Laurie Schluter

Von Willebrand Factor Drives the Association Between Elevated Factor VIII and Poor Outcomes in Patients With Ischemic Stroke

Background and Purpose— Despite clear roles of factor VIII (FVIII) and von Willebrand factor (vWF) in thrombosis, few studies have examined the relationship of these factors with acute ischemic stroke (AIS). We sought to determine whether concurrent elevation in FVIII and vWF was associated with adverse events and outcomes. Methods— From our prospective stroke registry, patients consecutively admitted with AIS between July 2008 and October 2013 were included if both FVIII and vWF were measured during admission. The primary outcome was the modified Rankin Scale score on discharge. Results— Among 1453 cases in our stroke registry, 148 patients with AIS met inclusion criteria; 62 patients (41.9%) had FVIII−/vWF−, 16 patients (10.8%) had FVIII+/vWF−, and 51 patients (34.5%) had FVIII+/vWF+. In the fully adjusted model, patients with FVIII+/vWF+ had increased odds of inpatient complications (odds ratio, 8.6; 95% confidence interval, 1.58–46.85; P=0.013) and neuroworsening (odds ratio, 3.2; 95% confidence interval, 1.18–8.73; P=0.022) than patients with FVIII−/vWF−. Adjusted for age, baseline stroke severity, and glucose, patients with FVIII+/vWF+ had increased odds of poor functional outcome (modified Rankin Scale>2; odds ratio, 2.87; 95% confidence interval, 1.16–7.06; P=0.021) than patients with FVIII−/vWF−. Conclusions— Concurrent FVIII/vWF elevation predicts higher odds of inpatient complications, neuroworsening, and worse functional outcomes for patients with AIS compared with patients with normal levels. Our findings suggest that FVIII and vWF levels may serve as clinically useful stroke biomarkers by providing risk profiles for patients with AIS.

A Model for Predicting Persistent Elevation of Factor VIII among Patients with Acute Ischemic Stroke.

BACKGROUND AND PURPOSE Elevated levels of coagulation factor VIII (FVIII) may persist independent of the acute-phase response; however, this relationship has not been investigated relative to acute ischemic stroke (AIS). We examined the frequency and predictors of persistently elevated FVIII in AIS patients. METHODS AIS patients admitted between July 2008 and May 2014 with elevated baseline FVIII levels and repeat FVIII levels drawn for more than 7 days postdischarge were included. The patients were dichotomized by repeat FVIII level for univariate analysis at 150% and 200% activity thresholds. An adjusted model was developed to predict the likelihood of persistently elevated FVIII levels. RESULTS Among 1616 AIS cases, 98 patients with elevated baseline FVIII had repeat FVIII levels. Persistent FVIII elevation was found in more than 75% of patients. At the 150% threshold, the prediction score ranged from 0 to 7 and included black race, female sex, prior stroke, hyperlipidemia, smoking, baseline FVIII > 200%, and baseline von Willebrand factor (vWF) level greater than 200%. At the 200% threshold, the prediction score ranged from 0-5 and included female sex, prior stroke, diabetes mellitus, baseline FVIII level greater 200%, and baseline vWF level greater than 200%. For each 1-point increase in score, the odds of persistent FVIII at both the 150% threshold (odds ratio [OR] = 10.4, 95% confidence interval [CI] 1.63-66.9, P = .0134) and 200% threshold (OR = 10.2, 95% CI 1.82-57.5, P = .0083) increased 10 times. CONCLUSION Because an elevated FVIII level confers increased stroke risk, our model for anticipating a persistently elevated FVIII level may identify patients at high risk for recurrent stroke. FVIII may be a target for secondary stroke prevention.

The Impact of Left Ventricular Hypertrophy and Diastolic Dysfunction on Outcome in Intracerebral Hemorrhage Patients

Background The objective of this study was to determine the prevalence of LVH and DD in patients presenting with supratentorial deep ICH and to determine if the presence of LVH or DD was an independent predictor of initial ICH volume, hematoma expansion, or poor outcome. Methods A cross-sectional study was performed on ICH patients who presented from 7/2008 to 12/2010. Cases were excluded if ICH was traumatic, lobar, infratentorial, secondary to elevated international normalized ratio, suspicious for underlying structural malformation, or where surgical evacuation was performed. Logistic and linear regressions were used to assess the ability of LVH to predict ICH imaging characteristics and patient outcomes. Results After adjusting for use of hemostatic agents, LVH was not a significant independent predictor of initial ICH volume (P = 0.344) or 33% volume expansion (P = 0.378). After adjusting for age, infectious complications, and use of hemostatic agents, LVH was not a significant independent predictor of poor functional outcome (P = 0.778). Similar results were seen for DD. Conclusion In our sample, patients with deep ICH and LVH were more likely to develop IVH, but LVH was not a significant independent predictor of initial ICH volume, hematoma expansion, or poor short-term outcome.

Factor VIII in Acute Cerebral Ischemia Pilot Study: Biomarker in Patients With Large Vessel Occlusion?:

We conducted a prospective serial laboratory cohort study to assess the correlation of factor VIII (FVIII) levels in response to thrombolysis in patients with large vessel occlusion (LVO) and acute ischemic stroke (AIS). Patients with AIS with anterior circulation LVO were eligible for enrollment if treated within 4.5 hours from last seen normal with intravenous tissue plasminogen activator (tPA). Patients (n = 29) had a mean age of 71 years and median National Institute of Health Stroke Scale of 14. Baseline pre-tPA FVIII was not significantly correlated with clot burden score (−0.147, P = .447) or vessel recanalization (−0.133, P = .499). Median FVIII decreased significantly from baseline to 6 hours post-tPA (282% to 161%, P = .002), but delta in FVIII level did not correlate with vessel recanalization (0.013, P = .948). There was no difference between median FVIII level at baseline and 90 days post-AIS. FVIII level decreased significantly after tPA, but baseline FVIII level and early change in FVIII level were not significant predictors of clot burden, vessel recanalization after thrombolysis, or symptomatic hemorrhage.

Left Atrial Enlargement on Transthoracic Echocardiography Predicts Left Atrial Thrombus on Transesophageal Echocardiography in Ischemic Stroke Patients

Background. Transesophageal echocardiogram (TEE) is superior to transthoracic echocardiogram (TTE) in detecting left atrial thrombus (LAT), a risk factor for stroke, but is costly and invasive, carrying a higher risk for complications. Aims. To determine the utility of using left atrial enlargement (LAE) on TTE to predict LAT on TEE. Methods. AIS patients who presented in 06/2008–7/2013 and underwent both TTE and TEE were identified from our prospective stroke registry. Analysis consisted of multivariate logistic regression with propensity score adjustment and receiver operating characteristic (ROC) area under the curve (AUC) analyses. Results. 219 AIS patients underwent both TTE and TEE. LAE on TTE was detected in 113 (51.6%) of AIS patients. Patients with LAE on TTE had higher proportion of LAT on TEE (8.4% versus 1.0%, p = 0.018). LAE on TTE predicted increased odds of LAT on TEE (OR = 8.83, 95% CI 1.04–74.83, p = 0.046). The sensitivity and specificity for LAT on TEE by LAE on TEE were 88.89% and 52.20%, respectively (AUC = 0.7054, 95% CI 0.5906–0.8202). Conclusions. LAE on TTE can predict LAT detected on TEE in nearly 90% of patients. This demonstrates the utility of LAE on TTE as a potential screening tool for LAT, potentially limiting unneeded costs and complications associated with TEE.