Methods to Correct Drug-Induced Coagulopathy in Bleeding Emergencies: A Comparative Review

Anticoagulant and antiplatelet therapy have become increasingly popular. The goal of therapy is to prevent venous thromboembolism and platelet aggregation, respectively. Traditional anticoagulant and antiplatelet drugs are quickly being replaced with novel medications with more predictable pharmacokinetics. Unfortunately, these drugs carry the risk of uncontrolled hemorrhage because of drug-induced coagulopathy. Uncontrolled hemorrhage continues to be a major cause of preventable death: hemorrhage accounts for approximately 30% of trauma-related deaths, second to brain injury. Controlling hemorrhage while dealing with comorbidities remains a challenge to clinicians. There are many gaps in care and knowledge that contribute to the struggle of treating this patient population.

This literature review is focused on the most effective ways to achieve hemostasis in a patient with drug-induced coagulopathy. The antiplatelet therapies aspirin, clopidogrel, ticlopidine, pasugrel, and ticagrelor are analyzed. Anticoagulant therapies are also reviewed, including warfarin, rivaroxaban, apixaban, edoxaban, and dabigatran. In addition, viscoelastic testing and platelet function assays are reviewed for their ability to monitor drug effectiveness and to accurately depict the patient's ability to clot. This review focuses on articles from the past 10 years. However, there are limitations to the 10-year restriction, including no new research posted within the 10-year timeline on particular subjects. The most recent article was then used where current literature did not exist (within 10 years).

Traditional anticoagulants have unpredictable pharmacokinetics and can be difficult to correct in bleeding emergencies. Vitamin K has been proven to reliably and effectively reverse the effect of vitamin K antagonists (VKAs) while having a lower anaphylactoid risk than frozen plasma. Prothrombin complex concentrates should be used when there is risk of loss of life or limb. Frozen plasma is not recommended as a first-line treatment for the reversal of VKAs. Novel anticoagulants have specific reversal agents such as idarucizumab for dabigatran and andexxa alfa for factor Xa (FXa) inhibitors. Although reliable, these drugs carry a large price tag. As with traditional anticoagulants, cheaper alternative therapies are available such as prothrombin complex concentrates. Finally, static coagulation testing works well for routine therapeutic drug monitoring but may not be appropriate during bleeding emergencies. Viscoelastic testing such as thromboelastography and rotational thromboelastometry depict in vivo hemostatic properties more accurately than static coagulation assays. Adding viscoelastic testing into resuscitation protocols may guide blood product usage more efficiently.

This review is intended to be used as a guide. The topics covered in this review should be used as a reference for treating the conditions described. This review article also covers laboratory testing and is meant as a guide for physicians on best practices. These findings illustrate recommended testing and reversal techniques based off evidence-based medicine and literature.