Plasma levels of direct oral anticoagulants in atrial fibrillation patients at the time of embolic stroke: a pilot prospective multicenter study.

BACKGROUND: Patients with atrial fibrillation (AF) who are on long-term direct oral anticoagulants (DOAC) with low anti-Xa or anti-IIa levels may be at higher risk of recurrent stroke. However, no prospective post-marketing study has investigated these DOAC plasma levels at the time of embolic stroke. The aim of this study was to assess the anti-Xa (rivaroxaban, apixaban) and anti-IIa (dabigatran) plasma levels in DOAC-treated AF patients at the time of acute embolic stroke. PATIENTS AND METHODS: We prospectively identified 43 patients with AF on long-term DOAC who experienced embolic strokes. We compared the DOAC plasma levels of these patients with a control sample of 57 patients who tolerated long-term therapeutic dose DOAC therapy without any adverse event. DOAC levels were assessed with drug-specific anti-Xa chromogenic analysis (rivaroxaban, apixaban) and with Hemoclot Thrombin Inhibitor assay (dabigatran). RESULTS: Dabigatran-treated patients with stroke had significantly lower anti-IIa levels when compared with the trough (40.7 ± 36.9 vs. 85.4 ± 57.2 ng/mL, p < 0.05) and peak samples of the controls (40.7 ± 36.9 vs. 138.8 ± 78.7 ng/mL, p < 0.001). Similarly, there were significantly lower anti-Xa levels in apixaban-treated patients with stroke compared to the trough control samples (72.4 ± 46.7 vs. 119.9 ± 81.7 ng/mL, p < 0.05), and in rivaroxaban- and apixaban-treated patients when compared to peak control samples (rivaroxaban: 42.7 ± 31.9 vs. 177.6 ± 38.6 ng/mL, p < 0.001; apixaban: 72.4 ± 46.7 vs. 210.9 ± 88.7 ng/mL, p < 0.001). CONCLUSION: This observational study showed significantly lower anti-IIa and anti-Xa plasma levels in AF patients with embolic stroke compared to those who tolerated long-term therapeutic dose DOAC therapy.

Novel missense variant of CACNA1A gene in a Slovak family with episodic ataxia type 2.

INTRODUCTION: Episodic ataxias (EAs) are rare dominantly inherited neurological disorders characterized by recurrent episodes of ataxia lasting minutes to hours. The most common subtype is EA type 2 (EA2) caused by pathogenic variants of calcium voltage-gated channel subunit alpha1 A gene (CACNA1A) on chromosome 19p13. SUBJECTS AND METHODS: We examined a Slovak three-generation family. Genomic DNA of the family members was extracted from peripheral blood and amplified by polymerase chain reaction. CACNA1A variants were screened by Sanger sequencing. RESULTS: We identified four family members with recurrent episodes of ataxia. Complex differential diagnosis was performed. Genetic analysis with direct sequencing revealed a novel heterozygous variant of CACNA1A - c.5264A>G (p.Glu1755Gly) located in the pore loop of domain IV of calcium channel alpha-1A subunit. CONCLUSION: We identified a novel missense variant of a voltage-dependent P/Q-type calcium channel alpha-1A subunit in a Slovak three-generation family with recurrent episodes of ataxia. The heterozygous missense variant resulted in changing a highly conserved glutamic acid within the pore loop of domain IV.

The safety and efficacy of Heparin and Nadroparin compared to placebo in acute ischemic stroke - pilot study.

AIMS: This study aimed to compare the efficacy and safety of heparin and nadroparin in order to provide an additional therapeutic option for patients with acute ischemic stroke in, whom systemic thrombolysis was excluded, or thrombectomy could not be performed. METHODS: We describe a prospective randomized double-blind placebo-controlled pilot study in acute ischemic stroke. The therapeutic window was between 4.5 and 24 h after the onset of stroke. During the first 24 h of treatment, the patients divided into 3 groups received placebo, heparin or nadroparin (in therapeutic doses). During the following 48 h, each patient received nadroparin in the therapeutic dose. 24 h after start of treatment they began taking 100 mg aspirin daily. The primary safety indicator was incidence of complications such as intracerebral or systemic hemorrhage, or death. Efficacy was primarily monitored by the neurological modified Rankin Scale (mRS) at 90 days. RESULTS: There were no signs of intracerebral or systemic bleeding in the cohort of 87 patients. Two patients died - one (3.7%) in the heparin and one (3.8%) in the placebo group due to causes not connected with the treatment. There was a statistically significant difference in mRS on the 90th day between the heparin and placebo groups (21 (80%) vs 13 (50%), P=0.0350) and between the nadroparin and placebo groups (29 (85%) vs 13 (50%), P=0.0031). CONCLUSION: The results show that the treatment with heparin and nadroparin is safe and effective. TRIAL REGISTRATION: Trial is registered in ClinicalTrials.gov: NCT01862978.