Point-of-Care Assessment of Direct Oral Anticoagulation in Acute Ischemic Stroke: Protocol for a Prospective Observational Diagnostic Accuracy Study

Abstract

Background: Treatment of ischemic stroke with recombinant tissue plasminogen activator (rtPA) for intravenous thrombolysis (IVT) must be delivered within a narrow time window after symptom onset. This effective hyperacute treatment can be administered after ruling out active anticoagulation with direct oral anticoagulants (DOAC). Whenever this is impractical, e.g. due to aphasia, plasmatic DOAC levels are measured with a consequent delay in the IVT decision making process ranging from 30 to 60 minutes time. This study will test the hypothesis that hyperacute point-of-care assessment of clotting time in the patient’s whole blood has sufficient diagnostic accuracy to determine immediately whether stroke patients are pretreated with DOAC. Methods/ Design: This will be a prospective single-center diagnostic accuracy study in 1850 consecutive acute ischemic stroke patients at a tertiary stroke center in Saxony, Germany. Presence of active anticoagulation with DOAC will be determined by point-of-care quantification of clotting time via whole blood viscoelastic testing (ClotPro®) using Russell venom viper and Ecarin assay compared to high performance liquid chromatography-tandem mass-spectrometry as reference standard. Discussion: Viscoelastic point-of-care assessment of clotting time in whole blood might improve swift delivery of time-sensitive hyperacute treatment with IVT in stroke patients.

Enhancing Anticoagulation Monitoring and Therapy in Patients Undergoing Microvascular Reconstruction in Maxillofacial Surgery: A Prospective Observational Trial

“…IN-test also uses CaCI2 to recalcify the samples but also involves ellagic acid for coagulation activation. RVV test with the addition of snake venom RVV-V (Russell viper venom factor V activator) provides a possibility for rapid detection of Xa inhibitors as well as low molecular weight heparin, potentially enabling fast decision taking regarding relevant plasma levels [ 34 ]. In the TPA essay, recombinant tissue plasminogen activator (r-tPA; 650 ng/mL) is used to cleave plasminogen to plasmin as a potent activator of fibrinolysis.…”

Management and Prognosis of Acute Stroke in Atrial Fibrillation

“…Recommendations regarding the use of IVT in DOAC patients vary between countries based on different patient selection strategies [56]. The inconsistencies in guidelines on IVT treatment in DOAC patients are the result of current uncertainty regarding monitoring of drug effects in DOAC-treated patients.…”

Direct oral anticoagulants (DOACs): From the laboratory point of view

“…Cut-off values for detecting clinically-relevant drug levels showed high levels of sensitivity and specificity. There are specific reagents for the Clot-Pro ® analyzer that are sensitive to DOACs (RVV test and ECA test) (82).…”

“…The reportable range of quantitation is 20-500 ng mL -1 , which is adequate for assessing both, peak and trough concentrations. Given that the implementation of quality control is necessary to ensure the overall quality of the system, it is recommended to perform daily internal quality control (IQC) using two levels (low and high concentrations) of the control samples (82)(83)(84)(85). In order to verify the accuracy of the system, there are also external quality assessment (EQA) providers available.…”