DVT Prophylaxis of the Medical Patient

1. DVT Prophylaxis of the Medical Patient Akella Chendrasekhar MD

2. Case • Mr. Smith- 71 y/o man admitted to general medicine ward service. • HPI: gradually increased sob over 3 days assoc. with new productive cough, rhinorrhea, and fatigue. • PMH: COPD, CHF (LVEF 35%), CRI (creat 2.5) • ROS: No h/o DVT/PE. • PE: VSS with SPO2 93% on RA • Barrel chested, b/l expiratory wheezes, prolonged expiratory phase, • CXR: hyperexpanded, no infiltrate, consolidation or edema. • DX: COPD Exacerbation

3. Does this patient need DVT prophylaxis? • Yes with LMW heparin • Yes with Heparin SQ BID • No, the risk of heparin complications is too high • I really don’t know

4. Does this man need DVT prophylaxis? • Why worry about VTE in inpatients? • What is the prevalence of DVT/PE in hospitalized medical patients? • Is this man at risk for venous thromboembolism? • What are effective methods of prophylaxis? • What adjustments need to be made based on his history of renal insufficiency?

5. Importance • What % of all hospital related deaths due to fatal PE? • 7-10% • What % of these pts had NO premorbid symptoms? • 70-90% • 200,000 potentially preventable annual deaths due to PE in the US Sandler DA JR Soc Med 1989; 82, Lindblad B Br Med J 1991; 302.

6. Prevalence in Medical Pts • 3 large-scale randomized studies (5500 medically ill patients) • DVT identified w/ screening studies • Patients receiving no prophylaxis: • VTE 11-15% of patients • Proximal DVT- 4-5% of patients • Rates similar to moderate-high risk general surgery patients. • Samana, MM NEJM, 1999; Leizorovicz, A Circulation 2004; Cohen, AT J Thromb Haemost, 2003.

7. Prevalence ACCP Guidelines, Chest. 2005.

8. Prevalence Pendleton, R. Amer J. Hematology 2005.

9. Prevalence • 3 out of 4 hospital pts dying from PE have NOT had recent surgery… • 2.5% of medical patients immobilized with multiple clinical problems suffer fatal PE. • National DVT Free Registry • 60% of patients dx with acute DVT were in the peri-hospitalization period • 60% of cases were in non-surgical patients! • Haas, S. Seminars in Thrombosis and Haemostasis, 2002; Goldhaber, SZ Am J Cardiol 2004.

10. Risk Factors • Heterogeneous population! • Need to consider: • Acute medical condition (MI, pneumonia, etc.) • Underlying risk factors (h/o VTE, estrogen use, etc.) • Medical interventions (central venous catheters, chemotherapy, etc.) • Relative contribution of various risk factors still being defined.

11. Risk Factors • Acute medical conditions well accepted as high risk: • MI (24% VTE risk) • Decompensated CHF (40% VTE risk) • Acute Stroke (30-75% VTE risk) • Spinal Cord Injury (up to 100%) • MICU admission (13-33*% VTE risk, *½ of these were proximal leg vein thromboses) • Central venous catheters (25-46% VTE risk) • Malignancy • Haas, S. Seminars in Thrombosis and Hemostasis, 2002; Pendleton, Amer J Hematology, 2005.

12. Abstracted from Pendleton, R. Amer J Hemat 2005.

13. Current Rates of Prophylaxis • IMPROVE study • Ongoing multinational observational cohort study in acutely ill medical patients • Only 34% of potentially at risk patients are receiving any prophylaxis! • Only ½ of patients who would have met criteria used for MEDENOX study received any VTE prophylaxis. Anderson FA, IMPROVE; Blood 2003.

14. What Should We Use for Prophylaxis? • Mechanical compression devices? (compression stockings, IPC devices) • Unfractionated heparin BID? • Unfractionated heparin TID? • Low Molecular Weight Heparin? (Enoxaparin, Daltaparin) • Fondaparinux?

15. What Do We Know About Prophylaxis? • What are the most common regimens in the US? • UFH BID, mechanical compression devices • Which regimens have the least data to support them? • UFH BID, mechanical compression devices • What are characteristics of the ideal prophylaxis regimen? • Effective • Safe • Cost-effective

16. Key VTE Prevention Trials **MEDENOX study included 20 mg enoxaparin arm which was no more effective than placebo. Pendleton, R. Amer J. Hemat. 2005

18. *Remember that MEDENOX found enoxaparin 20 mg no more effective than placebo, therefore calling into doubt efficacy of bid heparin dosing.

19. How did we do at Wyckoff Heights Medical Center?

20. Initial evaluation of DVT/PE risk in hospitalized surgical patients has become the standard of care. • As the patient is hospitalized and his/her condition evolves so does the DVT/PE risk.

21. Hypothesis • In the absence of changing level of care, the DVT/PE risk does change in hospitalized surgical patients.

22. Methods • Census based retrospective data analysis of 96 patients admitted to a 350 bed community hospital in Brooklyn, NY. • Hospital policy requires DVT/PE assessment of all patients upon admission. • Surgical patients DVT/PE risks were re-evaluated at variable times over a 1 month interval ranging from 1 day to 78 days post-admission. • This re-evaluation was done using the same hospital risk-assessment-score as was completed upon admission. • Risk assessment was performed using the hospital scoring system [1 = low risk, 2 = moderate risk, 3 = high risk, 4 = very high risk]. • Patients with DVT/PE were excluded from the analysis.

23. Data • Data was collected for 53 men, 43 women. • Gender did not correlate with DVT/PE risk. • Mean age: 60 years old.

24. Results • In the absence of changing level of care, 76/96 patients’ DVT/PE risk category changed as these patient’s were hospitalized. • Initial prophylaxis in the very high risk group was significantly lower compared to other groups. • The appropriateness of prophylaxis upon re-assessment was significantly reduced in ¾ risk groups.

25. Appropriateness of Prophylaxis Table 1: Statistical difference between Appropriateness of Initial vs. Re-assessment prophylaxis.

26. Figure 1: Appropriateness of Initial vs. Reassessment Prophylaxis.

27. Risk level change Figure 3: Risk level at Reassessment Figure 2: Risk level at Initial Assessment

28. Conclusion 1.) DVT/PE risk should be re-assessed on a regular basis as risk categorization frequently changes. 2.) High risk patients should be closely monitored as many are being under-treated.

29. When did this change in risk take place?

30. DVT risk score change over hospital days

31. DVT risk category change over hospital days

32. What in the risk assessment caused the increase in risk for DVT?

33. Increase in risk factors seen • Sepsis • Increased from 60 % to 85 % day 23 • Planned major surgery change in risk • Change day 23 • Planned minor surgery change in risk • Day 1 2 • Duration of bed rest change in risk • Day 3 4

34. Complications of Prophylaxis • Bleeding • Major bleeding rates no different from placebo in major trials w/ enoxaparin, dalteparin, and fondaparinux (rates 0.2-1.7%) • HIT • Develops in 1.4% of medically ill pts exposed to preventive doses of UFH. • Potentially catastrophic- thrombosis rates as high as 60%. • LMWH’s 8-10X’s less likely to cause HIT. • Fondaparinux does not cause HIT. Girolami, B. Blood 2003; Warkentin TE, Br J Haematol 2003. Pendleton, R. Am J Hematol 2005.

35. When do we see the greatest risk of bleeding complications with prophylaxis? • Heart failure patients • Post surgical patients • Renal failure patients • I don’t know

36. Special Populations • Obesity • Renal Insufficiency • Elderly

37. Obesity • Anti Xa levels with fixed dose LMWH regimens correlate negatively with BMI in critically ill patients. (Priglinger U, 2003) • Standard prophylactic regimens twice as likely to fail in orthopedic pts with BMI >32. • BMI >32 VTE rate 32% vs 17% for BMI <32. (Samama, MM, 1995) • Non-randomized study in bariatric surg pts- suggested decreased DVT rates w/ enoxaparin 40 mg bid vs 30 mg bid. (Scholten, DJ, 2002) • No data to guide adjustments in therapy. • Options include: • Use standard dose • Add mechanical measures • Empiric dose adjustments

38. Renal Insufficiency • Delayed renal clearance of LMWH’s and Fondaparinux problematic. • Lack of outcomes based data. • FDA approved enoxaparin 30 mg qd for pts with creat clearance <30 ml/min based on pharmacokinetic data alone. • Additional options include UFH, mechanical devices.

39. Patients with HIT • Avoid UFH or LMWH’s. • Direct thrombin inhibitor- Argatroban to continue until platelet count increases to over 100 k • Remember thrombosis risk is still elevated even after stopping heparin.

40. Elderly Patients • Mahe et al. monitored anti-Xa levels in 68 consecutive hospitalized elderly patients (mean age 82) receiving enoxaparin for prophylaxis. • By day 2 over half had levels in the therapeutic range. • Lack of safety data with use of UFH as well. • Lack of outcomes data. • Consider empiric dose reduction or use of mechanical devices alone for elderly patients with low body weight and/or marginal creatinine clearance (30-60 ml/min). Mahe, I, Pathophysiol Haemost Thromb 2002., Pendleton R, Am J Hemat 2005.

41. Take Home Points • The majority of hospitalized medical patients are at increased risk for VTE. • In the absence of contraindicatons, prophylaxis should be provided for patients based on assessment of risks. • Risk changes during hospitalization and needs to be assessed. • Safe and Effective preventive regimens include: • Enoxaparin 40 mg SC daily • Daltaparin 5000 IU SC daily • Fondaparinux 2.5 mg sc daily • UFH 5000 units SC every 8hrs *Must use clinical judgement for unique patient groups with lack of data.