Drugs That Prevent or Treat Blood Clots

97358302.jpg
Science Photo Library - STEVE GSCHMEISSNER/Getty Images

 

Thrombosis, or abnormal blood clotting, is often a very dangerous condition that produces two general types of medical problems. 

First, thrombosis inside an artery can block the flow of blood, producing damage to the organs that are supplied by the blocked artery. Myocardial infarctions (heart attacks) usually involve thrombosis within a coronary artery, and thrombotic strokes are caused by thrombosis within one of the arteries that supply the brain.

Second, thrombosis that occurs inside a vein or inside the heart can embolize. That is, the blood clot can break off and travel through the vascular system, doing damage wherever it finally lodges. A pulmonary embolus is caused by a blood clot that embolizes to the lungs (typically, from a vein in the leg). Embolic strokes are caused by a blood clot that travels to the brain, usually from a thrombus within the heart, most often in association with atrial fibrillation

Drugs That Prevent or Treat Blood Clots

People who are at elevated risk to develop a dangerous thrombosis often need treatment either to prevent this condition from occurring, or to attempt to dissolve blood clots that have already formed. There are three general categories of drugs that are commonly used to prevent or treat thrombosis — the anticoagulant drugs, the fibrinolytic drugs, and the anti-platelet drugs.

While each of these drugs has its own profile of adverse effects, one side effect common to all of them is excessive bleeding. So all of these drugs must be used with appropriate precautions.

Anticoagulant Drugs

The anticoagulant drugs inhibit one or more of the clotting factors. Clotting factors are a group of blood proteins that are responsible for blood clotting.

These drugs include:

Heparin. Heparin is an intravenous drug that has an immediate (within seconds) inhibitory effect on the clotting factors. Doctors can adjust its dosage frequently, as needed, by monitoring the partial thromboplastin time (PTT) blood test. The PTT reflects how much the clotting factors have been inhibited. (That is, it reflects the "thinness" of the blood.) Heparin is used exclusively in hospitalized patients.

Low Molecular Weight Heparin: enoxaparin (Lovenox), dalteparin (Fragmin). These drugs are purified derivatives of heparin. Their major advantage over heparin is that they can be given as skin injections (which almost anyone can learn to do in a few minutes) instead of intravenously, and they do not need to be closely monitored with blood tests. So, unlike heparin, they can be administered with relative safety on an outpatient basis.

Newer Intravenous or Subcutaneously-Administered Anticoagulant Drugs. Several "heparin-like" anticoagulant drugs have been developed, including argatroban, bivalirudin (Angiomax), fondaparinux (Arixtra) and lepirudin (Refludan). The optimal time and place to use all of these drugs are being slowly worked out.

Warfarin (Coumadin). Until recently, warfarin was the only orally administered anticoagulant drug available.

The biggest problem with warfarin has been in adjusting its dosage. When first taken, warfarin’s dosage must be stabilized over a period of weeks with frequent blood tests (the INR blood test). Even after stabilization the INR still needs to be monitored periodically, and the dosage of warfarin often requires re-adjustment. So, getting to and maintaining the "right" dose of warfarin has always been difficult and inconvenient.

"New" Oral Anticoagulant Drugs - The NOAC Drugs. Because the optimal dose of warfarin can be relatively difficult to manage, drug companies have worked for years to come up with "warfarin-substitutes" — that is, anticoagulant drugs that can be taken orally.

Four of these new oral anticoagulant drugs (the NOAC drugs) have now been approved.

These are dabigtran (Pradaxa), rivaroxaban (Xarelto), apixaban ( Eliquis), and edoxaban (Savaysa).  The chief advantage of all these drugs is that they can be given in fixed daily dosages, and do not require blood tests or dosage adjustments. However, as is the case with all drugs, there are downsides to the NOAC drugs. Read more about the NOAC drugs.

Fibrinolytic Drugs

Streptokinase, urokinase, alteplase, reteplase, tenecteplase. These powerful drugs are given acutely and intravenously to dissolve blood clots that are in the process of forming. For the most part, their use is limited to patients who are within the first few hours of an acute heart attack or stroke, and they are given in the to attempt to re-open a blocked artery and prevent permanent tissue damage. 

The fibrinolytic drugs (which are often referred to as the “clot busters”), can be tricky to use. and they carry a substantial risk of bleeding complications. However, in the right circumstances, the use of these drugs can prevent death or disability from a heart attack or stroke. Of the fibrinolytic drugs, streptokinase is used most frequently worldwide, because it is relatively cheap. In the United States, tenecteplase is currently the drug of choice because it appears to cause fewer disastrous bleeding consequences, and is easier to administer than the other drugs in this group.

Anti-Platelet Drugs

Three groups of drugs are used to reduce the "stickiness" of platelets, the tiny blood elements that form the nucleus of a blood clot. By inhibiting the ability of platelets to clump together, the anti-platelet drugs inhibit blood clotting. These drugs are most effective in preventing abnormal blood clots from forming in arteries, and are much less effective at preventing thrombosis in the veins. 

Aspirin and dipyridamole​ (Aggrenox). These drugs have a modest effect on platelet "stickiness" but cause fewer bleeding-related adverse effects than the other anti-platelet drugs. They are often used in an attempt to reduce the risk of heart attack or stroke in people whose risk is elevated.

Ticlopidine (Ticlid), clopidogrel (Plavix) and prasugrel (Effient). These drugs are more powerful (and therefore riskier) than aspirin and dipyridamole. They are commonly used when the risk of arterial clotting is especially high. Their most common application is in people who have received coronary artery stents. Their use regarding stents — specifically, decisions about when and how long to use them — have been controversial.

IIb/IIIa Inhibitors: abciximab (ReoPro), eptifibatide (Integrilin), tirofiban (Aggrastat). The IIb/IIIa inhibitor drugs are the most powerful group of platelet inhibitors. They inhibit a receptor on the surface of platelets (the so-called IIb/IIIa receptor) that is essential for platelet stickiness. Their chief usage is to prevent acute clotting after interventional procedures (such as angioplasty and stent placement) ,and in patients with acute coronary artery syndrome. These drugs are very expensive and (in general) must be given intravenously.

A Word From Verywell

Several drugs are in clinical use to help to prevent or treat blood clots. They have different mechanisms of action, different risks, and are used under different clinical circumstances. Using any of these drugs always carries the risk of abnormal bleeding, and they should be employed only when their benefits are likely to outweigh those risks. When managing thrombosis, it is critically important for the doctor to choose the right drug, under the right circumstance.

Sources:

Franchini M, Mannucci PM. New Anticoagulants in Internal Medicine: an Update. Eur J Intern Med 2010; 21:466.

Kearon C, Akl E, Omelas J, et al. Antithrombotic Therapy for VTE Disease. CHEST Guideline and Expert Panel Report. Chest 2016;149:315. 

Weitz JI, Hirsh J, Samama MM, American College of Chest Physicians. New Antithrombotic Drugs: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133:234S.

Continue Reading