Hemorrhage in a setting of anticoagulation (ACA) is a serious medical emergency associated with high morbidity and mortality. Patients on ACA for mechanical valves or cardiac assist devices (CAD) and who are bleeding are at even greater risk because ACA reversal may not be possible in these patients. These patients are typically considered to be high-risk for open surgical repair and are more commonly treated today by endovascular approaches. For example, gastrointestinal bleeding (GIB), one of the most common forms of internal hemorrhage and life-threatening medical emergencies seen in the ACA patient today, affects approximately 500,000 patients annually in the US. In fact, studies have shown that up to 40% develop GIB following CAD implant (AA). The rate of mortality drastically increases from 10% to 40% if bleeding occurs during a hospitalization for another illness, especially when complicated by ACA. Over the past 30 years, open surgical treatment of GIB has been largely replaced by minimally invasive endovascular interventions. This approach involves delivery of metallic coils spanning the bleeding site; these coils induce thrombosis to occlude the vessel. However, there are significant drawbacks to coil embolization; most important is recurrent bleeding or persistent bleeding in anticoagulated and in coagulopathy patients who are unable to produce a thrombus. When re-bleeding or break-through bleeding occurs following coil embolization, risk of mortality increases 10-fold (6). We hypothesize that by using a cutting-edge off-the-shelf injectable hemostatic biomaterial, we can reduce morbidity/mortality; and for the first time, we can treat bleeding patients that are on anticoagulation or are coagulopathic (i.e., disseminated intravascular coagulation (DIC)). Our novel approach uses a universal shear-thinning biomaterial (STB) that creates an impenetrable cast of the bleeding vessel without relying on thrombosis for efficacy. In this proposal, we will further optimize the three candidate STB formulations (Aim 1), test them in in vitro and ex vivo artery models (Aim 2) and finally evaluate the performance of the STBs in the anticoagulated porcine models of embolization (Aim 3).

Public Health Relevance

Hemorrhage in a setting of anticoagulation is a serious medical emergency associated with high morbidity and mortality especially in patients with mechanical valves or cardiac assist devices. We propose to develop a universal ?one-size-fits-all? shear-thinning biomaterial that could be delivered using endovascular catheters to create an impenetrable cast of the bleeding vessel that does not require thrombosis for efficacy, making re- bleeding and break-through bleeding in the gastrointestinal tract a non-issue.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL137193-01
Application #
9301809
Study Section
Medical Imaging Study Section (MEDI)
Program Officer
Warren, Ronald Q
Project Start
2017-06-01
Project End
2022-03-31
Budget Start
2017-06-01
Budget End
2018-03-31
Support Year
1
Fiscal Year
2017
Total Cost
$614,299
Indirect Cost
$115,500
Name
Mayo Clinic, Arizona
Department
Type
Other Domestic Non-Profits
DUNS #
153665211
City
Scottsdale
State
AZ
Country
United States
Zip Code
85259
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