Acessibilidade / Reportar erro

Avaliação do risco de sangramento na profilaxia do tromboembolismo venoso

Resumo

O tromboembolismo venoso (TEV) é uma das principais causas preveníveis de morbimortalidade em pacientes hospitalizados, sendo a embolia pulmonar (EP) fatal possivelmente a sua primeira manifestação. Diretrizes nacionais e internacionais recomendam o uso de modelos de avaliação de risco para a prescrição de profilaxia do TEV em pacientes hospitalizados. Apesar das evidências e diretrizes de apoio, o uso da tromboprofilaxia permanece abaixo do ideal, o que pode resultar da baixa conscientização dos benefícios da profilaxia, mas também pode refletir o medo de complicações hemorrágicas, justificando a subutilização da tromboprofilaxia em todo o mundo. A avaliação do risco de sangramento é, portanto, necessária para a adequação de profilaxia e deve ser realizada de forma concomitante à avaliação do risco de trombose. O objetivo desta revisão é salientar a importância da avaliação conjunta do risco de TEV e do risco de sangramento em pacientes hospitalizados.

Palavras-chave:
trombose venosa; embolia pulmonar; profilaxia; hemorragia; segurança do paciente; avaliação de risco

Abstract

Venous thromboembolism (VTE) is one of the main preventable causes of morbidity and mortality in hospitalized patients and fatal pulmonary embolism (PE) may be its first manifestation. Several national and international guidelines recommend using risk assessment models for prescription of VTE prophylaxis in hospitalized patients. Despite evidence and guidelines supporting VTE prevention, use of VTE prophylaxis in hospitalized patients remains suboptimal, which may be because of low awareness of the benefits of VTE prophylaxis, but might also reflect fear of bleeding complications in these patients, since this constitutes one of the main reasons for underutilization of thromboprophylaxis worldwide. Bleeding risk assessment is therefore necessary for adequate prophylaxis prescription and should be carried out concurrently with assessment of the risk of thrombosis. The purpose of this review is to highlight the importance of jointly assessing risk of VTE and risk of bleeding in hospitalized patients.

Keywords:
venous thrombosis; pulmonary embolism; prophylaxis; hemorrhage; patient safety; risk assessment

INTRODUÇÃO

O tromboembolismo venoso (TEV) é uma das principais causas preveníveis de morbimortalidade em pacientes hospitalizados11 Geerts WH, Bergqvist D, Pineo GF, et al. Prevention of venous thromboembolism: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines, 8th ed. Chest. 2008;133(6, Supl):381S-453S. http://dx.doi.org/10.1378/chest.08-0656. PMid:18574271.
http://dx.doi.org/10.1378/chest.08-0656...
,22 Caprini JA. Identification of patient venous thromboembolism risk across the continuum of care. Clin Appl Thromb Hemost. 2011;17(6):590-9. http://dx.doi.org/10.1177/1076029611404217. PMid:21593024.
http://dx.doi.org/10.1177/10760296114042...
. A embolia pulmonar (EP) fatal é frequentemente a primeira manifestação de TEV e pode representar até 10% de todas as mortes hospitalares22 Caprini JA. Identification of patient venous thromboembolism risk across the continuum of care. Clin Appl Thromb Hemost. 2011;17(6):590-9. http://dx.doi.org/10.1177/1076029611404217. PMid:21593024.
http://dx.doi.org/10.1177/10760296114042...
,33 Sandler DA, Martin JF. Autopsy proven pulmonary embolism in hospital patients: are we detecting enough deep vein thrombosis? J R Soc Med. 1989;82(4):203-5. http://dx.doi.org/10.1177/014107688908200407. PMid:2716016.
http://dx.doi.org/10.1177/01410768890820...
. Os pacientes hospitalizados apresentam risco de TEV devido à presença de fatores adquiridos ou hereditários, como obesidade, câncer, TEV prévio, trombofilias, trauma, cirurgia, infarto agudo do miocárdio, acidente vascular cerebral, idade avançada, insuficiência cardíaca congestiva, infecção aguda, imobilidade e admissão em unidades de terapia intensiva, entre outros44 Geerts WH, Pineo GF, Heit JA, et al. Prevention of venous thromboembolism: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004;126(3, Supl):338S-400S. http://dx.doi.org/10.1378/chest.126.3_suppl.338S. PMid:15383478.
http://dx.doi.org/10.1378/chest.126.3_su...

5 Cohen AT, Tapson VF, Bergmann JF, et al. Venous thromboembolism risk and prophylaxis in the acute hospital care setting (ENDORSE study): a multinational cross-sectional study. Lancet. 2008;371(9610):387-94. http://dx.doi.org/10.1016/S0140-6736(08)60202-0. PMid:18242412.
http://dx.doi.org/10.1016/S0140-6736(08)...
-66 Decousus H, Tapson VF, Bergmann JF, et al. Factors at admission associated with bleeding risk in medical patients: findings from the IMPROVE investigators. Chest. 2011;139(1):69-79. http://dx.doi.org/10.1378/chest.09-3081. PMid:20453069.
http://dx.doi.org/10.1378/chest.09-3081...
.

Diretrizes nacionais e internacionais recomendam o uso de modelos de avaliação de risco [risk assessment model (MAR)] para a profilaxia farmacológica ou mecânica em pacientes clínicos77 Kahn SR, Lim W, Dunn AS, et al. Prevention of VTE in nonsurgical patients: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2, Supl):e195S-226S. http://dx.doi.org/10.1378/chest.11-2296. PMid:22315261.
http://dx.doi.org/10.1378/chest.11-2296...

8 Gould MK, Garcia DA, Wren SM, et al. Prevention of VTE in nonorthopedic surgical patients antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2, Supl):e227S-77S. http://dx.doi.org/10.1378/chest.11-2297. PMid:22315263.
http://dx.doi.org/10.1378/chest.11-2297...

9 Rocha AT, Paiva EF, Lichtenstein A, Milani R Jr, Cavalheiro CF, Maffei FH. Risk-assessment algorithm and recommendations for venous thromboembolism prophylaxis in medical patients. Vasc Health Risk Manag. 2007;3(4):533-53. PMid:17969384.

10 Royal College of Obstetrician & Gynaecologists − RCOG. Reducing the risk of venous thromboembolism during pregnancy and the puerperium. London: Royal College of Obstetricians & Gynaecologists; 2015. (Green-Top Guideline; no. 37a).

11 Barbar S, Noventa F, Rossetto V, et al. A risk assessment model for the identification of hospitalized medical patients at risk for venous thromboembolism: the Padua Prediction Score. J Thromb Haemost. 2010;8(11):2450-7. http://dx.doi.org/10.1111/j.1538-7836.2010.04044.x. PMid:20738765.
http://dx.doi.org/10.1111/j.1538-7836.20...

12 Spyropoulos AC, Anderson FA Jr, Fitzgerald G, et al. Predictive and associative models to identify hospitalized medical patients at risk for VTE. Chest. 2011;140(3):706-14. http://dx.doi.org/10.1378/chest.10-1944. PMid:21436241.
http://dx.doi.org/10.1378/chest.10-1944...

13 Chopard P, Spirk D, Bounameaux H. Identifying acutely ill medical patients requiring thromboprophylaxis. J Thromb Haemost. 2006;4(4):915-6. http://dx.doi.org/10.1111/j.1538-7836.2006.01818.x. PMid:16634771.
http://dx.doi.org/10.1111/j.1538-7836.20...
-1414 Samama MM, Cohen AT, Darmon JY, et al. A comparison of enoxaparin with placebo for the prevention of venous thromboembolism in acutely ill medical patients. N Engl J Med. 1999;341(11):793-800. http://dx.doi.org/10.1056/NEJM199909093411103. PMid:10477777.
http://dx.doi.org/10.1056/NEJM1999090934...
, cirúrgicos88 Gould MK, Garcia DA, Wren SM, et al. Prevention of VTE in nonorthopedic surgical patients antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2, Supl):e227S-77S. http://dx.doi.org/10.1378/chest.11-2297. PMid:22315263.
http://dx.doi.org/10.1378/chest.11-2297...
,1515 Caprini JA. Thrombosis risk assessment as a guide to quality patient care. Dis Mon. 2005;51(2-3):70-8. http://dx.doi.org/10.1016/j.disamonth.2005.02.003. PMid:15900257.
http://dx.doi.org/10.1016/j.disamonth.20...
,1616 Rogers SO Jr, Kilaru RK, Hosokawa P, Henderson WG, Zinner MJ, Khuri SF. Multivariable predictors of postoperative venous thromboembolic events after general and vascular surgery: results from the patient safety in surgery study. J Am Coll Surg. 2007;204(6):1211-21. http://dx.doi.org/10.1016/j.jamcollsurg.2007.02.072. PMid:17544079.
http://dx.doi.org/10.1016/j.jamcollsurg....
ou obstétricos1010 Royal College of Obstetrician & Gynaecologists − RCOG. Reducing the risk of venous thromboembolism during pregnancy and the puerperium. London: Royal College of Obstetricians & Gynaecologists; 2015. (Green-Top Guideline; no. 37a)., visando à melhor estratégia de prevenção. Contudo, o risco de TEV não pode ser avaliado isoladamente. O risco de sangramento, induzido ou potencializado pelos anticoagulantes, também deve ser avaliado simultaneamente quando se considera a adequação da tromboprofilaxia66 Decousus H, Tapson VF, Bergmann JF, et al. Factors at admission associated with bleeding risk in medical patients: findings from the IMPROVE investigators. Chest. 2011;139(1):69-79. http://dx.doi.org/10.1378/chest.09-3081. PMid:20453069.
http://dx.doi.org/10.1378/chest.09-3081...
,77 Kahn SR, Lim W, Dunn AS, et al. Prevention of VTE in nonsurgical patients: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2, Supl):e195S-226S. http://dx.doi.org/10.1378/chest.11-2296. PMid:22315261.
http://dx.doi.org/10.1378/chest.11-2296...
,99 Rocha AT, Paiva EF, Lichtenstein A, Milani R Jr, Cavalheiro CF, Maffei FH. Risk-assessment algorithm and recommendations for venous thromboembolism prophylaxis in medical patients. Vasc Health Risk Manag. 2007;3(4):533-53. PMid:17969384..

Embora diversos estudos reportem baixas taxas de sangramento relacionadas à farmacoprofilaxia1111 Barbar S, Noventa F, Rossetto V, et al. A risk assessment model for the identification of hospitalized medical patients at risk for venous thromboembolism: the Padua Prediction Score. J Thromb Haemost. 2010;8(11):2450-7. http://dx.doi.org/10.1111/j.1538-7836.2010.04044.x. PMid:20738765.
http://dx.doi.org/10.1111/j.1538-7836.20...
,1717 Leizorovicz A, Cohen AT, Turpie AG, Olsson CG, Vaitkus PT, Goldhaber SZ. Randomized, placebo-controlled trial of dalteparin for the prevention of venous thromboembolism in acutely ill medical patients. Circulation. 2004;110(7):874-9. http://dx.doi.org/10.1161/01.CIR.0000138928.83266.24. PMid:15289368.
http://dx.doi.org/10.1161/01.CIR.0000138...
,1818 Cohen AT, Davidson BL, Gallus AS, et al. Efficacy and safety of fondaparinux for the prevention of venous thromboembolism in older acute medical patients: randomised placebo-controlled trial. BMJ. 2006;332(7537):325-9. http://dx.doi.org/10.1136/bmj.38733.466748.7C. PMid:16439370.
http://dx.doi.org/10.1136/bmj.38733.4667...
, o medo de eventos hemorrágicos é uma das principais justificativas da sua subutilização em todo o mundo66 Decousus H, Tapson VF, Bergmann JF, et al. Factors at admission associated with bleeding risk in medical patients: findings from the IMPROVE investigators. Chest. 2011;139(1):69-79. http://dx.doi.org/10.1378/chest.09-3081. PMid:20453069.
http://dx.doi.org/10.1378/chest.09-3081...
. A identificação de condições com potencial risco de sangramento e a implementação de MAR são, portanto, fundamentais para o uso adequado da tromboprofilaxia1919 Stuck AK, Spirk D, Schaudt J, Kucher N. Risk assessment models for venous thromboembolism in acutely ill medical patients: a systematic review. Thromb Haemost. 2017;117(4):801-8. http://dx.doi.org/10.1160/TH16-08-0631. PMid:28150851.
http://dx.doi.org/10.1160/TH16-08-0631...
.

O objetivo desta revisão é salientar a importância da avaliação conjunta do risco de TEV e do risco de sangramento em pacientes hospitalizados.

AVALIAÇÃO DE RISCO TROMBÓTICO VERSUS RISCO DE SANGRAMENTO

Inúmeros MARs de TEV estão disponíveis, tanto para pacientes clínicos quanto cirúrgicos, e direcionam as principais recomendações de tromboprofilaxia com base na estratificação de risco77 Kahn SR, Lim W, Dunn AS, et al. Prevention of VTE in nonsurgical patients: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2, Supl):e195S-226S. http://dx.doi.org/10.1378/chest.11-2296. PMid:22315261.
http://dx.doi.org/10.1378/chest.11-2296...

8 Gould MK, Garcia DA, Wren SM, et al. Prevention of VTE in nonorthopedic surgical patients antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2, Supl):e227S-77S. http://dx.doi.org/10.1378/chest.11-2297. PMid:22315263.
http://dx.doi.org/10.1378/chest.11-2297...

9 Rocha AT, Paiva EF, Lichtenstein A, Milani R Jr, Cavalheiro CF, Maffei FH. Risk-assessment algorithm and recommendations for venous thromboembolism prophylaxis in medical patients. Vasc Health Risk Manag. 2007;3(4):533-53. PMid:17969384.

10 Royal College of Obstetrician & Gynaecologists − RCOG. Reducing the risk of venous thromboembolism during pregnancy and the puerperium. London: Royal College of Obstetricians & Gynaecologists; 2015. (Green-Top Guideline; no. 37a).

11 Barbar S, Noventa F, Rossetto V, et al. A risk assessment model for the identification of hospitalized medical patients at risk for venous thromboembolism: the Padua Prediction Score. J Thromb Haemost. 2010;8(11):2450-7. http://dx.doi.org/10.1111/j.1538-7836.2010.04044.x. PMid:20738765.
http://dx.doi.org/10.1111/j.1538-7836.20...

12 Spyropoulos AC, Anderson FA Jr, Fitzgerald G, et al. Predictive and associative models to identify hospitalized medical patients at risk for VTE. Chest. 2011;140(3):706-14. http://dx.doi.org/10.1378/chest.10-1944. PMid:21436241.
http://dx.doi.org/10.1378/chest.10-1944...

13 Chopard P, Spirk D, Bounameaux H. Identifying acutely ill medical patients requiring thromboprophylaxis. J Thromb Haemost. 2006;4(4):915-6. http://dx.doi.org/10.1111/j.1538-7836.2006.01818.x. PMid:16634771.
http://dx.doi.org/10.1111/j.1538-7836.20...

14 Samama MM, Cohen AT, Darmon JY, et al. A comparison of enoxaparin with placebo for the prevention of venous thromboembolism in acutely ill medical patients. N Engl J Med. 1999;341(11):793-800. http://dx.doi.org/10.1056/NEJM199909093411103. PMid:10477777.
http://dx.doi.org/10.1056/NEJM1999090934...

15 Caprini JA. Thrombosis risk assessment as a guide to quality patient care. Dis Mon. 2005;51(2-3):70-8. http://dx.doi.org/10.1016/j.disamonth.2005.02.003. PMid:15900257.
http://dx.doi.org/10.1016/j.disamonth.20...
-1616 Rogers SO Jr, Kilaru RK, Hosokawa P, Henderson WG, Zinner MJ, Khuri SF. Multivariable predictors of postoperative venous thromboembolic events after general and vascular surgery: results from the patient safety in surgery study. J Am Coll Surg. 2007;204(6):1211-21. http://dx.doi.org/10.1016/j.jamcollsurg.2007.02.072. PMid:17544079.
http://dx.doi.org/10.1016/j.jamcollsurg....
. O modelo mais adequado de avaliação ainda não está definido1919 Stuck AK, Spirk D, Schaudt J, Kucher N. Risk assessment models for venous thromboembolism in acutely ill medical patients: a systematic review. Thromb Haemost. 2017;117(4):801-8. http://dx.doi.org/10.1160/TH16-08-0631. PMid:28150851.
http://dx.doi.org/10.1160/TH16-08-0631...
. Na estratificação de risco de TEV, devemos utilizar um modelo validado para a população em questão aplicado de forma sistemática nas principais etapas de assistência: admissão hospitalar, transição entre setores e alta hospitalar. Essa última avaliação é particularmente importante nos pacientes que mantêm fatores de risco para TEV na alta, como, por exemplo, a imobilidade prolongada22 Caprini JA. Identification of patient venous thromboembolism risk across the continuum of care. Clin Appl Thromb Hemost. 2011;17(6):590-9. http://dx.doi.org/10.1177/1076029611404217. PMid:21593024.
http://dx.doi.org/10.1177/10760296114042...
. A escolha da melhor estratégia de tromboprofilaxia deve considerar, simultaneamente, o risco de TEV e o risco potencial de sangramento2020 Key NS, Khorana AA, Kuderer NM, et al. Venous thromboembolism prophylaxis and treatment in patients with Cancer: ASCO clinical practice guideline update. J Clin Oncol. 2020;38(5):496-520. http://dx.doi.org/10.1200/JCO.19.01461. PMid:31381464.
http://dx.doi.org/10.1200/JCO.19.01461...
,2121 National Institute for Health and Care Excellence – NICE. Venous thromboembolism in over 16s: reducing the risk of hospital-acquired deep vein thrombosis or pulmonary embolism: NICE guideline [NG89]. London: NICE; 2019. [citado 2020 mar 30]. https://www.nice.org.uk/guidance/ng89/resources
https://www.nice.org.uk/guidance/ng89/re...
.

São consideradas contraindicações absolutas ao uso de anticoagulantes o sangramento ativo, grave ou potencialmente fatal, não reversível com intervenção médica ou cirúrgica, incluindo qualquer sangramento ativo em local crítico (intracraniano, pericárdico, retroperitoneal, intraocular, intra-articular e intraespinhal), hipertensão arterial maligna não controlada, coagulopatia grave não compensada, disfunção plaquetária ou distúrbios primários de hemostasia graves, trombocitopenia persistente (< 20.000/mm3) e procedimentos invasivos de alto risco em local crítico, como punção lombar e raquianestesia em pacientes cujo procedimento cirúrgico é planejado no período de 6 a 12 horas seguintes2020 Key NS, Khorana AA, Kuderer NM, et al. Venous thromboembolism prophylaxis and treatment in patients with Cancer: ASCO clinical practice guideline update. J Clin Oncol. 2020;38(5):496-520. http://dx.doi.org/10.1200/JCO.19.01461. PMid:31381464.
http://dx.doi.org/10.1200/JCO.19.01461...
. Outros fatores associados ao risco aumentado de sangramento são a trombocitopenia induzida pela heparina (TIH), o uso concomitante de antiagregantes plaquetários e/ou anti-inflamatórios não hormonais e a disfunção renal, principalmente quando utilizados anticoagulantes de eliminação renal [heparina de baixo peso molecular (HBPM) e fondaparinux]1515 Caprini JA. Thrombosis risk assessment as a guide to quality patient care. Dis Mon. 2005;51(2-3):70-8. http://dx.doi.org/10.1016/j.disamonth.2005.02.003. PMid:15900257.
http://dx.doi.org/10.1016/j.disamonth.20...
. Em pacientes que apresentam clearance de creatinina < 30 mL/min, recomenda-se a redução da dose de HBPM, monitoramento da ação anticoagulante ou substituição por heparina não fracionada (HNF)44 Geerts WH, Pineo GF, Heit JA, et al. Prevention of venous thromboembolism: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004;126(3, Supl):338S-400S. http://dx.doi.org/10.1378/chest.126.3_suppl.338S. PMid:15383478.
http://dx.doi.org/10.1378/chest.126.3_su...
. A revisão periódica de ambos os riscos, principalmente nas mudanças de quadro clínico, ajuda a orientar a melhor estratégia para a profilaxia2121 National Institute for Health and Care Excellence – NICE. Venous thromboembolism in over 16s: reducing the risk of hospital-acquired deep vein thrombosis or pulmonary embolism: NICE guideline [NG89]. London: NICE; 2019. [citado 2020 mar 30]. https://www.nice.org.uk/guidance/ng89/resources
https://www.nice.org.uk/guidance/ng89/re...
(Figura 1).

Figura 1
Recomendações de profilaxia de tromboembolismo venoso (TEV) segundo estratificação do risco de TEV versus risco de sangramento. Adaptado de: National Institute for Health and Care Excellence – NICE. NG892121 National Institute for Health and Care Excellence – NICE. Venous thromboembolism in over 16s: reducing the risk of hospital-acquired deep vein thrombosis or pulmonary embolism: NICE guideline [NG89]. London: NICE; 2019. [citado 2020 mar 30]. https://www.nice.org.uk/guidance/ng89/resources
https://www.nice.org.uk/guidance/ng89/re...
.

Modelos de avaliação de risco de TEV

Entre os principais MARs de TEV em pacientes clínicos, estão a Diretriz Brasileira de Prevenção de TEV em pacientes clínicos hospitalizados99 Rocha AT, Paiva EF, Lichtenstein A, Milani R Jr, Cavalheiro CF, Maffei FH. Risk-assessment algorithm and recommendations for venous thromboembolism prophylaxis in medical patients. Vasc Health Risk Manag. 2007;3(4):533-53. PMid:17969384. e os escores de Padua1111 Barbar S, Noventa F, Rossetto V, et al. A risk assessment model for the identification of hospitalized medical patients at risk for venous thromboembolism: the Padua Prediction Score. J Thromb Haemost. 2010;8(11):2450-7. http://dx.doi.org/10.1111/j.1538-7836.2010.04044.x. PMid:20738765.
http://dx.doi.org/10.1111/j.1538-7836.20...
, Genebra1313 Chopard P, Spirk D, Bounameaux H. Identifying acutely ill medical patients requiring thromboprophylaxis. J Thromb Haemost. 2006;4(4):915-6. http://dx.doi.org/10.1111/j.1538-7836.2006.01818.x. PMid:16634771.
http://dx.doi.org/10.1111/j.1538-7836.20...
e IMPROVE (International Medical Prevention Registry on Venous Thromboembolism)1212 Spyropoulos AC, Anderson FA Jr, Fitzgerald G, et al. Predictive and associative models to identify hospitalized medical patients at risk for VTE. Chest. 2011;140(3):706-14. http://dx.doi.org/10.1378/chest.10-1944. PMid:21436241.
http://dx.doi.org/10.1378/chest.10-1944...
. Para a avaliação de pacientes cirúrgicos, são recomendados os escores de Caprini1515 Caprini JA. Thrombosis risk assessment as a guide to quality patient care. Dis Mon. 2005;51(2-3):70-8. http://dx.doi.org/10.1016/j.disamonth.2005.02.003. PMid:15900257.
http://dx.doi.org/10.1016/j.disamonth.20...
e Rogers1616 Rogers SO Jr, Kilaru RK, Hosokawa P, Henderson WG, Zinner MJ, Khuri SF. Multivariable predictors of postoperative venous thromboembolic events after general and vascular surgery: results from the patient safety in surgery study. J Am Coll Surg. 2007;204(6):1211-21. http://dx.doi.org/10.1016/j.jamcollsurg.2007.02.072. PMid:17544079.
http://dx.doi.org/10.1016/j.jamcollsurg....
, que definem o risco de TEV com base nas características dos pacientes e no perfil de cada cirurgia. Mulheres hospitalizadas durante a gravidez, no puerpério ou no período de até seis semanas após aborto espontâneo ou interrupção da gravidez, devem ser avaliadas quanto à necessidade de farmacoprofilaxia2121 National Institute for Health and Care Excellence – NICE. Venous thromboembolism in over 16s: reducing the risk of hospital-acquired deep vein thrombosis or pulmonary embolism: NICE guideline [NG89]. London: NICE; 2019. [citado 2020 mar 30]. https://www.nice.org.uk/guidance/ng89/resources
https://www.nice.org.uk/guidance/ng89/re...
. O MAR mais utilizado nesse perfil de pacientes foi desenvolvido pelo Royal College of Obstetricians and Gynecologists (RCOG)1010 Royal College of Obstetrician & Gynaecologists − RCOG. Reducing the risk of venous thromboembolism during pregnancy and the puerperium. London: Royal College of Obstetricians & Gynaecologists; 2015. (Green-Top Guideline; no. 37a).,2121 National Institute for Health and Care Excellence – NICE. Venous thromboembolism in over 16s: reducing the risk of hospital-acquired deep vein thrombosis or pulmonary embolism: NICE guideline [NG89]. London: NICE; 2019. [citado 2020 mar 30]. https://www.nice.org.uk/guidance/ng89/resources
https://www.nice.org.uk/guidance/ng89/re...
.

Apesar da recomendação de avaliação concomitante do risco de TEV versus risco de sangramento durante o cuidado do paciente hospitalizado, são escassos os MARs de sangramento no contexto da profilaxia de TEV1919 Stuck AK, Spirk D, Schaudt J, Kucher N. Risk assessment models for venous thromboembolism in acutely ill medical patients: a systematic review. Thromb Haemost. 2017;117(4):801-8. http://dx.doi.org/10.1160/TH16-08-0631. PMid:28150851.
http://dx.doi.org/10.1160/TH16-08-0631...
. Poucos são os modelos que associam essas duas características99 Rocha AT, Paiva EF, Lichtenstein A, Milani R Jr, Cavalheiro CF, Maffei FH. Risk-assessment algorithm and recommendations for venous thromboembolism prophylaxis in medical patients. Vasc Health Risk Manag. 2007;3(4):533-53. PMid:17969384.,1212 Spyropoulos AC, Anderson FA Jr, Fitzgerald G, et al. Predictive and associative models to identify hospitalized medical patients at risk for VTE. Chest. 2011;140(3):706-14. http://dx.doi.org/10.1378/chest.10-1944. PMid:21436241.
http://dx.doi.org/10.1378/chest.10-1944...
,2121 National Institute for Health and Care Excellence – NICE. Venous thromboembolism in over 16s: reducing the risk of hospital-acquired deep vein thrombosis or pulmonary embolism: NICE guideline [NG89]. London: NICE; 2019. [citado 2020 mar 30]. https://www.nice.org.uk/guidance/ng89/resources
https://www.nice.org.uk/guidance/ng89/re...
(Tabela 1).

Tabela 1
Lista de modelos de avaliação de risco (MAR) de tromboembolismo venoso (TEV) e de sangramento de acordo com a população estudada99 Rocha AT, Paiva EF, Lichtenstein A, Milani R Jr, Cavalheiro CF, Maffei FH. Risk-assessment algorithm and recommendations for venous thromboembolism prophylaxis in medical patients. Vasc Health Risk Manag. 2007;3(4):533-53. PMid:17969384.

10 Royal College of Obstetrician & Gynaecologists − RCOG. Reducing the risk of venous thromboembolism during pregnancy and the puerperium. London: Royal College of Obstetricians & Gynaecologists; 2015. (Green-Top Guideline; no. 37a).

11 Barbar S, Noventa F, Rossetto V, et al. A risk assessment model for the identification of hospitalized medical patients at risk for venous thromboembolism: the Padua Prediction Score. J Thromb Haemost. 2010;8(11):2450-7. http://dx.doi.org/10.1111/j.1538-7836.2010.04044.x. PMid:20738765.
http://dx.doi.org/10.1111/j.1538-7836.20...

12 Spyropoulos AC, Anderson FA Jr, Fitzgerald G, et al. Predictive and associative models to identify hospitalized medical patients at risk for VTE. Chest. 2011;140(3):706-14. http://dx.doi.org/10.1378/chest.10-1944. PMid:21436241.
http://dx.doi.org/10.1378/chest.10-1944...

13 Chopard P, Spirk D, Bounameaux H. Identifying acutely ill medical patients requiring thromboprophylaxis. J Thromb Haemost. 2006;4(4):915-6. http://dx.doi.org/10.1111/j.1538-7836.2006.01818.x. PMid:16634771.
http://dx.doi.org/10.1111/j.1538-7836.20...

14 Samama MM, Cohen AT, Darmon JY, et al. A comparison of enoxaparin with placebo for the prevention of venous thromboembolism in acutely ill medical patients. N Engl J Med. 1999;341(11):793-800. http://dx.doi.org/10.1056/NEJM199909093411103. PMid:10477777.
http://dx.doi.org/10.1056/NEJM1999090934...

15 Caprini JA. Thrombosis risk assessment as a guide to quality patient care. Dis Mon. 2005;51(2-3):70-8. http://dx.doi.org/10.1016/j.disamonth.2005.02.003. PMid:15900257.
http://dx.doi.org/10.1016/j.disamonth.20...
-1616 Rogers SO Jr, Kilaru RK, Hosokawa P, Henderson WG, Zinner MJ, Khuri SF. Multivariable predictors of postoperative venous thromboembolic events after general and vascular surgery: results from the patient safety in surgery study. J Am Coll Surg. 2007;204(6):1211-21. http://dx.doi.org/10.1016/j.jamcollsurg.2007.02.072. PMid:17544079.
http://dx.doi.org/10.1016/j.jamcollsurg....
,2121 National Institute for Health and Care Excellence – NICE. Venous thromboembolism in over 16s: reducing the risk of hospital-acquired deep vein thrombosis or pulmonary embolism: NICE guideline [NG89]. London: NICE; 2019. [citado 2020 mar 30]. https://www.nice.org.uk/guidance/ng89/resources
https://www.nice.org.uk/guidance/ng89/re...
.

Esse cenário é bastante distinto daquele encontrado na avaliação de risco de sangramento aplicada à anticoagulação plena na prevenção dos fenômenos tromboembólicos da fibrilação atrial ou no tratamento de TEV. Dez MARs de sangramento estão disponíveis com esse objetivo. Seis deles são aplicáveis aos casos dos pacientes que fazem uso de anticoagulantes orais na fibrilação atrial (ABC2222 Hijazi Z, Oldgren J, Lindbäck J, et al. The novel biomarker-based ABC (age, biomarkers, clinical history) − bleeding risk score for patients with atrial fibrillation: a derivation and validation study. Lancet. 2016;387(10035):2302-11. http://dx.doi.org/10.1016/S0140-6736(16)00741-8. PMid:27056738.
http://dx.doi.org/10.1016/S0140-6736(16)...
, ORBIT2323 O’Brien EC, Simon DJN, Thomas LE, et al. The ORBIT bleeding score: a simple bedside score to assess bleeding risk in atrial fibrillation. Eur Heart J. 2015;36(46):3258-64. http://dx.doi.org/10.1093/eurheartj/ehv476. PMid:26424865.
http://dx.doi.org/10.1093/eurheartj/ehv4...
, ATRIA2424 Fang MC, Go AS, Chang Y, et al. A new risk scheme to predict warfarin-associated hemorrhage: the ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation) study. J Am Coll Cardiol. 2011;58(4):395-401. http://dx.doi.org/10.1016/j.jacc.2011.03.031. PMid:21757117.
http://dx.doi.org/10.1016/j.jacc.2011.03...
, HAS-BLED2525 Pisters R, Lane DA, Nieuwlaat R, de Vos CB, Crijns HJ, Lip GY. A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest. 2010;138(5):1093-100. http://dx.doi.org/10.1378/chest.10-0134. PMid:20299623.
http://dx.doi.org/10.1378/chest.10-0134...
, HEMORR2HAGES2626 Gage BF, Yan Y, Milligan PE, et al. Clinical classification schemes for predicting hemorrhage: results from the National Registry of Atrial Fibrillation (NRAF). Am Heart J. 2006;151(3):713-9. http://dx.doi.org/10.1016/j.ahj.2005.04.017. PMid:16504638.
http://dx.doi.org/10.1016/j.ahj.2005.04....
, Shireman2727 Shireman TI, Mahnken JD, Howard PA, Kresowik TF, Hou Q, Ellerbeck EF. Development of a contemporary bleeding risk model for elderly warfarin recipients. Chest. 2006;130(5):1390-6. http://dx.doi.org/10.1378/chest.130.5.1390. PMid:17099015.
http://dx.doi.org/10.1378/chest.130.5.13...
), três no tratamento anticoagulante de TEV (VTE-BLED2828 Klok FA, Hösel V, Clemens A, et al. Prediction of bleeding events in patients with venous thromboembolism on stable anticoagulation treatment. Eur Respir J. 2016;48(5):1369-76. http://dx.doi.org/10.1183/13993003.00280-2016. PMid:27471209.
http://dx.doi.org/10.1183/13993003.00280...
, Ruiz-Gimenez2929 Ruíz-Giménez N, Suarez C, Gonzalez R, et al. Predictive variables for major bleeding events in patients presenting with documented acute venous thromboembolism: findings from the RIETE Registry. Thromb Haemost. 2008;100(1):26-31. http://dx.doi.org/10.1160/TH08-03-0193. PMid:18612534.
http://dx.doi.org/10.1160/TH08-03-0193...
, Kuijer3030 Kuijer PM, Hutten BA, Prins MH, Büller HR. Prediction of the risk of bleeding during anticoagulant treatment for venous thromboembolism. Arch Intern Med. 1999;159(5):457-60. http://dx.doi.org/10.1001/archinte.159.5.457. PMid:10074953.
http://dx.doi.org/10.1001/archinte.159.5...
) e um misto (OBRI3131 Beyth RJ, Quinn LM, Landefeld CS. Prospective evaluation of an index for predicting the risk of major bleeding in outpatients treated with warfarin. Am J Med. 1998;105(2):91-9. http://dx.doi.org/10.1016/S0002-9343(98)00198-3. PMid:9727814.
http://dx.doi.org/10.1016/S0002-9343(98)...
). Esses escores evidenciam situações de aumento do risco de sangramento associado à anticoagulação plena e auxiliam na aplicação de estratégias que ajudam a minimizar o risco de hemorragia por meio da intervenção em fatores de risco modificáveis3232 Zulkifly H, Lip GYH, Lane DA. Bleeding risk scores in atrial fibrillation and venous thromboembolism. Am J Cardiol. 2017;120(7):1139-45. http://dx.doi.org/10.1016/j.amjcard.2017.06.058. PMid:28800833.
http://dx.doi.org/10.1016/j.amjcard.2017...
.

RISCO DE SANGRAMENTO NA FARMACOPROFILAXIA

Avaliação de risco de sangramento em pacientes clínicos

IMPROVE Bleeding Risk Score

O principal MAR de sangramento associado à farmacoprofilaxia em pacientes clínicos hospitalizados é o IMPROVE Bleeding Risk Score66 Decousus H, Tapson VF, Bergmann JF, et al. Factors at admission associated with bleeding risk in medical patients: findings from the IMPROVE investigators. Chest. 2011;139(1):69-79. http://dx.doi.org/10.1378/chest.09-3081. PMid:20453069.
http://dx.doi.org/10.1378/chest.09-3081...
,77 Kahn SR, Lim W, Dunn AS, et al. Prevention of VTE in nonsurgical patients: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2, Supl):e195S-226S. http://dx.doi.org/10.1378/chest.11-2296. PMid:22315261.
http://dx.doi.org/10.1378/chest.11-2296...
. Decousus et al.66 Decousus H, Tapson VF, Bergmann JF, et al. Factors at admission associated with bleeding risk in medical patients: findings from the IMPROVE investigators. Chest. 2011;139(1):69-79. http://dx.doi.org/10.1378/chest.09-3081. PMid:20453069.
http://dx.doi.org/10.1378/chest.09-3081...
utilizaram uma análise multivariada para identificar e pontuar fatores na admissão hospitalar associados ao risco de sangramento em pacientes clínicos agudamente doentes. Com base nos dados do IMPROVE1212 Spyropoulos AC, Anderson FA Jr, Fitzgerald G, et al. Predictive and associative models to identify hospitalized medical patients at risk for VTE. Chest. 2011;140(3):706-14. http://dx.doi.org/10.1378/chest.10-1944. PMid:21436241.
http://dx.doi.org/10.1378/chest.10-1944...
, um estudo observacional multicêntrico desenvolvido para avaliar os padrões de profilaxia de TEV em mais de 15.000 pacientes clínicos, os autores verificaram a incidência de sangramento e identificaram os fatores, na admissão, associados ao risco de sangramento66 Decousus H, Tapson VF, Bergmann JF, et al. Factors at admission associated with bleeding risk in medical patients: findings from the IMPROVE investigators. Chest. 2011;139(1):69-79. http://dx.doi.org/10.1378/chest.09-3081. PMid:20453069.
http://dx.doi.org/10.1378/chest.09-3081...
. O sangramento maior foi definido como sangramento fatal e/ou sintomático em uma área ou órgão crítico e/ou sangramento que resultou em queda de hemoglobina ≥ 2 g/dL ou levou à transfusão de dois ou mais concentrados de hemácias66 Decousus H, Tapson VF, Bergmann JF, et al. Factors at admission associated with bleeding risk in medical patients: findings from the IMPROVE investigators. Chest. 2011;139(1):69-79. http://dx.doi.org/10.1378/chest.09-3081. PMid:20453069.
http://dx.doi.org/10.1378/chest.09-3081...
. O sangramento não maior, mas clinicamente relevante, foi caracterizado como hemorragia gastrointestinal, hematúria macroscópica de duração > 24 h, epistaxe substancial com necessidade de intervenção, epistaxe recorrente e/ou de duração de pelo menos cinco minutos, hematomas extensos (> 5 cm de diâmetro), sangramento intra-articular, menorragia ou metrorragia ou ainda outro sangramento importante que necessitasse de intervenção médica66 Decousus H, Tapson VF, Bergmann JF, et al. Factors at admission associated with bleeding risk in medical patients: findings from the IMPROVE investigators. Chest. 2011;139(1):69-79. http://dx.doi.org/10.1378/chest.09-3081. PMid:20453069.
http://dx.doi.org/10.1378/chest.09-3081...
,3333 Schulman S, Kearon C. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost. 2005;3(4):692-4. http://dx.doi.org/10.1111/j.1538-7836.2005.01204.x. PMid:15842354.
http://dx.doi.org/10.1111/j.1538-7836.20...
.

A incidência cumulativa de sangramentos hospitalares descritos como maiores e não maiores até 14 dias após a internação foi de 3,2% (1,2% de sangramento maior e 2,0% de sangramento não maior clinicamente relevante)66 Decousus H, Tapson VF, Bergmann JF, et al. Factors at admission associated with bleeding risk in medical patients: findings from the IMPROVE investigators. Chest. 2011;139(1):69-79. http://dx.doi.org/10.1378/chest.09-3081. PMid:20453069.
http://dx.doi.org/10.1378/chest.09-3081...
.

Os fatores de risco, na admissão, independentemente associados ao risco de sangramento foram66 Decousus H, Tapson VF, Bergmann JF, et al. Factors at admission associated with bleeding risk in medical patients: findings from the IMPROVE investigators. Chest. 2011;139(1):69-79. http://dx.doi.org/10.1378/chest.09-3081. PMid:20453069.
http://dx.doi.org/10.1378/chest.09-3081...
: úlcera gastroduodenal ativa, sangramento nos três meses anteriores à admissão e contagem de plaquetas < 50.000/mm3. Outros fatores de risco de sangramento incluíram idade avançada, insuficiência hepática e/ou renal, permanência em unidade de terapia intensiva, presença de cateter venoso central, doença reumática, câncer e sexo masculino, fatores que também estão relacionados ao aumento do risco de TEV66 Decousus H, Tapson VF, Bergmann JF, et al. Factors at admission associated with bleeding risk in medical patients: findings from the IMPROVE investigators. Chest. 2011;139(1):69-79. http://dx.doi.org/10.1378/chest.09-3081. PMid:20453069.
http://dx.doi.org/10.1378/chest.09-3081...
. Cada um dos fatores acima, com ponderação apropriada, foi inserido neste MAR (Tabela 2). Os autores também elaboraram um recurso on-line no qual o risco de sangramento pode ser avaliado3434 University of Massachusetts Medical School – UMMS [site na Internet]. Worcester, MA: UMASS; 2020. [citado 2020 jun 17]. http://www.outcomesumassmed.org/IMPROVE/bleeding_risk_score.cfm
http://www.outcomesumassmed.org/IMPROVE/...
.

Tabela 2
IMPROVE Bleeding Risk Score.

Mais da metade dos episódios de sangramento maior ocorreu em 10% dos pacientes hospitalizados que tiveram escore de risco de sangramento ≥ 766 Decousus H, Tapson VF, Bergmann JF, et al. Factors at admission associated with bleeding risk in medical patients: findings from the IMPROVE investigators. Chest. 2011;139(1):69-79. http://dx.doi.org/10.1378/chest.09-3081. PMid:20453069.
http://dx.doi.org/10.1378/chest.09-3081...
. Desse modo, os autores consideraram como alto risco de sangramento a pontuação no IMPROVE Bleeding Risk Score ≥ 7 e como baixo risco a pontuação < 7. As taxas de sangramento maior, em comparação às taxas de qualquer sangramento (definido como maior ou não maior clinicamente relevante) nos pacientes com escore < 7 foram respectivamente 0,4% e 1,5%. Naqueles com escore ≥ 7, a taxa de sangramento maior foi de 4,1% e a de qualquer sangramento, 7,9%66 Decousus H, Tapson VF, Bergmann JF, et al. Factors at admission associated with bleeding risk in medical patients: findings from the IMPROVE investigators. Chest. 2011;139(1):69-79. http://dx.doi.org/10.1378/chest.09-3081. PMid:20453069.
http://dx.doi.org/10.1378/chest.09-3081...
.

Profilaxia mecânica foi mais utilizada em pacientes com escore de sangramento ≥ 7, comparada ao escore < 7 (16,3% versus 8,9%, respectivamente). Por outro lado, a profilaxia farmacológica foi utilizada em proporções semelhantes em pacientes com escore de risco de < 7 e ≥ 7 (48,9% versus 49,3%, respectivamente)66 Decousus H, Tapson VF, Bergmann JF, et al. Factors at admission associated with bleeding risk in medical patients: findings from the IMPROVE investigators. Chest. 2011;139(1):69-79. http://dx.doi.org/10.1378/chest.09-3081. PMid:20453069.
http://dx.doi.org/10.1378/chest.09-3081...
.

Este MAR ajuda, portanto, a decidir sobre a profilaxia farmacológica ou mecânica em pacientes clínicos de alto risco de TEV66 Decousus H, Tapson VF, Bergmann JF, et al. Factors at admission associated with bleeding risk in medical patients: findings from the IMPROVE investigators. Chest. 2011;139(1):69-79. http://dx.doi.org/10.1378/chest.09-3081. PMid:20453069.
http://dx.doi.org/10.1378/chest.09-3081...
. Pode ser aplicado em associação com o escore IMPROVE para risco de TEV, permitindo a ponderação do risco e do benefício na escolha da melhor estratégia de tromboprofilaxia. Esse escore já foi validado em outras populações de pacientes clínicos3535 Hostler DC, Marx ES, Moores LK, et al. Validation of the international medical prevention registry on venous thromboembolism bleeding risk score. Chest. 2016;149(2):372-9. http://dx.doi.org/10.1378/chest.14-2842. PMid:26867833.
http://dx.doi.org/10.1378/chest.14-2842...
,3636 Rosenberg DJ, Press A, Rosenberg DJ, et al. External validation of the IMPROVE Bleeding Risk Assessment Model in medical patients. Thromb Haemost. 2016;116(3):530-6. http://dx.doi.org/10.1160/TH16-01-0003. PMid:27307054.
http://dx.doi.org/10.1160/TH16-01-0003...
.

Avaliação de risco de sangramento em pacientes cirúrgicos

A taxa de sangramento associada à farmacoprofilaxia em pacientes cirúrgicos varia de acordo com o perfil da cirurgia. Uma metanálise de 52 estudos randomizados sobre farmacoprofilaxia de TEV em pacientes de cirurgia geral relatou que os sangramentos menores são comuns e abrangem hematomas no local de aplicação (~7%), hematoma da ferida (~6%), sangramento no local do dreno (~2%) e hematúria (~2%)3737 Leonardi MJ, McGory ML, Ko CY. The rate of bleeding complications after pharmacologic deep venous thrombosis prophylaxis: a systematic review of 33 randomized controlled trials. Arch Surg. 2006;141(8):790-7, discussion 797-9. http://dx.doi.org/10.1001/archsurg.141.8.790. PMid:16924087.
http://dx.doi.org/10.1001/archsurg.141.8...
. As complicações hemorrágicas maiores, no entanto, foram incomuns e incluíram sangramento gastrointestinal (0,2%) ou retroperitoneal (< 0,1%)3737 Leonardi MJ, McGory ML, Ko CY. The rate of bleeding complications after pharmacologic deep venous thrombosis prophylaxis: a systematic review of 33 randomized controlled trials. Arch Surg. 2006;141(8):790-7, discussion 797-9. http://dx.doi.org/10.1001/archsurg.141.8.790. PMid:16924087.
http://dx.doi.org/10.1001/archsurg.141.8...
. A descontinuação da profilaxia ocorreu em 2% dos pacientes e a reoperação subsequente por sangramento em menos de 1%. Da mesma forma, os pacientes com um ou mais fatores de risco individuais de sangramento foram considerados de alto risco no pós-operatório3737 Leonardi MJ, McGory ML, Ko CY. The rate of bleeding complications after pharmacologic deep venous thrombosis prophylaxis: a systematic review of 33 randomized controlled trials. Arch Surg. 2006;141(8):790-7, discussion 797-9. http://dx.doi.org/10.1001/archsurg.141.8.790. PMid:16924087.
http://dx.doi.org/10.1001/archsurg.141.8...
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Estimativas do risco inicial de sangramento em cirurgia

O risco inicial de sangramento foi pouco estudado em pacientes cirúrgicos não ortopédicos. A estratificação de risco de sangramento maior foi estimada pelo American College of Chest Physicians (ACCP) nos seguintes grupos de pacientes cirúrgicos88 Gould MK, Garcia DA, Wren SM, et al. Prevention of VTE in nonorthopedic surgical patients antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2, Supl):e227S-77S. http://dx.doi.org/10.1378/chest.11-2297. PMid:22315263.
http://dx.doi.org/10.1378/chest.11-2297...
: geral/abdominal/pélvica (~1%), bariátrica (< 1%), plástica/reconstrutiva (0,5 a 1,8%), vascular (0,4 a 1,8%), cardíaca [~5% (alto risco)], torácica (1%), neurocirurgia/craniotomia (1 a 1,5%), coluna vertebral (<0,5%) e trauma grave [3,4 a 4,7% (alto risco)].

Nas cirurgias ortopédicas, as estimativas de risco inicial de sangramento na ausência de profilaxia são heterogêneas devido às características distintas das populações e das técnicas cirúrgicas utilizadas3838 Falck-Ytter Y, Francis CW, Johanson NA, et al. Prevention of VTE in orthopedic surgery patients: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2, Supl):e278S-325S. http://dx.doi.org/10.1378/chest.11-2404. PMid:22315265.
http://dx.doi.org/10.1378/chest.11-2404...
. Estima-se um risco de sangramento maior, variando de 2 a 4% nas cirurgias ortopédicas com duração acima de 45 minutos e na artroplastia bilateral de joelhos. Procedimentos menores, como artroscopias, cirurgias de ombro, mãos e pés, são considerados de menor risco de sangramento (< 2%)3939 Spyropoulos AC, Douketis JD. How i treat anticoagulated patients undergoing an elective procedure or surgery. Blood. 2012;120(15):2954-62. http://dx.doi.org/10.1182/blood-2012-06-415943. PMid:22932800.
http://dx.doi.org/10.1182/blood-2012-06-...
. As taxas de sangramento maior em pacientes submetidos a profilaxia de TEV variaram de 0,1% a 3,1% nos estudos de artroplastia de quadril e de 0,2% a 1,4% nos estudos de artroplastia de joelho, sugerindo haver pouca interferência dos anticoagulantes no risco de sangramento desses grupos de pacientes4040 Dahl OE, Quinlan DJ, Bergqvist D, Eikelboom JW. A critical appraisal of bleeding events reported in venous thromboembolism prevention trials of patients undergoing hip and knee arthroplasty. J Thromb Haemost. 2010;8(9):1966-75. http://dx.doi.org/10.1111/j.1538-7836.2010.03965.x. PMid:20586919.
http://dx.doi.org/10.1111/j.1538-7836.20...
.

Risco de sangramento em situações especiais

Trombocitopenia

As diretrizes atuais sobre profilaxia de TEV são baseadas em ensaios clínicos randomizados que excluem os indivíduos de risco potencialmente alto de sangramento, limitando, portanto, as recomendações específicas sobre farmacoprofilaxia em pacientes com trombocitopenia e/ou disfunção plaquetária4141 Tufano A, Guida A, Di Minno MN, Prisco D, Cerbone AM, Di Minno G. Prevention of venous thromboembolism in medical patients with thrombocytopenia or with platelet dysfunction: a review of the literature. Semin Thromb Hemost. 2011;37(3):267-74. http://dx.doi.org/10.1055/s-0031-1273090. PMid:21455860.
http://dx.doi.org/10.1055/s-0031-1273090...
. Essas condições estão presentes em pelo menos 25% dos indivíduos hospitalizados e são representadas por uma série de patologias, como púrpura trombocitopênica idiopática, púrpura trombocitopênica trombótica, síndrome do anticorpo antifosfolipídeo (SAF), TIH, coagulação intravascular disseminada, plaquetopenia induzida por medicamentos, insuficiência hepática, renal e medular e câncer4141 Tufano A, Guida A, Di Minno MN, Prisco D, Cerbone AM, Di Minno G. Prevention of venous thromboembolism in medical patients with thrombocytopenia or with platelet dysfunction: a review of the literature. Semin Thromb Hemost. 2011;37(3):267-74. http://dx.doi.org/10.1055/s-0031-1273090. PMid:21455860.
http://dx.doi.org/10.1055/s-0031-1273090...
. Os valores mínimos de plaquetas para a utilização da farmacoprofilaxia também não são uniformes, variando entre 50.000 e 100.000/mm3.66 Decousus H, Tapson VF, Bergmann JF, et al. Factors at admission associated with bleeding risk in medical patients: findings from the IMPROVE investigators. Chest. 2011;139(1):69-79. http://dx.doi.org/10.1378/chest.09-3081. PMid:20453069.
http://dx.doi.org/10.1378/chest.09-3081...
,99 Rocha AT, Paiva EF, Lichtenstein A, Milani R Jr, Cavalheiro CF, Maffei FH. Risk-assessment algorithm and recommendations for venous thromboembolism prophylaxis in medical patients. Vasc Health Risk Manag. 2007;3(4):533-53. PMid:17969384.,1111 Barbar S, Noventa F, Rossetto V, et al. A risk assessment model for the identification of hospitalized medical patients at risk for venous thromboembolism: the Padua Prediction Score. J Thromb Haemost. 2010;8(11):2450-7. http://dx.doi.org/10.1111/j.1538-7836.2010.04044.x. PMid:20738765.
http://dx.doi.org/10.1111/j.1538-7836.20...
,1515 Caprini JA. Thrombosis risk assessment as a guide to quality patient care. Dis Mon. 2005;51(2-3):70-8. http://dx.doi.org/10.1016/j.disamonth.2005.02.003. PMid:15900257.
http://dx.doi.org/10.1016/j.disamonth.20...
,2121 National Institute for Health and Care Excellence – NICE. Venous thromboembolism in over 16s: reducing the risk of hospital-acquired deep vein thrombosis or pulmonary embolism: NICE guideline [NG89]. London: NICE; 2019. [citado 2020 mar 30]. https://www.nice.org.uk/guidance/ng89/resources
https://www.nice.org.uk/guidance/ng89/re...
. O IMPROVE Bleeding Risk Score66 Decousus H, Tapson VF, Bergmann JF, et al. Factors at admission associated with bleeding risk in medical patients: findings from the IMPROVE investigators. Chest. 2011;139(1):69-79. http://dx.doi.org/10.1378/chest.09-3081. PMid:20453069.
http://dx.doi.org/10.1378/chest.09-3081...
considera como referência o limite de plaquetas de 50.000/mm3, enquanto a diretriz NICE2121 National Institute for Health and Care Excellence – NICE. Venous thromboembolism in over 16s: reducing the risk of hospital-acquired deep vein thrombosis or pulmonary embolism: NICE guideline [NG89]. London: NICE; 2019. [citado 2020 mar 30]. https://www.nice.org.uk/guidance/ng89/resources
https://www.nice.org.uk/guidance/ng89/re...
estabelece o ponto de corte em 75.000/mm3. O risco de sangramento espontâneo aumenta dramaticamente quando há contagens de plaquetas de < 10.000 a 20.000/mm3 e varia de acordo com a causa da trombocitopenia4141 Tufano A, Guida A, Di Minno MN, Prisco D, Cerbone AM, Di Minno G. Prevention of venous thromboembolism in medical patients with thrombocytopenia or with platelet dysfunction: a review of the literature. Semin Thromb Hemost. 2011;37(3):267-74. http://dx.doi.org/10.1055/s-0031-1273090. PMid:21455860.
http://dx.doi.org/10.1055/s-0031-1273090...
.

Hepatopatia crônica

A trombocitopenia ou disfunção plaquetária associadas a anormalidades da coagulação são comuns em pacientes com cirrose hepática4141 Tufano A, Guida A, Di Minno MN, Prisco D, Cerbone AM, Di Minno G. Prevention of venous thromboembolism in medical patients with thrombocytopenia or with platelet dysfunction: a review of the literature. Semin Thromb Hemost. 2011;37(3):267-74. http://dx.doi.org/10.1055/s-0031-1273090. PMid:21455860.
http://dx.doi.org/10.1055/s-0031-1273090...
. No entanto, esses pacientes apresentam alta incidência de trombose venosa portal e idiopática, o que significa que a coagulopatia da cirrose não protege contra a trombose4141 Tufano A, Guida A, Di Minno MN, Prisco D, Cerbone AM, Di Minno G. Prevention of venous thromboembolism in medical patients with thrombocytopenia or with platelet dysfunction: a review of the literature. Semin Thromb Hemost. 2011;37(3):267-74. http://dx.doi.org/10.1055/s-0031-1273090. PMid:21455860.
http://dx.doi.org/10.1055/s-0031-1273090...
. As situações associadas à trombocitopenia leve/moderada (> 50.000/mm3) não devem interferir nas decisões de prevenção de TEV. Na trombocitopenia grave (< 50.000/mm3), no entanto, a profilaxia deve ser considerada individualmente4141 Tufano A, Guida A, Di Minno MN, Prisco D, Cerbone AM, Di Minno G. Prevention of venous thromboembolism in medical patients with thrombocytopenia or with platelet dysfunction: a review of the literature. Semin Thromb Hemost. 2011;37(3):267-74. http://dx.doi.org/10.1055/s-0031-1273090. PMid:21455860.
http://dx.doi.org/10.1055/s-0031-1273090...
. Em uma revisão sistemática sobre tromboprofilaxia e trombocitopenia, Tufano et al.4141 Tufano A, Guida A, Di Minno MN, Prisco D, Cerbone AM, Di Minno G. Prevention of venous thromboembolism in medical patients with thrombocytopenia or with platelet dysfunction: a review of the literature. Semin Thromb Hemost. 2011;37(3):267-74. http://dx.doi.org/10.1055/s-0031-1273090. PMid:21455860.
http://dx.doi.org/10.1055/s-0031-1273090...
propõem recomendações especificas para o uso de profilaxia farmacológica (Tabela 3).

Tabela 3
Estratégia de prevenção do TEV em pacientes com cirrose e/ou trombocitopenia.

Síndrome anticorpo antifosfolipídeo (SAF)

Em pacientes com SAF e trombocitopenia, a tendência trombótica é geralmente muito superior ao risco de sangramento4141 Tufano A, Guida A, Di Minno MN, Prisco D, Cerbone AM, Di Minno G. Prevention of venous thromboembolism in medical patients with thrombocytopenia or with platelet dysfunction: a review of the literature. Semin Thromb Hemost. 2011;37(3):267-74. http://dx.doi.org/10.1055/s-0031-1273090. PMid:21455860.
http://dx.doi.org/10.1055/s-0031-1273090...
. A profilaxia de TEV deve ser avaliada nessa população, especialmente naqueles considerados de alto risco, como, por exemplo, os pacientes positivos para os três anticorpos antifosfolipídios: anticoagulante lúpico, anticardiolipina e anti ß2 glicoproteína I (triplo-positivo)4141 Tufano A, Guida A, Di Minno MN, Prisco D, Cerbone AM, Di Minno G. Prevention of venous thromboembolism in medical patients with thrombocytopenia or with platelet dysfunction: a review of the literature. Semin Thromb Hemost. 2011;37(3):267-74. http://dx.doi.org/10.1055/s-0031-1273090. PMid:21455860.
http://dx.doi.org/10.1055/s-0031-1273090...
. O Global APS Score (GAPSS) é um MAR que analisa o perfil dos anticorpos antifosfolipídios e fatores de risco cardiovascular e pode ser útil para avaliar o risco de eventos trombóticos em pacientes portadores de lúpus eritematoso sistêmico, porém ainda não foi validado4242 Lim W. Prevention of thrombosis in antiphospholipid syndrome. Hematology. 2016;2016(1):707-13. http://dx.doi.org/10.1182/asheducation-2016.1.707. PMid:27913550.
http://dx.doi.org/10.1182/asheducation-2...
.

Até 30% dos pacientes portadores de SAF podem apresentar trombocitopenia (< 100.000/ mm3), porém o sangramento é raro e normalmente está associado à SAF catastrófica, trombocitopenia imune ou naqueles que desenvolvem anticorpos contra protrombina ou outros fatores da coagulação4242 Lim W. Prevention of thrombosis in antiphospholipid syndrome. Hematology. 2016;2016(1):707-13. http://dx.doi.org/10.1182/asheducation-2016.1.707. PMid:27913550.
http://dx.doi.org/10.1182/asheducation-2...
.

Pacientes oncológicos

O câncer é um fator de risco independente e importante para o desenvolvimento de TEV4343 Farge D, Bounameaux H, Brenner B, et al. International clinical practice guidelines including guidance for direct oral anticoagulants in the treatment and prophylaxis of venous thromboembolism in patients with cancer. Lancet Oncol. 2016;17(10):e452-66. http://dx.doi.org/10.1016/S1470-2045(16)30369-2. PMid:27733271.
http://dx.doi.org/10.1016/S1470-2045(16)...
. Por outro lado, pacientes com câncer são propensos a sangramentos, associados às complicações dos tumores, frequência aumentada de procedimentos cirúrgicos e trombocitopenia associada à quimioterapia sistêmica, tornando a prevenção do TEV um grande desafio nessa população. A profilaxia do TEV deve ser considerada em pacientes hospitalizados com câncer mesmo na presença de trombocitopenia, principalmente nos que têm múltiplos fatores de risco para TEV4343 Farge D, Bounameaux H, Brenner B, et al. International clinical practice guidelines including guidance for direct oral anticoagulants in the treatment and prophylaxis of venous thromboembolism in patients with cancer. Lancet Oncol. 2016;17(10):e452-66. http://dx.doi.org/10.1016/S1470-2045(16)30369-2. PMid:27733271.
http://dx.doi.org/10.1016/S1470-2045(16)...
,4444 Key NS, Bohlke K, Falanga A. Venous thromboembolism prophylaxis and treatment in patients with cancer: ASCO clinical practice guideline update summary. J Oncol Pract. 2019;15(12):661-4. http://dx.doi.org/10.1200/JOP.19.00368.
http://dx.doi.org/10.1200/JOP.19.00368...
. Nos pacientes que apresentam valores de plaquetas > 80.000/mm3, recomenda-se o uso de farmacoprofilaxia em dose padrão4343 Farge D, Bounameaux H, Brenner B, et al. International clinical practice guidelines including guidance for direct oral anticoagulants in the treatment and prophylaxis of venous thromboembolism in patients with cancer. Lancet Oncol. 2016;17(10):e452-66. http://dx.doi.org/10.1016/S1470-2045(16)30369-2. PMid:27733271.
http://dx.doi.org/10.1016/S1470-2045(16)...
,4444 Key NS, Bohlke K, Falanga A. Venous thromboembolism prophylaxis and treatment in patients with cancer: ASCO clinical practice guideline update summary. J Oncol Pract. 2019;15(12):661-4. http://dx.doi.org/10.1200/JOP.19.00368.
http://dx.doi.org/10.1200/JOP.19.00368...
. Se a contagem de plaquetas estiver abaixo de 80.000/mm3, a conduta deve ser considerada individualmente4343 Farge D, Bounameaux H, Brenner B, et al. International clinical practice guidelines including guidance for direct oral anticoagulants in the treatment and prophylaxis of venous thromboembolism in patients with cancer. Lancet Oncol. 2016;17(10):e452-66. http://dx.doi.org/10.1016/S1470-2045(16)30369-2. PMid:27733271.
http://dx.doi.org/10.1016/S1470-2045(16)...
,4444 Key NS, Bohlke K, Falanga A. Venous thromboembolism prophylaxis and treatment in patients with cancer: ASCO clinical practice guideline update summary. J Oncol Pract. 2019;15(12):661-4. http://dx.doi.org/10.1200/JOP.19.00368.
http://dx.doi.org/10.1200/JOP.19.00368...
. Recomenda-se monitoramento cuidadoso quanto a efeitos indesejáveis relacionados ao uso do anticoagulante versus risco de TEV4343 Farge D, Bounameaux H, Brenner B, et al. International clinical practice guidelines including guidance for direct oral anticoagulants in the treatment and prophylaxis of venous thromboembolism in patients with cancer. Lancet Oncol. 2016;17(10):e452-66. http://dx.doi.org/10.1016/S1470-2045(16)30369-2. PMid:27733271.
http://dx.doi.org/10.1016/S1470-2045(16)...
,4444 Key NS, Bohlke K, Falanga A. Venous thromboembolism prophylaxis and treatment in patients with cancer: ASCO clinical practice guideline update summary. J Oncol Pract. 2019;15(12):661-4. http://dx.doi.org/10.1200/JOP.19.00368.
http://dx.doi.org/10.1200/JOP.19.00368...
. No caso de contraindicação à profilaxia farmacológica, deve-se otimizar o uso da profilaxia mecânica.

Insuficiência Renal Crônica (IRC)

A IRC é uma doença de caráter paradoxal do ponto de vista da coagulação, pois, ao mesmo tempo em que aumenta o risco de TEV devido à injúria/disfunção endotelial, hiperreatividade plaquetária inicial, aumento da formação de fibrina e diminuição da atividade do sistema fibrinolítico, aumenta o risco de hemorragia maior com a piora progressiva da função renal e consequente decréscimo da adesão e agregação plaquetária4545 Aursulesei V, Costache II. Anticoagulation in chronic kidney disease: from guidelines to clinical practice. Clin Cardiol. 2019;42(8):774-82. http://dx.doi.org/10.1002/clc.23196. PMid:31102275.
http://dx.doi.org/10.1002/clc.23196...
. Embora o IMPROVE Bleeding Risk Score66 Decousus H, Tapson VF, Bergmann JF, et al. Factors at admission associated with bleeding risk in medical patients: findings from the IMPROVE investigators. Chest. 2011;139(1):69-79. http://dx.doi.org/10.1378/chest.09-3081. PMid:20453069.
http://dx.doi.org/10.1378/chest.09-3081...
pontue a IRC de acordo com a sua gravidade (um ponto para IRC moderada e 2,5 pontos para IRC severa), os MARs de TEV para pacientes clínicos (Diretriz Brasileira de Prevenção-de TEV99 Rocha AT, Paiva EF, Lichtenstein A, Milani R Jr, Cavalheiro CF, Maffei FH. Risk-assessment algorithm and recommendations for venous thromboembolism prophylaxis in medical patients. Vasc Health Risk Manag. 2007;3(4):533-53. PMid:17969384. e os escores de Padua1111 Barbar S, Noventa F, Rossetto V, et al. A risk assessment model for the identification of hospitalized medical patients at risk for venous thromboembolism: the Padua Prediction Score. J Thromb Haemost. 2010;8(11):2450-7. http://dx.doi.org/10.1111/j.1538-7836.2010.04044.x. PMid:20738765.
http://dx.doi.org/10.1111/j.1538-7836.20...
, Genebra1313 Chopard P, Spirk D, Bounameaux H. Identifying acutely ill medical patients requiring thromboprophylaxis. J Thromb Haemost. 2006;4(4):915-6. http://dx.doi.org/10.1111/j.1538-7836.2006.01818.x. PMid:16634771.
http://dx.doi.org/10.1111/j.1538-7836.20...
e IMPROVE1212 Spyropoulos AC, Anderson FA Jr, Fitzgerald G, et al. Predictive and associative models to identify hospitalized medical patients at risk for VTE. Chest. 2011;140(3):706-14. http://dx.doi.org/10.1378/chest.10-1944. PMid:21436241.
http://dx.doi.org/10.1378/chest.10-1944...
) e pacientes cirúrgicos (escore de Caprini1515 Caprini JA. Thrombosis risk assessment as a guide to quality patient care. Dis Mon. 2005;51(2-3):70-8. http://dx.doi.org/10.1016/j.disamonth.2005.02.003. PMid:15900257.
http://dx.doi.org/10.1016/j.disamonth.20...
e Rogers1616 Rogers SO Jr, Kilaru RK, Hosokawa P, Henderson WG, Zinner MJ, Khuri SF. Multivariable predictors of postoperative venous thromboembolic events after general and vascular surgery: results from the patient safety in surgery study. J Am Coll Surg. 2007;204(6):1211-21. http://dx.doi.org/10.1016/j.jamcollsurg.2007.02.072. PMid:17544079.
http://dx.doi.org/10.1016/j.jamcollsurg....
) não incluem a IRC como fator de risco de trombose. Esse equilíbrio frágil entre o risco aumentado de TEV e o risco de hemorragia torna a farmacoprofilaxia do TEV um desafio particular especialmente naqueles com IRC avançada (clearance de creatinina 15-29 mL/min) ou falência renal terminal (clearance de creatinina < 15 mL/min), por várias razões, incluindo o fato de não haver um MAR específico para esse grupo de pacientes4545 Aursulesei V, Costache II. Anticoagulation in chronic kidney disease: from guidelines to clinical practice. Clin Cardiol. 2019;42(8):774-82. http://dx.doi.org/10.1002/clc.23196. PMid:31102275.
http://dx.doi.org/10.1002/clc.23196...
.

Com relaçao às opções de profilaxia farmacológica, as evidências são insuficientes para concluir que o uso de HNF na dose de 5.000 UI três vezes/dia aumente o risco de eventos hemorrágicos graves e menores em pacientes com clearence de creatinina < 30 mL/min em comparação a pacientes sem disfunção renal severa ou que a enoxaparina aumente significativamente o risco de sangramento maior em comparação a HNF nesse perfil de pacientes4646 Singh S, Haut ER, Brotman DJ, et al. Pharmacologic and mechanical prophylaxis of venous thromboembolism among special populations. Rockville: Agency for Healthcare Research and Quality; 2013..

Como proceder no caso de pacientes com aumento do risco de sangramento

No caso dos pacientes hospitalizados que apresentam alto risco de TEV associado a alto risco de sangramento ou que têm contraindicação do uso de anticoagulantes, os métodos mecânicos de prevenção de TEV, como compressão pneumática intermitente, meias de compressão graduadas e bomba venosa plantar são recomendados66 Decousus H, Tapson VF, Bergmann JF, et al. Factors at admission associated with bleeding risk in medical patients: findings from the IMPROVE investigators. Chest. 2011;139(1):69-79. http://dx.doi.org/10.1378/chest.09-3081. PMid:20453069.
http://dx.doi.org/10.1378/chest.09-3081...
. Quando as opções de profilaxia mecânica são utilizadas, a transição para um agente farmacológico deve ser considerada assim que o risco de sangramento se tornar baixo ou for revertido.

CONCLUSÃO

A adequação do uso de farmacoprofilaxia deve estar alinhada com a minimização do risco de sangramento para que os pacientes classificados como de alto risco de desenvolvimento de TEV obtenham benefício clínico real da tromboprofilaxia.

Diversas diretrizes de prevenção de TEV orientam sobre os principais fatores implicados no risco de sangramento. No entanto, até o momento, o único MAR validado que permite a identificação dos pacientes clínicos na admissão hospitalar sob risco de sangramento é o IMPROVE Bleeding Risk Score66 Decousus H, Tapson VF, Bergmann JF, et al. Factors at admission associated with bleeding risk in medical patients: findings from the IMPROVE investigators. Chest. 2011;139(1):69-79. http://dx.doi.org/10.1378/chest.09-3081. PMid:20453069.
http://dx.doi.org/10.1378/chest.09-3081...
,3636 Rosenberg DJ, Press A, Rosenberg DJ, et al. External validation of the IMPROVE Bleeding Risk Assessment Model in medical patients. Thromb Haemost. 2016;116(3):530-6. http://dx.doi.org/10.1160/TH16-01-0003. PMid:27307054.
http://dx.doi.org/10.1160/TH16-01-0003...
. Os pacientes com pontuação < 7 podem receber farmacoprofilaxia com segurança66 Decousus H, Tapson VF, Bergmann JF, et al. Factors at admission associated with bleeding risk in medical patients: findings from the IMPROVE investigators. Chest. 2011;139(1):69-79. http://dx.doi.org/10.1378/chest.09-3081. PMid:20453069.
http://dx.doi.org/10.1378/chest.09-3081...
. Por outro lado, pacientes com alto risco de sangramento (pontuação ≥ 7), mas que apresentam simultaneamente alto risco de TEV, devem ter as decisões relativas à profilaxia avaliadas de forma individualizada e dinâmica ao longo da internação, até a alta hospitalar. Nos pacientes submetidos à cirurgia, é necessário considerar o potencial risco de sangramento do procedimento em conjunto com os fatores de risco individuais para definir a melhor estratégia de prevenção de TEV.

  • Como citar: Chindamo MC, Marques MA. Avaliação do risco de sangramento na profilaxia do tromboembolismo venoso. J Vasc Bras. 2021;20:e20200109. https://doi.org/10.1590/1677-5449.200109
  • Fonte de financiamento: Nenhuma.
  • O estudo foi realizado no Hospital Barra D'Or - Rede D'Or São Luiz, Rio de Janeiro, RJ, Brasil.

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Datas de Publicação

  • Publicação nesta coleção
    28 Abr 2021
  • Data do Fascículo
    2021

Histórico

  • Recebido
    17 Jun 2020
  • Aceito
    13 Out 2020
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