correlated to the study outcomes. The challenges of reaching consensus during protocol development would allow identification of equipoise for certain clinical scenarios, obviating the need of trials, or the use of consensus techniques, before diagnostic/therapeutic protocols could be adopted.
In conclusion, the develoment of a multidisciplinary task force (i.e. pediatric radiologists, oncologists, hematologists, molecular biology experts), which, for the most part, is already in place (i.e. COG), would be instrumental to foster research on this extremely clinically relevant area.

Name of idea submitter and other team members who worked on this idea Leonardo R. Brandao, MD, MSc;

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Goal 2: Reduce Human Disease

Venous Thromboembolism

There is a great need for the development and evaluation of biomarkers for the study of venous thromboembolism (VTE) pathophysiology and risk assessment.

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

Details on the impact of addressing this CQ or CC

Recent efforts to evaluate biomarkers for VTE occurrence and recurrence have led to the identification of multiple potential candidates, including P-selectin, E-selectin, D-dimer, various microparticles, and various inflammatory cytokines. However, no specific biomarker has yet emerged for routine clinical use for individual VTE risk stratification and personal targeted therapeutics. The development of improved animal models will advance the study of VTE pathophysiology, allowing for more accurate evaluation of emerging biomarkers and initial assessments of potential advanced therapeutic interventions. Also, the identification and prioritization of novel VTE biomarkers will be needed to help improve our understanding of the molecular mechanisms underlying VTE, so as to shepherd the development of novel mechanisms of therapy beyond anticoagulation.

Name of idea submitter and other team members who worked on this idea Alice Kuaban on behalf of the American Society of Hematology (ASH)

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Goal 2: Reduce Human Disease

Mechanisms of Uterine Hemostasis

What are the mechanisms of uterine hemostasis?
Endogenous mechanisms of uterine hemostasis protect women from the bleeding challenges of miscarriage, childbirth, and menstruation. Dysregulation of these mechanisms has implications for the critical public health problems of hormonally-induced venous thromboembolism and hormonally-induced arterial thromboembolism (myocardial infarction and stroke). Our current understanding... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

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Urgent clinical questions hinge on understanding the mechanisms of hormonally-induced thrombosis – questions about how women with various underlying cardiovascular conditions, hematological conditions such as sickle cell disease, and endocrinological conditions such as obesity are differentially affected by endogenous and exogenous hormones.

The additional impact of identifying the mechanisms of uterine hemostasis is potentially improving the global health problem of maternal and gynecological hemorrhage. If there is failure of normal uterine hemostasis after childbirth there is the potential for massive postpartum hemorrhage. If there is failure of normal hemostasis during the menstrual cycle there is the potential for acute heavy menstrual bleeding (acute menorrhagia).

Feasibility and challenges of addressing this CQ or CC

An understanding of the mechanisms of uterine hemostasis provides the basis for understanding hormonally-induced thrombosis and vice versa. The paradigms of pregnancy; assisted reproductive technologies; contraception; and postmenopausal hormone replacement provide four clinical scenarios across the life cycle where female hormones or their synthetic counterparts provide opportunities for insight into mechanisms of hormonally-induced thrombosis. The NIH/NHLBI can and should support studies that elucidate the mechanisms of uterine hemostasis and hormonally-induced thrombosis and should make such studies a scientific priority. The NIH/NHLBI has the capacity and resources. Studies would include basic science, translational and clinical studies. Although studies would benefit from the participation of other institutes and from the contribution of multiple disciplines, NHLBI should take the lead.

Research efforts should be accompanied by cross-disciplinary training opportunities. The Building Interdisciplinary Research Careers in Women’s Health (BIRCWH) program is a mentored career development program which connects junior faculty to senior faculty with shared research interests in either women’s health or sex differences research. Junior faculty are supported by institutions who receive grants from the Office of Research on Women's Health (ORWH) and BIRCWH program co-sponsors – multiple institutes which as yet do not include the NHLBI.

Name of idea submitter and other team members who worked on this idea Andra James

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Goal 2: Reduce Human Disease

New anti-thrombotic approaches with minimal adverse effect of bleeding

All current anti-thrombotic drugs have the adverse effect of excessive bleeding, which is associated with mortality and poor prognosis. Thus, there is a need to develop new generations of anti-thrombotics that have minimal adverse effect of bleeding.

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

Name of idea submitter and other team members who worked on this idea Xiaoping Du

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Goal 2: Reduce Human Disease

mechansisms of post thrombotic syndrome

No good medical therapy exists to prevent and treat post thrombotic syndrome, the most common sequlae from a deep vein thrombosis. Recent trial data suggests that compression stockings do not prevent PTS, and thrombolysis is expensive and risky. The basic mechanisms related to fibrosis of the vein wall are not well understood.

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

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Further research into this area, both at the human and animal model level would allow potential translation of novel agents without the risks of anticoagulatnts, as well as shine light on basic fibrotic vascular disease processes.

Feasibility and challenges of addressing this CQ or CC

Doable with both well defined human patients, and animal models of the disease that are similar to humans

Name of idea submitter and other team members who worked on this idea peter henke

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Goal 2: Reduce Human Disease

Targeting Inflammation in Venous Thromboembolism

What is the role of inflamation in venous thromboembolism, both DVT and PE. If the inflammatory response can be controlled, then clot formation should be able to be decreased or eliminated without bleeding potential. The effect of the inflammatory response on the wall of the veins, both in the legs and the lungs, leads to changes that result in pain and swelling (legs) and pulmonary artery hypertension (lungs). Inhibiting... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

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I would suggest that studies addressing this issue using new targeted anti-inflammatory medications be supported in both large animal models (close to human) and in clinical translational studies.

Feasibility and challenges of addressing this CQ or CC

This is feasible and doable - there is data suggesting that inflamatory inhibition with agents that target the selectins (for example) lead to a lessening of thrombosis, and decreases in vein wall damage, all without bleeding potential. These conepts in animals need to be evaluated in clinical studies. Additionally, there are other off-shoots such as studies with biomarkers of inflammation and how they can be helpful in making the diagnosis and predicting the response to therapies.

Name of idea submitter and other team members who worked on this idea Thomas Wakefield

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Goal 2: Reduce Human Disease

Thrombprophylaxis in cancer patients

What is needed to identify the cancer patients that would benefit from thromboprophylaxis and the agents that should be used?

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

Details on the impact of addressing this CQ or CC

The close relationship between cancer and thrombosis has been known since the days of Armand Trousseau, who first described the clinical association between idiopathic venous thromboembolism (VTE) and occult malignancy in 1865. Today, we know that some cancers are associated with a hypercoagulable state and up to four-fold increase in thrombosis risk, with chemotherapy elevating this risk even more. Thrombosis has a significant impact on the morbidity and mortality of cancer; therefore, it is important to identify which patients may be at higher risk than others, especially before starting chemo-radiotherapy or surgery. However, there is no standard of care for thromboprophylaxis in cancer patients. Identification specific groups of risk for thrombosis and appropriate anticoagulation regimen, especially in mid-level risk groups, would provide direct benefit to the outcome in cancer patients.

Feasibility and challenges of addressing this CQ or CC

Epidemiologic and population-based studies provide detailed information on the scale of the problem and the identification of VTE risk factors, including those related to the tumor (tumor type, clinical stage, chemotherapy, use of anti-angiogenic drugs or erythropoietic growth factors, and insertion of central venous catheters), and those related to individual patient characteristics (sex, race, age, previous VTE history, immobilization, and obesity). Additional factors and biomarkers of thrombosis have been established in recent years. A new generation of oral anticoagulants that potentially can make thromboprophylaxis in cancer patients safer and easier, has been developed. All these achievements may transform the current empirical nature of anticoagulants use in cancer to scientifically justified, efficient and safe thromboprophylaxis.

 

 

While there is a clear progress in our understanding of the mechanisms associated with the development of malignancy, we know little of the mechanisms of cancer-related thrombosis. There is evident lack of collaboration between basic scientists and clinical oncologists, which would be required for natural history and biomarker studies. Efficient collaboration is required between National Cancer Institute and National Heart, Lung, and Blood Institute to coordinate efforts and leverage resources in addressing this important research and clinical challenge.

Name of idea submitter and other team members who worked on this idea NHLBI Staff

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Goal 2: Reduce Human Disease

What are the Determinants of Short Term Prediction of Heart Attacks?

In spite of many years of research, we still cannot predict the short term risk of a heart attack or sudden CHD death. Most CHD deaths occur outside of the hospital. In spite of improvement of out-of-hospital emergency care, most “sudden death events” are still not successfully resuscitated.

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

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There is strong evidence of interrelationship between inflammation, thrombogenesis, especially activation of tissue factor and platelets, and risk of a heart attack or sudden death. This is especially true in individuals who have pneumonia, influenza, etc. but also perhaps in relationship to environmental factors such as air pollution. Development of early identification and treatment approaches could substantially reduce CHD mortality.

Feasibility and challenges of addressing this CQ or CC

The NHLBI has certainly had a major commitment in studying the interrelationship between inflammation and CHD. However, there is a need to go into the field and evaluation the interrelationship between inflammation, especially infection, drug therapies and short term acute precipitation of heart attacks. For example, there is suggestive evidence that older individuals on aspirin who have pneumonia may have reduced risk of a heart attack and sudden CHD death. Further studies linking work at the National Institute of Allergy and Infectious Diseases and the Heart and Lung Institute should attempt to further understand the interrelationships between infection, inflammation, and activation of tissue factor and platelets, and risk of thrombosis and heart attack and whether specific drug therapies, especially in high risk older individuals or even among individuals who have had previous CVD or high atherosclerotic burden, whether newer drugs could substantially reduce the risk of a heart attack.

Name of idea submitter and other team members who worked on this idea Lewis H. Kuller, MD, DrPH

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Goal 2: Reduce Human Disease

Maternal mortality due to Hemostatic Disorders

Can we decrease maternal mortality and morbidity due to hemorrhage or thrombosis?

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

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Hemorrhage and thrombosis remain major causes of maternal mortality in the US. New approaches are needed to decrease these tragic deaths.

Feasibility and challenges of addressing this CQ or CC

Clinical/basic study of risk factors/biomarkers to better define women at risk and clinical trials are needed to compare treatments.

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