Auto-Anticoagulation and VTE Prophylaxis in Cirrhosis: Clinical Insights and Case Analysis

1. Auto Anti-coagulation and VTE Prophylaxis Hilary Rowe, BScPharm VIHA Pharmacy Resident 2009-10 Internal Medicine Rotation November 5th, 2009

2. Outline • Objectives • Patient Case • Background • Clinical Question • Review of Evidence • Recommendation • Monitoring

3. Objectives • Review pathophysiology for auto anti-coagulation & clinical presentation • Discuss evidence of auto anti-coagulation • Discuss therapeutic options for VTE prophylaxis

4. Mr. JE • ID: 33 yo Caucasian male, ht 170cm, wt 55kg • CC: ER by ambulance Sept 1/09 for weakness & falls-jaundice, ascites • HPI Oct 19/09: Small esophageal varices, ascites • PMHx: chronic lower back pain, alcohol abuse x 14 years

5. Mr. JE • Meds PTA: None • Allergies: None • SH: Homeless, estranged from family, smoker (30 pack yr hx), drinks 26 oz (780mL) vodka a day x 14 yrs • Discharge Plan: To family

6. Review of Systems

7. Review of Systems

8. Review of Systems

9. Review of Systems

10. Medical Problems List • Alcohol addiction • Alcoholic cirrhosis • Ascites • Esophageal varices • Anemia of chronic disease & iron deficiency anemia • Chronic lower back pain

11. DRP’s • JE is at increased risk of COPD, CVD and cancer secondary to smoking, requiring tobacco cessation counseling • JE has a mixed anemia secondary to iron deficiency and anemia of chronic disease, requiring monitoring of his anemia therapy

12. DRP’s • JE is at an increased risk of VTE requiring assessment of his need for DVT prophylaxis despite his elevated INR of 1.9

13. Alcoholic Liver Cirrhosis • Decrease in pro-coagulants • Can’t make II, VII, IX, X • Decrease in anti-coagulants • Can’t make Protein C, S & antithrombin III • PT & INR measures activity of pro-coagulants and doesn’t capture changes in anti-coagulants • PT does not predict bleeding risk

15. Risk Factors For VTE • Recent surgery or major trauma • Immobility or paralysis • Malignancy • Previous VTE • >80 years • Smoking • Varicose veins • Inherited or acquired thrombophilia

16. CTU Discussion Rounds • Team discussed that patient had been in hospital for a significant amount of time and might need VTE prophylaxis • Team wanted to know if his elevated INR of 1.9 would protect him?

17. Clinical Question

18. Search Strategy • PubMed, Embase, Google • Search terms: • Liver cirrhosis • Risk of Thromboembolism • DVT, Pulmonary embolism • Auto anticoagulation • Found • 2 retrospective case control studies

19. Northup et al. Am J Gastroenterol 2006

20. Northup et al. Am J Gastroenterol 2006

21. Northup et al. Am J Gastroenterol 2006 • Lower albumin in patients with VTE • *38-53g/L normal, 1g/dL=10g/L • Elevated INR did not protect patients from VTE

22. Northup et al. Am J Gastroenterol 2006 • Results: • VTE in cirrhosis patients 113/21,000 (0.5%) • -74/113 (65.5%) DVT • -22/113 (19.5%) PE • -17/113 (15%) Both DVT & PE • -Serum albumin independently predicts VTE (p<0.001, OR 0.24 95% CI 0.10-0.55)

23. Northup et al. Am J Gastroenterol 2006

24. Northup et al. Am J Gastroenterol 2006 Conclusions • Deficiencies of antithrombin III, protein C & protein S are associated with ↑ risk of VTE • Serum albumin may be indicator for level of proteins made by liver such as Antithrombin III, protein C & S ↑ INR does not decrease risk of VTE

25. Sogaard et al. Am J Gastroenterol 2009

26. Sogaard et al. Am J Gastroenterol 2009 • Unprovoked VTE=patient without diagnosis of cancer before or within 90 days of VTE, or diagnosis of fracture, trauma, surgery, pregnancy 90 days before VTE • Each case matched with 5 population controls without a VTE by age, gender, county • Patients with several VTE’s had their first event used

27. Sogaard et al. Am J Gastroenterol 2009

28. Sogaard et al. Am J Gastroenterol 2009 Results • 20% (99,444/496,872) had a VTE • 22% (67,519/308,614) had unprovoked VTE

29. Sogaard et al. Am J Gastroenterol 2009 Limits • Retrospective • Relied on coding of Danish nationwide registry for diagnosis of VTE • No data on lifestyle factors • Declining risk of VTE in past 10 years • Is this due to prophylaxis?

30. Sogaard et al. Am J Gastroenterol 2009 Conclusion • Both cirrhotic and non-cirrhotic liver disease are risk factors for VTE

31. Goals of Therapy Patients Goals • Abstinent from alcohol Team Goals • Prevent VTE • Prevent hospitalization • Decrease morbidity & mortality • Minimize adverse drug events • Keep patient abstinent (quality of life) • Find housing (quality of life)

32. Therapeutic Options • No DVT prophylaxis • Sequential compression devices • Heparin 5000 units sc bid • Dalteparin 5000 units sc daily

33. Recommendation • Dalteparin 5000 units subcutaneous daily • Try to mobilize patient as soon as possible • Initiate smoking cessation counseling

34. Monitoring

35. Monitoring

36. summary Summary Question: Does elevated INR protect patient from a VTE? Answer: • ↑ INR does not decrease risk of VTE • ↓ albumin independently predicts VTE risk Future: • Study VTE prophylaxis in this population & predict benefit & risk of bleed

37. Questions?

38. References • Northup PG, McMahon MM, Ruhl AP et al. Coagulopathy does not fully protect hospitalized cirrhosis patients from peripheral venous thromboebolism. Am J Gastroenterol 2006;101:1523-28. • Sogaard KK, Horvath-Puho E, Gronbaek H et al. Risk of venous thromboembolism in patients with liver disease: a nationwide population-based case-control study. Am J Gastroenterol 2009;104:96-101.