• Thrombotic Disorders
• Critical Care
• Toxicology

• Thrombotic Disorders
• Critical Care
• Toxicology
• Emergency Medicine

Nilesh Patel, DO, St Joseph's Regional Medical Center, Paterson, New Jersey, USA, presented the latest drug developments and guidelines regarding hemostasis. He discussed tranexamic acid (TXA) for the reversal of bleeding in target-specific oral anticoagulants (TSOAs) and the use of thromboelastography (TEG) for monitoring hemostasis in trauma and critically ill patients.

TXA is an antifibrinolytic agent that reversibly binds plasminogen, blocks plasmin, stabilizes clot formation, and combats hyperfibrinolysis. It is administered intravenously or orally at variable doses. TXA is more potent than aminocaproic acid. It prolongs thrombin time and can be monitored with TEG. TXA is used for patients undergoing surgery to decrease bleeding and blood transfusions and for patients with bleeding disorders.

The CRASH-2 trial [Shakur H et al. Lancet. 2010] of TXA included 20 211 trauma patients at risk for significant hemorrhage, and it demonstrated that TXA significantly reduced all-cause mortality (14.5% vs 16%; P = .0035) with similar vascular occlusive events (1.7% vs 2%) as compared to placebo. The military study MATTERs [Morrison JJ et al. Arch Surg. 2012] included 896 patients with combat injuries, and it found that patients treated with TXA vs no TXA had reduced mortality (17.4% vs 23.9%; P = .03). However, in a single-center US study, mortality in high-risk trauma patients treated with TXA was 27%, as compared with 17% without TXA (P < .05) [Valle EJ et al. J Trauma Acute Care Surg. 2014]. The PATCH study [Mitra B et al. Emerg Med Australas. 2014] is evaluating early administration of TXA in severely injured patients to try to resolve some of this uncertainty.

A 1983 New England Journal of Medicine study in patients with acute upper gastrointestinal bleeding found that in-hospital mortality was 6.3% with TXA vs 13.5% with placebo (P = .0092). A review of TXA treatment in patients with upper gastrointestinal bleeding found significant improvements in death rates but no significant improvement in rebleeding rates, need for transfusion, or surgery [Morgan A, Jeffrey-Smith A. Emerg Med J. 2012]. TXA for routine use in gastrointestinal bleeds needs more prospective data before widespread use can be endorsed.

TSOAs include the direct thrombin inhibitor, dabigatran, and the factor Xa inhibitors rivaroxaban and apixaban. Dabigatran does not require monitoring, but increasing numbers of patients receiving dabigatran have developed bleeding complications. In a prospective review of patients admitted to the hospital for dabigatran- or warfarin-induced bleeding, patients receiving dabigatran had more gastrointestinal bleeding (80% vs 48%), less intracranial bleeding (0% vs 32%), and a shorter hospital stay (3.5 vs 6.0 days) [Berger R et al. Ann Emerg Med. 2013].

Dr Patel stated that while the TSOAs do not need laboratory monitoring and have lower rates of drug-drug and drug-food interactions, there is no established antidote for patients who are bleeding or need surgery. Routine supportive care, activated charcoal within 2 hours, and hemodialysis have been suggested for patients on direct thrombin inhibitors with bleeding emergencies [Kaatz S et al. Am J Hematol. 2012]. Prothrombin complex concentrate has been shown experimentally to reverse the anticoagulant effect of rivaroxaban but not dabigatran in healthy patients [Eerenberg ES et al. Coagulation. 2011]; prothrombin complex concentrates can be considered for use in bleeding emergencies related to both drug classes based on limited data.

TEG is a coagulation test that provides rapid assessment of the coagulation cascade. Studies of TEG have found that test abnormalities correlate with increased transfusion rates and mortality [Carroll RC et al. Transl Res. 2009] and that TEG results were accurate when compared with a formal assay [Reed MJ et al. Eur J Emerg Med. 2013]. TEG may find nice use in bleeding trauma patients to guide coagulation-directed therapy and resuscitation.

Dr Patel concluded that more data are needed for treating hemostasis with TXA outside of trauma populations. More data are also needed to find the optimal reversal strategies for bleeding emergencies on TSOAs. Finally, TEG is an upcoming coagulation assay that shows promise in our bleeding patients.

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