Search

Background:The Redual PCI trial has demonstrated the safety of dabigatran and ticagrelor or clopidogrel combination in preventing strokes in patients with atrial fibrillation. There was 15.4% risk of hemorrhage in the dabigatran/ticagrelor or clopidrogel arm, lower than that of triple therapy with warfarin, aspirin and ticagrelor or clopidogrel. While idarucizumab is an effective antidote for dabigatran, there is no good method for antagonizing both dabigatran and ticagrelor. We tested in this study a hemadsorbtion method for removing dabigatran that we had previously successfully applied in the removal of ticagrelor from human blood.Methods:100 mL 4% BSA solution pre-incubated with dabigatran was passed through 10, 20 and 40 mL sorbent columns and dabigatran concentrations was measured from the affluent and effluent solution using LC-MS/MS. For testing the effect of dabigatran removal on the aPTT value one human volunteer was administered oral dabigatran etexilate mesilate 150 mg. Plasma was collected 4 hours after dabigatran administration and then in three experiments 20 mL of collected plasma was circulated through three different 10 mL CytoSorb columns over a duration of 5 minutes. aPTT was measured from the baseline plasma prior to drug administration, plasma post drug collection and the adsorbed plasma as well.Results:Dabigatran concentration, as measured by LC-MS/MS, decreased from 1456?331 nM (greater than the therapeutic level of 743 nM) to 67?59 nM (P=0.002) with the 10 mL CytoSorb column, while with the 40 mL column it dropped to undetectable levels. In one human volunteer experiment the aPTT was on average 29.2 ? 0.4 in the 3 baseline samples, 34.7 ? 1.8 seconds after oral dabigatran (mixed plasma), and 25 ? 0.7 seconds after plasma was passed through CytoSorb (adsorbed plasma) (P=0.000025 and 0.0000002 for comparison between baseline plasma and mixed plasma, as well as the dabigatran mixed plasma and post-adsorption values respectively).Conclusion:Dabigatran is robustly removed by a sorbent hemadsorption method already proven successful for the P2Y12 receptor antagonist ticagrelor. Dabigatran removal restores the aPTT to below baseline values, suggesting that sorbent hemadsorption may reverse the anticoagulant effect of this drug.

Background:Direct oral anticoagulants are currently the drugs of choice for stroke prophylaxis in patients with atrial fibrillation. While an antidote is currently available - andexanet alfa, its limitations - including a high tag price per unit dose - may eventually render his clinical use relatively cumbersome. We test in this work a method of edoxaban removal using sorbent technology.Objective:The aim of this study was to test CytoSorb and Porapak Q 50-80 mesh for removal of the anticoagulant drug edoxaban from human plasma and 4% bovine serum albumin (BSA) solution.Methods:We circulated 100 mL of edoxaban solution during 6 first-pass cycles through 40 mL sorbent columns (containing either CytoSorb in 3 passes or Porapak Q 50-80 mesh in the remaining 3) during experiments using human plasma and 4% BSA solution as drug vehicles, using an experimental circuit as in Figure 1. Drug concentration was measured by liquid chromatography tandem mass spectrometry.Results:Edoxaban concentration in 2 experiments performed with human plasma dropped from 276.8 ? 0 ng/mL to 2.7 ng/mL and undetectable levels respectively with CytoSorb or Porapak Q 50-80 mesh (P=0.0031, Table). The average edoxaban concentration decreased from 407 ng/mL ? 216 ng/mL to 3.3 ng/mL ? 7 ng/mL (p=0.017, Table), for a removal rate of 99% across all 6 samples of human plasma (2 samples) and BSA solution (4 samples). In 4 out of the 6 adsorbed samples the drug levels were undetectable.Conclusion:Sorbent mediated technology may represent a viable pathway for edoxaban removal from human plasma or albumin solution.

Vulnerable plaques, which are responsible for most acute ischemic events, are presently invisible to x-ray angiography. Their primary morphological features include a thin or ulcerated fibrous cap, a large necrotic core, superficial foam cells, and intraplaque hemorrhage. We present evidence that multimodal spectroscopy (MMS), a novel method that combines diffuse reflectance spectroscopy (DRS), intrinsic fluorescence spectroscopy (IFS), and Raman spectroscopy (RS), can detect these markers of plaque vulnerability. To test this concept, we perform an MMS feasibility study on 17 human carotid artery specimens. Following the acquisition of spectra, each specimen is histologically evaluated. Two parameters from DRS, hemoglobin concentration and a scattering parameter, are used to detect intraplaque hemorrhage and foam cells; an IFS parameter that relates to the amount of collagen in the topmost layers of the tissue is used to detect the presence of a thin fibrous cap; and an RS parameter related to the amount of cholesterol and necrotic material is used to detect necrotic core. Taken together, these spectral parameters can generally identify the vulnerable plaques. The results indicate that MMS provides depth-sensitive and complementary morphological information about plaque composition. A prospective in vivo study will be conducted to validate these findings.

Objective and Methods We analyzed the association between serum Troponin I (TnI) = 1.5 ng/ml and clinical variables within a group of congestive heart failure (CHF) patients with low clinical suspicion of acute myocardial infarction (MI). We define low clinical suspicion of MI as no chest pain or ECG ischemic findings and no history of MI. To establish whether the CHF patients with TnI = 1.5 ng/ml had experienced an acute coronary event, we compared them with individuals admitted for a non-Q MI. Results: We included 40 CHF patients with low clinical suspicion of MI (CHF group) and 49 with chest pain (CP) characteristic of an acute coronary event (CP group). Four patients with CHF (CHF high TnI subgroup) and 13 patients with CP (non-Q MI subgroup) had serum TnI values = 1.5 ng/ml. The mean Gensini coronary atherosclerosis score was significantly lower in the former subgroup than in the latter one (0.67 ± 1.15 vs. 28.5 ± 15.28, p = 0.009). The percentage of asynergic regions on left ventriculogram was 0 in CHF high TnI subgroup, significantly lower than in the non-Q MI subgroup (27%). Significant association within the CHF group was found between TnI = 1.5 ng/ml and left ventricular hypertrophy by electrocardiographic criteria (ECG-LVH) (p = 0.004), blood pressure (BP) = 200 systolic or 100 mm Hg diastolic (p = 0.015), pulmonary edema (p = 0.004), and creatinine = 1.5 mg/dl (p = 0.015). Conclusion: In a group of CHF patients with low clinical suspicion of MI, TnI = 1.5 ng/ml did not indicate an MI. Rather, the elevated TnI was associated with ECG-LVH, BP = 200 systolic or 100 mm Hg diastolic, pulmonary edema and creatinine = 1.5 mg/dl.