Warfarin therapy in intravenous drug abusers

1. Warfarin therapy in intravenous drug abusers Dewsbury and District Hospital Anticoagulant Service

2. The Problem INR

3. Case History(1) • 32 y Male Heroin addict for 8 years • Extensive Femoral vein thrombosis associated with a groin abscess at an injection site. • Admitted and treated with antibiotics and subcutaneous Tinzaparin for 6 days and warfarin • INR at discharge 2.3 • Poor attendance record at anticoagulant clinic defaulted from follow-up after 4 visits

4. Case History(2) • Developed acute breathlessness one evening and started coughing large quantities of fresh blood • Collapsed at home and died before the ambulance could be called • Post mortem examination revealed extensive intrapulmonary haemorrhage • Toxicology showed plasma warfarin level 2.9mg/ml

5. Audit of warfarin therapy in intravenous drug abusers • Dewsbury and District Hospital 500 bed DGH catchment population approximately 170,000 • Audit period 1/10/02 - 30/9/03 • 178 patients with DVT • 40 patients known iv heroin abusers • 9 female, 31 male • Median age 32 y Range 20-39 y

6. % of results in target range

7. % of results below target range

8. % of results above target range

9. Attendance Record 7 11 6 16

10. Complications of over - anticoagulation • 5 episodes in 5 patients INR > 8.0 • 14 episodes in 8 patients INR > 5.0 • I gum/nose bleeding INR 8.0 • 1 petechial rash INR 7.7 • 1 life threatening GI INR 19 haemorrhage

11. Complications of under- anticoagulation • 1 Recurrent thrombosis INR 2.1 • 1 Probable thrombosis extension INR 1.0 • No cases of pulmonary embolus

12. Problems with anticoagulant management of IV drug users • Compliance with warfarin taking • Compliance with warfarin monitoring • Pharmacological interaction between street drugs and warfarin • Possible effect of erratic life style e.g. poor diet ERRATIC CONTROL • Possible risk of femoral puncture

13. DVT in intravenous drug abusers • Anecdotally common • Very limited published data • Iliofemoral DVT following iv heroin, methadone or temazepam reported • Labropoulos et al (1996) reported 47 iv drug users with suspected DVT. Diagnosis confirmed in 63%, 10 had bilateral DVT. 3 patients suffered a PE • 7 cases of upper limb DVT following cocaine injection from USA • Other smaller case series from Norway, Brazil, Spain and Switzerland

14. Ilio-femoral drug use in North East Scotland(Mackenzie et al Postgrad Med J 2000;76:561-565) • 20 IVDU 1994-1999 with USS proven ilio-femoral DVT, I had PE • Median duration of iv drug use was 6.5 y • 9 had coexistent groin abscesses • 18 treated with sc Tinzaparin (175iu/kg once daily) including 3 initially treated with iv unfractionated heparin • 2 self discharged on day 0 and day 3 • Initial hospital treatment with LMWH was for a median of 10.5 days (range 3-40) • Tinzaparin was administered post discharge in 15 patients and given for a median of 6.5 weeks (range 2-12) • 13 patients self administered, 1 attended GP and 1 Hospital ward

15. Outcome of Tinzaparin therapy • At 3 months 8 patients had no residual symptoms, 8 had chronic swelling and 4 lost to follow-up • No patient suffered a pulmonary embolus • Compliance with self injected Tinzaparin is unknown • Review 6 months post discharge, 9/14 patients readmitted with drug injection related problems • 12 months post discharge, 10/12 patients readmitted 3 with recurrent thrombosis • Authors suggest that self-injected LMWH after initial course of hospital treatment is management of choice • 6 weeks if symptoms resolve 12 weeks for severe cases

16. Injecting drug use in women in Glasgow(McColl et al B J Haem 2001:112:641-643) • Studied 322 women aged 16-70 with objectively confirmed DVT or PE • 44/206 (21.4%) cases of DVT were associated with iv drug abuse (52.4% DVT cases in women <40) • Further 38 iv drug users with probable DVT were reviewed • Total 82 women with iv drug related DVT studied • All treated with sc heparin of unknown duration • Only 2 discharged on warfarin • None known to suffer a PE

17. What is the role of Low Molecular Weight Heparin for the long term treatment of DVT(Cochrane review April 2003) 7 studies reviewed • Das et al 1996: 110 patients. Warfarin vs Dalteparin 5000iu daily for 3 months • Gonzalez et al 1999: 185 patients. Coumarin vs enoxaparin 40mg daily for 3 months • Hamann et al 1998: 200 patients. Phenprocoumon vs Dalteparin 5000 iu for 3-6months • Lopaciuk et al 1999: 202 patients. Acenocoumarol vs Nadroparin (85 anti-Xa units per kg) for 3 months • Lopez et al 2001: 158 patients. Acenocoumarol vs Nadroparin 1025 anti-Xa iu/10kg for 3-6 months • Pini et al 1994: 187 patients. Warfarin vs Enoxaparin 40mg/day for 3 months • Veiga et al 2000: 100 patients> Acenocoumarol vs Enoxaparin 40mg/day for 3-6months

18. What is the role of Low Molecular Weight Heparin for the long term treatment of DVT(Cochrane review April 2003) • Analysis of pooled data showed a non-significant reduction in DVT favouring LMWH BUT on reanalysis omitting a potentially confounded study there was a non-significant risk reduction favouring vitamin K antagonists. • All studies combined showed a significant reduction (OR 0.38 (95% CI 0.15-0.94)) in the bleeding risk in favour of LMWH • Authors conclude “Treatment with LMWH is significantly safer than treatment with vitamin K antagonists and is possibly a safe alternative for some patients.”

19. Points for discussion • Should we accept patients with iv drug related DVT for warfarin treatment? • What is the role of LMWH therapy in these patients? • Which heparin preparation? • What dose? • What duration of treatment? • Who gives it? • What monitoring, assessment and follow-up is required?

20. The Team I would like to acknowledge the contribution of all Haematology department staff to the anticoagulant service but in particular - Katrina Randle Jayne Barker Andrea Ryan Sajid Khan Ann Stamper Richard Stead