Biocompatibility Considerations for Orally Inhaled and Nasal Drug Products and Other Drug--Device Combination Products.

Biocompatibility considerations have historically been important for orally inhaled and nasal drug products (OINDPs) and other drug-device combination products, because finished device components and packaging in these products are often in direct contact with formulation and the patient. The International Pharmaceutical Aerosol Consortium on Regulation and Science (IPAC-RS) discusses, in this article, the current regulatory landscape associated with biocompatibility and how biocompatibility is typically assessed for OINDPs, including risk management considerations and navigation of regulatory requirements. The article also describes current challenges related to alignment of regulatory expectations, particularly for drug-device combination products, and proposes some questions and topics for further discussion with regulatory agencies and other stakeholders to help advance alignment. To further illustrate current challenges and industry approaches to meeting biocompatibility requirements, we also present results of an IPAC-RS benchmarking survey and case studies.

Acute telestroke evaluations during the COVID-19 pandemic.

We sought to analyze the effect of COVID-19 on telestroke requests and to characterize patients remotely evaluated for acute ischemic stroke (AIS) during this time. This study is a retrospective database review of all telestroke requests at one academic vascular neurology center telestroke network with seven remote sites in the USA between March 15 and April 30, 2020. Data were compared with historical cohort spanning same time frame in 2019 using parametric or nonparametric methods as appropriate. Among telestroke requests, characteristics of age, gender, race/ethnicity, National Institutes of Health Stroke Scale (NIHSS), primary diagnosis of AIS or transient ischemic attack (TIA), and number of patients receiving intravenous alteplase (IV-rtPA) and endovascular therapy (ET) were recorded. There was a 53% decrease in telestroke evaluation requests in 2020 from 2019 (p < 0.00001). Mean NIHSS in 2020 was 9.1 (SD ± 8.4) and mean NIHSS in 2019 was 7.2 (SD ± 7.3) (p = 0.122). Among patients with primary diagnosis of suspected AIS or TIA, mean age was 60.5 years in 2020 (SD ± 17.5) and mean age of 67.0 years in 2019 (SD ± 16.0) (p = 0.038). A significant lower number of telestroke evaluations were performed with a higher mean NIHSS overall and a lower mean age among AIS/TIA-suspected patients. Higher NIHSS and severity in all telestroke evaluations reflect neurological manifestations of AIS and mimics, possibly influenced by COVID-19. The younger age of those with suspected AIS or TIA reflects thrombotic complications in atypical stroke populations.

Acute Large Vessel Ischemic Stroke in Patients With COVID-19-Related Multisystem Inflammatory Syndrome.

BACKGROUND: Acute ischemic stroke (AIS) is rare in children, and diagnosis is often delayed. Neurological involvement may occur in multisystem inflammatory syndrome in children (MIS-C), but very few cases of AIS in patients with MIS-C have been reported. PATIENT DESCRIPTIONS: We two patients with AIS presenting with large vessel occlusive disease in previously healthy adolescents recently exposed to SARS-CoV-2 infection. RESULTS: Both patients were subsequently diagnosed with and treated for MIS-C. Here, we discuss the course of their treatments and clinical responses. CONCLUSION: Early recognition and diagnosis of AIS with large vessel occlusion in children with MIS-C is critical to make available all treatment options to improve clinical outcomes.

Immune-mediated diseases and thromboembolic events: a modified Delphi panel.

INTRODUCTION: A multidisciplinary panel of physicians was convened to gain understanding of the relationship between thromboembolic events (TEs) and immune-mediated diseases (IMDs). The primary objective of the panel was to assess areas of consensus on the IMD most prone to TE as well as modifiable and unmodifiable factors that might exacerbate or mitigate the risk of TEs. METHODS: Thirteen nationally recognized physicians were selected based on their contributions to guidelines, publications and patient care. The modified Delphi panel consisted of four rounds of engagement: (1) a semi-structured interview, (2) an expert panel questionnaire, (3) an in-person panel discussion, and (4) a consensus statement survey. RESULTS: Ulcerative colitis and Crohn's disease were identified as two of four IMDs with the highest TE risk. Consensus was reached on several non-modifiable and modifiable characteristics of high-risk. Approaches to reduce TE incidence were identified such as altering treatment, requiring the monitoring of patients for TEs and modifying patient behaviors. Janus kinase inhibitors and corticosteroids were identified as therapies that required further evaluation given their potential TE risk. DISCUSSION: The panel reached a consensus that several IMDs are at an elevated risk of TEs. Physicians are unable to control most patient level risk factors but can control the therapies being used. Consequently, physicians should consider the specific IMD, be aware of TE risk factors, and take into account risk factors in selecting the therapies to optimally manage their conditions and to reduce the risk of TEs in this population.

Acute Ischemic Stroke and COVID-19: Experience From a Comprehensive Stroke Center in Midwest US.

Background: COVID-19 has been associated with increased risk of venous and arterial thromboembolism including ischemic stroke. We report on patients with acute ischemic stroke and concomitant COVID-19 in a diverse patient population. Methods: This is a retrospective analysis of patients hospitalized with acute ischemic stroke (AIS) and COVID-19 to our comprehensive stroke center in Chicago, IL, between March 1, 2020, and April 30, 2020. We reviewed stroke characteristics, etiologies, and composite outcomes. We then compared our cohort with historic patients with AIS without COVID-19 admitted in the same time frame in 2019 and 2020. Results: Out of 13 patients with AIS and COVID-19, Latinos and African-Americans compromised the majority of our cohort (76.8%), with age ranging from 31-80 years. Most strokes were cortical (84.6%) and more than 50% of patients had no identifiable source, and were categorized as embolic stroke of unknown source (ESUS). A trend toward less alteplase administration was noted in the COVID-19 stroke patients compared to the non-COVID group from 2020 and 2019 (7.1 vs. 20.7% p 0.435 and 7.1 vs. 27.2% p 0.178). Endovascular thrombectomy was performed in 3 (23%) patients. Systemic thrombotic complications occurred in 3 (23%) COVID-19 AIS patients. Median National Institutes of Health Stroke Scale and modified Rankin Scale at discharge were 11 (IQR 4-23) and 4 (IQR 3-4), respectively. In the logistic regression model corrected for age and sex, COVID-19 was associated with discharge to mRS > 2 (p 0.046, OR 3.82, CI 1.02-14.3). Eight patients (63.8%) were discharged home or to acute rehabilitation, and two deceased from COVID-19 complications. Conclusion: AIS in the setting of COVID-19 is associated with worse outcomes, especially among African-American and Latino populations. Large vessel disease with ESUS was common suggesting an increased risk of coagulopathy and endothelial dysfunction as a potential etiology.

Neurological manifestations and COVID-19: Experiences from a tertiary care center at the Frontline.

OBJECTIVE: To report neurological manifestations seen in patients hospitalized with Coronavirus disease 2019 (COVID-19) from a large academic medical center in Chicago, Illinois. METHODS: We retrospectively reviewed data records of 50 patients with COVID-19 who were evaluated by the neurology services from March 1, 2020 - April 30, 2020. Patients were categorized into 2 groups based on timing of developing neurological manifestations: the "Neuro first" group had neurological manifestations upon initial assessment, and the "COVID first" group developed neurological symptoms greater than 24 h after hospitalization. The demographics, comorbidities, disease severity and neurological symptoms and diagnoses of both groups were analyzed. Statistical analysis was performed to compare the two groups. RESULTS: A total of 50 patients (48% African American and 24% Latino) were included in the analysis. Most common neurological manifestations observed were encephalopathy (n = 30), cerebrovascular disease (n = 20), cognitive impairment (n = 13), seizures (n = 13), hypoxic brain injury (n = 7), dysgeusia (n = 5), and extraocular movement abnormalities (n = 5). The "COVID-19 first" group had more evidence of physiologic disturbances on arrival with a more severe/critical disease course (83.3% vs 53.8%, p 0.025). CONCLUSION: Neurologic manifestations of COVID-19 are highly variable and can occur prior to the diagnosis of or as a complication of the viral infection. Despite similar baseline comorbidities and demographics, the COVID-19 patients who developed neurologic symptoms later in hospitalization had more severe disease courses. Differently from previous studies, we noted a high percentage of African American and Latino individuals in both groups.

The Influence of Diffusion Weighted Imaging Lesions on Outcomes in Patients with Acute Spontaneous Intracerebral Hemorrhage.

BACKGROUND/OBJECTIVE: Diffusion weighted imaging (DWI) lesions have been well described in patients with acute spontaneous intracerebral hemorrhage (sICH). However, there are limited data on the influence of these lesions on sICH functional outcomes. We conducted a prospective observational cohort study with blinded imaging and outcomes assessment to determine the influence of DWI lesions on long-term outcomes in patients with acute sICH. We hypothesized that DWI lesions are associated with worse modified Rankin Scale (mRS) at 3 months after hospital discharge. METHODS: Consecutive sICH patients meeting study criteria were consented for an magnetic resonance imaging (MRI) scan of the brain and evaluated for remote DWI lesions by neuroradiologists blinded to the patients' hospital course. Blinded mRS outcomes were obtained at 3 months. Logistic regression was used to determine significant factors (p < 0.05) associated with worse functional outcomes defined as an mRS of 4-6. The generalized estimating equation (GEE) approach was used to investigate the effect of DWI lesions on dichotomized mRS (0-3 vs 4-6) longitudinally. RESULTS: DWI lesions were found in 60 of 121 patients (49.6%). The presence of a DWI lesion was associated with increased odds for an mRS of 4-6 at 3 months (OR 5.987, 95% CI 1.409-25.435, p = 0.015) in logistic regression. Using the GEE model, patients with a DWI lesion were less likely to recover over time between 14 days/discharge and 3 months (p = 0.005). CONCLUSIONS: DWI lesions are common in primary sICH, occurring in almost half of our cohort. Our data suggest that DWI lesions are associated with worse mRS at 3 months in good grade sICH and are predictive of impaired recovery after hospital discharge. Further research into the pathophysiologic mechanisms underlying DWI lesions may lead to novel treatment options that may improve outcomes associated with this devastating disease.

The Spectrum of Nontraumatic Convexity Subarachnoid Hemorrhage.

BACKGROUND: Nontraumatic convexity subarachnoid hemorrhage (cSAH) is a nonaneurysmal variant that is associated with diverse etiologies. METHODS: With IRB approval, we retrospectively reviewed consecutive nontraumatic cSAH from July 1, 2006 to July 1, 2016. Data were abstracted on demographics, medical history, neuroimaging, etiology, and clinical presentation. RESULTS: We identified 94 cases of cSAH. The cases were classified according to the following etiologies: reversible cerebral vasoconstriction syndrome (RCVS) 17 (18%), cerebral amyloid angiopathy (CAA) 15 (16%), posterior reversible encephalopathy syndrome 16 (17%), cerebral venous thrombosis 10 (11%), large artery occlusion 7 (7%), endocarditis 6 (6%), and cryptogenic 25 (27%). Early rebleeding occurred in 9 (10%) patients. Time from initial imaging to CT rebleeding was 40 hours (range, 5-74). CAA was associated with the highest mean age at 75.8 and RCVS the lowest at 47.6 years (P< .0001). Among patients with RCVS, initial vascular imaging was negative in 6 (35%), and repeat imaging documented vasoconstriction at a mean delay of 5 days (range, 3-16). CONCLUSION: There were significant differences among the subgroups in cSAH, with CAA presenting as older men with transient neurological deficits, and RCVS presenting as younger women with thunderclap headache. Rebleeding was seen in 10% of cSAH patients. One-third of RCVS patients with cSAH required repeat vascular imaging to diagnose vasoconstriction.

Fractal fluctuations in muscular activity contribute to judgments of length but not heaviness via dynamic touch.

The applied muscular effort to wield, hold, or balance an object shapes the medium by which action-relevant perceptual judgments (e.g., heaviness, length, width, and shape) are derived. Strikingly, the integrity of these judgments is retained over a range of exploratory conditions, a phenomenon known as perceptual invariance. For instance, judgments of length do not vary with the speed of rotation, despite the greater muscular effort required to wield objects at higher speeds. If not the amount of muscular effort alone, then what features of the neuromuscular activity implicated while wielding objects contribute to perception via dynamic touch? In the present study, we investigated how muscular activity mediates perception of heaviness and length of objects via dynamic touch. We measured EMG activity in biceps brachii and flexor carpi radialis as participants wielded objects of different moments of inertia. We found that variation in the amount of muscular effort (literally, root-mean-square values of EMG activity) predicted variations in judgments of heaviness but not length. In contrast, fluctuations in the activity of biceps brachii and flexor carpi radialis were fractal, and variation in the degree of fractality in the two muscles predicted variation in judgments of length. These findings reflect the distinct implications of dynamic touch for perception of heaviness and length. Perceptions of length can be derived from minimal effort, and muscular effort only shapes the medium from which judgments of length are derived. We discuss our findings in the context of the body as a multifractal tensegrity system, wherein perceptual judgments of length by wielding implicate, at least in part, rapidly diffusing mechanotransduction perturbations cascading across the whole body.

Muscular effort differentially mediates perception of heaviness and length via dynamic touch.

Our ability to perceive properties of handheld objects (e.g., heaviness, orientation, length, width, and shape) by wielding via dynamic touch is crucial for tooling and other forms of object manipulation-activities that are the basis of much human experience. Here, we investigated how muscular effort mediates perception of heaviness and length via dynamic touch. Twelve participants wielded nine occluded elongated objects of distinct moments of inertia and reported their perceptual judgments of heaviness and length. We measured the electromyography (EMG) activity of the participants' biceps brachii, flexor carpi radialis, and flexor carpi ulnaris muscles during wielding. Distinct single-valued functions of the eigenvalues I1 and I3 of the inertial tensor, I, closely predicted perceived heaviness and perceived length of the wielded objects. Perceived heaviness showed a direct and linear relationship with EMG activity of biceps brachii, flexor carpi radialis, and flexor carpi ulnaris. However, while perceived length showed a very weak relationship with EMG activity of biceps brachii, we found no association between perceived length and EMG activity of flexor carpi radialis and flexor carpi ulnaris. Our findings indicate that muscular effort contributes directly to perception of heaviness, but likely only serves as a medium for perception of length. While the same physical variable-i.e., the moment of inertia-provides the informational support for perception of heaviness and length, distinct psychophysiological processes underlie perception of heaviness and length via dynamic touch.

Location of a grasped object's effector influences perception of the length of that object via dynamic touch.

Perception of properties of a grasped object via dynamic touch (wielding) contributes to dexterity in tool use (e.g., using a hammer, screwdriver) and sports (e.g., hockey, tennis). These activities differ from simple object manipulation in that they involve making contact with an intended target. In the present study, we examined whether and how making (percussive) contact with a target influences perception of the length of a grasped object via dynamic touch. Making contact with a target by the tip resulted in a more accurate perception of the length than simple wielding. However, making contact with the target at a point along the length did not influence the accuracy of perception. These findings suggest that the location of a grasped object's effector influences perception of properties of that object via dynamic touch. We discuss these findings in terms of time-varying properties of vibrations generated by the percussive contact of the grasped object and target.

Mobile Real-time Tracking of Acute Stroke Patients and Instant, Secure Inter-team Communication - the Join App.

PURPOSE: The primary correlate to survival and preservation of neurologic function in patients suffering from an acute ischemic stroke is time from symptom onset to initiation of therapy and reperfusion. Communication and coordination among members of the stroke team are essential to maximizing efficiency and subsequently early reperfusion. In this work, we aim to describe our preliminary experience using the Join mobile application as a means to improve interdisciplinary team communication and efficiency. MATERIALS AND METHODS: We describe our pilot experience with the initiation of the Join mobile application between July 2015 and July 2016. With this application, a mobile beacon is transported with the patient on the ambulance. Transportation milestone timestamps and geographic coordinates are transmitted to the treating facility and instantly communicated to all treatment team members. The transport team / patient can be tracked en route to the treating facility. RESULTS: During our pilot study, 62 patients were triaged and managed using the Join application. Automated time-stamping of critical events, geographic tracking of patient transport and summary documents were obtained for all patients. Treatment team members had an overall favorable impression of the Join application and recommended its continued use. CONCLUSION: The Join application is one of several components of a multi-institutional, interdisciplinary effort to improve the treatment of patients with acute ischemic stroke. The ability of the treatment team to track patient transport and communicate with the transporting team may improve reperfusion time and, therefore, improve neurologic outcomes.

Predictors of false-positive stroke thrombectomy transfers.

BACKGROUND: Most patients with large vessel occlusion (LVO) stroke need to be transferred to receive thrombectomy. To save time, the decision to transfer often relies on clinical scales as a surrogate for LVO rather than imaging. However, clinical scales have been associated with high levels of diagnostic error. The aim of this study is to define the susceptibility to overdiagnosis of our current transfer decision process by measuring the rate of non-treatment transfers, the most common reasons for no treatment and potential predictors. METHODS: Clinical and transfer data on consecutive patients transferred to a single endovascular capable centre for possible thrombectomy via stroke code activation were retrospectively reviewed. Whether patients underwent the procedure, why they did not undergo the procedure, and other clinical and logistical predictors were recorded. χ2 tests and multivariate logistic regression analysis were performed. RESULTS: From 2015 to 2016, 105/192 transferred patients (54%) did not undergo thrombectomy and the most common reason was absence of a LVO found on CTA after transfer (71/104 (68%)). 14/16 (88%) with a National Institutes of Health Stroke Scale (NIHSS) score <10 did not undergo thrombectomy while 41/78 (52%) with a NIHSS>20 underwent thrombectomy (p<0.001). Helicopter use was associated with no treatment (p=0.004) while arrival within 5 hours was associated with treatment (p<0.001). CONCLUSIONS: Clinical scales appear to overdiagnose LVO and may be responsible for the majority of our stroke code transfers not undergoing thrombectomy. Primary stroke centres therefore have reason to develop the capability to rapidly acquire and interpret a CTA in patients with suspected LVO prior to transfer. Such efforts may reduce the costs associated with unnecessary thrombectomy transfers.

Participation in a Tele-Stroke Program Improves Timeliness of Intravenous Thrombolysis Delivery.

BACKGROUND: We sought to assess the effects of participation in a tele-stroke program on timeliness of intravenous tissue plasminogen activator (IVtPA) administration. METHODS: Among 259 consecutive acute ischemic stroke patients treated with IVtPA through the Rush tele-stroke program, we compared two cohorts: Period 1 (July 2011 to June 2013) and Period 2 (July 2013 to July 2014). We collected data on demographics, National Institutes of Health Stroke Scale (NIHSS), and times of last known normal (LKN), initiation of tele-stroke consult, and IVtPA administration. RESULTS: The mean age was 69.6 years, 56% were female, the mean NIHSS was 11.8, and 41.7% patients were transferred to the hub site. The mean time from initiation of tele-stroke consult to IVtPA administration was 42.2 min. Time from initiation of tele-stroke consult to IVtPA administration improved from Period 1 to Period 2 (49.9 min vs. 35 min, p < 0.0001). This improvement was due to faster mean time from initiation of tele-stroke consult to IVtPA advised (17.4 min vs. 12.5 min, p < 0.0001) and faster mean time from IVtPA advised to administration (33.1 min vs. 22.5 min, p < 0.0001). The mean time from LKN to IVtPA given was also significantly improved (148.6 min vs. 160.9 min, p 0.045). CONCLUSIONS: Participation in a tele-stroke program associated with improvement in the timeliness of IVtPA delivery.

Three-Month Outcomes Are Poor in Stroke Patients with Cancer Despite Acute Stroke Treatment.

INTRODUCTION: Stroke risk is increased in cancer patients. Prognosis in these patients is poor, with higher in-hospital mortality and increased subsequent mortality. However, data on stroke in cancer patients are limited, specifically regarding acute stroke treatment and functional outcomes. We aim to determine the functional outcomes of cancer patients admitted with acute stroke. MATERIALS AND METHODS: We retrospectively reviewed patients carrying a diagnosis of cancer who were admitted with acute ischemic stroke between March 2013 and February 2016. Demographics, cerebrovascular risk factors, stroke characteristics including acute treatment, and characteristics of their cancer history and treatment were abstracted. The primary outcome measures included in-hospital mortality and 3-month functional outcome (as assessed by the modified Rankin Scale [mRS] score, with mRS scores of 3-6 considered poor functional outcome). Further outcome measures included length of stay and discharge destination. FINDINGS: Forty-nine patients met the inclusion criteria, with a median admission National Institutes of Health Stroke Scale score of 8. Twelve patients (24.4%) underwent acute stroke treatment. The most common stroke etiology was hypercoagulability of malignancy (21, 42.9%). The three-month mortality was 46.9%; half of survivors had poor functional outcome. Functional outcomes did not differ by cancer type, stage, or year since diagnosis; on multivariate analysis only high admission NIHSS score was associated with poor functional outcome (P = .002). CONCLUSION: Nearly half of patients with cancer and stroke die within 3 months, and functional outcome is poor for 50% of 3-month survivors despite consideration of acute stroke treatment. Future research should address the role of hypercoagulability in the outcome prediction of stroke patients with cancer.

MRI Detection of Cerebral Infarction in Subarachnoid Hemorrhage.

OBJECTIVE: To investigate magnetic resonance imaging (MRI) detection of cerebral infarction (CI) in patients presenting with subarachnoid hemorrhage (SAH). BACKGROUND: CI is a well-known complication of SAH that is typically detected on computed tomography (CT). MRI has improved sensitivity for acute CI over CT, particularly with multiple, small, or asymptomatic lesions. METHODS: With IRB approval, 400 consecutive SAH patients admitted to our institution from August 2006 to March 2011 were retrospectively reviewed. Traumatic SAH and secondary SAH were excluded. Data were collected on demographics, cause of SAH, Hunt Hess and World Federation of Neurosurgical Societies grades, and neuroimaging results. MRIs were categorized by CI pattern as single cortical (SC), single deep (SD), multiple cortical (MC), multiple deep (MD), and multiple cortical and deep (MCD). RESULTS: Among 123 (30.8 %) SAH patients who underwent MRIs during their hospitalization, 64 (52 %) demonstrated acute CI. The mean time from hospital admission to MRI was 5.7 days (range 0-29 days). Among the 64 patients with MRI infarcts, MRI CI pattern was as follows: MC in 20 (31 %), MCD in 18 (28 %), SC in 16 (25 %), SD in 3 (5 %), MD in 2 (3 %), and 5 (8 %) did not have images available for review. Most infarcts detected on MRI (39/64 or 61 %) were not visible on CT. CONCLUSIONS: The use of MRI increases the detection of CI in SAH. Unlike CT studies, MRI-detected CI in SAH tends to involve multiple vascular territories. Studies that rely on CT may underestimate the burden of CI after SAH.

Periprocedural Risk of Stroke Is Elevated in Patients with End-Stage Renal Disease on Hemodialysis.

OBJECTIVE: To describe the most common clinical factors and stroke etiologies in a case series of patients with end-stage renal disease on hemodialysis (ESRD/HD) with transient ischemic attack (TIA) or ischemic stroke (IS). BACKGROUND: Prior studies have shown that patients on HD are at an elevated risk of stroke, but these studies have focused on the overall stroke risk. This case series sought to determine the percentage of acute ischemic events that occur during or immediately after HD. METHODS: ICD-9 codes were used to identify IS and TIA patients with ESRD/HD admitted to the stroke service from August 22, 2011, to June 21, 2014. Charts were reviewed to determine the age, sex, and race/ethnicity of the cohort. TIA/IS diagnosis was confirmed by a vascular neurologist. Clinical factors were assessed, including: onset during or shortly after HD, defined as occurring within 12 h of HD; the presence of a lesion on diffusion-weighted MRI; hypotension, hyponatremia, or hypoglycemia at symptom onset; the stroke etiology; the presence of focal neurologic deficits; whether the patient was in the window period for intravenous tissue plasminogen activator (IVtPA) upon presentation, and whether the patient received IVtPA. RESULTS: We identified 34 ESRD/HD patients with a diagnosis of TIA/stroke in the specified time period. A majority of patients (70.6%) were African American. Patient age ranged from 32 to 84 years, with a median age of 67 years. Twenty-seven patients (79.4%) had confirmed ischemic infarcts on diffusion-weighted MRI. Seven patients (20.6%) were diagnosed with TIA. In 13 patients (38.2%), symptom onset occurred during or shortly after HD. Of these 13 patients, 8 (61.5%) had symptom onset during HD. Three patients (8.8%) had documented hypotension near the time of symptom onset, and 2 (5.9%) were hyponatremic on presentation to the emergency department. The distribution of stroke etiologies was as follows: 4 (11.8%) watershed distribution, 1 (2.9%) large artery atherosclerosis, 2 (20.6%) small vessel disease, 10 (29.4%) cardioembolic, and 9 (26.5%) cryptogenic. In 28 patients (82.4%), focal neurologic deficits were observed on presentation. Nine patients (26.5%) arrived within the window period for IVtPA, and 4 (11.8%) were eligible and received IVtPA. CONCLUSIONS: Of all patients with ESRD on HD admitted to the stroke service over the study period, over one third (38.3%) had the onset of their ischemic event during or shortly after HD, and nearly one quarter (23.5%) had the onset during HD. While clinicians may be tempted to attribute neurologic changes after HD to metabolic etiologies, they should also be aware that HD represents a period of elevated risk for acute ischemia.

Elevated international normalized ratio as a manifestation of post-thrombolytic coagulopathy in acute ischemic stroke.

BACKGROUND: A serious complication of intravenous tissue plasminogen activator (tPA) in acute ischemic stroke is hemorrhage. Coagulation factors that may potentially increase the risk of bleeding after tPA are not well understood. METHODS: We retrospectively reviewed 284 acute ischemic stroke patients who received tPA. Post-tPA coagulopathy was defined as a documented elevation of international normalized ration (INR) > 1.5 within 24 hours after IV tPA without a known cause. RESULTS: We identified 21 (7.4%) patients with an elevated INR post-thrombolysis. The mean age was 68.3 years (standard deviation ± 11.9) and 57% were male. The mean initial National Institutes of Health Stroke Scale (pre-tPA) was 15.8 (range, 4-35). Liver disease or alcohol abuse was noted in 19%. There were 2 tPA protocol violations who received more than 90 mg tPA. The mean post-tPA INR was 2.03 (range, 1.5-4.7) and the elevation in INR was documented within a mean 5.4 hours (range, 1-15) after tPA initiation. Repeat INR levels returned to normal during their hospital stay in 19 patients. Hypofibrinogenemia was noted in 10 of 12 patients who had fibrinogen levels drawn within 48 hours after tPA initiation and in all 7 patients with fibrinogen levels drawn the same time as the elevated INR. Among the 6 patients with bleeding complications, 2 patients had symptomatic intracerebral hemorrhage. CONCLUSIONS: We report an under-recognized early transient coagulopathy associated with elevated INR in stroke patients after treatment with tPA.