Feasibility of rapid measurement of Rivaroxaban plasma levels in patients with acute stroke.

Plasma levels of Rivaroxaban (RivLev) might be useful to guide therapeutic decisions in patients with acute stroke under Rivaroxaban. A prerequisite for the potential clinical usefulness is their rapid availability in emergency situations. Single-center explorative analysis from the Novel-Oral-Anticoagulants-in-Stroke-Patients-registry (NOACISP, cinicaltrials.gov:NCT02353585). We included consecutive patients with acute ischemic or hemorrhagic stroke under Rivaroxaban (last intake <48 h) in which RivLev determined by an automated anti-factor Xa-based chromogenic assay (Hyphen-Biomed, France) are available. Primary endpoint was the turnaround time (TAT), defined as time from registration of the blood sample in the lab to first result published. Furthermore, we studied, whether TAT is influenced by (1) on- and off-hour-measurements and (2) early versus later patient arrival (cut-off: 270 min after symptom onset). Thirty-eight patients met the eligibility criteria (mean age 77 years, 44 % female). TAT was 34 min (IQR 29-65 min). TATs were similar for on- (n = 14; median 34 min; IQR 30-56 min) and off-hours-TATs (n = 24; median 35 min; IQR 29-75 min) as well as for early (n = 16; median 33 min; IQR 30-40 min) and late patient arrival (n = 22, median 34 min, IQR 28-58 min; all nonsignificant.). Taking into account RivLev in the decision process about the use of intravenous thrombolysis, three patients received intravenous thrombolysis on an individualized basis, none of them with bleeding complications. Emergency measurement of RivLev among patients with acute stroke is available within a median of 34 min and therefore feasible for ED use. Due to the rapid availability, further research to evaluate the role of RivLev in order to guide acute treatment decisions is warranted.

Next generation sequencing analysis of patients with familial cervical artery dissection.

BACKGROUND: The cause of cervical artery dissection is not well understood. We test the hypothesis that mutations in genes associated with known arterial connective tissue disorders are enriched in patients with familial cervical artery dissection. PATIENTS AND METHODS: Patient duos from nine pedigrees with familial cervical artery dissection were analyzed by whole exome sequencing. Single nucleotide variants in a panel of 11 candidate genes (ACTA2, MYH11, FBN1, TGFBR1, TGFBR2, TGFB2, COL3A1, COL4A1, SMAD3, MYLK and SLC2A10) were prioritized according to functionality (stop-loss, nonsense, and missense variants with polyphen-2 score ≥0.95). Variants classified as "benign" or "likely benign" in the ClinVar database were excluded from further analysis. For comparison, non-benign stop-loss, nonsense and missense variants with polyphen-2 score ≥0.95 in the same panel of candidate genes were identified in the European non-Finnish population of the ExAC database (n = 33,370). RESULTS: Non-benign Single nucleotide variants in both affected patients were identified in four of the nine cervical artery dissection families (COL3A1; Gly324Ser, FBN1: Arg2554Trp, COL4A1: Pro116Leu, and TGFBR2: Ala292Thr) yielding an allele frequency of 22.2% (4/18). In the comparison group, 1782 variants were present in 33,370 subjects from the ExAC database (allele frequency: 1782/66,740 = 2.7%; p = 0.0008; odds ratio = 14.2; 95% confidence interval = 3.8-52.9). CONCLUSION: Cervical artery dissection families showed enrichment for non-benign variants in genes associated with arterial connective tissue disorders. The observation that findings differed across families indicates genetic heterogeneity of familial cervical artery dissection.

Early recurrent ischemic stroke in stroke patients undergoing intravenous thrombolysis.

BACKGROUND: We assessed the incidence of early recurrent ischemic stroke in stroke patients treated with intravenous tissue-type plasminogen activator (tPA) and the temporal pattern of its occurrence compared with symptomatic intracranial hemorrhage (ICH). METHODS AND RESULTS: Prospectively collected, population-based data for 341 consecutive acute stroke patients (62% men; mean age, 66 years) treated with tPA according to the National Institute of Neurological Disorders and Stroke study protocol at 8 medical centers in Switzerland (3 academic and 5 community) between January 2001 and November 2004 were retrospectively analyzed. The primary outcome measure was neurological deterioration > or = 4 points on the National Institutes of Health Stroke Scale occurring within 24 hours of tPA treatment and caused either by recurrent ischemic stroke (defined as the occurrence of new neurological symptoms suggesting involvement of initially unaffected vascular territories and evidence of corresponding ischemic lesions on cranial computed tomography scans, in the absence of ICH) or by ICH. Early recurrent ischemic stroke was diagnosed in 2 patients (0.59%; 95% confidence interval, 0.07% to 2.10%) and symptomatic ICH in 15 patients (4.40%; 95% confidence interval, 2.48% to 7.15%). Both recurrent ischemic strokes occurred during thrombolysis, whereas symptomatic ICHs occurred 2 to 22 hours after termination of tPA infusion. CONCLUSIONS: Recurrent ischemic stroke is a rare cause of early neurological deterioration in acute stroke patients undergoing intravenous thrombolysis, with a different temporal pattern compared with that of symptomatic ICH.