A 63-year-old man comes to the emergency department because of 1 hour of sudden-onset chest pain. He developed the pain after eating dinner and did not have relief with antacids. His other medical problems include hypertension, hyperlipidemia, and type 2 diabetes mellitus. In the emergency department, his blood pressure is 100/60 mm Hg, pulse is 100/min, and respirations are 18/min. His EKG shows ST-segment depression in the inferior leads, and his cardiac serum troponin T is positive. The following anticoagulants are being considered for treatment: Which of the following anticoagulants is most effective in inactivating thrombin?

Question

A 63-year-old man comes to the emergency department because of 1 hour of sudden-onset chest pain.  He developed the pain after eating dinner and did not have relief with antacids.  His other medical problems include hypertension, hyperlipidemia, and type 2 diabetes mellitus.  In the emergency department, his blood pressure is 100/60 mm Hg, pulse is 100/min, and respirations are 18/min.  His EKG shows ST-segment depression in the inferior leads, and his cardiac serum troponin T is positive.  The following anticoagulants are being considered for treatment:  Which of the following anticoagulants is most effective in inactivating thrombin?

Quizplus · Accepted Answer

This patient presents with findings consistent with acute coronary syndrome, with ongoing injury as evidenced by the positive troponin. An important component of therapy involves not only treating the existing clot but also preventing its propagation. The coagulation cascade amplifies the generation of thrombin, which activates platelets to form a plug and also helps convert fibrinogen to fibrin to reinforce the platelet plug. Antithrombin can inhibit both Factor Xa in the coagulation cascade and also thrombin. 11ec160b_3bda_342b_9249_db00768af80e_MD0001_00 Both unfractionated heparin and low molecular weight heparin (LMWH) contain a pentasaccharide sequence that binds to antithrombin and causes a conformational change that increases its ability to inactivate Factor Xa. However, heparin must bind to both antithrombin and thrombin together to form a ternary complex to inactivate thrombin. Only unfractionated heparin (not LMWH) has a pentasaccharide chain long enough (>18 saccharide units) to bind to both antithrombin and thrombin. As a result, unfractionated heparin has equal activity against Factor Xa and thrombin, while LMWH has greater activity against Factor Xa than thrombin. (Choice A) Enoxaparin is a low molecular weight heparin that has fewer of the required long saccharide units that bind to thrombin and less antithrombotic activity compared to unfractionated heparin. (Choice B) Fondaparinux is a synthetic pentasaccharide Factor Xa inhibitor. It has none of the required long saccharide units that bind to thrombin and much lower antithrombin activity compared to unfractionated heparin. Educational objective: Both unfractionated heparin and LMWH can bind to antithrombin to increase its activity against Factor Xa. Only unfractionated heparin is able to bind to both antithrombin and thrombin to allow antithrombin to inactivate thrombin. __________ References: Role of ternary complexes, in which heparin binds both antithrombin and proteinase, in the acceleration of the reactions between antithrombin and thrombin or factor Xa (http://www.ncbi.nlm.nih.gov/pubmed/3782075)

A 63-Year-Old Man Comes to the Emergency Department Because of 1