Aspirin Response Testing Aids TBI Management in Small Study

DETROIT – Incorporation of aspirin response testing can improve traumatic brain injury management algorithms, a small study suggests.

"It allows us to identify and thereby treat occult platelet inhibition, target platelet transfusion to those who are truly platelet inhibited, and assures adequate response to platelet therapy when it is given," Dr. Joshua Bautz said at the annual meeting of the Central Surgical Association.

The rising use of antiplatelet medications in America’s aging population has prompted many trauma centers to use empiric transfusion of platelet therapy in the setting of traumatic brain injury (TBI) when use of aspirin and other antiplatelet medications are suspected. But the approach is not without consequences.

Aspirin response testing (ART), which was originally designed for use in cardiac patients to assess the effectiveness of antiplatelet medication, has taken on a second role of objectively evaluating platelet inhibition in the setting of TBI when aspirin use is suspected.

Dr. Bautz reported on 84 patients, median age 78 years, who presented from 2008 to 2009 at the University of Pittsburgh Medical Center with a TBI confirmed on head computed tomography (CT). Of these, 45% had a subdural hematoma, 27% a subarachnoid hemorrhage, and 16.5% a combination of hemorrhages.

In all, 36 had a known aspirin history and 48 had no known history or an unobtainable history of aspirin use.

Platelet inhibition was defined by an aspirin response test of less than 550 aspirin response units (ARU) on the VerifyNow Aspirin Test (Accumetrics Inc., San Diego). Patients found to be inhibited received platelet transfusion and a repeat ART test was performed 1 hour following transfusion. If the follow-up ART test again showed platelet inhibition, additional platelets were transfused until the patient was no longer suppressed.

In all, 42% of patients with no known history of aspirin use were objectively shown to have aspirin inhibition, said Dr. Bautz, a second-year resident at the university. In contrast, only two patients with a known aspirin history had normal platelet function and 34 had aspirin inhibition.

As expected, patients with a known aspirin history had significantly lower ART results than did those with an unknown aspirin history (mean 471 ARUs vs. 564 ARUs), he said. All other outcomes were similar between groups including head CT progression (26.5% vs. 27%), craniotomy (5.6% vs. 8.5%) and mortality (11% vs. 6.4%).

When the researchers looked at the effect of platelet inhibition on follow-up ART testing, 64% of the 54 patients with an initial positive ART test showed reversal of platelet inhibition on their first follow-up ART test.

"This means that almost one-third of patients did not show a return to normal platelet functioning after a single transfusion of platelets," he said. Nine patients were taken urgently to the OR, died, or were given comfort medications only.

Of the 16 nonresponders, 12 (77%) ultimately showed reversal of their platelet inhibition on follow-up platelet administration and ART testing. Three patients, however, did not return to normal platelet functioning, despite more than three platelet transfusions. Dr. Bautz pointed out.

Initial responders received a significantly greater volume of platelets than did nonresponders (median eight platelet packs vs. six platelet packs), suggesting a dose-response relationship, he said. The mean increase was 70 ARUs per six-pack of platelets.

"A standard six-pack of platelets may not be sufficient, suggesting a benefit of post-transfusion ART," he said.

In all, 91% of patients were restored to normal platelet function.

In regression analysis, there was no significant association between aspirin history or ART results and CT progression, mortality, craniotomy or composite outcomes. Subgroup analysis, however, revealed a trend toward higher mortality for nonresponders, Dr. Bautz said.

"A significant number of traumatic brain injury patients may have occult aspirin inhibition, which is not revealed by history alone," he concluded. "This is in contrast to a rather small number of patients that were shown to have normal platelet functioning and a known history of aspirin, despite high levels of aspirin insensitivity in our population."

Overall, 25% of patients in the series showed progression on follow-up CT, 13% required a craniotomy, and 9.4% died.

The study excluded patients with a history of platelet inhibitors other than aspirin, ongoing use of warfarin (Coumadin), or an International Normalized Ratio of more than 1.5 and those with any epidural component to their TBI.

Invited discussant Dr. Maggie Brandt, with St. Joseph Mercy Hospital in Ann Arbor, Mich., said "the idea of testing for platelets is really spot on and really relevant, but I don’t know if its practical for this problem."

In particular, Dr. Brandt was troubled by the number of patients who did not have a history of aspirin therapy, but were aspirin inhibited, and said it is unclear whether this is a function of other comorbidities or of the test itself. She asked whether ADT testing should be conducted in all TBI patients and whether it is practical to do so based on cost and turnaround time.

Dr. Bautz explained that the high number of patients without an aspirin history in the study is likely because these patients were unable to provide a history upon presentation for TBI. "It is in this setting, that we feel our test is of the most value," he said.

The test typically takes 40 minutes, including laboratory and transport time, and costs about $40 per test, he said.

Audience member Dr. Jonathan Saxe, professor of surgery at Wright State University in Dayton, Ohio, said that brain injury itself has been known to cause issues with aspirin testing and asked whether the brain injuries in the cohort could be causing the platelet test to be abnormal rather than the aspirin. He also pointed out that his group published a similar study finding no impact on mortality with platelet transfusion in elderly TBI patients taking aspirin or clopidogrel (Am. Surg. 2009;75:1100-3). "So I’m wondering, if giving platelets really does anything," he said.

Dr. Bautz said that the ADT test has demonstrated a sensitivity of almost 100% and specificity of 88% at his institution for showing aspirin inhibition. "So it is our belief these patients are on aspirin and that is the cause of their platelet inhibition."

A randomized controlled trial using objective measures of platelet inhibition is necessary to quantify platelet administration in patients presenting with TBI, he said.

The authors reported no conflicts of interest.

DETROIT – Incorporation of aspirin response testing can improve traumatic brain injury management algorithms, a small study suggests.

"It allows us to identify and thereby treat occult platelet inhibition, target platelet transfusion to those who are truly platelet inhibited, and assures adequate response to platelet therapy when it is given," Dr. Joshua Bautz said at the annual meeting of the Central Surgical Association.

The rising use of antiplatelet medications in America’s aging population has prompted many trauma centers to use empiric transfusion of platelet therapy in the setting of traumatic brain injury (TBI) when use of aspirin and other antiplatelet medications are suspected. But the approach is not without consequences.

Aspirin response testing (ART), which was originally designed for use in cardiac patients to assess the effectiveness of antiplatelet medication, has taken on a second role of objectively evaluating platelet inhibition in the setting of TBI when aspirin use is suspected.

Dr. Bautz reported on 84 patients, median age 78 years, who presented from 2008 to 2009 at the University of Pittsburgh Medical Center with a TBI confirmed on head computed tomography (CT). Of these, 45% had a subdural hematoma, 27% a subarachnoid hemorrhage, and 16.5% a combination of hemorrhages.

In all, 36 had a known aspirin history and 48 had no known history or an unobtainable history of aspirin use.

Platelet inhibition was defined by an aspirin response test of less than 550 aspirin response units (ARU) on the VerifyNow Aspirin Test (Accumetrics Inc., San Diego). Patients found to be inhibited received platelet transfusion and a repeat ART test was performed 1 hour following transfusion. If the follow-up ART test again showed platelet inhibition, additional platelets were transfused until the patient was no longer suppressed.

In all, 42% of patients with no known history of aspirin use were objectively shown to have aspirin inhibition, said Dr. Bautz, a second-year resident at the university. In contrast, only two patients with a known aspirin history had normal platelet function and 34 had aspirin inhibition.

As expected, patients with a known aspirin history had significantly lower ART results than did those with an unknown aspirin history (mean 471 ARUs vs. 564 ARUs), he said. All other outcomes were similar between groups including head CT progression (26.5% vs. 27%), craniotomy (5.6% vs. 8.5%) and mortality (11% vs. 6.4%).

When the researchers looked at the effect of platelet inhibition on follow-up ART testing, 64% of the 54 patients with an initial positive ART test showed reversal of platelet inhibition on their first follow-up ART test.

"This means that almost one-third of patients did not show a return to normal platelet functioning after a single transfusion of platelets," he said. Nine patients were taken urgently to the OR, died, or were given comfort medications only.

Of the 16 nonresponders, 12 (77%) ultimately showed reversal of their platelet inhibition on follow-up platelet administration and ART testing. Three patients, however, did not return to normal platelet functioning, despite more than three platelet transfusions. Dr. Bautz pointed out.

Initial responders received a significantly greater volume of platelets than did nonresponders (median eight platelet packs vs. six platelet packs), suggesting a dose-response relationship, he said. The mean increase was 70 ARUs per six-pack of platelets.

"A standard six-pack of platelets may not be sufficient, suggesting a benefit of post-transfusion ART," he said.

In all, 91% of patients were restored to normal platelet function.

In regression analysis, there was no significant association between aspirin history or ART results and CT progression, mortality, craniotomy or composite outcomes. Subgroup analysis, however, revealed a trend toward higher mortality for nonresponders, Dr. Bautz said.

"A significant number of traumatic brain injury patients may have occult aspirin inhibition, which is not revealed by history alone," he concluded. "This is in contrast to a rather small number of patients that were shown to have normal platelet functioning and a known history of aspirin, despite high levels of aspirin insensitivity in our population."

Overall, 25% of patients in the series showed progression on follow-up CT, 13% required a craniotomy, and 9.4% died.

The study excluded patients with a history of platelet inhibitors other than aspirin, ongoing use of warfarin (Coumadin), or an International Normalized Ratio of more than 1.5 and those with any epidural component to their TBI.

Invited discussant Dr. Maggie Brandt, with St. Joseph Mercy Hospital in Ann Arbor, Mich., said "the idea of testing for platelets is really spot on and really relevant, but I don’t know if its practical for this problem."

In particular, Dr. Brandt was troubled by the number of patients who did not have a history of aspirin therapy, but were aspirin inhibited, and said it is unclear whether this is a function of other comorbidities or of the test itself. She asked whether ADT testing should be conducted in all TBI patients and whether it is practical to do so based on cost and turnaround time.

Dr. Bautz explained that the high number of patients without an aspirin history in the study is likely because these patients were unable to provide a history upon presentation for TBI. "It is in this setting, that we feel our test is of the most value," he said.

The test typically takes 40 minutes, including laboratory and transport time, and costs about $40 per test, he said.

Audience member Dr. Jonathan Saxe, professor of surgery at Wright State University in Dayton, Ohio, said that brain injury itself has been known to cause issues with aspirin testing and asked whether the brain injuries in the cohort could be causing the platelet test to be abnormal rather than the aspirin. He also pointed out that his group published a similar study finding no impact on mortality with platelet transfusion in elderly TBI patients taking aspirin or clopidogrel (Am. Surg. 2009;75:1100-3). "So I’m wondering, if giving platelets really does anything," he said.

Dr. Bautz said that the ADT test has demonstrated a sensitivity of almost 100% and specificity of 88% at his institution for showing aspirin inhibition. "So it is our belief these patients are on aspirin and that is the cause of their platelet inhibition."

A randomized controlled trial using objective measures of platelet inhibition is necessary to quantify platelet administration in patients presenting with TBI, he said.

The authors reported no conflicts of interest.

DETROIT – Incorporation of aspirin response testing can improve traumatic brain injury management algorithms, a small study suggests.

"It allows us to identify and thereby treat occult platelet inhibition, target platelet transfusion to those who are truly platelet inhibited, and assures adequate response to platelet therapy when it is given," Dr. Joshua Bautz said at the annual meeting of the Central Surgical Association.

The rising use of antiplatelet medications in America’s aging population has prompted many trauma centers to use empiric transfusion of platelet therapy in the setting of traumatic brain injury (TBI) when use of aspirin and other antiplatelet medications are suspected. But the approach is not without consequences.

Aspirin response testing (ART), which was originally designed for use in cardiac patients to assess the effectiveness of antiplatelet medication, has taken on a second role of objectively evaluating platelet inhibition in the setting of TBI when aspirin use is suspected.

Dr. Bautz reported on 84 patients, median age 78 years, who presented from 2008 to 2009 at the University of Pittsburgh Medical Center with a TBI confirmed on head computed tomography (CT). Of these, 45% had a subdural hematoma, 27% a subarachnoid hemorrhage, and 16.5% a combination of hemorrhages.

In all, 36 had a known aspirin history and 48 had no known history or an unobtainable history of aspirin use.

Platelet inhibition was defined by an aspirin response test of less than 550 aspirin response units (ARU) on the VerifyNow Aspirin Test (Accumetrics Inc., San Diego). Patients found to be inhibited received platelet transfusion and a repeat ART test was performed 1 hour following transfusion. If the follow-up ART test again showed platelet inhibition, additional platelets were transfused until the patient was no longer suppressed.

In all, 42% of patients with no known history of aspirin use were objectively shown to have aspirin inhibition, said Dr. Bautz, a second-year resident at the university. In contrast, only two patients with a known aspirin history had normal platelet function and 34 had aspirin inhibition.

As expected, patients with a known aspirin history had significantly lower ART results than did those with an unknown aspirin history (mean 471 ARUs vs. 564 ARUs), he said. All other outcomes were similar between groups including head CT progression (26.5% vs. 27%), craniotomy (5.6% vs. 8.5%) and mortality (11% vs. 6.4%).

When the researchers looked at the effect of platelet inhibition on follow-up ART testing, 64% of the 54 patients with an initial positive ART test showed reversal of platelet inhibition on their first follow-up ART test.

"This means that almost one-third of patients did not show a return to normal platelet functioning after a single transfusion of platelets," he said. Nine patients were taken urgently to the OR, died, or were given comfort medications only.

Of the 16 nonresponders, 12 (77%) ultimately showed reversal of their platelet inhibition on follow-up platelet administration and ART testing. Three patients, however, did not return to normal platelet functioning, despite more than three platelet transfusions. Dr. Bautz pointed out.

Initial responders received a significantly greater volume of platelets than did nonresponders (median eight platelet packs vs. six platelet packs), suggesting a dose-response relationship, he said. The mean increase was 70 ARUs per six-pack of platelets.

"A standard six-pack of platelets may not be sufficient, suggesting a benefit of post-transfusion ART," he said.

In all, 91% of patients were restored to normal platelet function.

In regression analysis, there was no significant association between aspirin history or ART results and CT progression, mortality, craniotomy or composite outcomes. Subgroup analysis, however, revealed a trend toward higher mortality for nonresponders, Dr. Bautz said.

"A significant number of traumatic brain injury patients may have occult aspirin inhibition, which is not revealed by history alone," he concluded. "This is in contrast to a rather small number of patients that were shown to have normal platelet functioning and a known history of aspirin, despite high levels of aspirin insensitivity in our population."

Overall, 25% of patients in the series showed progression on follow-up CT, 13% required a craniotomy, and 9.4% died.

The study excluded patients with a history of platelet inhibitors other than aspirin, ongoing use of warfarin (Coumadin), or an International Normalized Ratio of more than 1.5 and those with any epidural component to their TBI.

Invited discussant Dr. Maggie Brandt, with St. Joseph Mercy Hospital in Ann Arbor, Mich., said "the idea of testing for platelets is really spot on and really relevant, but I don’t know if its practical for this problem."

In particular, Dr. Brandt was troubled by the number of patients who did not have a history of aspirin therapy, but were aspirin inhibited, and said it is unclear whether this is a function of other comorbidities or of the test itself. She asked whether ADT testing should be conducted in all TBI patients and whether it is practical to do so based on cost and turnaround time.

Dr. Bautz explained that the high number of patients without an aspirin history in the study is likely because these patients were unable to provide a history upon presentation for TBI. "It is in this setting, that we feel our test is of the most value," he said.

The test typically takes 40 minutes, including laboratory and transport time, and costs about $40 per test, he said.

Audience member Dr. Jonathan Saxe, professor of surgery at Wright State University in Dayton, Ohio, said that brain injury itself has been known to cause issues with aspirin testing and asked whether the brain injuries in the cohort could be causing the platelet test to be abnormal rather than the aspirin. He also pointed out that his group published a similar study finding no impact on mortality with platelet transfusion in elderly TBI patients taking aspirin or clopidogrel (Am. Surg. 2009;75:1100-3). "So I’m wondering, if giving platelets really does anything," he said.

Dr. Bautz said that the ADT test has demonstrated a sensitivity of almost 100% and specificity of 88% at his institution for showing aspirin inhibition. "So it is our belief these patients are on aspirin and that is the cause of their platelet inhibition."

A randomized controlled trial using objective measures of platelet inhibition is necessary to quantify platelet administration in patients presenting with TBI, he said.

The authors reported no conflicts of interest.