News From The International Stroke Conference 2007, San Francisco, February 7-9, 2007

March 1, 2007

Although current guidelines require physicians to confirm whether a patient’s platelet count is 100,000/µL or higher before administering tissue plasminogen activator (tPA), researchers concluded that this testing might be a poor use of precious time. Bryon P. Jackson, MD, an intern, and colleagues at the University of Pennsylvania Medical Center, Philadephia, conducted a retrospective record review of patients with ischemic stroke. He and coresearchers determined which patients had a platelet count lower than 100,000/µL and whether these patients had a known history of thrombocytopenia or conditions associated with this disorder, such as metastatic cancer, hematologic malignancy, or recent bleeding, or presentation with sepsis or shock.

PERFORMING PLATELET COUNT BEFORE tPA MAY BETIME-WASTING. Although current guidelines requirephysicians to confirm whether a patient's plateletcount is 100,000/µL or higher before administeringtissue plasminogen activator (tPA), researchers concludedthat this testing might be a poor use of precioustime. Bryon P. Jackson, MD, an intern, and colleaguesat the University of Pennsylvania MedicalCenter, Philadephia, conducted a retrospective recordreview of patients with ischemic stroke. He and coresearchersdetermined which patients had a plateletcount lower than 100,000/µL and whether these patientshad a known history of thrombocytopenia orconditions associated with this disorder, such as metastaticcancer, hematologic malignancy, or recent bleeding,or presentation with sepsis or shock.

Of the 1852 patients in the study, 82 (4.4%) had aplatelet count lower than 100,000/µL. Only 73 of thesepatients had ischemic stroke; of these, 67 had thrombocytopeniaor conditions associatedwith the disorder. That is,on presentation, only 6 (0.3%)stroke patients had unsuspectedlow platelet counts, whichwere only mildly decreased, atlevels higher than 65,000/µL.

IMAGING ASSISTANCE EXTENDSTREATMENT WINDOW FOR tPA.Using perfusion CT, the windowfor use of intravenous tPAcan be safely extended from 3to 6 hours in some patients, reportedPatrik Michel, MD, associatephysician in the Departmentof Neurology at theCentre Hospitalier UniversitaireVaudois Lausanne, Switzerland.He and colleaguesevaluated patients who werepresented at a stroke center after3 hours with a National Institutesof Health Stroke Scale(NIHSS) score of 6 to 22. Patientshad to have a minimal penumbra for the infarctsize in the territory of the middle cerebral artery(MCA), and a maximal core size of 30% of the MCAterritory.

Of the 15 patients who were selected to undergotreatment with tPA after 3 hours, recanalization at 24hours was achieved in 60%. One patient experiencedintracerebral hemorrhage, and 1 patient died within 90days. The research team concluded that intravenoustPA can be used in patients 3 to 6 hours after stroke ifperfusion CT shows salvagable tissue and no extensivecore volume. Patient outcomes in this study were comparableto recanalization rates in patients who receivedintravenous tPA within the first 3 hours after stroke.

INTRA-ARTERIAL THROMBOLYSIS ELICITS "LAZARUS PHENOMENON."About 25% of patients experienced immediateimprovement after treatment with intra-arterialthrombolysis within 6 hours of acute ischemic stroke.The patients had a 50% decrease in NIHSS scores. Thesudden restoration was dubbed the "Lazarus phenomenon"by Gregory A. Christoforidis, MD, associateprofessor in the Department of Radiology, andfellow researchers at OhioState University College ofMedicine, Columbus.

Investigators reviewed prospectivelycollected clinical information,arteriograms, andCT scans obtained within 24hours after intra-arterial thrombolysisin 102 patients. Themean time to treatment was208 minutes in the 24.5% of patientswho had a 50% decreasein NIHSS scores. The meantime to treatment in the patientswho did not show rapidrecovery was 306 minutes.

The researchers found thatincidence of recovery could beincreased by shorter time to intra-arterial thrombolysis, goodpial collateral formation, andreperfusion flow of greaterthan 50%. The authors alsonoted that while the intra-arterialdelivery of a thrombolyticresults in a higher local concentration of the drug, therisk of bleeding could be increased.

Christoforidis and colleagues also presented astudy demonstrating that an intra-arterial tPA dose of50 to 100 mg may be more effective than a lower dose,although it may be associated with higher rates ofhemorrhage. The researchers conducted a retrospectiveanalysis of 54 patients with acute ischemic strokeusing angiograms and CT scans collected within 24hours following treatment.

Analysis showed that infarct volume, plateletcount, and tPA dose of 50 to 100 mg were associatedwith higher hemorrhage rates and volumes and withsymptomatic hemorrhage. However, the rate of reperfusionwas improved by 61.5% in those patientswho received the higher doses. The researchers recommendedthat physicians consider doing plateletcounts and examining other predictors of infarct volumebefore using higher doses of tPA.

PREDICTIVE INSTRUMENT HELPS CLINICIANS IDENTIFY CANDIDATESFOR tPA. To help physicians determine whichpatients should receive tPA, researchers from the Tufts-New England Medical Center in Boston created theStroke-Thrombolytic Predictive Instrument (TPI). Developedby David Kent, MD, clinical investigator atthe Institute for Clinical Research and Health PolicyStudies and attending physician in internal medicineand colleagues at Tufts-New England Medical Center,the tool aims to provide physicians with patient-specificfunctional outcomes with and without the use ofthrombolytics.

The researchers developed the tool using data from5 major clinical trials that tested tPAwithin 6 hours afterstroke, accruing information from a total of 2184patients. Along with treatment with tPA, 7 factors affectedthe likelihood of a good outcome: age, diabetes,stroke severity, sex, prior stroke, systolic blood pressure,and time from symptom onset. The effects of tPAwere modified by the following factors: sex, priorstroke, systolic blood pressure, and time from symptomonset. In the prediction of bad outcomes, onlyage, stroke severity, and serum glucose level were significant,and treatment with tPA was not.

Within the 3-hour time window, the median predictedgood outcome for treatment with tPA was42.9%. For those without tPA, the median predictedabsolute benefit was 12.5%. The proportion of patientswho were predicted to have better outcomes with tPAthan without was 93% in patients treated within the3-hour time window and 67% for patients treatedwithin 3 to 6 hours from stroke. The researchers concludedthat further testing of tPA is warranted.

PATIENTS WITH NEGATIVE CTA MAY BENEFIT FROMTHROMBOLYSIS. Patients without evidence of a clot onCT angiography (CTA) should not be excluded fromthrombolytic treatment, according to a team from theSaint Anne's Faculty Hospital, Brno, Czech Republic.The team reviewed data on patients who had beentreated with intravenous thrombolytic therapy within3 hours of stroke symptom onset from August 2003 toJuly 2006. Of 91 patients who underwent intravenousthrombolysis and CTA, 26 (29%) had negative CTA.

Mean age of these 26 patients was 70 years. Themedian infarct volume was 9.7 cm3. Median baselineNIHSS score was 11. At time of discharge, the modifiedRankin Score was 0 to 1 in 9 (34.6%) of these patientsand 0 to 2 in 16 (61.5%). Because good outcomeswere achieved in about a third of the group, the researchersemphasized that such patients should notbe excluded when considering thrombolytic therapybut that differential diagnosis should be carefullyexamined.

THE RESPECTIVE CITATIONS THAT CORRESPOND WITHTHESE NEWS SUMMARIES ARE:

  • Jackson BP, Messe S, Weiner M, Cucchiara BL. Utilityof checking platelet count prior to thrombolysis inacute ischemic stroke. Stroke. 2007;38:501-502.
  • Michel P, Wintermark M, Reichart M, et al. Perfusion-CT guided intravenous thrombolysis between 3and 6 hours: feasibility and safety study in 15 patients.Stroke. 2007;38:510-511.
  • Christoforidis GA, Mohammad Y, Yang M. Factorsassociated with a "Lazarus phenomenon" 24 hoursfollowing intraarterial thrombolytic treatment in ischemicstroke. Stroke. 2007;38:507.
  • Christoforidis GA, Mohammad Y, Karakasis C, etal. Hemmorhage rates and outcomes associated withthe use of 100 mg intraarterial tPA for thrombolysisin acute ischemic stroke. Stroke. 2007;38:504.
  • Kent DM, Selker HP, Ruth R, et al. The Stroke-TPI: apredictive instrument for intravenous thrombolysis inacute ischemic stroke. Stroke. 2007;38:499.
  • Mikulk R, Reif M, Goldemund D. Outcome of patientswith negative CT angiography treated with intravenousthrombolysis. Stroke. 2007;38:501.