Jornal Vascular Brasileiro
https://jvascbras.org/article/doi/10.1590/S1677-54492011000200009
Jornal Vascular Brasileiro
Review Article

Novos anticoagulantes para a profilaxia do tromboembolismo venoso em cirurgias ortopédicas de grande porte

New anticoagulants for the prophylaxis of venous thromboembolism

Ricardo de Alvarenga Yoshida; Winston Bonetti Yoshida; Hamilton de Almeida Rollo

http://dx.doi.org/10.1590/S1677-54492011000200009 J Vasc Bras, vol.10, n2, p.145-153, 2011
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Resumo

Após cerca de 50 anos de experiência com a heparina e antagonistas da vitamina K (AVK), pesquisas e estudos com novos anticoagulantes vêm evoluindo de forma crescente nos últimos anos. Embora consagrados pelo uso, os anticoagulantes tradicionais têm limitações importantes em termos de controle laboratorial, complicações, efeitos colaterais, interações com medicamentos e dieta. A heparina não fracionada (HNF) tem interação com proteínas plasmáticas e parede vascular, pode desencadear trombocitopenia induzida pela heparina (TIH), só pode ser administrada por via parenteral, exige controle laboratorial pelo teste da tromboplastina parcial ativada (TTPa), pode provocar osteoporose e alopecia quando usada por períodos prolongados e sua produção tem origem biológica. A AVK tem a vantagem de poder ser ministrada por via oral, mas o controle (feito pela razão normatizada internacional) pode ser difícil em alguns casos, já que tem início de ação demorado, janela terapêutica estreita, interação com dieta e grande número de medicamentos, pode provocar necrose de pele em portadores de deficiência de antitrombina e de proteínas C e S, e pode induzir alterações fetais quando usada na gravidez. Na década de 1980, surgiram as heparinas de baixo peso molecular, que foram uma evolução da heparina não fracionada, pois apresentaram maior biodisponibilidade, dosagem por peso corporal, sem necessidade de controle laboratorial, administração por via subcutânea, menor risco de trombocitopenia induzida pela heparina, e eficácia e segurança similares à heparina não fracionada. Na última década surgiram, então, uma série de novos anticoagulantes no mercado, os quais têm apresentado resultados promissores em várias situações de profilaxia e tratamento do tromboembolismo venoso. Nesta revisão, são apresentados as novas heparinas de baixo peso molecular, as heparinas de ultrabaixo peso molecular, os pentassacarídeos, os novos inibidores diretos do fator Xa e inibidores do fator IIa.

Palavras-chave

Anticoagulantes, heparina, heparina de baixo peso molecular, varfarina, revisão, tromboembolia venosa

Abstract

After about 50 years of experience with heparin and vitamin K antagonists (VKA), research and clinical studies of new anticoagulants have recently evolved . Although traditional anticoagulants have proven to be clinically useful, they have important limitations in terms of laboratory control, complications, side effects and interactions with medications and food. .Unfractionated heparin interacts with plasma proteins and the vascular wall, may trigger thrombocytopenia, can only be administered parenterally, requires control by the laboratory test of partial thromboplastin time, may cause osteoporosis and alopecia when used for long periods and it is produced from biological sources. VKA have the advantage of being administered orally, but the control (made by the international normalized ratio) can be difficult in some cases, since they have delayed onset of action and metabolism and a narrow therapeutic window. They also interact with foods and with a large number of medications, can cause skin necrosis in patients with antithrombin and protein C and S deficiencies and may induce fetal changes when prescribed in pregnancy. In the 1980´s the low-molecular-weight heparins were developed and proved to be an evolution over unfractionated heparin, because of their greater bio-availability, fixed dose per body weight, no need for laboratory control, subcutaneous administration, lower risk of heparin-induced thrombocytopenia, and efficacy and safety similar to unfractionated heparin. Over the last decade, a series of new anticoagulants have appeared in the market and shown promising results in several situations of venous thromboembolism prophylaxis and treatment. In the present review, the new low-molecular-weight heparins, ultra-low molecular weight heparin, pentasaccharides and the new direct inhibitors of factor Xa and factor IIa.are addressed.

Keywords

Anticoagulants, heparin, heparin, low-molecular-weight, warfarin, review, venous thromboembolism

References

Haas S. New anticoagulants - towards the development of an "ideal" anticoagulant. Vasa.. 2009;38:13-29.

Hirsh J, O'Donnell M, Eikelboom JW. Beyond unfractionated heparin and warfarin: current and future advances. Circulation.. 2007;116:552-60.

Bianchini P, Osima B, Parma B, Nader HB, Dietrich CP, Casu B. Fractionation and structural features of two heparin families with high antithrombotic, antilipemic and anticoagulant activities. Arzneimittelforschung.. 1985;35:1215-9.

Oliveira L, Franco R. Novas drogas anticoagulantes. Medicina, Ribeirão Preto.. 2001;34:276-81.

Laux V, Perzborn E, Heitmeier S, von Degenfeld G, Dittrich-Wengenroth E, Buchmuller A. Direct inhibitors of coagulation proteins - the end of the heparin and low-molecular-weight heparin era for anticoagulant therapy?. Thromb Haemost.. 2009;102:892-9.

Benmira S, Banda ZK, Bhattacharya V. Old versus new anticoagulants: focus on pharmacology. Recent Pat Cardiovasc Drug Discov.. 2010;5:120-37.

Garcia D. Novel anticoagulants and the future of anticoagulation. Thromb Res.. 2009;123(^s4):S50-5.

Weitz JI. New oral anticoagulants in development. Thromb Haemost.. 2010;103:62-70.

Turpie AG. Oral, direct factor Xa inhibitors in development for the prevention and treatment of thromboembolic diseases. Arterioscler Thromb Vasc Biol.. 2007;27:1238-47.

Warkentin TE, Greinacher A, Koster A, Lincoff AM. Treatment and prevention of heparin-induced thrombocytopenia: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest.. 2008;133:340S-380S.

Hirsh J, Bauer KA, Donati MB, Gould M, Samama MM, Weitz JI. Parenteral anticoagulants: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest.. 2008;133:141S-159S.

Cavalheiro-Filho C, Chamone Dde A, Rached RA, Maffei FH. Heparins - current status. Rev Assoc Med Bras.. 2008;54:471-2.

Bauer KA. New oral anticoagulants in development: potential for improved safety profiles. Rev Neurol Dis.. 2010;7:1-8.

Haas S. New oral Xa and IIa inhibitors: updates on clinical trial results. J Thromb Thrombolysis.. 2008;25:52-60.

Spyropoulos AC. Brave new world: the current and future use of novel anticoagulants. Thromb Res.. 2008;123(^s1):S29-35.

Borlina LP, Cavalcanti e Silva EL, Ghislandi C, Timi JRR. Conhecimento sobre anticoagulantes orais e seu manejo por médicos de pronto atendimento. J Vasc Bras.. 2010;9(2):24-28.

Eikelboom JW, Weitz JI. New anticoagulants. Circulation.. 2010;121:1523-32.

Kearon C, Kahn SR, Agnelli G, Goldhaber S, Raskob GE, Comerota AJ. Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest.. 2008;133:454S-545S.

Ansell J, Hirsh J, Hylek E, Jacobson A, Crowther M, Palareti G. Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest.. 2008;133:160S-198S.

Buller HR, Agnelli G, Hull RD, Hyers TM, Prins MH, Raskob GE. Antithrombotic therapy for venous thromboembolic disease: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest.. 2004;126:401S-428S.

Hirsh J, Guyatt G, Albers GW, Harrington R, Schunemann HJ. Executive summary: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest.. 2008;133:71S-109S.

Apostolakis S, Lip GY, Lane DA, Shantsila E. The Quest for New Anticoagulants: From Clinical Development to Clinical Practice. Cardiovasc Ther.. 2010:1-11.

Mattar L, Maffei FH, Lastoria S, Yoshida WB, Rollo HA, Fabris VE. Comparative study of the action of topical heparinoids on the evolution of experimental thrombophlebitis. Braz J Med Biol Res.. 1988;21:1047-8.

Maffei FH, Rollo HA, Fabris VE. Prevention of experimental venous thrombosis induced by contrast medium in the rat. Acta Radiol Diagn (Stockh).. 1980;21:249-52.

Rollo HA, Maffei FH, Yoshida WB, Lastoria S, Curi PR, Mattar L. Heparin, heparin plus ASA and dipyridamole, and arteriovenous fistula as adjuvant methods to prevent rethrombosis after venous thrombectomy: Experimental study in rabbits. Int Angiol.. 1991;10:88-94.

Maffei FH, Pinto AM, Fabris VE, Lastoria S, Rollo HD. [Experimental venous thrombosis in guinea pigs: effect of heparin and drugs affecting platelet function (author's transl)]. Rev Bras Pesqui Med Biol.. 1977;10:369-78.

Harenberg J, Kakkar A, Bergqvist D, Barrowcliffe T, Casu B, Fareed J. Recommendations on biosimilar low-molecular-weight heparins. J Thromb Haemost.. 2009;7:1222-5.

Samama MM, Gerotziafas GT. Newer anticoagulants in 2009. J Thromb Thrombolysis.. 2010;29:92-104.

Etapas de desenvolvimento de um novo fármaco. 2010.

El Dib RP. Como praticar a medicina baseada em evidências. J Vasc Bras.. 2007;6:1-4.

Weitz JI. Factor Xa or thrombin: is thrombin a better target?. J Thromb Haemost.. 2007;5(^s1):65-7.

Kakkar VV. Treatment of venous thromboembolism: experience with bemiparin. Pathophysiol Haemost Thromb.. 2002;32:406-7.

Martinez-Gonzalez J, Vila L, Rodriguez C. Bemiparin: second-generation, low-molecular-weight heparin for treatment and prophylaxis of venous thromboembolism. Expert Rev Cardiovasc Ther.. 2008;6:793-802.

Navarro-Quilis A, Castellet E, Rocha E, Paz-Jimenez J, Planes A. Efficacy and safety of bemiparin compared with enoxaparin in the prevention of venous thromboembolism after total knee arthroplasty: a randomized, double-blind clinical trial. J Thromb Haemost.. 2003;1:425-32.

Gomez-Outes A, Lecumberri R, Pozo C, Rocha E. New anticoagulants: focus on venous thromboembolism. Curr Vasc Pharmacol.. 2009;7:309-29.

Kakkar AK. Low- and ultra-low-molecular-weight heparins. Best Pract Res Clin Haematol.. 2004;17:77-87.

Turpie AGG, Agnelli G, Fisher W, George D, Kakkar AV, Lassen MR. Benefit-to-risc profile of the ultra-molecular weight heparin (ULMWH) semuloparin for prevention of venous thromboembolism (VTE): a meta-analysis. Pathophysiol Haemost Thromb.. 2010;37:OC332.

Reynolds NA, Perry CM, Scott LJ. Fondaparinux sodium: a review of its use in the prevention of venous thromboembolism following major orthopaedic surgery. Drugs.. 2004;64:1575-96.

Turpie AG, Bauer KA, Eriksson BI, Lassen MR. Fondaparinux vs enoxaparin for the prevention of venous thromboembolism in major orthopedic surgery: a meta-analysis of 4 randomized double-blind studies. Arch Intern Med.. 2002;162:1833-40.

Paty I, Trellu M, Destors JM, Cortez P, Boelle E, Sanderink G. Reversibility of the anti-FXa activity of idrabiotaparinux (biotinylated idraparinux) by intravenous avidin infusion. J Thromb Haemost.. 2010;8:722-9.

Harenberg J, Vukojevic Y, Mikus G, Joerg I, Weiss C. Long elimination half-life of idraparinux may explain major bleeding and recurrent events of patients from the van Gogh trials. J Thromb Haemost.. 2008;6:890-2.

Buller HR, Cohen AT, Davidson B, Decousus H, Gallus AS, Gent M. Idraparinux versus standard therapy for venous thromboembolic disease. N Engl J Med.. 2007;357:1094-104.

Garcia D, Libby E, Crowther MA. The new oral anticoagulants. Blood.. 2010;115:15-20.

Lassen MR, Bauer KA, Eriksson BI, Turpie AG. Postoperative fondaparinux versus preoperative enoxaparin for prevention of venous thromboembolism in elective hip-replacement surgery: a randomised double-blind comparison. Lancet.. 2002;359:1715-20.

Lassen MR, Ageno W, Borris LC, Lieberman JR, Rosencher N, Bandel TJ. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty. N Engl J Med.. 2008;358:2776-86.

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.

Turpie AG, Lassen MR, Davidson BL, Bauer KA, Gent M, Kwong LM. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty (RECORD4): a randomised trial. Lancet.. 2009;373:1673-80.

Turpie AG, Lassen MR, Eriksson BI, Gent M, Berkowitz SD, Misselwitz F. Pooled analysis of four rivaroxaban studies: effects on symptomatic events and bleeding. J Thromb Haemost.. 2009;7:Abs OC-WE-004.

Zikria JC, Ansell J. Oral anticoagulation with factor Xa and thrombin inhibitors: on the threshold of change. Curr Opin Hematol.. 2009;16:347-56.

Lassen MR, Raskob GE, Gallus A, Pineo G, Chen D, Hornick P. Apixaban versus enoxaparin for thromboprophylaxis after knee replacement (ADVANCE-2): a randomised double-blind trial. Lancet.. 2010;375:807-15.

Lassen MR, Raskob GE, Gallus A, Pineo G, Chen D, Portman RJ. Apixaban or enoxaparin for thromboprophylaxis after knee replacement. N Engl J Med.. 2009;361:594-604.

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.

Fuji T, Wang CJ, Fujita S, Tachibana S, Kawai Y, Koretsune Y. Edoxaban versus enoxaparin for thromboprophylaxis after knee arthroplasty: the Stars E-3 trial. Pathophysiol Haemost Thromb.. 2010;37:OC297.

Turpie AG, Bauer KA, Davidson BL, Fisher WD, Gent M, Huo MH. A randomized evaluation of betrixaban, an oral factor Xa inhibitor, for prevention of thromboembolic events after total knee replacement (EXPERT). Thromb Haemost.. 2009;101:68-76.

Wolowacz SE, Roskell NS, Plumb JM, Caprini JA, Eriksson BI. Efficacy and safety of dabigatran etexilate for the prevention of venous thromboembolism following total hip or knee arthroplasty. A meta-analysis. Thromb Haemost.. 2009;101:77-85.

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