Faculty Bibliography

BACKGROUND/OBJECTIVE/OBJECTIVE:Desmopressin (DDAVP) has been suggested for antiplatelet medication reversal in patients with traumatic brain injury (TBI) but there are limited data describing its effect on clinical outcomes. The purpose of this study was to evaluate the effect of DDAVP on hematoma expansion and thrombosis in patients with TBI who were prescribed pre-injury antiplatelet medications. METHODS:Consecutive adult patients who were admitted to our level I trauma center and prescribed pre-injury antiplatelet medications between July, 2012, and May, 2018, were retrospectively identified. Patients were excluded if their hospital length of stay was < 24 h, if DDAVP was administered by any route other than intravenous, if they received a DDAVP dose < 0.3 mcg/kg or there was no evidence of brain hemorrhage on computed tomography (CT) scan. Patients were stratified based on the use of DDAVP, and the incidence of hematoma expansion was compared between groups. Thrombotic events were reviewed as a secondary outcome. Multivariate analysis was utilized to control for confounding variables. RESULTS:Of 202 patients included in analysis, 158 (78%) received DDAVP. The mean age was 76 ± 12 years; the most common injury mechanism was falls (76%); 69% had acute subdural hematoma, and 49% had multi-compartmental hemorrhage. Initial Glasgow coma score was between 13 and 15 for 91% of patients. Aspirin was the most common antiplatelet regimen prescribed (N = 151, 75%), followed by dual antiplatelet regimens (N = 26, 13%) and adenosine diphosphate (ADP)-receptor inhibitors (N = 25, 12%). The incidence of hematoma expansion was 14% and 30% for patients who did and did not receive DDAVP, respectively (p = 0.015). After controlling for age, injury severity score, multi-compartmental hemorrhage, and receipt of pre-injury high-dose aspirin (> 81 mg), ADP-receptor inhibitors, oral anticoagulants, prothrombin complex concentrates or platelets in a multivariate analysis, the association between DDAVP and hematoma expansion remained significant (adjusted OR 0.259 [95% CI 0.103-0.646], p = 0.004). Thrombotic events were similar between the two groups (DDAVP, 2.5%, no DDAVP, 4.5%; p = 0.613). CONCLUSIONS:DDAVP was associated with a lower incidence of hematoma expansion in patients with mild TBI who were prescribed pre-injury antiplatelet medications. These results justify a randomized controlled trial to further evaluate the role of DDAVP for this indication.

Andexanet-alpha is a specific reversal agent for direct factor Xa inhibitors (dFXaI). We aimed to project utilization rates and cost of andexanet for reversal of dFXaI-related major hemorrhage compared to 4-factor prothrombin complex concentrates (4F-PCC). A retrospective, multicenter review was conducted between 1/1/2014 and 7/15/2018 of patients who received 4F-PCC for reversal of dFXaI-related life-threatening hemorrhages. Total hospital reimbursements/patient were calculated based on national average MS-DRG payments adjusting for Medicare discounts. The projected cost for andexanet (based on dose and insurance) and % reimbursement/patient was compared to the actual cost of 4F-PCC. Hemostasis at 24 h (excellent/good vs. poor) and 30-day thrombotic complications were assessed. Of 126 patients who received 4F-PCC to reverse dFXaI, 46 (~ 10 per-year) met inclusion criteria. The median projected cost of andexanet was $22,120/patient, compared to $5670/patient for 4F-PCC (P < 0.001). The median hospital reimbursement was $11,492/hospitalization. The projected cost of andexanet alone would exceed the entire hospital reimbursement in 74% of patients by a median of $7604, while 4F-PCC cost exceeded the total hospital payments in 7% of patients in the same cohort (P < 0.001). Hemostasis was excellent/good in 72% of patients post-4F-PCC, compared to 82% in andexanet trials. Thromboembolic events occurred in 4% of patients following 4F-PCC versus 10% in andexanet trials. The projected cost of andexanet would exceed the national average hospital reimbursement/patient in nearly 75% of patients by over $7500/hospitalization. 4F-PCC was significantly less expensive, had lower rates of thrombosis, but also lower rates of good/excellent hemostasis compared to published data for andexanet.

Introduction The 5 seminal mechanical thrombectomy (MT) trials had a median age of 68 years. Though some of these trials included nonagenarians, there is little data on their outcomes. We aimed to compare the procedural, discharge outcomes and complications, of MT for acute ischemic stroke (AIS) in nonagenarians versus younger patients(<=69) Methods Patients with AIS admitted to two comprehensive stroke centers were enrolled prospectively in a registry. Rates of MT were compared between nonagenarians vs <=69. Among those who underwent MT, procedural outcomes, complications, and discharge disposition were compared in propensity scorematched groups (matched for NIHSS, pre-stroke mRS, IV-tPA administration and T IG grade>=2b) of nonagenarians to patients<=69. Good discharge disposition was defined as a discharge to home/acute rehabilitation. Results Of the 3010 AIS patients, 46/297 (16%) nonagenarians underwent MT compared to 159/1337 (12%) patients <=69 (P=0.091) with TICI>=2b of 89% vs 94%; p=0.238 respectively. 78 patients (N=39 >=90, N=39 <69) were propensity score-matched with a median admission NIHSS of 22 and 19, and median ASPECTS of 9 and 9, respectively (both P>0.05). Those <69 more often had Ml occlusions than nonagenarians (84% vs 50%, P=0.035), whereas ICA (10% vs 13%, p=0.76), and M2 (21% vs 43%, p=0.19) occlusions were similar between the two groups. Time to groin puncture (100+/-65 vs 76+/-34; p=0.124), revascularization time (134+/-72 vs 110+/-54; p=0.145), complication rates (0 vs 5.1%; p=0.494) and inhospital deaths (11% vs 24%; p=0.155) were similar among the two groups. 44% of nonagenarians had good discharge disposition, compared to 51% of patients <69 years (p=0.650) Conclusions We present one of the largest series of MT among nonagenarians with 89% successful recanalization rates. In propensity score analysis almost half of nonagenarians (44%) were discharged to home/rehab, which is comparable to a younger cohort (51%). Aggressive management is warranted in the oldest of the old

BACKGROUND AND PURPOSE/OBJECTIVE:Early neurologic improvement (ENI) in patients treated with alteplase has been shown to correlate with functional outcome. However, the definition of ENI remains controversial and has varied across studies. We hypothesized that ENI defined as a percentage change in the National Institute of Health Stroke Scale (NIHSS) score (percent change NIHSS score) at 24-hours would better correlate with favorable outcomes at 3 months than ENI defined as the change in NIHSS score (delta NIHSS score) at 24 hours. METHODS:Retrospective analysis of prospectively collected single-center quality improvement data was performed of all acute ischemic stroke (AIS) patients treated with alteplase. We examined delta NIHSS score and percent change NIHSS score in unadjusted and adjusted logistic regression models as predictors of a favorable outcome at 3 months (defined as mRS 0-1). RESULTS:Among 586 patients who met the inclusion criteria, 194 (33.1%) had a favorable outcome at 3 months. In fully adjusted models, both delta NIHSS score (OR per point decrease 1.27; 95% confidence interval [CI] 1.19-1.36) and percent change NIHSS score (OR per 10 percent decrease 1.17; 95% CI 1.12-1.22) were associated with favorable functional outcome at 3 months. Receiver operating characteristic (ROC) curve comparison showed that the area under the ROC curve for percent change NIHSS score (.755) was greater than delta NIHSS score (.613) or admission NIHSS (.694). CONCLUSIONS:Percentage change in NIHSS score may be a better surrogate marker of ENI and functional outcome in AIS patients after receiving acute thrombolytic therapy. More studies are needed to confirm our findings.

BACKGROUND:There is limited data on predictors of symptomatic intracranial haemorrhage (sICH) in patients who underwent mechanical thrombectomy. In this study, we aim to determine those predictors with external validation. METHODS:and t tests to identify independent predictors of sICH with p<0.1. Significant variables were then combined in a multivariate logistic regression model to derive an sICH prediction score. This score was then validated using data from the Blood Pressure After Endovascular Treatment multicentre prospective registry. RESULTS:We identified 578 patients with acute ischaemic stroke who received thrombectomy, 19 had sICH (3.3%). Predictive factors of sICH were: thrombolysis in cerebral ischaemia (TICI) score, Alberta stroke program early CT score (ASPECTS), and glucose level, and from these predictors, we derived the weighted TICI-ASPECTS-glucose (TAG) score, which was associated with sICH in the derivation (OR per unit increase 1.98, 95% CI 1.48 to 2.66, p<0.001, area under curve ((AUC)=0.79) and validation (OR per unit increase 1.48, 95% CI 1.22 to 1.79, p<0.001, AUC=0.69) cohorts. CONCLUSION/CONCLUSIONS:High TAG scores are associated with sICH in patients receiving mechanical thrombectomy. Larger studies are needed to validate this scoring system and test strategies to reduce sICH risk and make thrombectomy safer in patients with elevated TAG scores.