Page 2449 - Hematology_ Basic Principles and Practice ( PDFDrive )

Chapter 149 Antithrombotic Drugs 2187

intracranial hemorrhage also were similar with both treatments, 8. Wallentin L, Becker RC, Budaj A, et al: Ticagrelor versus clopidogrel in
patients given tenecteplase had fewer noncerebral bleeds and a reduced patients with acute coronary syndromes. N Engl J Med 361:1045–1057,
need for blood transfusions compared with those treated with t-PA. 2009.
The improved safety profile of tenecteplase likely reflects its enhanced 9. Cannon CP, Harrington RA, James S, et al: Comparison of ticagrelor
fibrin specificity. These properties have prompted studies comparing with clopidogrel in patients with a planned invasive strategy for acute
tenecteplase with alteplase in patients with acute ischemic stroke. 41 coronary syndromes (PLATO): a randomised double-blind study. Lancet
375:283–293, 2010.
10. Mahaffey KW, Wojdyla DM, Carroll K, et al: Ticagrelor compared with
Reteplase clopidogrel by geographic region in the Platelet Inhibition and Patient
Outcomes (PLATO) trial. Circulation 124:544–554, 2011.
A recombinant t-PA derivative, reteplase is a single-chain variant that 11. Sacco RL, Diener HC, Yusuf S, et al: Aspirin and extended-release
lacks the finger, epidermal growth factor, and first kringle domains dipyridamole versus clopidogrel for recurrent stroke. N Engl J Med
(see Fig. 149.11). This truncated derivative has a molecular weight 359:1238–1251, 2008.
of 39,000. Reteplase binds fibrin more weakly than t-PA because it 12. Tricoci P, Huang Z, Held C, et al: Thrombin-receptor antagonist vora-
lacks the finger domain. Because it is produced in Escherichia coli, paxar in acute coronary syndromes. N Engl J Med 366:20–33, 2012.
reteplase is not glycosylated. This endows it with a plasma half-life 13. Morrow DA, Braunwald E, Bonaca MP, et al: Vorapaxar in the secondary
longer than that of t-PA. Consequently, reteplase is given as two prevention of atherothrombotic events. N Engl J Med 366:1404–1413,
intravenous boluses, which are separated by 30 minutes. Clinical 2012.
trials have demonstrated that reteplase is at least as effective as 14. Eikelboom JW, Weitz JI: New anticoagulants. Circulation 121:1523–
streptokinase for treatment of acute myocardial infarction, but the 1532, 2010.
agent is not superior to t-PA. 42 15. Baker NC, Lipinski MJ, Lhermusier T, et al: Overview of the 2014
Food and Drug Administration Cardiovascular and Renal Drugs
Advisory Committee meeting about vorapaxar. Circulation 130:1287–
Desmoteplase 1294, 2014.
15a. Kearon C, Ginsberg JS, Julian JA, et al: Comparison of fixed-dose
A recombinant form of the full-length plasminogen activator isolated weight-adjusted unfractionated heparin and low-molecular-weight
from the saliva of the vampire bat, desmoteplase (see Fig. 149.11) is heparin for acute treatment of venous thromboembolism. JAMA
43
more fibrin specific than t-PA. Although preliminary studies with 296(8):935–942, 2006.
desmoteplase for treatment of acute ischemic stroke were promising, 16. Cuker A, Cines DB: How I treat heparin-induced thrombocytopenia.
further development has been halted. Blood 119:2209–2218, 2012.
17. Yusuf S, Mehta SR, Chrolavicius S, et al: Comparison of fondaparinux
and enoxaparin in acute coronary syndromes. N Engl J Med 354:1464–
CONCLUSIONS AND FUTURE DIRECTIONS 1476, 2006.
18. Manolopoulos VG, Ragia G, Tavridou A: Pharmacogenetics of couma-
Arterial and venous thrombosis reflects a complex interplay among rinic oral anticoagulants. Pharmacogenomics 11:493–496, 2010.
the vessel wall, platelets, the coagulation system, and the fibrinolytic 19. Ageno W, Gallus AS, Wittkowsky A, et al: Oral anticoagulant therapy:
pathways. Activation of coagulation also triggers inflammatory antithrombotic therapy and prevention of thrombosis, 9th ed: American
pathways that may contribute to thrombogenesis. A better under- College of Chest Physicians Evidence-Based Clinical Practice Guidelines.
standing of the biochemistry of blood coagulation and advances in Chest 141(2 Suppl):e44S–e88S, 2012.
structure-based drug design have identified new targets and resulted 20. Whitlock RP, Sun JC, Fremes SE, et al: Antithrombotic and thrombolytic
in the development of novel antithrombotic drugs. Well-designed therapy for valvular disease. Chest 141(2 Suppl):e576S–e600S, 2012.
clinical trials have provided detailed information on which drugs to 21. Connolly SJ, Ezekowitz MD, Yusuf S, et al: Dabigatran versus warfarin
use and when to use them. Despite these advances, however, arterial in patients with atrial fibrillation. N Engl J Med 361:1139–1151,
and venous thromboembolic disorders remain a major cause of 2009.
morbidity and mortality. Therefore the search for better targets and 22. Eikelboom JW, Wallentin L, Connolly SJ, et al: Risk of bleeding with 2
more potent or more convenient antiplatelet, anticoagulant, and doses of dabigatran compared with warfarin in older and younger patients
fibrinolytic drugs continues. with atrial fibrillation: an analysis of the randomized evaluation of long-
term anticoagulant therapy (RE-LY) trial. Circulation 123:2363–2372,
2011.
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