Vol. 11, Issue 1

A New Oral Anticoagulant

Atrial Fibrillation (AF) is the most common type of cardiac arrhythmia or abnormal heart rhythm involving the upper two heart chambers. It is named for the fibrillations or quivering of the heart muscles in the atria, instead of well controlled and coordinated muscle contractions that are normally observed. It is diagnosed by observation of an abnormal pulse or better yet by the absence of P waves in an electrocardiogram. When AF is experienced, the risk of stroke following abnormal blood clot formation is greatly increased, resulting from this abnormal heart activity. Risk of AF increases with age.

Warfarin has been in use for over 50 years, and continues to be the standard oral anticoagulant. It does, however, have drawbacks. Thromboprophylaxis with warfarin is influenced by genetic differences in metabolism, concurrent medication use, vitamin K intake, drug interactions, and alcohol consumption among others. To keep patients within the INR target range, regular monitoring and dosage adjustments are needed. Warfarin is used for therapy of AF as well as veneous thromboembolism (VTE) and pulmonary embolism (PE), though the recommended therapeutic ranges are different depending on the disease state being treated.

The search for alternative orally administered drugs led to the development of Pradaxa® (dabigatran etexilate). Pradaxa® is an oral direct thrombin inhibitor that was discovered and developed by Boehringer Ingelheim. It is the first new oral anticoagulant approved in the U.S. in more than 50 years, and was approved for the treatment of AF at the end of October, 2010.

Dabigatran (Pradaxa®) is a member of a new class of drugs called Direct Thrombin Inhibitors (DTIs). DTIs are a new class of anticoagulants that bind directly to thrombin and block its interaction with its substrates. Dabigatran inhibits free thrombin, fibrin-bound thrombin, and fibrin-induced platelet aggregation. Other DTIs include argatroban, hirudin, and bivalirudin.

Studies on Pradaxa® indicate that this new oral anticoagulant has a rapid onset and predictable anticoagulation action. There is also no evidence to suggest it interacts with food, while its potential to interact with other drugs is considered low.

The Ecarin Chromogenic Assay (ECA) from Diagnostica Stago, Inc. (Stago), is a highly-specific tool for determining the exact direct thrombin inhibitor (DTI) concentration in plasma without interference from abnormal prothrombin or fibrinogen levels.

ECA results are independent of coagulation factors and plasmatic inhibitors within the sample; and as it is not influenced by lupus anticoagulants, the assay allows for specific determinations. ECA is insensitive to heparin, LMWH, danaparoid, fondaparinux and direct factor Xa antagonists. This facilitates bridging and transition to other anticoagulants, and dosage adaptation in high- risk patients. Additionally, the ECA dose response results are linear and do not plateau at elevated concentrations. The ECA kit is for research use only in the United States and Canada, and is not for use in diagnostic procedures.

For additional information, contact us at 1-800-222-COAG (2624) or customer.care@stago-us.com

References:

1. Direct Thrombin Inhibitors, The New England Journal of Medicine 2005, 353: 1028-1040
2. Journal of Thrombosis and Haemostasis, Volume 7 Supplement 2, July 2009
3. Diagnostica Stago, Inc. Press Release October 1, 2010 4. Venous Disease Coalition