How do anticoagulants (blood thinners) directly cause bleeding?

From the Guidelines

Anticoagulants directly cause bleeding by interfering with the body's normal blood clotting mechanisms, and the risk of bleeding complications can be managed by carefully interrupting or reversing anticoagulation therapy, as outlined in the 2024 AHA/ACC/ACS/ASNC/HRS/SCA/SCCT/SCMR/SVM guideline for perioperative cardiovascular management for noncardiac surgery 1.

Mechanism of Bleeding

Anticoagulants work by targeting different parts of the coagulation cascade, which is the series of chemical reactions that form blood clots. Common anticoagulants include warfarin, which inhibits vitamin K-dependent clotting factors; direct oral anticoagulants (DOACs) like apixaban, rivaroxaban, and dabigatran, which target specific clotting factors; and heparin, which enhances the activity of antithrombin. When these medications excessively thin the blood, normal hemostasis (the process that stops bleeding) becomes impaired.

Risk of Bleeding

The risk of bleeding complications increases with higher doses, drug interactions that enhance anticoagulant effects, older age, kidney or liver dysfunction, and concurrent use of medications like aspirin or NSAIDs. According to the guideline, procedures with higher bleeding risks (eg, neuraxial anesthesia) should be performed with complete interruption of OAC, and time reversal of OAC is always preferred, but this may not be feasible for urgent or emergency procedures with moderate or high bleeding risk 1.

Management of Bleeding Risk

The guideline recommends a team-based approach to managing perioperative bleeding risk and DOAC or VKA schedule, especially in high thrombotic risk patients or when undergoing procedures with higher risks of adverse outcome, should bleeding occur. The measurement of coagulation parameters, drug levels, or both may identify ongoing drug effects, and rapid reversal of OAC can be achieved with prothrombin complex concentrates, andexanet alfa for factor Xa inhibitors, or idarucizumab for dabigatran 1.

Key Points

• Anticoagulants interfere with the body's normal blood clotting mechanisms, increasing the risk of bleeding complications.
• The risk of bleeding complications can be managed by carefully interrupting or reversing anticoagulation therapy.
• Procedures with higher bleeding risks should be performed with complete interruption of OAC.
• Time reversal of OAC is always preferred, but this may not be feasible for urgent or emergency procedures with moderate or high bleeding risk.
• A team-based approach is recommended for managing perioperative bleeding risk and DOAC or VKA schedule.

From the FDA Drug Label

Use of anticoagulants, including apixaban, may increase the risk of bleeding in the fetus and neonate. Labor or delivery All patients receiving anticoagulants, including pregnant women, are at risk for bleeding. Apixaban tablets use during labor or delivery in women who are receiving neuraxial anesthesia may result in epidural or spinal hematomas Coadministration of antiplatelet agents, fibrinolytics, heparin, aspirin, and chronic NSAID use increases the risk of bleeding

The anticoagulant apixaban directly causes bleeding by increasing the risk of bleeding in patients, particularly when used in combination with other medications such as antiplatelet agents, fibrinolytics, heparin, aspirin, and chronic NSAID use. This is because apixaban works by inhibiting factor Xa, which is essential for blood clotting, thereby increasing the risk of bleeding. Key points to consider include:

• Bleeding risk: Apixaban increases the risk of bleeding, particularly major bleeding, in patients.
• Combination therapy: Coadministration of apixaban with other medications that increase the risk of bleeding, such as antiplatelet agents and fibrinolytics, further increases the risk of bleeding.
• Neuraxial anesthesia: Apixaban use during labor or delivery in women receiving neuraxial anesthesia may result in epidural or spinal hematomas.
• Pregnancy and lactation: Apixaban may increase the risk of bleeding in the fetus and neonate, and breastfeeding is not recommended during treatment with apixaban tablets 2, 2, 2.

From the Research

Mechanism of Anticoagulant-Induced Bleeding

• Anticoagulants are known to increase the risk of bleeding due to their mechanism of action, which involves inhibiting the coagulation cascade 3, 4, 5, 6, 7.
• The direct oral anticoagulants (DOACs), such as dabigatran, rivaroxaban, apixaban, and edoxaban, work by inhibiting specific factors in the coagulation cascade, including thrombin and factor Xa 5, 6.
• This inhibition can lead to an increased risk of bleeding, particularly in patients with underlying conditions such as renal insufficiency or elderly populations 3, 4.

Factors Contributing to Bleeding Risk

• The risk of bleeding is higher among certain patient populations, including the elderly and those with renal insufficiency 3, 4.
• The type and dose of anticoagulant used can also impact the risk of bleeding, with some anticoagulants carrying a higher risk than others 7.
• The presence of other medical conditions, such as bleeding disorders or concomitant use of other medications that increase bleeding risk, can also contribute to the overall risk of bleeding 4, 5.

Reversal of Anticoagulation

• In the event of bleeding, reversal of anticoagulation may be necessary to prevent further bleeding and promote hemostasis 4, 5, 6.
• Specific reversal agents, such as idarucizumab for dabigatran and andexanet alfa for factor Xa inhibitors, are available and can be used to rapidly reverse anticoagulation 5, 6.
• Prothrombin complex concentrates may also be used as an alternative to specific reversal agents in some cases 6.