Thromboembolic disorders are one of the disorders for which we are still on the look out for a safe and efficient drug. Despite the widespread use of antithrombotic drugs for the prevention and treatment of arterial and venous thrombosis, thromboembolic diseases continue to be a major cause of death and disability worldwide. This shows our inefficiency in searching efficacious and safe antithrombotic drugs. We have reached the basic mechanism of thrombus formation and by interrupting various steps of this mechanism, we can prevent as well as treat thromboembolic disorders. In continuation of Aspirin, now, we are using Clopidogrel, Ticlopidine and GpIIb/IIIa inhibitors (Abciximab, Tirofiban and Eptifibatide). Warfarin is an old antithrombotic drug which is still being used; but due to various side effects and drug interactions, we are bound to use newer drugs. Newer antiplatelet drugs include Prasugrel, Ticagrelor and Cangrelor, whereas newer thrombin inhibitors are Ximelgatran and Dabigatran. Apixaban is also a newer entry in this category as factor Xa inhibitor. Idrabiotaparinux is an indirect inhibitor of Xa as it accelerates the activity of antithrombin. Moreover, researches and trials for better and safe drugs are ongoing.
del Zoppo GJ. Virchow′s triad: The vascular basis of cerebral injury. Rev Neurol Dis 2008;5:S12-21.
Becker RC, Meade TW, Berger PB, Ezekowitz M, O′Connor CM, Vorchheimer DA, et al. The primary and secondary prevention of coronary artery disease: American College of Chest Physicians Evidence Based Clinical Practice Guidelines. (8th edition). Chest 2008;133:776S-814S.
Goodman SG, Menon V, Cannon CP, Steg G, Ohman EM, Harrington RA, et al. Acute ST-segment elevation myocardial infarction: American College of Chest Physicians Evidence- Based Clinical Practice Guidelines (8th Edition). Chest 2008;133:708S-75S.
Geerts WH, Bergqvist D, Pineo GF, Heit JA, Samama CM, Lassen MR, et al. Prevention of venous thromboembolism: American College of Chest Physicians Evidence Based Clinical Practice Guidelines (8th Edition). Chest 2008;133:381S-453S.
Kearon C, Kahn SR, Agnelli G, Goldhaber S, Raskob GE, Comerota AJ, et al. Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008;133:454S-545S.
Ruggeri ZM. Platelets in atherothrombosis. Nat Med 2002;8:1227-34.
Sharma HL, Sharma KK. Drugs affecting coagulation, fibrinolysis and platelet functions. Principles of pharmacology. 1st ed. Hyderabad: Paras medical publishers; 2007. p. 693.
Richard NM. Haemodynamic disorders, Thromboembolic disease and Shock. In: Kumar V, Abbas AK, Fausto N, editors. Robbins and Cotran Pathologic basis of disease. 7th ed. Pennsylvania: Elsevier Publications; 2004. p.126-7.
Gaussem P, Reny JL, Thalamas C, Chatelain N, Kroumova M, Jude B, et al. The specific thromboxane receptor antagonist S18886: Pharmacokinetic and pharmacodynamic studies. J Thromb Haemost 2005;3:1437-45.
Fitzgerald DJ, Fragetta J, FitzGerald GA. Prostaglandin endoperoxides modulate the response to thromboxane synthase inhibition during coronary thrombosis. J Clin Invest 1988;82:1708-13.
Sharma HL, Sharma KK. Drugs affecting coagulation, fibrinolysis and platelet functions. Principles of pharmacology. 1st ed. Hyderabad: Paras Medical Publishers; 2007. p. 703.
Jakubowski JA, Matsushima N, Asai F, Naganuma H, Brandt JT, Hirota T, et al. A multiple dose study of prasugrel (CS-747), a novel thienopyridine P2Y12 inhibitor, compared with clopidogrel in healthy humans. Br J Clin Pharmacol 2006;63:421-30.
Wiviott SD, Braunwald E, McCabe CH, Montalescot G, Ruzyllo W, Gottlieb S, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2007;357:2001-15.
Leonardi S, Rao SV, Harrington RA, Bhatt DL, Gibson CM, Roe MT, et al. Rationale and design of the randomized, double-blind trial testing INtraveNous and Oral administration of elinogrel, a selective and reversible P2Y(12)-receptor inhibitor, versus clopidogrel to eVAluate Tolerability and Efficacy in nonurgent Percutaneous Coronary Interventions patients (INNOVATE-PCI). Am Heart J 2010;160:65-72.
Oestreich JH. Elinogrel, a reversible P2Y12 receptor antagonist for the treatment of acute coronary syndrome and prevention of secondary thrombotic events. Curr Opin Investig Drugs 2010;11:340-8.
Berger JS, Roe MT, Gibson CM, Kilaru R, Green CL, Melton L, et al. Safety and feasibility of adjunctive antiplatelet therapy with intravenous elinogrel, a direct-acting and reversible P2Y12 ADP-receptor antagonist, before primary percutaneous intervention in patients with ST-elevation myocardial infarction: The Early Rapid ReversAl of platelet thromboSis with intravenous Elinogrel before PCI to optimize reperfusion in acute Myocardial Infarction (ERASE MI) pilot trial. Am Heart J 2009;158:998-1004.
Chackalamannil S, Ahn HS, Xia Y, Doller D, Foster C. Potent non-peptide thrombin receptor antagonists. Curr Med Chem Cardiovasc Hematol Agents 2003;1:37-45.
Sharma HL, Sharma KK. Drugs affecting coagulation, fibrinolysis and platelet functions. Principles of pharmacology. 1st ed. Hyderabad: Paras Medical Publishers; 2007. p. 704.
Chew DP, Bhatt DL, Sapp S, Topol EJ. Increased mortality with oral platelet glycoprotein IIb/IIIa antagonists: A metanalysis of phase III multicenter randomized trials. Circulation 2001;103:201-6.
Schneider DJ, Taatjes DJ, Sobel BE. Paradoxical inhibition of fibrinogen binding and potentiation of a granule release by specific types of inhibitors of glycoprotein IIb-IIIa. Cardiovasc Res 2000;45:437-46.
Wakefield TW, Myers DD, Henke PK. Mechanisms of venous thrombosis and resolution. Arterioscler Thromb Vasc Biol 2008;28:387-91.
Massberg S, Brand K, Page S, Bergmeier W, Richter T, Lorenz M, et al. A critical role of platelet adhesion in the initiation of atherosclerotic lesion formation. J Exp Med 2002;196:887-96.
Croce K, Libby P. Intertwining of thrombosis and inflammation in atherosclerosis. Curr Opin Hematol 2007;14:55-61.
Myers D, Wrobleski S, Londy F, Fex B, Hawley A, Schaub R, et al. New and effective treatment of experimentally induced venous thrombosis with anti-inflammatory rPSGL-Ig. Thromb Haemost 2002;87:374-82.
Weitz JI. Factor Xa or thrombin:is thrombin a better target? J Thromb Haemost 2007;5:65-72.
Testa L, Andreotti F, Biondi-Zoccai GG, Burzotta F, Bellocci F, Crea F, et al. Ximelagatran/Melagatran against conventional anticoagulation: a meta-analysis based on 22, 639 patients. Int J Cardiol 2007;122:117-24.
Blech S, Ebner T, Ludwig Schwellinger E, Stangier J, Roth W. The metabolism and disposition of the direct thrombin inhibitor, Dabigatran, in humans. Drug Metab Dispos 2008;36:386-99.
Stangier J, Stahle H, Rathgen K, Fuhr R. Pharmacokinetics and pharmacodynamics of the direct oral thrombin inhibitor dabigatran in healthy elderly subjects. Clin Pharmacokinet 2008;47:47-59.
Furugohri T, Shiozaki Y, Muramatsu S, Honda Y, Matsumoto C, Isobe K, et al. Different antithrombotic properties of factor Xa inhibitor and thrombin inhibitor in rat thrombosis models. Eur J Pharmacol 2005;514:35-42.
Eriksson BI, Borris LC, Friedman RJ, Haas S, Huisman MV, Kakkar AK, et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty. N Engl J Med 2008;358:2765-75.
Kakkar AK, Brenner B, Dahl OE, Eriksson BI, Mouret P, Muntz J, et al. Extended duration rivaroxaban versus short-term enoxaparin for the prevention of venous thromboembolism after total hip arthroplasty: A double-blind, randomised controlled trial. Lancet 2008;372:31-9.
Turpie Alexander GG, Lassen MR, Kakkar AK, Eriksson B, Misselwitz F, Bandel TJ, et al. A pooled analysis of four pivotal studies of rivaroxaban for the prevention of venous thromboembolism after orthopedic surgery: Effect on symptomatic venous thromboembolism, death and bleeding. Blood 2008;112:36a.
Lassen MR, Ageno W, Borris LC, Lieberman JR, Rosencher N, Bandel TJ, et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty. N Engl J Med 2008;358:2776-86.
Lassen MR, Davidson BL, Gallus A, Pineo G, Ansell J, Deitchman D. The efficacy and safety of apixaban, an oral, direct factor Xa inhibitor, as thromboprophylaxis in patients following total knee replacement. J Thromb Haemost 2007;5:2368-75.
Weitz JI, Connolly SJ, Patel I, Salazar D, Rohatagi S, Mendell J, et al. Randomised, parallel-group, multicentre, multinational phase 2 study comparing edoxaban, an oral factor Xa inhibitor, with warfarin for stroke prevention in patients with atrial fibrillation. Thromb Haemost 2010;104:633-41.
Raskob G, Cohen AT, Eriksson BI, Puskas D, Shi M, Bocanegra T, et al. Oral direct factor Xa inhibition with edoxaban for thromboprophylaxis after elective total hip replacement: A randomised double-blind dose-response study. Thromb Haemost 2010;104:642-9.
Gross PL, Weitz JI. New anticoagulants for treatment of venous thromboembolism. Arterioscler Thromb Vasc Biol 2008;28:380-6.
Walenga JM, Hoppensteadt DA. Monitoring the new antithrombotic drugs. Semin Thromb Hemost 2004;30:683-95.
Johnson SG, Witt DM, Eddy TR, Delate T. Warfarin and antiplatelet combination use among commercially insured patients enrolled in an anticoagulation management service. Chest 2007;131:1500-7.
Schulman S, Spencer FA. Antithrombotic drugs in coronary artery disease: Risk benefit ratio and bleeding. J Thromb Haemost 2010;8:641-50.
Delaney JA, Opatrny L, Brophy JM, Suissa S. Drug-drug interactions between antithrombotic medications and the risk of gastrointestinal bleeding. CMAJ 2007;177:347-51.
Leon MB, Baim DS, Popma JJ, Gordon PC, Cutlip DE, Ho KK, et al. A clinical trial comparing three antithrombotic-drug regimens after coronary-artery stenting: Stent Anticoagulation Restenosis Study Investigators. N Engl J Med 1998;339:1665-71.
Ansell J, Hirsh J, Hylek E, Jacobson A, Crowther M, Palareti G, American College of Chest Physicians. Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008;133:160S-98S.
Schulman S, Bijsterveld NR. Anticoagulants and their reversal. Transfus Med Rev 2007;21:37-48.
American Society of Anesthesiologists Task Force on Perioperative Blood Transfusion and Adjuvant Therapies. Practice guidelines for perioperative blood transfusion and adjuvant therapies: An updated report by the American Society of Anethesiologists Task Force on Perioperative Blood Transfusion and Adjuvant Therapies. Anesthesiology 2006;105:198-208.
O′Shaughnessy DF, Atterbury C, Bolton Maggs P, Murphy M, Thomas D, Yates S, et al. Guidelines for the use of fresh-frozen plasma, cryoprecipitate and cryosupernatant. Br J Haematol 2004;126:11-28.
Ingerslev J, Vanek T, Culic S. Use of recombinant factor VIIa for emergency reversal of anticoagulation. J Postgrad Med 2007;53:17-22.
Crowther MA, Warkentin TE. Managing bleeding in anticoagulated patients with a focus on novel therapeutic agents. J Thromb Haemost 2009;7:107-10.
Kessler CM. Current and future challenges of antithrombotic agents and anticoagulants: Strategies for reversal of hemorrhagic complications. Semin Hematol 2004;41:44-50.