Vitamin K Antagonists and Direct Thrombin Inhibitors: Present and Future

2005 ◽  
Vol 19 (1) ◽  
pp. 69-85 ◽  
Author(s):  
Graham F. Pineo ◽  
Russell D. Hull
Keyword(s):  
Vitamin K ◽  
Vitamin K Antagonists ◽  
Thrombin Inhibitors ◽  
Direct Thrombin Inhibitors

scholarly journals A REVIEW ON A COMPARATIVE STUDY ON EFFECTIVENESS AND SAFETY OF NOVEL ORAL ANTICOAGULANTS IN PATIENTS WITH ATRIAL FIBRILLATION

2019 ◽  
Vol 7 (2) ◽  
Author(s):  
Priyanka P K ◽  
Mathew George ◽  
Lincy Joseph
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K ◽  
Therapeutic Option ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Novel Oral Anticoagulants ◽  
Thrombin Inhibitors ◽  
Direct Thrombin Inhibitors ◽  
Systemic Embolism ◽  
Anticoagulant Drugs

Atrial fibrillation (AF) is characterized as an extremely rapid and disorganized atrial activation. These irregular heartbeats will cause blood to collect within the heart and potentially form a clot, which can travel to a person’s brain and cause a stroke. AF increases stroke risk by 3 to 5 fold. Vitamin K antagonists (VKAs) are highly effective for the prevention of stroke, mainly of ischemic origin, in patients with AF. For this reason, VKAs are currently recommended in all AF patients at moderate to high risk for stroke or systemic embolism (SSE). VKAs have significant limitations, particularly their unpredictable anticoagulant response and numerous food and drug interactions, mandating regular laboratory monitoring. These limitations make treatment with VKAs problematic for many patients; as a result, only about half of all potentially eligible AF patients are treated with VKAs. Over the last several years, novel oral anticoagulant drugs (NOACs), including direct thrombin inhibitors (dabigatran) and factor Xa inhibitors (apixaban & rivaroxaban), have been developed. New orally administered anticoagulant drugs have emerged as potential alternatives to VKAs for the prevention of ischaemic stroke or systemic embolism in patients with chronic atrial fibrillation. Novel oral anticoagulants (NOACs), due to their a lot of predictable therapeutic result and more favorable haemorrhagic risk profile, represent a particularly attractive therapeutic option in AF patients. Keywords:  Novel oral anticoagulants (NOACs), Vitamin K antagonist (VKAs), Atrial fibrillation, Apixaban, Dabigatran, Rivaroxaban.

Effect of Melagatran on Prothrombin Time Assays Depends on the Sensitivity of the Thromboplastin and the Final Dilution of the Plasma Sample

2001 ◽  
Vol 86 (08) ◽  
pp. 611-615 ◽  
Author(s):  
Angela Menschiek-Lundin ◽  
Karin Wåhlander ◽  
Tomas Lindahl ◽  
Christer Mattsson
Keyword(s):  
Prothrombin Time ◽  
Vitamin K ◽  
Plasma Sample ◽  
Anticoagulant Activity ◽  
Vitamin K Antagonists ◽  
Thrombin Inhibitors ◽  
Thrombin Inhibitor ◽  
Direct Thrombin Inhibitors ◽  
Sensitivity Index ◽  
Response Curves

SummaryProthrombin time (PT) assays are clotting methods that measure the activity of vitamin K-dependent coagulation factors (F) II, VII, and X. There are three main types of PT assays in general usage, namely the Quick assay, Owren’s assay and PT dry chemistry test cards. PT assays were initially developed to monitor dose-adjustments of vitamin K antagonists such as warfarin. The aim of the present study was to investigate whether commercially available PT assays are suitable for evaluating the anticoagulant activity of direct thrombin inhibitors. Melagatran, a reversible direct thrombin inhibitor, was added to human plasma at concentrations ranging from 0.1 to 2.0 μmol/l. Seventeen different commercially available PT kits were used, including thirteen Quick reagents, two Owren reagents and two PT test cards. The sensitivity of the different reagents, expressed as the concentration of melagatran that doubled the prothrombin time (IC50) varied widely, with Thromboplastin S and Thromboplastin HS being the most sensitive (IC50 = 0.9 μmol/l). The reagents with apparently the lowest sensitivity were the two Owren reagents Nycotest PT and SPA 50 with an IC50 of 2.2 and 2.9 μmol/L, respectively. This is most likely due to a higher dilution of melagatran in these assays compared to the dilution in the Quick assays. The results were also dependent on the International Sensitivity Index (ISI) of each reagent. The concentration of melagatran that produced an International Normalized Ratio (INR) of 2 was calculated from dose-response curves for each assay, and these results revealed that reagents with a high ISI value gave an INR of 2 at much lower concentrations of melagatran (0.5-0.7 μmol/L) than those with an ISI-values around one (0.9-1.2 μmol/L). It was found that INR depends not only on the plasma concentration of melagatran, but also on the sensitivity of the PT reagent and on the final dilution of the plasma sample in the prothrombin time assay. Thus, since the same melagatran concentration can be associated with widely varying PT/INR results depending on the specific assay used it is concluded that PT assays and INR can not be used to monitor melagatran activity.

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