A Review: Venous Thromboembolism Prophylaxis. Ryan P. Merkow, MD University of Colorado Denver Department of Surgery 8/17/09

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1 A Review: Venous Thromboembolism Prophylaxis Ryan P. Merkow, MD University of Colorado Denver Department of Surgery 8/17/09

2 Objectives Why should we care? Epidemiology Risk Factors Pharmacology Clinical guidelines

3 Why Should We Care? Among > 7 million discharges 1 : Second most common complication Second most common cause of excess LOS Third most common cause of excess mortality Without prophylaxis, 10 80% will have VTE Abundance of evidence that prophylaxis can reduce VTE VTE prophylaxis reduces overall healthcare costs 2 1 Zhan et al., JAMA Avorn et al., Circulation 2004.

4 Why Should We Care?

5 Epidemiology High prevalence without prophylaxis 1,2,3 Fatal PE in % in general surgery without prophylaxis 1, 2 1 Nicolaides et al., Br J Surg Geerts et al., Chest Collins et al., NEJM 1988.

6 Epidemiology International Perspective Cohen et al., Lancet 2008.

7 Risk Factors

8 Pharmacology - Heparin Sulfated polysaccharide MW ,000 Da Binds antithrombin III Only 1/3 molecules bind ATIII Inhibits IIa, Xa Also bind platelets, macrophages, endothelial cells Hirsh et al., Chest 2004.

9 Pharmacology Low Molecular Weight Heparin Depolymerized UFH MW 4,000 5,000 Da Binds antithrombin III Affinity mostly for Xa Reduced binding to proteins, cells Hirsh et al., Chest 2004.

10 UFH vs. LMWH

11 Clinical Guidelines Goal: to prevent a common, complicated, potentially devastating, and costly problem Simple answers rarely provide adequate solutions to complicated problems Thousands of studies over 40 years Different methodologies, study populations, inclusion/exclusion criteria, type of prophylaxis American College of Chest Physicians Evidence Based Clinical Practice Guidelines

12

13 Clinical Guidelines General surgery Bariatric surgery Laparoscopy Trauma Surgical oncology

14 Clinical Guidelines

15 General Surgery Does VTE prophylaxis reduce events? Collins et al., NEJM 1988 Meta-analysis of 46 randomized clinical trials LDUH (BID or TID) vs. None after major operations DVT: 22% to 9%; OR 0.3: NNT 7 Symptomatic PE: 2.0% to 1.3%; OR 0.5: NNT 143 Fatal PE: 0.8% to 0.3%; OR 0.4; NNT 182

16 General Surgery What regimen is best? LMWH vs. UFH: Meta-analysis ( ), 51 studies In double blind studies, no difference in DVT, PE, death, hemorrhage, hematoma or transfusion Recommendation: LDUH or LMWH Mismetti et al., Br J Surg 2001.

17 Bariatric Surgery Incidence DVT: 0.2%-5.4% PE: 0.1% VTE: 3.4/1000 discharges Optimal regimen, dosing, timing unknown Recommendation: treat like mod/high risk surgery patients LDUH TID, LMWH at approp dose Mason et al., Obes Surg Poulose et al., Am Surg Flum et al., NEJM 2009.

18 Laparoscopy Competing factors: Surgical trauma less Shorter hospital stays Operating times longer Pneumoperitoneum, reverse Trendelenburg VA NSQIP ,771 patients Multivariable analysis Laparoscopy least risk Gangireddy, Henderson et al., J Vasc Surg 2007

19 Laparoscopy Risk extremely low No difference between groups Recommendation: no prophylaxis except early mobilization Geerts et al., Chest 2008.

20 Trauma Incidence Among the highest VTE risk DVT risk exceeds 50% without prophylaxis PE 3 rd most common cause of death for pts surviving beyond 24 hours With prophylaxis in high risk patient DVT 0.02% - 3.9% PE 0.01% 0.8% Geerts et al., NEJM 1994 Knudson et al., Ann Surg 2004 Cothren et al., World J Surg 2007

21 Trauma Randomized, double blind controlled trial N = 344 UFH BID vs. Enoxaparin Given <36 hrs No differences between groups No differences in bleeding (1.7% overall) HIT x 2 in UFH group Geerts et al., NEJM 1996.

22 Surgical Oncology Cancer increases risk of VTE by 4-6 times compared to those without cancer Cancer patients represent 15-20% of all those with thrombosis Agnelli et al., Ann Surg 2006

23 Surgical Oncology UFH vs. LMWH No difference in VTE Recommendation: at this time, either is adequate Mismetti et al., Br J Surg 2001.

24 Mechanical Prophylaxis Graduated compression stockings, intermittent pneumatic compression, venous foot pump No randomized trials in general surgery, most studies small, no standardized methods Appear to have an additive effect with pharmacologic prophylaxis Must be used correctly Recommendations: Use in mod/high risk patients, and in patients at high risk for bleeding

25 Summary * LMWH at appropriate weight based dose Geerts et al., Chest 2008.

26 Our Colleagues Sara Cheng, MD, PhD, Dept of Anesthesiology Randomized, prospective, blinded trial: SQ heparin vs. intravenous heparin (PTT goal 40-45) in post surgical SICU patients Hypothesis: Intravenous Goal-directed heparin is more appropriate than SQ heparin for preventing VTE in SICU patients. Critically ill patients do not absorb heparin, and have variable heparin requirements

27 Conclusions Surgery patients are at significant risk for VTE Prophylaxis reduces this risk Physicians and hospitals are evaluated on these adverse events Hospitals should develop standardized protocols to ensure patients receive the appropriate VTE prophylaxis

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