Laboratory Monitoring of Parenteral Direct Thrombin Inhibitors

Abstract

Argatroban and bivalirudin are parenteral direct inhibitors of the activity of thrombin, but, unlike heparin, can inhibit both soluble as well as clot-bound thrombin. These agents do not require antithrombin as a cofactor for activity. The parenteral direct thrombin inhibitors (DTIs) can be used in a variety of settings, including heparin-induced thrombocytopenia (HIT) or an allergy to heparin, and patients requiring anticoagulation for an invasive cardiovascular intervention. Both agents have a relatively short half-life in patients without organ system failure and are typically administered by continuous infusion. Argatroban is primarily eliminated by the liver, while bivalirudin is removed by a combination of proteolytic cleavage by thrombin and renal clearance mechanisms. Several laboratory tests are available for monitoring the anticoagulant effects of the DTIs: the activated partial thromboplastin time (aPTT) and the activated clotting time (ACT) are the most commonly used assays, but on occasion, the thrombin time may be useful. Other coagulation assays such as the dilute thrombin time (dTT), chromogenic anti-IIa assays, and the ecarin clotting time (ECT) can be used. The intensity of anticoagulation with DTIs depends on the indication for use. For patients with HIT, the target aPTT is 1.5 to 3.0 and 1.5 to 2.5 times the patient's baseline value for argatroban and bivalirudin, respectively. DTI anticoagulation used during percutaneous coronary intervention can be measured using ACT. Both DTIs may cause an elevation in the international normalized ratio depending on their plasma concentration. This article will review the use of parenteral DTIs and related laboratory assays for assessing the anticoagulant effect of these drugs.

Study on Structure Activity Relationship of Natural Flavonoids against Thrombin by Molecular Docking Virtual Screening Combined with Activity Evaluation In Vitro

“…In clinical practice, there are some effective anti-thrombin inhibitors such as bivalirudin, argatroban, heparin among others. However, the cost of treatment with these drugs is expensive and also associated with serious side effects [2][3][4]. These reasons underscore the need to seek and discover safer, affordable and effective natural thrombin inhibitors for the treatment of thrombotic disease.…”

Biomaterials-Mediated Tumor Infarction Therapy

“…Li et al applied it to the treatment of vascular infarction ( Li et al, 2018 ). The half-life of thrombin in the body is relatively short, which hinders its clinic use ( Van Cott et al, 2017 ). To enable thrombin to persist for a longer time in the body, Li et al combined it with a nanorobot to prevent the thrombin from being metabolized during transit to the target tumor cells.…”

Blood Conservation and Hemostasis Management in Pediatric Cardiac Surgery

“…This often predicts higher heparin dosing in infants than weight-based dosing, which theoretically prevents hemostatic activation on CPB and better preservation of hemostatic functions post-CPB. A protocol based on the HMS adjusted for infants reduced bleeding in a neonatal trial (48). The accuracy and limitations of the technology (c. 1990's) and its role in this era remains a subject of debate.…”