Reverse the effects of new anticoagulant drugs

Reverse the effects of new anticoagulant drugs - Oral anticoagulant warfarin (Coumadin) became available for prescription in 1954.

This anticoagulant medication commanded national attention when President Dwight Eisenhower received the drug as part of their treatment after a heart attack. No other oral anticoagulant has been developed and marketed in the United States through 2010 successfully. 

Warfarin is a dangerous drug. With insulin, which is responsible for most emergency hospital admissions due to adverse drug reactions. While insulin causes hypoglycemia, warfarin is notorious for major bleeding complication. 

Warfarin is littered with hundreds of drug-drug and drug-food interactions. The optimal dose is determined by monitoring the level of anticoagulant in the blood. Standard intensity anticoagulation with warfarin is generally directed to achieve the results of blood tests prothrombin expressed as international normalized ratio (INR) in the range of 2.0 to 3.0. If the INR is above 3.0, the warfarin dose is reduced to prevent excessive bleeding. 

If the INR is less than 2.0, the warfarin dose is increased to prevent excessive blood clotting. This approach is slow, cumbersome and frustrating. Although the INR tests within the desired range, catastrophic bleeding complications, such as bleeding in the brain, may occur. 

Patients and healthcare professionals complain of the difficulties and disadvantages of trying to use warfarin correctly. Multiple algorithms and genetic testing were even made with the hope of getting an easy to follow dosage, but these efforts have been disappointing in general.

 
Enter the new anticoagulants

In five remarkable years covering 2010-2014, four new oral anticoagulants have been pivotal trials for the prevention of stroke due to atrial fibrillation and treatment of pulmonary embolism and deep vein thrombosis Atrial. 

The four new drugs have improved safety profiles as warfarin, and some are more effective than warfarin for the prevention of stroke in patients with atrial fibrillation. The four were quickly approved by the Food and Drug Administration for the treatment of these thrombotic diseases. 

One, dabigatran (Pradaxa) is a direct thrombin inhibitor - that is, the coagulation factor II (thrombin) is enabled. The other three - rivaroxaban (Xarelto), apixaban (Eliquis) and apixaban (Savaysa) - inactive coagulation factor X. 

No specific objective of these new anticoagulants requires regular monitoring laboratory. They are administered in fixed doses. Virtually no restrictions on foods such as green leafy vegetables, as there are with warfarin. And there are only about a dozen major drug interactions. 

As this wave of new oral anticoagulants hit the market, there were predictions (which proved to be false) that warfarin would quickly become a frequently used anticoagulant. A Harvard-affiliated Brigham and Women's Hospital, we have about 3,500 patients in our anticoagulation management service still receiving warfarin. So why the initial estimates were wrong? Why warfarin continue to send more "market share" of these anticoagulants target specific synthetic drugs? 

The biggest concern is that the new oral anticoagulants have not, until now, have specific antidotes to counter major bleeding. Warfarin is a vitamin K antagonist, at a dosage of vitamin K is an antidote to warfarin - although one that works slow and unreliable. But fear with the new oral anticoagulants was that rare episode of major bleeding can not be controlled or reversed quickly.

New antidotes open the way to greater use of new anticoagulants

The landscape has changed dramatically in October 2015 when the FDA approved an antidote to dabigatran etexilate antibodies. After rapid intravenous injection of the antidote, dabigatran is attracted by its own antibodies at least 300 times stronger than thrombin (coagulation factor II).

When dabigatran and binding of antibodies, thrombin is released etexilate and can do what they do best clotting factors to stop bleeding.
 

In an ongoing clinical trial, the anticoagulant dabigatran testing laboratory was reversed within minutes of the injection of the antibody antidote to dabigatran. Hospitals in the United States now has dabigatran of antibodies available for emergency use. 

Although the catastrophic hemorrhaging of new oral anticoagulants is extremely rare, the availability of antidotes reassure healthcare providers, patients and their families. Changes the psychology of prescription and balance leans more towards the new agents. 

As with rivaroxaban, apixaban and edoxaban, a universal antidote and is in the final stages of successful clinical development. This antidote is not an antibody, but it is interesting "bait" for these three anticoagulants, which coagulation factor X. 

The antidote aim is more attractive to anticoagulants is the X factor, but only slightly modifies the structure factor X. The decoy, which is inert, "dummy" Three of these anticoagulants. Then separate the coagulation factor X bind to lure and instead of releasing unbound X clotting factor to stop the bleeding. 

In short, these two antidotes are "backups" important to our arsenal of new anticoagulants. They allow us to prescribe new agents with more confidence.

By: Samuel Z Goldhaber,MD.