Anti-Clotting Drugs Increase Risk of Dangerous Bleeding In the Head

Millions of patients in the U.S. take anticoagulants (blood thinners) or antiplatelet medications to prevent the formation of potentially harmful clots in the heart, large veins or arteries. These antithrombotic (anti-clotting) drugs can offer great benefit by preventing devastating consequences of undesired clot formation, such as heart attacks, strokes, lung damage and, in some cases, death.

However, the benefits of antithrombotic drugs inevitably come at the price of an increased risk of potentially life-threatening bleeding. Treatment with these medicines always involves a careful balance between preventing harmful clots and avoiding dangerous bleeding. One of the most serious bleeding complications associated with antithrombotic drugs is subdural hematoma, which involves bleeding between the skull and the outer surface of the brain.

A recent well-designed study published in the Journal of the American Medical Association (JAMA) showed that the frequency of subdural hematomas is increasing and that this increase appears to be linked to greater use of antithrombotic drugs.[1] The study also assessed the degree of increased risk for different types and combinations of antithrombotic drugs.

Two ways to block clotting

The ability to form blood clots is essential for life. Two components of blood are necessary for clot formation. The first is a family of proteins called clotting factors that are made by the liver. When activated, these factors work together to build the supporting framework of a clot. The second component are cell-like structures called platelets that are produced in the bone marrow. Platelets clump together with the supporting framework made by the activated clotting factors to form a clot when a blood vessel is damaged. Blocking either component can interfere with clot formation.

Anticoagulant drugs work by interfering with one or more of the clotting factors. Warfarin (COUMADIN, JANTOVEN) — one of the oldest and most widely prescribed oral blood thinners — blocks vitamin K, which is needed for the production of several clotting factors. Apixaban (ELIQUIS), dabigatran (PRADAXA), edoxaban (SAVAYSA) and rivaroxaban (XARELTO) are newer blood thinners known as direct oral anticoagulants, and each of them blocks a single clotting factor.[2] Public Citizen’s Health Research Group currently recommends warfarin over these newer anticoagulants.

Other drugs can interfere with clot formation by blocking platelet function. Aspirin is the most commonly used medication that works in this way to prevent clots that could lead to heart attacks or strokes. Another is clopidogrel (PLAVIX).

The new JAMA study

Using national electronic databases that contained detailed medical and prescription drug information for people living in Denmark, the researchers identified 10,010 adults aged 20 to 89 who had been diagnosed for the first time with a subdural hematoma from 2000 to 2015.[3] They then compared these patients’ use of antithrombotic drugs with that of a group of approximately 400,000 control patients with similar age and sex who had not suffered a subdural hematoma.

Among the patients who had suffered a subdural hematoma, the average age was 69, 65 percent were men and nearly half were taking at least one antithrombotic drug. The researchers found that the rate of subdural hematomas for all adults aged 20 to 89 in Denmark increased from 11 per 100,000 people per year in 2000 to 19 per 100,000 people per year in 2015 — an increase of more than 70 percent. Among older patients aged 75 to 89, the rate increased from 55 per 100,000 people per year in 2000 to 100 per 100,000 people per year in 2015 — a near doubling of the rate. During this same 15-year period, the researchers found a parallel increase in the use of antithrombotic drugs by Danish patients.

For antiplatelet drugs, current users of low-dose aspirin were found to have a 24 percent increased risk of subdural hematoma — the lowest of all drugs evaluated in this study — and current users of clopidogrel had an 87 percent increased risk. For anticoagulants, current users of warfarin or other similar vitamin K blockers had a nearly fourfold increased risk of subdural hematoma, whereas current users of the newer direct oral anticoagulants had a 73 percent increased risk compared with those who were not current users of antithrombotic drugs.

The greatest increases in the risk of subdural hematoma were seen in patients who currently used warfarin (or a similar vitamin K blocker) combined with either low-dose aspirin (four times greater risk) or clopidogrel (eight times greater risk).

What You Can Do

Subdural hematomas typically occur following a blow to the head. In older patients, even relatively minor head injuries, such as those that may occur with a fall, can lead to a subdural hematoma. Signs and symptoms of such bleeding within the head may develop soon after experiencing head trauma or may appear slowly over many days to weeks.

If you are taking antithrombotic drugs and experience head trauma, you should seek medical attention immediately for any of the following: increasing headache, vomiting, dizziness, confusion, drowsiness, slurred speech or progressive loss of consciousness. Your loved ones should assist in monitoring you for such signs and symptoms after any head trauma.

References

[1] Gaist D, Garcia Rodriguez LA, Hellfritzsch M, et al. Association of antithrombotic drug use with subdural hematoma risk. JAMA. 2017;317(8):836-846.

[2] Levy JH, Spyropoulos AC, Samama CM, Douketis J. Direct oral anticoagulants: new drugs and new concepts. JACC Cardiovasc Interv. 2014;7(12):1333-1351.

[3] Gaist D, Garcia Rodriguez LA, Hellfritzsch M, et al. Association of antithrombotic drug use with subdural hematoma risk. JAMA. 2017;317(8):836-846.