Regional Anesthesia in Patients on Antithrombotic Drugs

Antithrombotic drugs, such as antiplatelet agents (APA) and anticoagulant therapies, are commonly prescribed for patients with cardiovascular disorders to prevent thrombosis, or blood clots. However, patients on antithrombotic medications are at increased risk of excessive blood loss during and after surgery with regional anesthesia.^1,2

Platelets, or thrombocytes, are small cellular components in blood whose function is the formation of blood clots to stop bleeding after injury. Internal signaling pathways in an activated platelet signal the release of molecules such as adenosine diphosphate (ADP), adrenaline, serotonin, thrombin, and thromboxane A2. Platelet glycoproteins then bind to fibrinogen, resulting in platelet aggregation and thrombus formation.¹ Acetylsalicylic acid, a commonly prescribed APA, inhibits thromboxane A2 production for the entire lifetime of a singular platelet (7–10 days). Ticagrelor is an APA that blocks critical G-protein activation and associated signaling pathways, while dipyridamole blocks the uptake of adenosine.¹ On the other hand, anticoagulant therapy prevents clot formation by disrupting the coagulation cascade. Most anticoagulants will either prevent the formation of coagulation factors such as factor IIa or inhibit the production of fibrin.^1,3

In late 2021, experts from the European Society of Anaethesiology and Intensive Care (ESAIC) and the European Society of Regional Anesthesia (ESRA) convened to discuss the extant literature on the prevention of excessive blood loss following regional anesthesia in patients on antithrombotic drugs.² After careful analysis, the committee recommended waiting at least 24 hours between the last intake of anticoagulant therapy and anesthesia administration. For antiplatelet drugs, such as aspirin, ticagrelor, clopidogrel, and prasugrel, the recommendation is a pre-operative waiting period of 3-7 days. ^2,4 Additionally, when combinations of antithrombotic drugs are used, the therapy-free time before anesthesia should be equivalent to that of the drug with the longest waiting period. Risk factors to consider include specific bleeding risks such as inherited bleeding disorders, acquired bleeding disorders, a history of significant bleeding, renal failure, hepatic failure, advanced age, female sex, and extreme body weight. An individual risk-benefit analysis must always be made, ideally in conjunction with the patient. Experts also found several reviews which suggest delaying the next antithrombotic drug dose for at least 48 to 72 hours after surgical intervention to prevent postoperative bleeding complications. Although the general recommendation is withdrawal of antithrombotic therapy some time before and after anesthetic administration, in situations where the risk of thromboembolism or ischemia is high, the anesthesiologist may decide to proceed without withdrawal.²

Healthcare teams must maintain their vigilance in the perioperative period to detect and manage excessive bleeding when the patient is undergoing anesthesia. During and after surgery, the team should look for persistent pain at the site of anesthesia, a drop in hemoglobin level, morphological skin changes, cardiovascular instabilities, or any neurologic deficits, as any of these symptoms should raise suspicion of a hemorrhagic complication due to regional anesthesia.²

In the future, more clinical trials may provide clearer and more standardized recommendations on the use of regional anesthesia in patients on antithrombotic therapy.

References

 

1. Mega, Jessica L., and Tabassome Simon. “Pharmacology of Antithrombotic Drugs: An Assessment of Oral Antiplatelet and Anticoagulant Treatments.” The Lancet, vol. 386, no. 9990, July 2015, pp. 281–91. https://doi.org/10.1016/S0140-6736(15)60243-4

1. Kietaibl, Sibylle, et al. “Regional Anaesthesia in Patients on Antithrombotic Drugs: Joint ESAIC/ESRA Guidelines.” European Journal of Anaesthesiology, vol. 39, no. 2, Feb. 2022, pp. 100–32. https://doi.org/10.1097/EJA.0000000000001600
2. Jiang, L., et al. “A Critical Role of Thrombin/PAR-1 in ADP-Induced Platelet Secretion and the Second Wave of Aggregation.” Journal of Thrombosis and Haemostasis, vol. 11, no. 5, May 2013, pp. 930–40. https://doi.org/10.1111/jth.12168
3. Douketis, James D., et al. “Perioperative Management of Antithrombotic Therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th Ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.” Chest, vol. 141, no. 2, Supplement, Feb. 2012, pp. e326S-e350S. https://doi.org/10.1378/chest.11-2298