Sasha Bakhru, CEO, Perosphere Technologies04.29.24
For healthcare providers, persistent challenges in diagnostic testing for coagulation have contributed to shortfalls that create difficulties in decision-making and treatment. For diagnosticians, the challenge has historically been that the assays available for evaluating coagulation are fairly specific to one drug or drug class or another.
Take PT/INR and aPTT as examples. PT/INR is a great test for warfarin, and aPTT is a great test for unfractionated heparin, but a patient can be fully warfarinized and have a normal aPTT and a patient could be fully heparinized and have a normal PT/INR. So, a normal value on each of these tests will not tell you that your patient may not be clotting normally.
These particular tests are, to a large extent, treated as general tests of coagulation status. They are not, and if taken as such, that can be dangerously misleading. For example, say a patient is fully anticoagulated on a DOAC, drugs for which these commonly used tests are not sensitive, however, the tests are ordered by the health care provider and come back normal. But because these tests are drug-class specific, the DOAC patient is fully anticoagulated but returns absolutely normal PT and aPTT results. This is highly problematic because the tests failed to discover the patient’s fully anticoagulated status, giving the provider what amounts to a false sense of security.
That's a significant challenge in a number of different contexts. Bleeds, stroke, emergency surgery, these are all areas where a care provider would want to know if a patient’s coagulation status is normal or abnormal. Based on the currently available tests, you could believe a patient’s coagulation status to be normal when it’s actually not.
There have been significant advancements in point-of-care testing in general for coagulation, including PT/INR, aPTT, ACT, or thromboelastography. The format of the tests, the turnaround times, and ease of use have all been improving. Rather than having to prepare everything manually (for example, mixing-up reagents de novo), there are kits and cartridges that these tests will accept, and much of the data processing required for tests is now already done for providers. Similarly, with thromboelastography for perioperative coagulation testing, especially when you're using unfractionated heparin, some of the currently available tests are much easier to use.
While those improvements and advancements are helpful in certain contexts, they aren’t helpful in others. In particular, the issue discussed above around anticoagulant testing remains the same. While there is now a faster, easier to use PT/INR test, it's still a PT/INR test for warfarin only, and despite these broad improvements, significant needs still aren’t being fully addressed. There is currently no universal diagnostic test that will tell you the coagulation status of a patient, agnostic to their anticoagulant drug.
There is growing recognition of this particular need. Certain trends in the conceptualization of diagnostic tools, especially the emergence of handheld, point-of-care devices, is having an influence on thinking throughout the industry. There's a growing, understandable desire for devices that work with smaller sample sizes and which provide quicker readouts; that's a common trend, and there are good reasons for it.
As a care provider, you may not always be in a conventional healthcare setting. Very often, providers need to conduct screenings and tests in environments such as ambulances, rural health clinics, the sites of natural disasters, field hospitals, relief camps, or other settings without ready access to lab facilities, cardiology units, or other resources. Under these circumstances, drawing a large blood sample and sending it out to a lab will simply be impractical. In that sense, the constraint of a small sample size and the need for a quick diagnostic result directly impact diagnostics and care.
What we are seeing now is the beginning of a trend in diagnostics that addresses these needs based on technological advances. Such technologies will have a positive impact on patient care and help improve accessibility, enhance precision and drive better reliability to achieve better outcomes.
The relationship between diagnostics and drugs is only going to get more intimate over time, and the more personalized we get, the better we can tailor care. While this has been especially true in coagulation testing, whether we are talking about coagulation or other diagnostic needs, having a way to evaluate drug effect at the point of care that yields answers that can be acted on in a relevant timeframe will empower physicians to make better, faster decisions.
There will be challenges in implementing advanced diagnostic technologies into clinical practice, and that will call for education and practical implementation strategies. Sometimes the problems a new technology can address are very clear to a physician because they’re dealing with the issues these technologies may solve for on a daily basis. However, in other cases, without the solution readily available, the problem may not even be apparent to the physician. And this requires educating the provider about the problems that new technology is able to address.
Introducing a technology that is truly new may also require education that helps providers to realize where it fits in a clinical setting. New advancements are not often easily accepted; that's where demonstrating the solutions’ utility and efficacy is needed. This kind of provider education requires an investment of time and effort, but it’s necessary in order to improve patient care. Only through this investment in education can point-of-care or bedside/office solutions be accepted and fit into clinical workflow, and provide physicians and nurses with rapid results, giving them the information they need to make informed clinical decisions.
In the case of acceptance of these new technologies, the regulatory environments are harmonizing in many respects. There used to be fairly significant differences between the regulatory requirements for a clearance of an in-vitro diagnostic point-of-care device in Europe versus the United States, for example. But now with the introduction of in vitro diagnostic device regulation, requirements that need to be met to demonstrate safety and efficacy in the EU are much closer to US regulations. In addition, there should be consideration given to those whose diagnostic solutions for approaching an orphan disease or serving a small fraction of a particular at-risk population, and it appears that regulators are more sensitive to this.
As the diagnostic industry moves forward, coagulation testing will evolve. In the past, the trend was toward specificity in the approach to coagulation testing. The industry went from aPTT and PT/INR, which again were largely drug-class specific, to developing chromogenic assays that are specific to one factor or another. But with the interplay between drugs and anticoagulant reversal agents that has emerged, we must move in the opposite direction; otherwise, diagnosticians are left in a situation where they can measure the activity of one particular factor, but because of the mechanism of action of the reversal or replacement therapy, they can't measure reversal using the same test. That leaves the diagnostician in a difficult position.
I believe the industry broadly recognizes this problem, and is moving toward a more global overall status. Because there's so much more interplay between the various drugs, reversal agents, and drug-drug interactions, moving toward a universal point-of-care solution that rapidly provides results within the workflow of the clinician is the only approach that makes sense for diagnosticians and for the patients they serve.
Sasha H. Bakhru, PhD, President and CEO, Perosphere Technologies: Dr. Bakhru is a Founder of Perosphere Inc. (now Perosphere Technologies Inc. and Perosphere Pharmaceuticals Inc.), an Adjunct Assistant Professor of Medical Science at Brown University, and Lecturer in Entrepreneurship.
He is a member of the Scientific Advisory Board of Amylyx Pharmaceuticals. Dr. Bakhru has co-authored over 30 publications, ten patents, and one book chapter. His work has been published in 40 conference proceedings and abstracts. Dr. Bakhru received a BS in Biomedical Engineering from Columbia University, an MSE from Johns Hopkins University in Materials Engineering, and a PhD from Carnegie Mellon University in Biomedical Engineering as a Dowd Fellow in the Institute for Complex Engineered Systems. He was winner of the 2008 Global MOOT Corp competition, and in 2009, received the Carnegie Mellon Tepper School of Business “Entrepreneur of the Year” and “Manufacturing Entrepreneur of the Year” alumni prizes.
Take PT/INR and aPTT as examples. PT/INR is a great test for warfarin, and aPTT is a great test for unfractionated heparin, but a patient can be fully warfarinized and have a normal aPTT and a patient could be fully heparinized and have a normal PT/INR. So, a normal value on each of these tests will not tell you that your patient may not be clotting normally.
These particular tests are, to a large extent, treated as general tests of coagulation status. They are not, and if taken as such, that can be dangerously misleading. For example, say a patient is fully anticoagulated on a DOAC, drugs for which these commonly used tests are not sensitive, however, the tests are ordered by the health care provider and come back normal. But because these tests are drug-class specific, the DOAC patient is fully anticoagulated but returns absolutely normal PT and aPTT results. This is highly problematic because the tests failed to discover the patient’s fully anticoagulated status, giving the provider what amounts to a false sense of security.
That's a significant challenge in a number of different contexts. Bleeds, stroke, emergency surgery, these are all areas where a care provider would want to know if a patient’s coagulation status is normal or abnormal. Based on the currently available tests, you could believe a patient’s coagulation status to be normal when it’s actually not.
There have been significant advancements in point-of-care testing in general for coagulation, including PT/INR, aPTT, ACT, or thromboelastography. The format of the tests, the turnaround times, and ease of use have all been improving. Rather than having to prepare everything manually (for example, mixing-up reagents de novo), there are kits and cartridges that these tests will accept, and much of the data processing required for tests is now already done for providers. Similarly, with thromboelastography for perioperative coagulation testing, especially when you're using unfractionated heparin, some of the currently available tests are much easier to use.
While those improvements and advancements are helpful in certain contexts, they aren’t helpful in others. In particular, the issue discussed above around anticoagulant testing remains the same. While there is now a faster, easier to use PT/INR test, it's still a PT/INR test for warfarin only, and despite these broad improvements, significant needs still aren’t being fully addressed. There is currently no universal diagnostic test that will tell you the coagulation status of a patient, agnostic to their anticoagulant drug.
There is growing recognition of this particular need. Certain trends in the conceptualization of diagnostic tools, especially the emergence of handheld, point-of-care devices, is having an influence on thinking throughout the industry. There's a growing, understandable desire for devices that work with smaller sample sizes and which provide quicker readouts; that's a common trend, and there are good reasons for it.
As a care provider, you may not always be in a conventional healthcare setting. Very often, providers need to conduct screenings and tests in environments such as ambulances, rural health clinics, the sites of natural disasters, field hospitals, relief camps, or other settings without ready access to lab facilities, cardiology units, or other resources. Under these circumstances, drawing a large blood sample and sending it out to a lab will simply be impractical. In that sense, the constraint of a small sample size and the need for a quick diagnostic result directly impact diagnostics and care.
What we are seeing now is the beginning of a trend in diagnostics that addresses these needs based on technological advances. Such technologies will have a positive impact on patient care and help improve accessibility, enhance precision and drive better reliability to achieve better outcomes.
The relationship between diagnostics and drugs is only going to get more intimate over time, and the more personalized we get, the better we can tailor care. While this has been especially true in coagulation testing, whether we are talking about coagulation or other diagnostic needs, having a way to evaluate drug effect at the point of care that yields answers that can be acted on in a relevant timeframe will empower physicians to make better, faster decisions.
There will be challenges in implementing advanced diagnostic technologies into clinical practice, and that will call for education and practical implementation strategies. Sometimes the problems a new technology can address are very clear to a physician because they’re dealing with the issues these technologies may solve for on a daily basis. However, in other cases, without the solution readily available, the problem may not even be apparent to the physician. And this requires educating the provider about the problems that new technology is able to address.
Introducing a technology that is truly new may also require education that helps providers to realize where it fits in a clinical setting. New advancements are not often easily accepted; that's where demonstrating the solutions’ utility and efficacy is needed. This kind of provider education requires an investment of time and effort, but it’s necessary in order to improve patient care. Only through this investment in education can point-of-care or bedside/office solutions be accepted and fit into clinical workflow, and provide physicians and nurses with rapid results, giving them the information they need to make informed clinical decisions.
In the case of acceptance of these new technologies, the regulatory environments are harmonizing in many respects. There used to be fairly significant differences between the regulatory requirements for a clearance of an in-vitro diagnostic point-of-care device in Europe versus the United States, for example. But now with the introduction of in vitro diagnostic device regulation, requirements that need to be met to demonstrate safety and efficacy in the EU are much closer to US regulations. In addition, there should be consideration given to those whose diagnostic solutions for approaching an orphan disease or serving a small fraction of a particular at-risk population, and it appears that regulators are more sensitive to this.
As the diagnostic industry moves forward, coagulation testing will evolve. In the past, the trend was toward specificity in the approach to coagulation testing. The industry went from aPTT and PT/INR, which again were largely drug-class specific, to developing chromogenic assays that are specific to one factor or another. But with the interplay between drugs and anticoagulant reversal agents that has emerged, we must move in the opposite direction; otherwise, diagnosticians are left in a situation where they can measure the activity of one particular factor, but because of the mechanism of action of the reversal or replacement therapy, they can't measure reversal using the same test. That leaves the diagnostician in a difficult position.
I believe the industry broadly recognizes this problem, and is moving toward a more global overall status. Because there's so much more interplay between the various drugs, reversal agents, and drug-drug interactions, moving toward a universal point-of-care solution that rapidly provides results within the workflow of the clinician is the only approach that makes sense for diagnosticians and for the patients they serve.
Sasha H. Bakhru, PhD, President and CEO, Perosphere Technologies: Dr. Bakhru is a Founder of Perosphere Inc. (now Perosphere Technologies Inc. and Perosphere Pharmaceuticals Inc.), an Adjunct Assistant Professor of Medical Science at Brown University, and Lecturer in Entrepreneurship.
He is a member of the Scientific Advisory Board of Amylyx Pharmaceuticals. Dr. Bakhru has co-authored over 30 publications, ten patents, and one book chapter. His work has been published in 40 conference proceedings and abstracts. Dr. Bakhru received a BS in Biomedical Engineering from Columbia University, an MSE from Johns Hopkins University in Materials Engineering, and a PhD from Carnegie Mellon University in Biomedical Engineering as a Dowd Fellow in the Institute for Complex Engineered Systems. He was winner of the 2008 Global MOOT Corp competition, and in 2009, received the Carnegie Mellon Tepper School of Business “Entrepreneur of the Year” and “Manufacturing Entrepreneur of the Year” alumni prizes.