Postgrad Med J (1993) 69, 115 - 116
`
`A) The Fellowship of Postgraduate Medicine, 1993
`
`Subcutaneous versus intravenous administration of
`heparin in the treatment of deep vein thrombosis; which do
`patients prefer? A randomized cross-over study
`
`A.M. Robinson, K.A. McLean, M. Greaves and K.S. Channer
`
`Department ofCardiology and Haematology, Royal Hallamshire Hospital, Sheffield S10 2JF, UK
`
`Patient preference for intravenous or subcutaneous heparin in the treatment of deep
`Summary:
`venous thrombosis was assessed in a randomized cross-over study. Twenty patients with venographically
`proven deep venous thrombosis were randomized to receive subcutaneous or intravenous heparin for 3 days
`followed by 3 days of the other treatment. Discomfort at the injection site, assessed by visual analogue
`scale, was significantly less for the subcutaneous than the intravenous administration route (P <0.001),
`mobility was thought to be better when receiving subcutaneous heparin (P < 0.005) and patients' overall
`preference was for subcutaneous treatment (P <0.001).
`
`Introduction
`
`The treatment of deep venous thrombosis (DVT) is
`anticoagulation with heparin. This is usually
`administered intravenously (IV), but can be given
`subcutaneously (SC). The efficacy of the two
`methods of delivery has been assessed in a number
`which individually
`of trials
`have produced
`conflicting results. However, an overview' suggests
`that there are no significant differences with respect
`death, pulmonary emboli and significant
`to
`haemorrhage.
`Complications can occur with both methods of
`administration. Intravenous heparin can lead to
`chemical phlebitis and bacteraemia,' whilst SC
`heparin is associated with bruising at the site of
`injection.2 It has been suggested that the SC route is
`preferable because it reduces the time spent by
`medical and nursing staff in administration,' and
`the risk of local complications such as chemical
`phlebitis and bacteraemia. No study has examined
`patient preference for either of the treatment
`modalities. This randomized cross-over study com-
`pares the patient acceptability for SC versus IV
`heparin in the treatment of DVT.
`
`Method
`
`Twenty patients (7 male; mean age 55 years, range
`20-85 years) admitted consecutively with a DVT,
`proven by venogram were entered into the study.
`Informed written consent was obtained from each
`patient and the study was approved by the hospital
`Ethics Committee. Each patient was randomly
`
`Correspondence: K.S. Channer, M.D.
`Accepted: 4 September 1992
`
`allocated to receive either calcium heparin SC twice
`daily (Calciparine, Sanofi, UK) or IV sodium
`heparin (PumpHep, Leo laboratories, Aylesbury,
`UK) by mains electric infusion pump. After 3 days
`the patients received the other treatment with total
`heparin treatment lasting for 6 days.
`When IV therapy was the first arm oftreatment a
`5,000 unit bolus was given, followed by 30,000
`units over 24 hours. The starting dose for sub-
`cutaneous heparin was 15,000 units twice daily.
`Activated partial thromboplastin time (APTT) was
`measured daily between 0900-1200 hours whilst
`IV heparin was administered and at 6 hours after
`the initial SC injection. The heparin dose was then
`adjusted to maintain the APTT between 1.5 and
`two times the upper limit of the control.
`On the third day of each treatment period blood
`samples were taken from all patients 3 hourly for
`the measurement of APTT and heparin con-
`centration from 0900 for 12 hours. This provided
`pharmacokinetic data to assess the efficacy of
`anticoagulation.
`The acceptability by the patients of the two
`methods of administration was assessed using
`visual analogue scales (VAS), for discomfort in the
`affected leg, pain at the injection site and mobility.
`The extremes (0-100 mm) of the first two scales
`were marked 'no discomfort' and 'severe discom-
`fort', and the scale for mobility was marked 'fully
`mobile' and 'bed bound'. Fresh scales were present-
`ed to the patients daily, who were also asked to
`express an overall preference for one or other form
`of treatment at the end of the study.
`Non-parametric statistical analyses were used
`and 95% confidence intervals are quoted. A pro-
`bability of P<0.05 was accepted as significant.
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`140-
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`120-
`
`o 1001
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`80
`
`40
`
`9:00
`
`12:00
`18:00
`15:00
`Time (24 hour clock)
`Figure 1
`This shows the mean and interquartile range
`for activated partial thromboplastin time during treat-
`ment with SC (@) and IV (0) heparin in 19 patients with
`deep vein thrombosis on the third day of each treatment
`period.
`
`21:00
`
`T
`
`.
`
`1.0
`
`0.8
`
`0.6
`
`C0
`
`C.
`
`o
`
`q.o 0.4
`C 0.2
`CL
`0.0
`
`9:00
`
`21:00
`
`15:00
`12:00
`18:00
`Time (24 hour clock)
`This shows the mean and interquartile range
`Figure 2
`for blood heparin level during treatment with SC (@) and
`IV (0) heparin in 19 patients with deep vein thrombosis
`on the third day of each treatment period.
`
`cost (£1.98/day for SC heparin compared with
`£2.30/day for IV heparin). Given that there is no
`difference in efficacy or safety, the most important
`factor should be patient acceptability. We suggest
`therefore that SC heparin is the treatment ofchoice
`in deep venous thrombosis.
`
`4. Andersson, G., Fagrell, B., Holmgren, K. et al. Subcutaneous
`administration of heparin; a randomised comparison with
`intravenous administration of heparin to patients with deep-
`vein thrombosis. Thromb Res 1982, 27: 631-639.
`5. Bentley, P.G., Kakkar, V.V., Scully, M.F. et al. An objective
`study of alternative methods of heparin administration.
`Thromb Res 1980, 18: 177-187.
`
`116
`
`A.M. ROBINSON et al.
`
`Results
`
`Nineteen patients completed the study, one being
`withdrawn because of bleeding whilst receiving IV
`heparin (APTT within the therapeutic range). The
`VAS scores were analysed by the Wilcoxon mat-
`ched pairs signed rank test. When the two methods
`of administration were compared for all the
`patients, significantly less discomfort was felt at the
`injection site (median (range)) for SC heparin
`(3 mm (0-61 mm)) compared with IV heparin
`(12mm (0-97mm), P<0.001, 95% confidence
`intervals for difference 1, 15 mm).
`of mobility was
`perception
`The patients'
`significantly better for the final 4 days of treatment
`when this was SC heparin (41 mm (0-100 mm))
`compared with IV heparin (72 mm (23-99 mm),
`P <0.005, 95% confidence intervals (12, 43 mm).
`The discomfort felt in the affected leg was no
`different for either method of treatment (P = 0.54).
`Heparin and APTT levels were not significantly
`different for either SC or IV heparin (Figures 1 and
`2). The proportion oftime for which the APTT was
`within the therapeutic range was similar
`to
`previous studies,' and there was no significant
`difference between IV (50%) and SC (46%).
`Fifteen of the 19 patients expressed a preference
`for the SC route for administration of heparin.
`Two preferred the IV route and two gave no
`preference (X2 = 10.5, P < 0.001).
`
`Discussion
`
`The majority of patients in this study preferred SC
`to IV heparin in the treatment of uncomplicated
`deep venous thrombosis. Published trials indicate
`that the two methods are equally efficient in the
`prevention of pulmonary emboli and that SC
`heparin is not associated with an increase in major
`complications.' -`
`There are several potential advantages of SC
`over IV heparin treatment, including a reduction in
`the time taken to administer, no break in treatment
`whilst a new heparin infusion is prepared and the
`
`References
`
`1. Hommes, D.W., Bura, A., Mazzolai, L., Buller, H.R. & ten
`Cate, J.W. Subcutaneous heparin compared with continuous
`intravenous heparin administration in the initial treatment of
`deep vein thrombosis. A meta-analysis. Ann Intern Med 1992,
`116: 279-284.
`2. Walker, M.G., Shaw, J.W., Thompson, G.J.L. et al. Sub-
`cutaneous calcium heparin versus intravenous sodium heparin
`in treatment of established acute deep vein thrombosis of the
`legs: a multicentre prospective randomised trial. Br Med J
`1987, 294: 1189-1192.
`3. Doyle, D.J., Turpie, A.G.G., Hirsh, J. et al. Adjusted sub-
`cutaneous heparin or continuous intravenous heparin in
`patients with acute deep vein thrombosis. Ann Intern Med
`1987, 107 (4): 441-445.
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