Showing 4 ideas for tag "hemorrhage"

Goal 2: Reduce Human Disease

Hemostatic treatment with plasma versus 4-factor PCC in the critically ill

For patients in the ICU with coagulopathy and associated World Health Organization (WHO) grade 3 or 4 bleeding, which hemostatic therapy -- plasma versus 4-factor prothrombin complex concentrates -- is preferred?

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

Details on the impact of addressing this CQ or CC

Bleeding is frequently encountered in the ICU and is associated with substantial morbidity and associated mortality. When bleeding occurs, coagulopathy is often present and the optimal coagulation factor management regimen remains a matter of debate. Traditionally (and presently in the US), plasma transfusion has been a cornerstone therapy for the replacement of coagulation factor content in this setting. Moreover, recent evidence supporting the use of plasma in the setting of trauma-related hemorrhage seems to have also generated a renewed enthusiasm for plasma transfusion in other critical care settings.

 

In many locations, there is interest in alternatives to plasma transfusion such as four-factor prothrombin complex concentrates (PCC4) for ICU patients with bleeding. In some locations, factor concentrates have entirely replaced plasma transfusion. However, evidence regarding the benefits and risks of PCC4 versus plasma in ICU patients is lacking. Therefore, we would aim to study the comparative efficacy and risks of a hemostatic strategy relying on PCC4 versus plasma for ICU patients with coagulopathy and bleeding.

Feasibility and challenges of addressing this CQ or CC

Coagulopathy and associated bleeding are common in the intensive care unit environment. Therefore, we believe a multicenter clinical trial evaluating the knowledge gap identified above would be feasible with NHLBI support. Of note, due to the labeled contraindication of disseminated intravascular coagulation for PCC4, such patients would need to be excluded from this trial. Similarly, coagulation abnormalities resulting from congenital coagulation factor deficiencies for which there is a specific coagulation factor product available would also be excluded.

Notably, improved management of coagulopathic bleeding has the potential to impact both clinical outcomes and healthcare resource utilization. Therefore, the outcomes of a trial addressing this knowledge gap would include patient-important outcomes (e.g. mortality, length of hospital stay, bleeding, transfusion-related respiratory complications, thromboembolic complications) as well as outcomes related to healthcare utilization (e.g. product cost, total blood products consumed, interventions required to achieve hemostasis such as surgery or embolization).

Name of idea submitter and other team members who worked on this idea Daryl J. Kor, MD and Walter H. Dzik, MD for the 2015 NHLBI State of the Science in Transfusion Medicine

Voting

28 net votes
43 up votes
15 down votes
Active

Goal 2: Reduce Human Disease

Liberal versus restrictive plasma prior to invasive procedures

At what INR threshold does prophylactic plasma transfusion, in non-bleeding critically ill patients who are planned to undergo an invasive procedure, prevent bleeding complications and improve patient outcomes?

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

Details on the impact of addressing this CQ or CC

Millions of plasma units continue to be transfused to non-bleeding critically ill patients. This practice persists despite the lack of high quality evidence indicating improved patient outcomes with prophylactic plasma transfusion triggered by the INR. Studies testing restrictive versus liberal transfusion triggers are now well-established in academic medicine for Red Blood Cell products. More recently, multicenter clinical trials of prophylactic platelet transfusion vs no-prophylaxis have been conducted as well. However, there remains substantial equipoise on the topic of prophylactic plasma transfusion. A large definitive clinical trial that aims to identify the INR threshold at which prophylactic plasma transfusion prevents bleeding complications in non-bleeding critically ill patients would impact clinical practice in a very meaningful way.

Feasibility and challenges of addressing this CQ or CC

Abnormal coagulation tests are common in the ICU and plasma is frequently administered in this specific clinical setting. Indeed, more plasma is administered in the ICU environment than in any other clinical area. Therefore, a multi-center clinical trial addressing the knowledge gap identified above would be feasible with NHLBI support.

Importantly, healthcare providers become increasingly uncomfortable with the avoidance of coagulation factor replacement as coagulation screening test results drift further from the normal range. To address this concern, an adaptive clinical trial may be desirable. In this design, a targeted cohort with modest elevations in the INR measurement would be screened for enrollment (e.g. INR results ranging from 1.5 - 2.0). If the avoidance of plasma transfusion is noted to be safe, the study would advance to the next stage of recruitment, targeting a higher range of INR values (e.g. 2.0 - 2.5).

Finally, the value of the INR in predicting bleeding complications is increasingly scrutinized. Therefore, it can be argued that the INR is not the ideal "trigger" for plasma transfusion. Despite this, it must be acknowledged that the INR remains the primary driver of decisions related to plasma transfusion. Therefore, a large definitive trial specifically detailing the the efficacy of the current practice versus a more conservative approach to prophylactic plasma transfusion would be practice changing and potentially very transformative.

Name of idea submitter and other team members who worked on this idea Daryl J. Kor, MD and Walter H. Dzik, MD for the 2015 NHLBI State of the Science in Transfusion Medicine

Voting

19 net votes
39 up votes
20 down votes
Active

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)

Details on the impact of addressing this CQ or CC

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

Voting

14 net votes
19 up votes
5 down votes
Active

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)

Details on the impact of addressing this CQ or CC

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.

Voting

-3 net votes
12 up votes
15 down votes
Active