Ce is strongly supported by Bloemen et al. [42], who demonstrated that
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Ce is strongly supported by Bloemen et al. [42], who demonstrated that the addition of a fixed concentration of any type of anticoagulant causes a highly variable inhibition of thrombin generation in different individuals. Hemostasis is a local process and occurs normally in minutes, and thrombin formation is limited [43]. Furie and Furie mentioned that after injury, the formation of fibrin is derived from the thrombin generated by the TF exposed from the vessel wall [44]. The process is circumscribed because the amount of exposed TF is small in a limited area, and activators are diluted in the bloodstream in a nonoccluded vessel. In contrast, arterial thrombosis occurs in areas of atherosclerotic plaque disruption. Atherosclerotic lesion disruption facilitates the interaction of the circulating blood with the inner components of the lesions, such as TF, and this interaction leads to the in vivo generation of thrombin. The stasis in a partially or fully occluded vessel determines the local increase of thrombin, both free and bound to fibrin. The flow-limiting effect of the disrupted lesion prevents dilution of the activators and favors the formation of larger or more stable thrombi. One of the purposes of antithrombotic therapy is to inhibit the pro-thrombotic activity of thrombin, either by interfering with its synthesis via inhibition of factor Xa (rivaroxaban, apixaban) or directly blocking its activity (dabigatran). The relatively small amount of thrombin that is formed in the case of hemostasis compared with thrombosis will be strongly affected by antithrombotic drugs with impaired hemostasis, and the potential consequence may be bleeding in a "locus minoris resistentiae" [45]. AlthoughAltman Thrombosis Journal 2014, 12:3 http://www.thrombosisjournal.com/content/12/1/Page 5 PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/13485127 ofmajor bleeding could be a reversible event, it is likely to lead clinicians to discontinue antithrombotic therapy, which in turn could increase the risk of myocardial infarction, stroke, and cardiovascular death. Therefore, therapeutic excesses can condition bleeding risk, and therapeutic limitation can increase thrombotic risk, especially when shortacting drugs such as the new oral anticoagulants are used. Hence, it is imperative to establish an appropriate method for monitoring new oral anticoagulants and to set the levels of safety and effectiveness by monitoring their anticoagulant effects.Competing interests The author declares that he has no competing interests. Acknowledgment I would like to thank (S)-1-Boc-2-Hydroxymethyl-piperazine Dr. Juan Jose Badimon, Mount Sinai School of Medicine, New York, for some comments, discussions, and some disagreements regarding this manuscript. Received: 27 September 2013 Accepted: 16 January 2014 Published: 3 February 2014 References 1. Gomes T, Mamdani MM, Holbrook AM, Paterson JM, Hellings C, Juurlink DN: Rates of hemorrhage during warfarin therapy for atrial fibrillation. CMAJ 2013, 185:E121 127. 2. Reussi C, Schiavi JE, Altman R, Yussem EE, Rouvier J: Unusual complications in the course of anticoagulant therapy. Am J Med 1969, 46:460?63. 3. Eikelboom JW, Mehta SR, Anand SS, Xie C, Fox KA, Yusuf S: Adverse impact of bleeding on prognosis in patients with acute coronary syndromes. Circulation 2006, 114:774?82. 4. Hart RG, Pearce LA, Aguilar MI: Meta-analysis: antithrombotic therapy to 3-(2,4-Dichlorophenoxy)azetidine prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/8833965 2007, 146:857?67. 5. Hirsh J: Oral anticoagulant drugs. N Engl J Med 1991, 324:1865?875.