Fibrinolytics/Thrombolytics

[chbare]

FL_Medic, I agree with Spock. We rarely administer fibrinolytics in our ER. If we can get the patient to a cath lab in time, all of the cardiologists in this area prefer that we not administer fibrinolytics. They tell us there are allot of complications during the procedure and CABG could be a nightmare.

Take care,

chbare.

[AZCEP]

Early Recurrent Stroke Linked to Tissue Plasminogen Activator

Caroline Cassels

July 27, 2006 — Early recurrent ischemic stroke (ERIS) has been linked to intravenous thrombolysis (IVT) with tissue-type plasminogen activator (tPA) in a report by researchers at the University of Zurich in Switzerland.

The prospective, population-based study is the first description of ERIS as the cause of early neurological deterioration in acute stroke patients undergoing IVT.

Of the 341 patients included in the study, 2 were deemed to have ERIS. Although the incidence of this complication was low, the researchers note that the presence of "multiple ischemic lesions in both patients suggests the disintegration and subsequent scattering of cardiac or aortic thrombi as the underlying etiology."

The study is published in the July 18 issue of Circulation, with first author Dimitrios Georgiadis, MD, from the University of Zurich.

Researchers analyzed data from 341 consecutive acute stroke patients treated with tPA at 8 medical centers in Switzerland between January 2001 and November 2004.

The study's primary end point was neurological deterioration of 4 or more points on the National Institutes of Health Stroke Scale (NIHSS) occurring within 24 hours of tPA treatment and caused by ERIS or intracranial hemorrhage (ICH).

Causative Role?

According to the study, ERIS was defined as the occurrence of new neurological symptoms suggesting involvement of initially unaffected vascular territories and evidence of corresponding ischemic lesions on cranial computed tomography (CCT) scans.

Administration of tPA was performed according to protocols based on the results of the 1996 National Institute of Neurological Disorders and Stroke (NINDS) study, which, among other guidelines, recommended that tPA be administered within 3 hours of stroke symptom onset and that a CT scan done before thrombolysis not show any major infarction, mass effect, edema, or hemorrhage.

Neurological deterioration and evidence of appropriately located ICH on CCT, magnetic resonance imaging (MRI) scans, or both were diagnosed as symptomatic intracranial hemorrhage (SICH).

The 2 patients diagnosed with ERIS both worsened within 1 hour of receiving tPA infusion. Brain infarcts and, in 1 patient, renal infarcts were scattered among different vascular territories.

These findings, the researchers write, are "highly suggestive of the disintegration and subsequent scattering of cardiac or aortic thrombi as the underlying etiology. Obviously, disintegration of thrombi can occur spontaneously and is not necessarily associated with tPA administration. Still, the fact that neurological deterioration occurred 40 to 50 minutes after tPA initiation in both cases strongly argues for a causative role of tPA."

A total of 15 patients were diagnosed with SICH. However, the researchers note that all of these events occurred between 2 and 22 hours after termination of tPA infusion.

The only definitive way to determine whether tPA causes ERIS would be to conduct a randomized trial comparing the incidence of ERIS between stroke patients with IVT and controls. Since this is ethically impossible, the authors point out that a registry of patients with ERIS following IVT would provide the neurology community with valuable information.

Clinical Implications

According to the authors, these findings should alert treating physicians to the fact that deterioration of patients during thrombolysis therapy is not necessarily due to ICH but can also be caused by ERIS.

In addition, they write that exclusion of ICH "should by no means prompt a wait-and-see attitude but rather should lead to urgent MRI studies and possibly additional therapeutic interventions such as local thrombolysis."

The demonstrated benefit of early IVT treatment and the low incidence of ERIS would not justify a delay in IVT initiation. However, the authors note that the true incidence of ERIS was potentially underestimated because they evaluated only those patients with a deterioration of 4 or more points on the NIHSS — a criterion that constitutes a severe worsening.

Call for New Treatment Guidelines

In an accompanying editorial, Louis R. Caplan, MD, from Beth Israel Deaconess Medical Center in Boston, Massachusetts, says the study's findings highlight the need to update tPA treatment protocols to reflect advances in imaging technology and current neurological practice.

Current treatment protocols, which include recommendations that tPA be administered only within 3 hours of symptom onset; that a CT scan done before thrombolysis not show any major infarction, mass effect, edema, or hemorrhage; and that treatment not be administered in patients with a deficit or minor signs or in patients who are improving, are outdated, he writes.

For instance, Dr. Caplan notes, several recent studies have shown that choosing patients using modern MRI protocols can extend patient selection beyond the current recommended 3-hour time limit. Furthermore, he writes that the time delay and severity of the clinical deficit do not reliably predict improvement after thrombolysis.

"Two studies showed that giving tPA between 3 and 6 hours after onset to patients with considerable at-risk tissue was an effective strategy," he writes.

According to Dr. Caplan, "research, experience, and therapeutic alternatives have come a long way since the NINDS trial was planned and reported. The present guidelines badly need to be updated to reflect these advances."

Circulation. 2006;114:237-241, 187-190.

[Ace844]

So these were embolic cva's and thrombi thrown as a result of loosened atherosclerotic plaque...am I reading that correctly?

[AZCEP]

With an ischemic event we can assume that it involved a plaque, since the formation of a clot would be difficult following tPA.

"multiple ischemic lesions in both patients suggests the disintegration and subsequent scattering of cardiac or aortic thrombi as the underlying etiology."

My guess, since the article doesn't specifically address it, would be the vulnerable plaque starts to break down following the tPA. Because the blood flow is increased, the plaque embolizes to the distal vascular bed. The fact that 2 of the 341 patients experienced the ERIS indicates an incident but not statistical significance.

The more interesting point of the article was the fact that there is a call for a revision in the usage of the fibrinolytics.

[Ace844]

well at least it wasn't hemmhorraghic complications or a bunch of 70 yo's with spontaeous DIC...the incidence was pretty low, and I would be curious to find out what their pre-TPA EF, PMH, LDL, HDL, etc.. was, etc...it will be interesting to see what their new guidelines will be though.

[FL_Medic]

I still don't see how we can exclude a bleed in the field.

[AZCEP]

History and physical exam is the short answer.

How do bleeds present? What conditions will a patient complain of when a bleed happens versus an occlusion? What historical factors make the presence of a bleed more likely? NO this assessment is not 100%, but it can give you pretty clear indications of whether a bleed is happening or not.

Here is some technology that might make it even easier to tell the difference.

InfraScan Announces First Patients Enroll in Clinical Trial in Brain Hematoma Detection

InfraScan, a medical device firm specializing in brain injury diagnostic products, announced today that more than 15 patients have been enrolled in its clinical trial for hematoma detection. The trials are taking place at Baylor College of Medicine in Houston and at the Hospital of the University of Pennsylvania in Philadelphia. InfraScan's lead product, the Infrascanner handheld brain hematoma detector, is a portable imaging device using near infrared (NIR) technology for the detection of hematoma, or bleeding in the brain, in people experiencing head trauma.

While CAT Scans (CT) are currently the diagnostic standard for hematomas, many head trauma patients do not quickly receive a CT scan - either because of accident site or due to CT availability issues. For patients with brain hematomas, rapid identification of the bleeding can play a significant role in efforts to maximize preservation of life and brain function. The Infrascanner can facilitate rapid identification by prioritizing patients for CT scanning and triaging patients requiring transport to a facility with neurosurgery capability.

"The Infrascanner clinical trial is a critical step in our efforts to bring this technology to military paramedics and civilian doctors," said Baruch Ben Dor, president and CEO of InfraScan. "Results of our prior research are very encouraging and we are confident that this next study will further demonstrate the utility of the Infrascanner. The next step in our development program will be an expected 510K application in early 2007."

The Infrascanner unit is based on a PDA platform with a wireless detector sensor. It detects hematoma based on differential NIR light absorption of the bleeding versus non-bleeding part of the brain. A pilot study with an earlier Infrascanner prototype involving more than 300 patients demonstrated high sensitivity for detecting bleeding in the brain and for rapidly detecting the onset of late bleedings.

"Patients with blood clots in the brain from trauma must be evaluated and operated on as soon as possible to minimize the injury to the brain. The hematoma detector may be useful at the scene of an accident or on a battlefield in identifying patients who should be taken directly to a hospital with neurosurgical specialists." said Claudia S. Robertson, MD, medical director of the Neurosurgical Intensive Care Unit at Ben Taub General Hospital and professor in the Neurosurgery Department of Baylor College of Medicine.

"We are looking forward to this study of a promising new device that we hope will facilitate rapid noninvasive detection of intracranial hematomas." said Eric L. Zager, MD, professor in the Neurosurgery Department of the Hospital of the University of Pennsylvania. He added, "If it is found to be effective, the Infrascanner could significantly improve the way our health system identifies patients who need emergent neurosurgical intervention. This device may be very useful in the field by paramedics in civilian or military settings, in emergency rooms, and intensive care units."

An estimated 1.5 million individuals seek medical treatment for head trauma in the U.S. each year, and the worldwide incidence of head trauma is approximately 10 million individuals. In addition to the Infrascanner's first application to brain hematoma, the company plans to pursue in the future a second application for the product in monitoring of stroke victims.

About InfraScan - InfraScan, Inc. is a medical device company that focuses on developing, commercializing and distributing hand-held diagnostic devices for head injuries and stroke. InfraScan's flagship product, the Infrascanner handheld brain hematoma detector is a portable imaging device using near infrared (NIR) technologies for the detection of bleeding in the brain in head trauma patients. The company has received early-stage funding from BioAdvance, the Biotechnology Greenhouse of Southeastern Pennsylvania, and from Ben Franklin Technology Partners of Southeastern Pennsylvania, and has received US Army and US Navy grants. For more information visit

[Ace844]

Here's a link to their website: http://www.infrascanner.com/

[FL_Medic]

not all bleeds present the same way, even neuro docs don't cancel out bleeds without scanning the dome.

Yes we can usually have a good idea if it's ischemic or a bleed, but we can never r/o a bleed. There is always the possibility.

[FL_Medic]

maybe with the scanner, I'll have to look more into it