News, Analysis, Trends, Management Innovations for
Clinical Laboratories and Pathology Groups

Hosted by Robert Michel

News, Analysis, Trends, Management Innovations for
Clinical Laboratories and Pathology Groups

Hosted by Robert Michel
Sign In

Brigham and Women’s Hospital Researchers Develop Blood Test That Enables Rapid Diagnosis of LVO Stroke in Non-hospital Settings

New technique could allow emergency responders to determine severity of LVO stroke while patient is still in the ambulance

Researchers at Brigham and Women’s Hospital in Massachusetts say they have developed a clinical laboratory test that can quickly determine whether a patient is experiencing one of the deadliest types of strokes, known as an ischemic large vessel occlusion (LVO) stroke. The development team believes this new assay could be deployed as a point-of-care test to enable faster diagnosis of stroke events.

The test combines measurement of two blood plasma biomarkers with an established clinical score used by clinicians and EMS personnel to assess stroke severity. Compared with current approaches, their technique more accurately differentiates LVO strokes from other types of strokes, making it more likely that patients receive appropriate treatment in a timely manner, the researchers said in a Brigham news release.

Dark Daily has long predicted that advances in technology and computing power would make it possible for pathologists and clinical laboratory scientists to combine multiple established biomarkers (individually not associated with the disease state targeted) with other clinical and patient data to create the ability to make an accurate and earlier diagnosis.

The researchers published their findings in the journal Stroke: Vascular and Interventional Neurology titled, “Prospective Validation of Glial Fibrillary Acidic Protein, d‐Dimer, and Clinical Scales for Acute Large‐Vessel Occlusion Ischemic Stroke Detection.”

Ultimately, Brigham’s research could “aid in the development of a point‐of‐care diagnostic test capable of guiding prehospital LVO stroke triage,” wrote Joshua Bernstock, MD, PhD, Clinical Fellow in Neurosurgery at Brigham and Women’s Hospital, lead author of the study, and colleagues.

“We have developed a game-changing, accessible tool that could help ensure that more people suffering from stroke are in the right place at the right time to receive critical, life-restoring care,” said Joshua Bernstock, MD, PhD (above), Clinical Fellow in Neurosurgery at Brigham and Women’s Hospital and lead author of the Brigham study that developed the clinical laboratory test that the researchers say can enable emergency caregivers to determine quickly and accurately if a patient is having an ischemic large vessel occlusion (LVO) stroke. (Photo copyright: Brigham and Women’s Hospital.)

Early Identification of LVO Stroke

As explained in the news release, an LVO stroke is a type of ischemic stroke caused by obstruction in a major brain artery. The researchers noted that LVO strokes account for “62% of poststroke disabilities and 96% of poststroke death.”

These strokes are readily treatable using endovascular thrombectomy (EVT), in which the blockages are surgically removed, the news release note. However, the researchers observed that EVT “requires specialized teams and equipment, limiting its availability to comprehensive stroke centers and other EVT‐capable centers.”

This can lead to delays as patients are transferred to those facilities, worsening outcomes and increasing the risk of death, the researchers wrote in Stroke: Vascular and Interventional Neurology. So, early identification of LVO stroke is key to ensuring patients receive timely treatment.

Identifying False Negatives/Positives

One challenge, the news release notes, is that brain bleeds (hemorrhagic stroke) can present similar symptoms, yet require “vastly different” treatment.

“A growing body of work has, therefore, evaluated prehospital stroke assessment scales in an effort to identify LVO strokes in the field,” the researchers wrote. “However, such severity scales lack the sensitivity and specificity required for triaging LVO patients with confidence, resulting in false negatives in patients with LVO as well as false positives in patients with stroke mimics or hemorrhagic stroke.”

As explained by EMS Aware, these assessment scales, such as FAST-ED (field assessment stroke triage for emergency destination) and RACE (rapid arterial occlusion evaluation), attempt to determine the severity of a stroke by assigning scores based on symptoms such as facial palsy, arm weakness, and speech difficulties.

To develop their test, Bernstock and colleagues proposed combining the scales with measurement of two blood proteins:

In their study, they attempted to validate cutoff values for the biomarkers and scales.

To do so, the researchers analyzed data from 323 patients admitted to a Florida hospital with suspected stroke between May 2021 and August 2022. Each was assigned to one of four diagnostic categories based on clinical data from their medical records, which included results of computed tomography (CT scan) or magnetic resonance angiography (MRA). The diagnostic categories included:

The patients were assessed using five stroke severity scales. The researchers used frozen blood samples from the patients to measure the biomarkers. They then used this data to determine the likelihood of LVO stroke and compared the results with the diagnoses as determined by the clinical data.

“Combinations of the blood biomarkers with the scales FAST‐ED or RACE showed the best performance for LVO detection, with a specificity of 94% (for either scale combination) and a sensitivity of 71% for both scales,” the researchers wrote.

Sensitivity was higher in patients who presented within the first six hours from onset of symptoms.

“Critically, application of the biomarker and stroke scale algorithms ruled out all patients with hemorrhage,” the researchers wrote. However, they also suggested that their algorithm could be adjusted to enable early identification of hemorrhagic stroke.

The researchers noted that they chose biomarker cutoffs to maximize specificity, so “a certain number of LVOs are missed. However, as such patients default into ‘standard‐of‐care’ triaging pathways, such a decision is unlikely to represent much clinical risk.”

Testing in the Field

The Brigham researchers used established biological biomarkers combined with modern computing—in combination with the scores from a field assessment test—to develop their new clinical laboratory test that identifies the type of stroke.

Their next step is to carry out “another prospective trial to measure the test’s performance when used in an ambulance,” the news release states. “They have also designed an interventional trial that leverages the technology to expedite the triage of stroke patients by having them bypass standard imaging and move directly to intervention.”

“In stroke care, time is brain,” Bernstock said. “The sooner a patient is put on the right care pathway, the better they are going to do. Whether that means ruling out bleeds or ruling in something that needs an intervention, being able to do this in a prehospital setting with the technology that we built is going to be truly transformative.”

More research and clinical studies are needed. However, the fact that the Brigham team wants to deploy this approach in ambulances is an indication that there is high clinical value from this approach.

Clinical pathologists and medical laboratory managers will want to watch the ongoing development and deployment of this new assay, whether it is run in near-patient settings or core clinical laboratories in support of patients presenting in emergency departments.

—Stephen Beale

Related Information:

Researchers Develop “Game-Changing” Blood Test for Stroke Detection

Prospective Validation of Glial Fibrillary Acidic Protein, d‐Dimer, and Clinical Scales for Acute Large‐Vessel Occlusion Ischemic Stroke Detection

New Blood Test Could Spot Dangerous Type of Stroke

Researchers Develop a Blood Test That Can Detect Stroke Quickly

Blood Test a ‘Game Changer’ for Faster Diagnosis, Treatment of LVO Stroke

New Rapid Blood Test Can Accurately Detect Stroke in Six Hours, Save Lives

Study at Boston’s Beth Israel Deaconess Medical Center Determines that 30% of All Clinical Laboratory Tests Are Overused or Medically Unnecessary

BIDMC researchers show that, on average, 30% of all lab tests may be unnecessary and that an equal percentage of tests should not be ordered at all

Every pathologist and clinical laboratory professional knows how often physicians order a medical laboratory test that is inappropriate or unnecessary. That is a problem because, each time a clinician orders an inappropriate test, patient harm is possible. Yet this issue gets little attention from the medical profession at large.

Thus, it is significant that researchers at Beth Israel Deaconess Medical Center (BIDMC), published a study last fall showing that 30% of all medical laboratory tests throughout medicine are overused! A different 30% of medical laboratory tests are underused, as well. (more…)

“Choosing Wisely” Program Wants to Encourage Better Utilization of Clinical Pathology Laboratory Tests

New lab test market could open up if research findings lead Consumer Reports and nine medical specialty associates join forces to target the overuse of certain diagnostic procedures, including some medical laboratory tests

For years, pathologists and physicians have spoken out about the overuse of medical laboratory tests and other diagnostic procedures. Now an interesting alliance of a medical specialty association and Consumer Reports has come together with a highly-publicized plan designed to reduce unnecessary or inappropriate testing by encouraging physicians to more deeply involve patients in the process.

It is the American Board of Internal Medicine Foundation (ABIMF) that is working with Consumer Reports. Their common goal is to stanch the overuse of unnecessary healthcare tests and procedures that do not improve patient outcomes and do run up healthcare costs. Experts estimate the wasteful use of healthcare resources accounts for as much as 30% of current healthcare costs in the United States.

The program is called “Choosing Wisely” (CW). According to a story in Modern Healthcare (MH), “Choosing Wisely” is a campaign to get physicians and patients to discuss whether a particular test is likely to improve patient health or outcome.

Choosing Wisely by Amc Soc Nephrologycrop

Pictured above is the press conference conducted by the American Board of Internal Medicine Foundation (ABIMF) to announce the launch of the “Choosing Wisely” campaign. The goal of this campaign is to reduce overutilization or unnecessary ordering of diagnostic procedures. Each of nine medical specialty associations has put forth a list of specific diagnostic procedures that should be part of this campaign and a number of clinical laboratory tests are on these lists. (Photo copyright by American Society of Nephrology.)

Participating in this initiative are about 375,000 physicians in nine specialty societies. Each of these nine medical specialty groups has identified five diagnostic tests or procedures within their specialty area that warrant re-evaluation by physicians and patients as to whether they will provide useful information or lead to a positive outcome. Clinical laboratory managers and pathologists will be interested to learn that a number of these medical specialty associations have included clinical laboratory tests on their respective lists.

“What we’re asking for is for people to have a conversation,” stated Daniel B. Wolfson, M.H.S.A., ABIM Foundation Executive Vice President and Chief Operating Officer, in the MH story. “These are not rules; they are guidelines used to guide most—but not all—cases,” he explained.

Writing in a commentary in The Huffington Post (HP), Donald M. Berwick, M.D., Chief Executive Officer of the Institute for Healthcare Improvement and former Administrator of the U.S. Centers for Medicare & Medicaid Services, called the program a game-changer. The physician specialty societies support their claims of overuse with copious scientific citations, Berwick noted.

“These societies have shown tremendous leadership in starting a long overdue and important conversation between physicians and patients about what care is really needed,” said Christine K. Cassel, M.D., President and Chief Executive Officer of the ABMF. “Physicians, working together with patients, can help ensure the right care is delivered at the right time for the right patient.” She was quoted in a Choosing Wisely press release.

According to the release, Consumer Reports is working with American Association of Retired People (AARP) and other organizations representing the lay public to get the word out about the “Choosing Wisely” campaign.

Specialist Physicians Identify Some Medical Laboratory Tests for Review

Below are listed the recommendations made by the different medical specialty associations that identify a clinical laboratory test:

American Academy of Allergy, Asthma & Immunology

  • Don’t perform unproven diagnostic tests, such as immunoglobulin G (IgG) testing or an indiscriminate battery of immunoglobulin E (IgE) tests, in the evaluation of allergy.
  • Don’t routinely do diagnostic testing in patients with chronic urticaria.
  • Don’t recommend replacement immunoglobulin therapy for recurrent infections unless impaired antibody responses to vaccines are demonstrated.

American Academy of Family Physicians

  • Don’t perform Pap smears on women younger than 21 or who have had a hysterectomy for non-cancer disease. read article.

American College of Physicians

  • In patients with low pretest probability of venous thromboembolism (VTE), obtain a high-sensitive D-dimer measurement as the initial diagnostic test; don’t obtain imaging studies as the initial diagnostic test.

American Society of Clinical Oncology

  • Don’t perform surveillance testing (biomarkers) or imaging… for asymptomatic individuals who have been treated for breast cancer with curative intent.
  • Don’t use white cell stimulating factors for primary prevention of febrile neutropenia for patients with less than 20% risk for this complication.

American Society of Nephrology

  • Don’t perform routine cancer screening for dialysis patients with limited life expectancies without signs or symptoms.
  • Don’t administer erythropoiesis-stimulating agents (ESAs) to chronic kidney disease (CKD) patients with hemoglobin levels greater than or equal to 10g/dL without symptoms or anemia.

In its coverage of the “Choosing Wisely” initiative, Clinical Laboratory News, a publication of  the American Association for Clinical Chemistry, (AACC) reported that the utilization changes CW seeks may sound like bad news for the lab,. But sometimes these types of program can end up promoting appropriate clinical laboratory testing over other options, the writer noted.

Medical laboratories should emphasize making sure the right clinical lab tests are used at the right time, suggested Stephen E. Kahn, Ph.D., Chair of AACC’s Evidence-Based Laboratory Medicine Committee.

The “Choosing Wisely” initiative, at a minimum, does provide another opportunity for pathologists and clinical laboratory managers to add value to physicians and their patients by helping clinicians have confidence they they are ordering the right test at the right time, supported by evidence-based medicine (EBM) guidelines.

—Pamela Scherer McLeod

Related Information:

U.S. Physician Groups Identify Commonly Used Tests or Procedures They Say Are Often Not Necessary

“Choosing Wisely”: Physicians Step to the Front in Health Care Reform

June 2012 Clinical Laboratory News: Screening Tests in the Age of Austerity

;