QCM-D surpassing clinical standard for the dose administration of new oral anticoagulant in the patient of coagulation disorders.

The study focuses the dose administration of dabigatran to avoid the deaths due to hemorrhagic complications and thromboembolic stroke in clinics worldwide. To target the issue, a novel emerging acoustic technology, namely ''Quartz Crystal Microbalance with Dissipation'' (QCM-D) has been applied, while the acoustic assays namely ''activated Partial Thromboplastin Time'' (aPTT) and ''Prothrombinase complex-induced Clotting Test'' (PiCT) have been compared with the standard methods in parallel. Both techniques have been applied to 300 samples, including 220 plasma samples of patients suffering coagulation disorders and 80 plasma samples of non-patients. In comparison, the coagulation times of the acoustic aPTT and PiCT yielded an excellent correlation with the standard methods with in analytical standard deviation limits. Finally, the acoustic aPTT assay is the ''gold standard'' for a dose administration of the new oral anticoagulant, where the Δf/ΔΓ ratio of the acoustic assay demonstrates that dabigatran with FEIBA 50 combination could be a safe remedy to avoid the deaths in clinics.

In vitro and ex vivo Measurement of Prophylactic Dabigatran Concentrations with a New Ecarin-Based Thromboelastometry Test.

BACKGROUND: An increasing number of oral anticoagulants has been approved, including dabigatran etexilate (DE). DE is a direct thrombin inhibitor that requires no routine monitoring, but, if necessary (e.g. urgent surgery etc.), the diluted thrombin time measured with Hemoclot® has shown reliable results. So far, no point-of-care (PoC) assay is available to measure DE effects. The EcaTEM assay uses ecarin to initiate the coagulation cascade at the step of thrombin generation and measures the clotting time (CT) by thromboelastometry. METHODS: This study investigated the correlation of the EcaTEM with standard laboratory assays in dabigatran-treated patients. Ten patients undergoing total hip or knee arthroplasty were included in the study. DE for thromboprophylaxis was started 4 h after surgery. Blood samples were taken before surgery as well as 2, 6 and 12 h after ingestion on the 3rd postoperative day. Dabigatran concentration (Hemoclot), activated partial thromboplastin time, thrombin time and CT EcaTEM were measured. RESULTS: Only CT EcaTEM and Hemoclot showed a correlation > 0.75 for all measurements. CONCLUSION: CT EcaTEM appears a valid PoC method parameter to detect thrombin inhibition and thus the presence of dabigatran beside diluted thrombin time at different concentration levels. This may represent an opportunity to identify the presence of dabigatran, e.g., in emergency situations.

Measurement and reversal of prophylactic and therapeutic peak levels of rivaroxaban: an in vitro study.

BACKGROUND: Rivaroxaban (Xarelto, Bayer HealthCare, Leverkusen, Germany) is a new oral anticoagulant drug. Anticoagulants may cause bleeding, thereby requiring reliable monitoring and efficient therapy. We investigated thromboelastometry versus routine coagulation tests to measure prophylactic and therapeutic concentrations of rivaroxaban and their reversal with prothrombin complex concentrate (PCC) and activated recombinant factor VII (rFVIIa) in vitro. METHODS: Rivaroxaban was solubilized, and PCC and rFVIIa were added in 2 concentrations to the rivaroxaban-spiked blood samples, and thromboelastometry and measurements were performed. RESULTS: Rivaroxaban increased tissue factor-activated clotting time (CT(ExTEM)) dose dependently. Activated partial prothrombin time (aPTT), prothrombin time ratio (PTR), and prothrombin time (PT) were changed significantly in both concentrations. Reversal with PCC in both dosages caused no significant change in the measured parameters. For prophylactic rivaroxaban dosage, rFVIIa changed the PT significantly but not CT(ExTEM), aPTT, and PTR. For therapeutic rivaroxaban dosage, the CT(ExTEM) was significantly reduced. The other parameters remained unaffected. CONCLUSIONS: Thromboelastometry can detect rivaroxaban effects. In vitro rFVIIa seems highly effective for reversal in contrast to PCC.