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

2. The Problem INR

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

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

5. Audit of warfarin therapy in intravenous drug abusers l Dewsbury and District Hospital 500 bed DGH catchment population approximately 170,000 l Audit period 1/10/02 - 30/9/03 l 178 patients with DVT l 40 patients known iv heroin abusers l 9 female, 31 male l 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 11 7 6 16

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

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

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

13. DVT in intravenous drug abusers l Anecdotally common l Very limited published data l Iliofemoral DVT following iv heroin, methadone or temazepam reported l 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 l 7 cases of upper limb DVT following cocaine injection from USA l 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) l 20 IVDU 1994-1999 with USS proven ilio-femoral DVT, I had PE l Median duration of iv drug use was 6.5 y l 9 had coexistent groin abscesses l 18 treated with sc Tinzaparin (175iu/kg once daily) including 3 initially treated with iv unfractionated heparin l 2 self discharged on day 0 and day 3 l Initial hospital treatment with LMWH was for a median of 10.5 days (range 3-40) l Tinzaparin was administered post discharge in 15 patients and given for a median of 6.5 weeks (range 2-12) l 13 patients self administered, 1 attended GP and 1 Hospital ward

15. Outcome of Tinzaparin therapy l At 3 months 8 patients had no residual symptoms, 8 had chronic swelling and 4 lost to follow-up l No patient suffered a pulmonary embolus l Compliance with self injected Tinzaparin is unknown l Review 6 months post discharge, 9/14 patients readmitted with drug injection related problems l 12 months post discharge, 10/12 patients readmitted 3 with recurrent thrombosis l Authors suggest that self-injected LMWH after initial course of hospital treatment is management of choice l 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) l Studied 322 women aged 16-70 with objectively confirmed DVT or PE l 44/206 (21.4%) cases of DVT were associated with iv drug abuse (52.4% DVT cases in women <40) l Further 38 iv drug users with probable DVT were reviewed l Total 82 women with iv drug related DVT studied l All treated with sc heparin of unknown duration l Only 2 discharged on warfarin l 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 1. Das et al 1996: 110 patients. Warfarin vs Dalteparin 5000iu daily for 3 months 2. Gonzalez et al 1999: 185 patients. Coumarin vs enoxaparin 40mg daily for 3 months 3. Hamann et al 1998: 200 patients. Phenprocoumon vs Dalteparin 5000 iu for 3-6months 4. Lopaciuk et al 1999: 202 patients. Acenocoumarol vs Nadroparin (85 anti-Xa units per kg) for 3 months 5. Lopez et al 2001: 158 patients. Acenocoumarol vs Nadroparin 1025 anti-Xa iu/10kg for 3-6 months 6. Pini et al 1994: 187 patients. Warfarin vs Enoxaparin 40mg/day for 3 months 7. 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) l 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. l All studies combined showed a significant reduction (OR 0.38 (95% CI 0.15-0.94)) in the bleeding risk in favour of LMWH l 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 l Should we accept patients with iv drug related DVT for warfarin treatment? l What is the role of LMWH therapy in these patients? 1. Which heparin preparation? 2. What dose? 3. What duration of treatment? 4. Who gives it? 5. 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