Showing 7 ideas for tag "hemostasis"

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 »

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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

What new methods of platelet preparation, processing, and storage are needed for hemostasis in various clinical conditions?

The limitations of 5-day 22˚ C storage significantly impacts platelet availability. It is critical that we develop new methods of collection, processing, storage to extend the storage time of platelets, and evaluate the use of whole blood. The attributes of these products must be understood to optimally alignment product attributes, clinical efficacy and safety with hemostatic needs in a variety of clinical states. Specifically,... more »

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

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Limitations of current storage methods challenge our ability to meet the increasing demands of cancer chemotherapy and complex surgeries as well as provide platelets to remote areas where trauma frequently occurs. Platelets are transfused to prevent or control bleeding without robust translational or clinical trial evidence of efficacy and safety. In patients with hypoproliferative thrombocytopenia receiving chronic platelet transfusion predominantly for prophylaxis, post-transfusion increments, survival time, and durable hemostatic efficacy are important; however, platelet transfusion alone does not prevent bleeding. The overall state of hemostasis, the endothelium and donor characteristics that affect platelet quality may be important considerations in selecting the best platelet product tailored to individual patients. Better laboratory and clinical measures of platelet function, efficacy and safety are essential for best use of these limited resources. These outcomes should span and link in-vitro testing, animal models, and clinical effects such as thrombotic events, immune, hemostatic, and endothelial effects. Extrinsic, recipient factors (e.g., immune deficiency, platelet or endothelial dysfunction) and intrinsic factors (e.g., donor specific or platelet preparation) should be considered. Systematic analysis of recipients and donors should be broad and include considerations of glycomics, metabolomics, proteomics, genomics, in vivo microscopy, and advanced imaging.

Feasibility and challenges of addressing this CQ or CC

Radiolabeled platelet recovery and survival methods are well established and feasible to perform at several centers within the US. Currently 4-6 million units of platelets and whole blood are transfused per year. It is very feasible to conduct clinical trials that compare methods of platelet preparation, processing, and storage in children and adults who require platelets for either prophylaxis or active bleeding. Multiple research networks that focus on both pediatric and adult transfusion medicine are motivated to perform the pre-clinical and clinical trials required to establish improved efficacy and safety of platelet-containing blood products.

Name of idea submitter and other team members who worked on this idea Terry Gernsheimer, University of Washington, for the 2015 NHLBI State of the Science in Transfusion Medicine

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Goal 4: Develop Workforce and Resources

Economic and Sustainable Infrastructure for Basic Scientists and Physician Researchers in Healthcare Networks

This will require a new process of partnerships between successful basic scientists and the physician who is committed to a synergistic relationship with the investigators in order to unravel the pathophysiology of disease. The failure of the part-time “MD trainee scientist” due to increasing clinical requirements to complete their fellowship, has only reinforced the impression that physicians no longer belong in the... more »

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More emphasis and financial support is needed to encourage mentoring of physician scientists who can truly implement the translational breakthroughs in basic science laboratories. Thus far, we have not seen the support needed to maintain physicians-researchers in implementation of translational breakthroughs once they leave the lab or the coverage of their research funding. Not only a patient tragedy, this is occurring at the very moment that national expansion of genomic services for diagnosis, phenotype-genotype associations, and revolutionary pharmacological breakthroughs are occurring on a daily basis. Without a robust network of investigators linked to the basic science investigators, these NIH funded breakthroughs will languish due to lack of an affective network of implementation and supportive biologic investigations.

Feasibility and challenges of addressing this CQ or CC

How can this be accomplished? NHLBI should fund innovative and collaborative partnerships nurtured between physician scientists and the basic researchers that rewards grantees for the development of a novel hospital based infrastructure that promotes a healthy and vibrant synergism between patient centered care, research and innovation.
This is a great example where the physician scientist can provide the much needed link between the patient and the basic science that offers the promise of cure and improved outcomes for all patients.

Name of idea submitter and other team members who worked on this idea Diane Nugent, MD and Hemostasis Thrombosis Research Society members

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Goal 2: Reduce Human Disease

Improve hemostatic outcomes in patients on extracorporeal life support

As patients who suffer a hemostatic complication (hemorrhage or thrombosis) while on extracorporeal membrane oxygenation (ECMO) have worse outcomes, how do optimize anticoagulation in this population to minimize complications and improve outcomes?

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

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Extracorporeal membrane oxygenation (ECMO) is being used earlier in adult and pediatric patients disease course to support them through reversible causes of heart and/or lung failure. Therefore, it's use has increased and, I speculate, will continue to increase.

Hemostatic complications, such as thrombosis and intracranial hemorrhages, limit the duration and intensity of ECMO support. Not surprisingly then, multiple studies show that ECMO patients who suffered a hemostatic complication have worse outcomes.

Every ECMO center builds their circuit a little different and has their own anticoagulation protocol, but yet, no one center treats enough patients on ECMO to power any robust study. To date, anticoagulation in ECMO is driven by some case series, retrospective single-center studies, and experience. We need multi-institutional studies to study this so that we can harness this technology to its fullest so that we can save lives and minimize morbidity.

Feasibility and challenges of addressing this CQ or CC

This CC is feasible in that the community of ECMO providers is small and cooperative and anticoagulation is a top concern amongst ECMO physicians. Multi-center study proposals have been submitted but, to date, not funded.

Obstacles include:
- The urgency: ECMO is usually initiated emergently so accruing and consenting patients (or their power of attorney) under the duress of ECMO is difficult, but as we have proven, is possible
- Vulnerable population: Many (if not most) patients who go on ECMO are neonates.
- Patient sample size. A huge ECMO center does 40-60 ECMO cases/year so many centers would need to be involved to accrue an adequate sample size
- Patient heterogeneity: Patients who are initiated on ECMO are very different. Differences in age, degree of heart failure versus lung failure, mechanism of lung and/or heart failure, whether they are post-operative and even who their surgeon is can all affect rates of hemostatic complications
- Variable clinical practice: Every ECMO center runs their ECMO different than the next so we would need to standardize some procedures before we could do a multi-center study.

Name of idea submitter and other team members who worked on this idea Trish Wong

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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 1: Promote Human Health

Hypothermia and hemostasis after severe trauma

There is a need to employ new molecular tools to delineate the difference between beneficial and uncontrolled shock-induced hypothermia, because data on hypothermia and hemostasis are incomplete or lacking, especially on the duration, depth and type of hypothermia.

 

availability of targeted resource grant funding

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

Details on the impact of addressing this CQ or CC

improvement of survival with life threatening traumatic injuries with new metabolically modulating strategies, including "simple hypothermia", improved understanding of the relationship between ischemia and reperfusion, the role of inflammatory and metabolic pathways, definition and identification of appropriate targets for therapy, the role for mechanical devices, and relationship between timely application of hypothermia and rewarming.

Feasibility and challenges of addressing this CQ or CC

the tools and animal models are available to study hemostatic and metabolic modulation/hypothermia in traumatic injury
Trauma is the major cause of death in young individuals in the US, and globally, with uncontrolled hemorrhage representing the major cause of preventable deaths. Hypothermia, used in life threatening cardiovascular states, also holds enormous promise for application in traumatic injuries. Early deployment (pre-hospital) of novel protective metabolically modulating strategies to attenuate cellular injury from shock and reperfusion, such as hypothermia could be beneficial. However, the relationship between hypothermia in traumatic setting is complex, with data suggesting detrimental outcomes if it occurred spontaneously. In contrast, hypothermia induced in a controlled manner can protect tissues from ischemic injury.

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

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