Newer, Safer Blood Thinners For Long-Term Use

Anticoagulant (blood thinning) medications prolong millions of lives.

By stopping the formation of blood clots, anticoagulants prevent catastrophic consequences of atrial fibrillation, deep vein thrombosis, venous thromboembolism, pulmonary embolism, congestive heart failure, stroke, heart attack (myocardial infarction), and genetic or acquired hypercoagulation disorders. Anticoagulants prevent blood from clotting in the lines leading from transfusion bags and in kidney dialysis machines. And they prevent the formation of potentially dangerous clots before, during, and after surgery.

All Anticoagulants Carry the Risk of Serious Side Effects

The clotting of blood is a multi-step process, and different anticoagulants stop different parts of the process. The coumarins, a group of drugs that includes warfarin, also known as Coumadin, which is more commonly used in the US and UK, and acenocoumarol and phenprocoumon, which are more commonly used in the rest of the world, act by antagonizing the effects of vitamin K. The coumarins bind to and deactivate an enzyme called vitamin K epoxide reductase, making it less available to activate the clotting of blood.

Long-term use of coumarins requires monthly monitoring of their levels in the bloodstream. Overdoses can cause serious bleeding. It's easy to mess up--and doctors only prescribe them for long-term use for specialized situations, such as prevention of blood clots after heart valve surgery.

Heparin, a naturally occurring protein usually extracted from pig intestines, and low molecular weight heparin (Lovenoxi), a more highly refined version of heparin, stop blood clots by activating a protein called antithrombin III, which prevents clotting of the blood. These medications are given by injection, but they do not have to be as closely monitored as some other anticoagulants, but severe bleeding is a real possibility. 

Oral Anticoagulants Easier to Use, Improving Safety

More recently, the pharmaceutical industry has developed a large number of oral anticoagulant medications, taken by mouth, not requiring an injection, that don't require frequent monitoring by doctors.

Another drug in this class is not on the market because it was found not actually to achieve its intended effect, reducing the risk of heart attack, but increased the risk of serious bleeding by 300%.

The very popular anticoagulant Brilinta (ticagrelor), sold outside the United States as Brilique or Possia, stops blood clots by acting as platelet activation factor (PAF) inhibitor, preventing blood platelets from clumping together to form a clot. Popular for preventing second heart attacks, this medication can cause severe bleeding in the liver and colon. Diabetics who have received coronary artery stents should not take Brilinta (although they still are likely to need a different coagulant drug).

And an even more popular anticoagulant drug that acts through the same mechanism, Plavix (clopidogrel), reduces the risk of heart attack after the placement of a stent in a coronary artery but can cause gastrointestinal bleeding in up to 2% of people who use it every year.

See Also: What do Anticoagulants do?

An Understandable Warning

Because all anticoagulants can cause unintended bleeding, all users must exercise caution not to suffer cuts, scrapes, or internal injuries. But because the easy to use oral anticoagulants can cause serious internal bleeding in the liver, many doctors have assumed that people who have liver disease simply cannot use them. Recent studies suggest this precaution may not be necessary.

How Safe Are Oral Anticoagulants For People Who Have Liver Disease?

Researchers reviewed 29 clinical trials involving 152,116 patients, of whom 83,513 were receiving the new oral anticoagulants. Clinical trials studied the effects of Eliquis (apixaban),  Lixiana (edoxaban), Pradaxa (dabigatran), Xarelto (rivaroxaban) and the discontinued drug darexaban. Since liver injury is particularly likely not to be detected until serious damage is done, and because the only treatment for liver damage when it is finally detected sometimes can is a liver transplant, the scientists looked at the effects of these popular new anticoagulant drugs on liver enzymes and bilirubin.

Only 1 to 2 people per 1000 users of these drugs, the researchers determined, is likely to develop drug-induced liver injury. When drug-induced liver injury occurs, it almost always occurs in the first six months the drug is used, enzyme levels rising after just one month. Peak levels of the enzymes associated with liver destruction occur in the second or third month.

The researchers found that the new medications Eliquis, Lixiana, and Xarelto are actually less likely to cause liver damage than Coumadin and Brilinta. When liver damage does occur, it seems to be associated less with the medication itself than with concomitant use low-molecular weight heparin (Lovenox) during hospital stays. 

But Are Eliquis, Lixiana, and Xarelto Safe for Almost Everybody?

People who use Eliquis, Lixiana, and Xarelto are not likely to suffer drug-induced liver damage unless they are also treated with Lovenox, given by injection, almost always in a hospital setting. But that does not mean that these drugs are safe for absolutely everyone.

• No one should take St. John's wort at the same time as taking any of these three drugs. St. John's wort competes for an enzyme that makes the medications active in the body, and reduces their effects on the blood.
• No one should have a "spinal tap" for anesthesia when taking any of these drugs. Dangerous bleeding inside the spine or brain may result.
• Certain antifungal drugs, such as ketocanozole, and certain antibiotics, such as rifampin, interfere with the action of liver enzymes needed to keep the medications active.
• Unlike Plavix, these medications may not be safe with Aspirin and other over the counter pain relievers.

Some people just don't respond to Plavix (clopidogrel). About 50% of people of Asian descent lack an enzyme the liver has to release to activate Plavix, so their best anticoagulant choices are likely to be Eliquis, Lixiana, and Xarelto, if the doctor does not want to go back to the use of Coumadin.

See Also: Most Common Liver Problems

But if you are taking Coumadin, Plavix, or Brilinta now, don't hesitate to ask your doctor whether Eliquis, Lixiana, or Xarelto might get better results. No anticoagulant medication is risk-free, but these medications are safer for nearly every user.