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![Heparins
• Compared with placebo, UFH was associated with a
significantly reduced risk of DVT (risk ratio [RR] 0.33; 95%
CI 0.26-0.42) and PE (RR 0.64; 95% CI 0.50-0.82)
• Compared with placebo, LMW reduces risk of DVT (RR
0.56; 95% CI 0.45-0.70) and PE (RR 0.37; 95% CI 0.21-0.64)
• When directly compared with UFH, LMW heparin was
associated with a significantly lower risk of DVT (RR 0.68;
95% CI 0.52-0.88) and injection site hematoma (RR 0.47;
95% C, 0.36-0.62)
• Neither UFH nor LMW heparin reduced mortality.
• Has similar risk of bleeding or thrombocytopenia](https://image.slidesharecdn.com/thromboprophylaxishabtam-240815203953-698e65ba/75/The-basics-about-thromboprophylaxis-by-misale-haile-22-2048.jpg)
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The basics about thromboprophylaxis by misale haile
- 1.
- 2. Introduction • PTE isthe most common preventable cause of hospital death. • 10% of inpatient death • Responsible for 150K-200K deaths per year in US • VTE occurs in 10-80% of hospitalized medical and surgical patients • 60% VTE cases occur in hospitalized, recently discharged (within3 months) or nursing home patients • Hospitalization has 130 times more risk of VTE
- 4. Risk factors forVTE in medical patients • Age >60 years • Previous VTE, • Cancer, • Prolonged Immobility, • Inherited or acquired hypercoagulable states • ICU admissions • Medical conditions like heart failure, stroke, COPD, sepsis, IBD • Pregnancy
- 5. Risk assessment • Low,Moderate, High risk • Padua prediction score • IMPROVE risk score – IMPROVE study
- 6. Padua prediction score •Prospective cohort, 1180 medical patients followed up to 90 days, 2007-2008, Padua, Italy • Primary outcome: risk of VTE in low and high risk patients, risk of VTE in high risk patients given adequate thromboprophylaxis in comparison with those who did not. • Findings • Low risk – 0.3% risk of VTE • High risk receiving adequate thromboprophylaxis – 2.2% risk of VTE • High risk not receiving adequate thromboprophylaxis – 11% risk of VTE • Conclusion: adequate thromboprophylaxis in high-risk patients during hospitalization leads to longstanding protection against thromboembolic events with a low risk of bleeding Barbar S, 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 Nov;8(11):2450-7
- 7.
- 8. Padua prediction score •Padua score <4 low risk • Pharmacologic thromboprophylaxis not strongly indicated • Consider mechanical thromboprophylaxis • Padua score ≥4 high risk • Pharmacologic thromboprophylaxis indicated • Use mechanical thromboprophylaxis if high risk of bleeding
- 9. IMPROVE study • Prospectivecohort study of physician practices in the provision of prophylaxis against venous thromboembolism (VTE) in hospitalized 15,000 medical patients from 56 hospitals in 11 countries, 2001-2005 • Key endpoints: type and duration of prophylaxis, death, clinically apparent VTE, and bleeding within 3 months of hospital discharge
- 10. IMPROVE study • Therate of VTE within 90 days of admission • 0.4 - 0.5% if none of these risk factors was present • 8 – 11% in those with the highest risk scores • In-hospital bleeding risk • Scored 0 to 15 In-hospital bleeding risk Score 1 0.5% Score 4 1.6% Score 7 4.1% Score 10 9.7% Score 15 14%
- 11.
- 12. Prevention of VTE •Primary prophylaxis • Pharmacologic or mechanical methods to prevent VTE • Secondary prophylaxis • Early detection and treatment of subclinical DVT • Objective screening tests • However, no single screening method (eg, contrast venography, venous ultrasound, MRI venography) has found universal acceptance for secondary prevention.
- 13. Rationale for thromboprophylaxis 1.VTE is common in hospitalized patients 2. VTE is fatal 3. VTE is preventable safely and inexpensively 4. VTE prevention is a standard of care
- 14. VTE prophylaxis • Costeffective method of preventing VTE • Appropriate VTE prophylaxis not often offered
- 15. VTE prophylaxis • ReducesVTE in hospitalized patients • Reduces mortality in surgical patients • Do not reduce overall mortality in medical patients • Comorbidities
- 16. VTE prophylaxis indications •ICU admissions • Medical patients older than 40 years of age who have limited mobility for ≥3 days, and have at least on thrombotic risk 1. Congestive heart failure, 2. Acute exacerbations of chronic pulmonary disease, 3. Stroke with paralysis, 4. Sepsis 5. Inflammatory bowel disease, 6. High degree of immobility, 7. Age >75 years, 8. Cancer 9. Previous episode of VTE
- 17. Ideal VTE prophylacticmethods • Ease of administration • Effective • Safety • Cost effective • No need for laboratory monitoring • Good compliance by physicians, patients
- 18. VTE prophylaxis options •Low dose unfractionated heparin, • Low molecular weight (LMW) heparins, • Fondaparinux • Intermittent pneumatic compression (IPC) and/or graduated compression stockings (GCS) • Oral factor Xa or factor IIa (thrombin) inhibitors
- 19. DVT prophylaxis • Preventionbetter than treatment – 40 – 60% efficacy • Mechanical methods – Early postop ambulation, Physiotherapy – Graded compression stockings – Intermittent pneumatic leg compression • Anticoagulants. Low-dose UFH or LMWH is the most common form of in-hospital prophylaxis – UFH 7500 unit SC BID, or 5000 unit SC TID – LMWH
- 21. Pharmacologic thromboprophylaxis • UFH, LMWheparin and fondaparinux are all superior to placebo in preventing venous thromboembolism (VTE)
- 22. Heparins • Compared withplacebo, UFH was associated with a significantly reduced risk of DVT (risk ratio [RR] 0.33; 95% CI 0.26-0.42) and PE (RR 0.64; 95% CI 0.50-0.82) • Compared with placebo, LMW reduces risk of DVT (RR 0.56; 95% CI 0.45-0.70) and PE (RR 0.37; 95% CI 0.21-0.64) • When directly compared with UFH, LMW heparin was associated with a significantly lower risk of DVT (RR 0.68; 95% CI 0.52-0.88) and injection site hematoma (RR 0.47; 95% C, 0.36-0.62) • Neither UFH nor LMW heparin reduced mortality. • Has similar risk of bleeding or thrombocytopenia
- 23. Heparins • Reduce DVTby 60% • Reduce PTE by 42% • Treatment with the heparin preparations resulted in a significant increase in major hemorrhage (RR 2.18; 95% CI 1.28-3.72) and minor hemorrhage (RR 1.74; 95% CI 1.26-2.41) when compared with placebo or no treatment
- 24. UFH • When comparedwith placebo, UFH given in a dose of 5000 units three times daily was significantly more effective in preventing DVT (RR 0.27; 95% CI 0.20-0.36) than UFH given in a dose of 5000 units twice daily (RR 0.52; 95% CI 0.28-0.96)
- 25. Dalteparin • PROTECT trial •Dalteparin 5000 units/day was not superior to unfractionated heparin (5000 units twice daily) in the prevention of proximal DVT, but the incidence of PE was significantly reduced in the dalteparin- treated group. • The incidence of major bleeding and of death was similar in the two groups Cook D, Meade M, et al . Dalteparin versus unfractionated heparin in critically ill patients. PROTECT trial. N Engl J Med 2011; 364:1305.
- 26. Extended duration prophylaxis •4 weeks vs standard regimen • EXCLAIM trial • Enoxaparin 40mg SC daily for 28 days Vs placebo after 10 days of standard thromboprophylaxis • Extended duration prophylaxis has significant reduction of VTE (2.5% Vs 4%) • Significant increase in major bleeding events (0.8 Vs 0.3) • Benefit observed in F, age >75, immobilized • ADOPT trial • Apixaban 2.5mg BID for 3 days Vs enoxaparin 40mg SC daily for 6-14 days • Efficacy is not different (2.7% for apixaban group Vs 3.06% in enoxaparin group, RR 0.87, 95% CI 0.63-1.25) • Major bleeding in apixaban group (0.47% Vs 0.19%, RR 2.58, 95% CI 1.02-7.24) • MAGELLAN study • Enoxaparin 40mg SC daily for 10 days followed by placebo Vs extended prophylaxis with rivaroxaban 10mg daily for 35 ± 4 days • Efficacy outcome event less in Rivaroxaban group • Safety outcome event more in rivaroxaban group • Conclusion: routine administration of post-discharge prophylaxis is not likely to be beneficial to the patients admitted for medical illness 1. Hull RD, Schellong SM, Tapson VF, et al. Extended-duration venous thromboembolism prophylaxis in acutely ill medical patients with recently reduced mobility: a randomized trial. Ann Intern Med 2010; 153:8. 2. Goldhaber SZ, Leizorovicz A, Kakkar AK, et al. Apixaban versus enoxaparin for thromboprophylaxis in medically ill patients. N Engl J Med 2011; 365:2167. 3. Cohen AT, Spiro TE, Büller HR, et al. Rivaroxaban for thromboprophylaxis in acutely ill medical patients. N Engl J Med 2013; 368:513. 4. Sharma A, Chatterjee S, Lichstein E, Mukherjee D. Extended thromboprophylaxis for medically ill patients with decreased mobility: does it improve outcomes? J Thromb Haemost 2012; 10:2053. 5. Albertsen IE, Larsen TB, Rasmussen LH, et al. Prevention of venous thromboembolism with new oral anticoagulants versus standard pharmacological treatment in acute medically ill patients: a system
- 27. Warfarin • Not recommended •Anticoagulant effect is delayed • Drug interactions with antibiotics and other drugs • Achieving target INR difficult in hospitalized medical patients due to comorbidities (liver dysfunction)
- 28. Aspirin • Reduces VTEby 20% • Not recommended
- 29. Mechanical methods • Indicatedfor patients with high risk of bleeding or have bleeding lesions like ICH, bleeding peptic ulcer • Shift to pharmacologic methods as soon as possible • Intermittent pneumatic compression (IPC) • Graduated compression stockings (GCS) • Venous foot pump (VFP)
- 30. Intermittent pneumatic compression • Enhanceblood flow in the deep veins prevent venous stasis • Reduces plasminogen activator inhibitor-1 (PAI-1) increasing endogenous fibrinolytic activity • Contraindication: ischemic PAD
- 31. Graduated compression stockings •GCS in medical patients, with or without low dose low molecular weight (LMW) heparin , found no added mortality benefit with the use of LMW heparin Kakkar AK, Cimminiello C, Goldhaber SZ, et al. Low-molecular-weight heparin and mortality in acutely ill medical patient s. N Engl J Med 2011; 365:2463.
- 32. Recommendations • For hospitalizedmedical patients without obvious risk factors for VTE, we suggest that anticoagulation not be employed ( Grade 1B ) • For most patients who are hospitalized with an acute medical illness, have at least one risk factor for VTE, and do not have an increased risk of bleeding, we recommend the use of prophylactic anticoagulation ( Grade 1B ) • VTE prophylaxis should typically continue until the patient is discharged from the hospital. We suggest against extending the duration of thromboprophylaxis beyond the period of the acute hospital stay (Grade 2B)