Warfarin therapy in intravenous drug abusers

Dewsbury and District Hospital Anticoagulant Service

The Problem

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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

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

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

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Attendance Record

Never Attended

Lost to Follow Up

Completed Course

Ongoing Treatment

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616

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

Complications of under- anticoagulation

1 Recurrent thrombosis INR 2.1

1 Probable thrombosis extension INR 1.0

No cases of pulmonary embolus

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

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

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

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

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

What is the role of Low Molecular Weight Heparin for the long term treatment of DVT

(Cochrane review April 2003)

7 studies reviewed1. 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 months3. Hamann et al 1998: 200 patients. Phenprocoumon vs Dalteparin

5000 iu for 3-6months4. 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 months6. Pini et al 1994: 187 patients. Warfarin vs Enoxaparin 40mg/day for 3

months7. Veiga et al 2000: 100 patients> Acenocoumarol vs Enoxaparin

40mg/day for 3-6months

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.”

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?

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?

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