Thrombophilias and stroke: diagnosis, treatment, and prognosis.
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Anticoagulants↗
Biomedical subjects
Steven R Levine
Publications and source records attributed to Steven R Levine.
The impact of imbalances in baseline stroke severity on outcome in the National Institute of Neurological Disorders and Stroke Recombinant Tissue Plasminogen Activator Stroke Study.
STUDY OBJECTIVE: The National Institute of Neurological Disorders and Stroke (NINDS) Recombinant Tissue Plasminogen Activator (rtPA) Stroke Study demonstrated a clinically meaningful and statistically significant benefit of tissue plasminogen activator (tPA). Adjusting for the baseline National Institutes of Health (NIH) Stroke Scale, the benefit of tPA remained. However, other authors suggest that an imbalance in baseline stroke severity between the tPA and placebo groups confounded the results. Another issue that has been raised concerns a possible increase in early mortality for individuals given tPA. In post hoc subgroup analysis, we describe the effect of tPA across a spectrum of time from stroke onset to treatment and stroke severity subgroups. Stroke severity was based on the NIH Stroke Scale. We also compare early mortality (2-week and 30-day) in the tPA and placebo groups. METHODS: Using combined data from the 2 NINDS rtPA Stroke Study trials, we performed post hoc subgroup analyses of 3-month favorable outcome (defined by the NIH Stroke Scale, Barthel, Rankin, and Glasgow Outcome Scales). We categorized patients from the trials into onset to treatment (0 to 90 minutes, 91 to 180 minutes) by NIH Stroke Scale (< or =5, 6 to 20, >20) subgroups. Analyses were adjusted for all variables previously shown to be associated with favorable outcome at 3 months. We also compared early mortality within onset-to-treatment subgroups. RESULTS: For all the 12 specified onset-to-treatment-NIH Stroke Scale subgroups, the adjusted odds ratio for a favorable 3-month outcome was greater than 1.0 and favored tPA. We detected no difference in mortality between patients treated with rtPA and those treated with placebo by 2 weeks posttreatment (rtPA=9%, placebo=13%; P =.49) or by 30 days (rtPA=11%, placebo=16%; P =.30). CONCLUSION: These are descriptive post hoc subgroup analyses. Using cut points defined in previous critiques of the NINDS trials, these analyses give results consistent with previous NINDS Study Group reports. Baseline NIH Stroke Scale imbalance does not account for the better outcome of rtPA-treated patients.
Brain Ischemia↗
Hypercoagulable states and stroke: a selective review.
Blood disorders have been implicated in approximately 5% to 10% of ischemic stroke, with an increased frequency in younger patients. Most disorders are associated with an increased thrombotic tendency and, therefore, an increased risk of ischemic stroke. Less commonly, a bleeding diathesis may predispose a patient to intracranial hemorrhage. While many conditions predisposing to thrombosis have been associated with stroke, there are relatively few prospective, epidemiological studies addressing hypercoagulable states and arterial stroke compared with the number of studies on the genetic thrombophilias, which are predominantly associated with venous thrombosis. When ordering tests of coagulation in stroke patients, one should keep in mind whether the results will influence therapy and/or patient outcome. It is generally not advocated to screen all stroke patients for a "hypercoagulable workup". Typically, patients to be screened for coagulation defects will have a prior history of one or more unexplained thromboembolic events. The yield for diagnosing a hypercoagulable state is typically greatest for young stroke patients or those with a family history of thrombosis and who have no other explanations for their stroke (cryptogenic stroke). The yield in typically low in unselected ischemic stroke patients and older patients. Treatment of a first stroke with a documented hypercoagulable state is typically long-term or indefinite duration warfarin, although there is a paucity of clinical trial data supporting this clinical approach.
Humans↗
Optimizing an individual's treatment in acute stroke: is a magnetic resonance map leading us towards the holy grail?
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Brain Mapping↗
Do gender and race impact the use of antithrombotic therapy in patients with stroke/TIA?
The authors examined the relationships between sex and race and antithrombotics prescribed at discharge in the Michigan Medicare population using retrospective medical record abstraction (n = 2,715) for the period January 1, 2001, to June 30, 2001. There were no differences in the use of antithrombotics at discharge by race or sex and no differences in the prescribing of aspirin, warfarin, aspirin/extended release dipyridamole, or clopidogrel by race or sex after adjustment for confounders.
Black or African American↗
In acute ischemic stroke, are asymptomatic intracranial hemorrhages clinically innocuous?
BACKGROUND: In patients with acute ischemic stroke, intracranial hemorrhages are categorized as symptomatic or asymptomatic based on the presence or absence of a clinically detectable neurological deterioration. Asymptomatic intracranial hemorrhages are believed by many to be clinically innocuous. We examined whether the occurrence of an asymptomatic intracranial hemorrhage affects functional outcome in patients with acute ischemic stroke (AIS) treated or not treated with recombinant tissue plasminogen activator (rt-PA). METHODS: We combined data from the NINDS rt-PA Stroke Trial and the ATLANTIS Trials, excluding patients with symptomatic intracranial hemorrhage (n=1193). We used generalized estimating equations to test whether asymptomatic intracranial hemorrhage altered the likelihood of a normal or near-normal outcome at 90 days, as measured across 4 commonly used functional outcome scales, controlling for other variables that affect outcome. To look at additional outcomes, including the likelihood of disability and death, we used logistic regression equations. Additionally, we systematically reviewed previous studies that assessed the effect of intracranial hemorrhage in AIS. RESULTS: In the combined database, the rate of asymptomatic intracranial hemorrhage was higher in rt-PA treated than in nontreated patients (9.9% versus 4.2%, P<0.0001). Controlling for other prognostic factors, the odds of a normal or near-normal outcome was lower when a patient had an asymptomatic intracranial hemorrhage, but this effect did not reach statistical significance (OR=0.69, 95% CI: 0.43 to 1.12, P=0.13). Similarly, the odds of not being moderately to severely disabled (modified Rankin Score < or =2) was also lower for patients with asymptomatic intracranial hemorrhage (OR=0.60, 95% CI: 0.33 to 1.08, P=0.09). Despite using a larger sample than any previously published study, the power in our study to detect a 30% decrease in the odds of a good outcome was inadequate ( approximately 32%). CONCLUSIONS: We could not confirm or exclude a clinically significant effect for asymptomatic intracranial hemorrhages based either on our analysis or on any previously published trial. Analysis of substantially larger databases are needed to assess the import of this common clinical event.
Aged↗
Association of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials.
BACKGROUND: Quick administration of intravenous recombinant tissue plasminogen activator (rt-PA) after stroke improved outcomes in previous trials. We aimed to analyse combined data for individual patients to confirm the importance of rapid treatment. METHODS: We pooled common data elements from six randomised placebo-controlled trials of intravenous rt-PA. Using multivariable logistic regression we assessed the relation of the interval from stroke onset to start of treatment (OTT) on favourable 3-month outcome and on the occurrence of clinically relevant parenchymal haemorrhage. FINDINGS: Treatment was started within 360 min of onset of stroke in 2775 patients randomly allocated to rt-PA or placebo. Median age was 68 years, median baseline National Institute of Health Stroke Scale (NIHSS) 11, and median OTT 243 min. Odds of a favourable 3-month outcome increased as OTT decreased (p=0.005). Odds were 2.8 (95% CI 1.8-4.5) for 0-90 min, 1.6 (1.1-2.2) for 91-180 min, 1.4 (1.1-1.9) for 181-270 min, and 1.2 (0.9-1.5) for 271-360 min in favour of the rt-PA group. The hazard ratio for death adjusted for baseline NIHSS was not different from 1.0 for the 0-90, 91-180, and 181-270 min intervals; for 271-360 min it was 1.45 (1.02-2.07). Haemorrhage was seen in 82 (5.9%) rt-PA patients and 15 (1.1%) controls (p<0.0001). Haemorrhage was not associated with OTT but was with rt-PA treatment (p=0.0001) and age (p=0.0002). INTERPRETATION: The sooner that rt-PA is given to stroke patients, the greater the benefit, especially if started within 90 min. Our results suggest a potential benefit beyond 3 h, but this potential might come with some risks.
Aged↗
Antiphospholipid antibodies and subsequent thrombo-occlusive events in patients with ischemic stroke.
CONTEXT: The presence of antiphospholipid antibodies (aPL) has been associated with vascular occlusive events. However, the role of aPL in predicting ischemic events, particularly recurrent ischemic stroke, is controversial. OBJECTIVE: To evaluate the effect of baseline aPL positivity (ie, positivity for anticardiolipin antibodies [aCL], lupus anticoagulant antibodies [LA], or both) on subsequent thrombo-occlusive events, including recurrent stroke. DESIGN, SETTING, AND PARTICIPANTS: The Antiphospholipid Antibodies and Stroke Study (APASS), a prospective cohort study within the Warfarin vs Aspirin Recurrent Stroke Study (WARSS), a randomized double-blind trial (N = 2206) conducted at multiple US clinical sites from June 1993 through June 2000 and comparing adjusted-dose warfarin (target international normalized ratio, 1.4-2.8) and aspirin (325 mg/d) for prevention of recurrent stroke or death. APASS participants were 1770 (80%) WARSS participants who consented to enroll in the APASS, with usable baseline blood samples drawn prior to randomization to the WARSS and analyzed for aPL status within 90 days of index stroke by a central independent laboratory. Quality assurance was performed on approximately 10% of samples by a second independent laboratory. MAIN OUTCOME MEASURE: Two-year rate of the composite end point of death from any cause, ischemic stroke, transient ischemic attack, myocardial infarction, deep vein thrombosis, pulmonary embolism, and other systemic thrombo-occlusive events. The primary analysis assessed the outcome associated with aPL positivity within each WARSS treatment group separately, after risk-factor adjustment (since these aPL-positive vs aPL-negative comparisons were not randomized). RESULTS: Of the 1770 APASS patients, 720 (41%) were classified as aPL-positive and 1050 (59%) as aPL-negative. There was no increased risk of thrombo-occlusive events associated with baseline aPL status in patients treated with either warfarin (relative risk [RR], 0.99; 95% confidence interval [CI], 0.75-1.31; P =.94), or aspirin (RR, 0.94; 95% CI, 0.70-1.28; P =.71). The overall event rate was 22.2% among aPL-positive and 21.8% among aPL-negative patients. There was no treatment x aPL interaction (P =.91). Patients with baseline positivity for both LA and aCL antibodies tended to have a higher event rate (31.7%) than did patients who tested negative for both antibodies (24.0%) (unadjusted RR, 1.36; 95% CI, 0.97-1.92; P =.07). Classification and regression tree analyses did not identify a specific LA test or aCL isotype or titer that was associated with increased risk of thrombo-occlusive event. CONCLUSIONS: The presence of aPL (either LA or aCL) among patients with ischemic stroke does not predict either increased risk for subsequent vascular occlusive events over 2 years or a differential response to aspirin or warfarin therapy. Routine screening for aPL in patients with ischemic stroke does not appear warranted.
Aged↗
Prediction of hospital disposition after thrombolysis for acute ischemic stroke using the National Institutes of Health Stroke Scale.
BACKGROUND: Early determination of discharge destination after acute stroke may promote earlier rehabilitation and reduce costs by shortening the duration of hospitalization. OBJECTIVE: To determine whether the National Institutes of Health Stroke Scale (NIHSS) score predicts disposition in stroke patients treated with thrombolysis. DESIGN: Cohort study. SETTING: Academic and community hospitals from 3 countries. PATIENTS: Five hundred forty-six patients with acute ischemic stroke treated with recombinant tissue plasminogen activator (rt-PA). INTERVENTIONS: Medical records were reviewed for demographic information, vascular risk factors, location of stroke, initial NIHSS score, acute hospital disposition, and complications of symptomatic or asymptomatic intracerebral hemorrhage (ICH). MAIN OUTCOME MEASURE: Discharge destination to home, acute rehabilitation, or nursing facility. RESULTS: In multinomial regression analysis, increasing NIHSS score was a robust and independent predictor of discharge to rehabilitation or nursing facilities, roughly doubling for each 5-point increment. Patients who developed symptomatic ICH were never discharged to home, but asymptomatic ICH had no significant independent effect on disposition. CONCLUSIONS: Stroke severity as determined by the admission NIHSS score is the major independent predictor of disposition after hospitalization and treatment with rt-PA for acute stroke in a broad-based population. However, symptomatic ICH after rt-PA is a catastrophic event that may preclude discharge to home.
Acute Disease↗
Pathophysiology and therapeutic targets for ischemic stroke.
The increased risk for stroke among those who have had a previous stroke or transient ischemic attack (TIA) and the tremendous burden of disability among stroke sufferers make both primary and secondary preventative strategies imperative. An understanding of the pathophysiology of stroke and TIA can help identify appropriate therapeutic targets.
Acute Disease↗
Virtual TeleStroke support for the emergency department evaluation of acute stroke.
OBJECTIVES: Telemedicine-enabled acute stroke consultation (TeleStroke) may be useful to determine eligibility for treatment with tissue plasminogen activator (tPA) and provide support to emergency departments without on-site stroke expertise. METHODS: Emergency physicians consulted with stroke neurologists via two-way videoconferencing in the evaluation of patients with possible acute stroke. History, neurologic examination, and computed tomography of the head were reviewed to determine eligibility for treatment with tPA. Interpretations of computed tomography were compared for inter-rater reliability between the neurologist and the neuroradiologist using a conventional workstation. Videotape and written records were analyzed to determine time intervals, patient management, and user satisfaction. RESULTS: The authors reviewed data from 24 patients evaluated over 27 months at an island-based hospital. The mean National Institutes of Health Stroke Scale score was 5.7 (range, 0-22). Fifteen patients arrived at the emergency department less than three hours after symptom onset; 12 were presented for TeleStroke consultation within three hours after symptom onset. Eight of these 12 (75%) had acute ischemic stroke, and six of these eight potentially eligible patients (75%) received intravenous tPA. There was very good agreement among all remote readers for detecting the one case of imaging exclusion (subdural hemorrhage). There were no protocol violations, and a mean (+/- SD) consult-to-needle time of 36 (+/- 15) minutes and door-to-needle time of 106 (+/- 22) minutes was achieved. Transfer was avoided in 11 patients. Physicians believed that TeleStroke consultation improved care in >95% of the cases. CONCLUSIONS: TeleStroke videoconferencing can support emergency department-based evaluation of acute stroke and may facilitate tPA delivery in neurologically underserved facilities. A prospective, randomized trial is needed to determine if these systems are superior to traditional telephone consultation.
Adult↗
Acute ischemic stroke in hospitalized medicare patients: evaluation and treatment.
BACKGROUND AND PURPOSE: This study describes several quality indicators of care in hospitalized stroke patients in Michigan from 1998 to 1999. SUMMARY OF REPORT: Median times from admission to head CT/MRI (89.5 minutes) and thrombolysis (113 minutes) exceeded recommended guidelines. Deep venous thrombosis prophylaxis was used in only 13.8% of eligible patients. CONCLUSIONS: Timing for brain imaging and acute ischemic stroke symptom onset need to be better documented, along with more provider education for routine deep venous thrombosis prophylaxis.
Acute Disease↗
HandiStroke: a handheld tool for the emergent evaluation of acute stroke patients.
BACKGROUND: The management of acute stroke is time-sensitive. Clinical decision making requires data not only from laboratory testing and neuroimaging, but also from a detailed history and neurologic examination. The neurologic examination provides baseline information and assists in differentiating acute stroke from its mimickers. There is a need for tools to facilitate the evaluation and decision making in the acute stroke patient to make the correct diagnosis and, when indicated, to properly administer intravenous thrombolytic therapy. OBJECTIVES: The goals of this project were to create a standardized, handheld software program to aid physicians in their evaluation of patients presenting to the emergency department (ED) with acute ischemic stroke, and to create an educational tool with which residents and other health care professionals can gain a level of proficiency in treating these patients. RESULTS: A comprehensive handheld tool was created that incorporates a National Institutes of Health Stroke Scale (NIHSS) calculator, inclusion criteria, absolute contraindications, and relative warnings for thrombolytic use (i.e., recombinant tissue plasminogen activator), and a weight-based dosing calculator that flows in a logical and clinically relevant format. Additionally, the program includes reference materials and guidelines for clinical management to further assist the clinician. CONCLUSIONS: Applications of this program include reformatting for use as a data-gathering tool in future clinical studies investigating the treatment of stroke patients, increasing the use and documentation of the NIHSS within the ED in acute ischemic stroke patients, and improving protocol adherence for rt-PA use.
Emergency Service, Hospital↗
Potassium depletion as a risk factor for stroke: will a banana a day keep your stroke away?
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Animals↗
Markers of increased risk of intracerebral hemorrhage after intravenous recombinant tissue plasminogen activator therapy for acute ischemic stroke in clinical practice: the Multicenter rt-PA Stroke Survey.
BACKGROUND: Intravenous recombinant tissue plasminogen activator (rtPA) is an effective therapy for acute ischemic stroke, but it is associated with risk of intracerebral hemorrhage (ICH). Our aim was to identify, in a large cohort of patients, readily available baseline factors that are associated with thrombolysis-related ICH. METHODS AND RESULTS: In a multicenter retrospective and prospective investigation of individual data from 1205 patients treated in routine clinical practice with intravenous rtPA within 3 hours of stroke symptom onset, 72 patients (6%) developed symptomatic ICH and 86 additional patients (7%) had asymptomatic ICH identified on a routine follow-up CT. In analyses based on clinical variables alone, the main attributes associated with ICH were a history of diabetes mellitus and cardiac disease, increasing stroke severity, advancing age, use of antiplatelet agents other than aspirin before stroke onset, and elevated pretreatment mean blood pressure. In additional analyses that incorporated baseline CT and laboratory findings (in a subset of patients), the main associations were early ischemic CT changes, in particular if exceeding one third of middle cerebral artery territory; increasing stroke severity; diabetes mellitus or elevated serum glucose; and lower platelet counts. Final independent attributes associated with parenchymatous hematoma, defined by purely radiologically based criteria, were similar to those of symptomatic ICH. CONCLUSIONS: Readily available factors can identify acute ischemic stroke patients at high and low risk for rtPA-related ICH. These factors require confirmation in a prospective cohort before clinical implementation.
Acute Disease↗
Stroke trials: what have we learned?
We reviewed the recent, major, therapeutic trials of intravenous thrombolytic therapy and ancrod for ischemic stroke. Randomized, controlled studies of acute ischemic stroke treatment were reviewed. Several post-FDA approval intravenous tPA studies were reviewed to understand the experience of this medication in practice. STAT trial was the major study using ancrod. Of multiple intravenous thrombolytic studies, the NINDS study of intravenous tPA was the only study to demonstrate a significantly higher percentage of patients with complete recovery or minimal deficit at three months. Studies in communities utilizing intravenous tPA for stroke illustrate the need for close adherence to the NINDS study protocol or else the risk of tPA use may exceed the benefits.
Ancrod↗
aPL and stroke in young women: more fuel for the stroke risk fire.
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Adolescent↗
Stroke knowledge and barriers to stroke prevention among African Americans: implications for health communication.
Stroke is a major cause of death and disability, especially among African Americans. Yet research on stroke knowledge and barriers to stroke prevention among African Americans is limited. This study used a 50-item questionnaire to conduct structured telephone interviews with 379 African American adults, 50 years or older. The questionnaire included questions on stroke knowledge, stroke risk behaviors, and barriers to stroke prevention. A stroke knowledge score was computed by assigning points for correct responses on knowledge items. The average stroke knowledge score of participants was 10.9, out of a maximum possible score of 27. Stroke knowledge was significantly related to the presence of hypertension, heart disease, diabetes, and family history of stroke. College education was significantly associated with older respondents' stroke knowledge. Younger college-educated respondents had more knowledge about the risky behaviors that lead to stroke than those with less education. Respondents preferred hospitals to churches or senior centers for receiving stroke information and for learning about stroke from their physicians. Stress and poor financial status were most frequently reported as barriers to stroke prevention. These findings have implications for developing more effective strategies for educating African Americans about stroke prevention.
Black or African American↗