Understanding the pathophysiology ofcompression
Compression bandages: principles anddefinitions
Cost-effectiveness of compression therapy
Compression therapy: a guide to safepractice
SENIOR EDITORIAL ADVISOR
Professor and Co-director, Centre for Research and Implementation of Clinical Practice, Wolfson
Insitute of Health Sciences, Thames Valley University, London, UK
Director, Surgical Materials Testing Laboratory, Princess of Wales Hospital, Bridgend, Wales, UK
Professor of Microcirculation, Department of Angiology, University of Rome, Italy
Senior Research Fellow, Department of Health Sciences, University of York, UK
Professor, Department of Dermatology and Phlebology, University of Bonn, Germany
J Javier Soldevilla Ágreda
Professor of Geriatric Care, EUE University of La Rioja, Logroño, Spain
Joan-Enric Torra i Bou
Coordinator, Interdisciplinary Chronic Wounds Unit, Hospital de Terrassa, Barcelona, Spain
Consultant Vascular Surgeon, Bradford Royal Infirmary, Bradford, UK
Angiologist Phlebologist, Department of Vascular Disease, American Hospital, Paris, France
publication are those of theauthors and do not necessarily
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Understanding compression therapy
The potential impact of compression therapy on ulcer healing has been highlighted innumerous studies across the world during the last decade. There can be few healthcareinterventions that can claim such dramatic effects on outcome. Patients reportimprovements in pain, mobility and general quality of life as a consequence of their ulcerhealing. It is therefore a salutary finding in producing this position document, that we arefar from being able to establish pan-European standards for compression therapy.
The physiological basis for compression therapy is, however, well established. Partsch, in
describing the mechanisms behind compression, shows how effective materials directlyimpact on venous, arterial and lymphatic function and on the inflammatory processes suchas white cell entrapment associated with ulceration. He highlights the potential differencesbetween individual compression systems when used in practice and the need to applyappropriate levels of compression. Technological advances in the last decade concerningelastomers have led to sophisticated developments in bandage and hosiery production.
Materials are now being developed that overcome some of the traditional problemsassociated with elastic bandages. New and creative approaches in this area are encouraging.
An understanding of Laplace’s Law and the inverse relationship between the radius of a
patient’s limb and the pressure applied is important in bringing the science of bandaging tothe art of compression. However, despite many attempts to measure the sub-bandagepressure, the evidence would suggest that this is often misleading. Clark, in the secondarticle, describes the limitations of the current standards in use and their variations acrosscountries. Europe now requires the development of a new standard. We must look for aneffective method of classifying bandages, perhaps similar to that being developed forcompression hosiery.
While in many countries in Europe compression is well established, in other countries the
reimbursement systems do not cover the bandages and hosiery materials, with manypatients being treated with dressings alone. Such a system must be challenged if we are tomove wound care forward. The issues of reimbursement are complex and resistance toplacing products into the systems are often based on a misplaced belief that this will escalatethe cost of care. In many countries there are few strategies to monitor the costs for thenumerous patients with ulceration and the real cost to the healthcare systems remainshidden. Franks and Posnett discuss the importance of treatments being both clinically andcost-effective where budgets are constrained and offer a method for evaluating the cost-effectiveness of a systematic treatment approach using high compression. Part of thestrategic mission of EWMA is to fight for equal standards of practice across the whole ofEurope. Gaining reimbursement for compression would be a major breakthrough that wemust strive to achieve.
The need for clear clinical guidelines has prompted the development of a recommended
treatment pathway by the International Leg Ulcer Advisory Board. In the final paper,Marston and Vowden discuss the scientific basis of the pathway and the important clinicalissues underpinning it. The literature is clear that compression is more effective than nocompression and that high compression is more effective than low compression. With thedevelopment of new bandage systems and large randomised controlled trials of currentregimens, the picture concerning the differences between them should become clearer in thenext few years. Compression, however, is only one part of effective care provision. Thepathway stresses the importance of correct assessment, particularly the identification of
arterial disease, and the role of the multidisciplinary team in ensuring safe practice. For
compression therapy to reach its true potential it is important that patient care is well
delivered within effective, multidisciplinary services.
We hope this document will stimulate an international debate which will allow for the
University, London, UK.
Immediate Past President,
reclassification and a furtherance of the art and science of compression therapy across
Understanding the pathophysiological
effects of compression
Compression has been used for many centuries in the treatment of oedema and
other venous and lymphatic disorders of the lower limb, but the exact
mechanisms of action remain poorly understood. This paper considers the
physiological and biochemical effects of compression.
If an oncotic pressure gradient exists across a semi-permeable membrane, such as acapillary wall, water is drawn across the barrier until the concentrations on both sidesare equal. (Oncotic pressure is the osmotic pressure
created by protein colloids inplasma.) The relationship between these factors is summarised in Starling’s equation1.
The amount of lymph formed depends upon the permeability of the capillary wall
(filtration coefficient) and the gradient of hydrostatic and oncotic pressure betweenblood and tissue. The hydrostatic pressure difference causes filtration, while the oncoticpressure difference causes reabsorption (Figure 1).
Oedema, the accumulation of fluid in extra-vascular tissue, occurs as a result of complexinteractions involving the permeability of capillary walls and the hydrostatic andoncotic pressure gradients that exist between the blood vessels and surrounding tissue.
Starling’s equation suggests that the application of external compression will
counteract the loss of capillary fluid by increasing local tissue pressure and reinforcereabsorption by squeezing fluid into the veins and lymph vessels. This in turn will helpto resolve oedema (Figure 1). Various causes of oedema are identified in Table 1.
Depending upon the amount of pressure applied, a compression bandage may
influence the internal volume of veins, arteries and lymph vessels. Structures near thesurface of the skin are compressed more than the deep vessels. This is because thecompressive force is partly dissipated by compression of the surrounding tissues.
Nuclear medical investigations have shown that compression removes more water
than protein from the tissue, increasing oncotic tissue pressure. This results in a rapidreaccumulation of oedematous fluid if compression is not sustained2.
Table 1 | Causes of oedema
represents net filtration force
(which is the origin of lymph)
is the filtration coefficient
is capillary blood pressure
is tissue pressure
is capillary oncotic pressure
Hypoalbuminaemia, nephrotic syndrome, Hypoproteinaemic oedema
is tissue oncotic pressure
In a standing individual blood flows slowly through the veins. The venous pressure,which equals the weight of the blood column between the foot and right atrium, isabout 80-100 mmHg. During walking, however, blood flow is accelerated by thecombined action of the calf muscle pump and the foot pump, which in patients withcompetent valves, decreases the volume of venous blood in the foot and reducesvenous pressure to about 10-20 mmHg.
If the valves in the large veins become incompetent due to primary degeneration or
University of Vienna, Departmentof Dermatology, Vienna,
post-thrombotic damage, blood will oscillate up and down in those segments lacking
UNDERSTANDING COMPRESSION THERAPY
Figure 1 | Compression
The resulting retrograde (backward) flow in the veins of the lower leg (venous
works against filtration
reflux) leads to a reduced fall in venous pressure during walking (ambulatory venous
hypertension). This causes fluid loss into the tissues and the formation of oedema.
Compression of veins with incompetent valves produces an increase in orthograde(towards the heart) flow and a reduction in venous reflux.
The application of adequate levels of compression reduces the diameter of major
veins as demonstrated by phlebography and Duplex ultrasound3. This has the effect ofreducing local blood volume4, by redistributing blood towards central parts of thebody. As this can lead to an increase in the preload of the heart and affect cardiacoutput by about 5%5 (Figure 2), bilateral bandaging of the thighs and lower legsshould be avoided in patients with borderline cardiac function.
Reducing the diameter of major blood vessels will have the secondary effect of
increasing flow velocity, provided the arterial flow remains unchanged. The clinicalsignificance of these effects depends upon the relationship between the intravenoushydrostatic pressure and the degree of external compression applied. In a supine (lyingdown) individual, pressures in excess of about 10 mmHg over the calf are sufficient toreduce venous stasis, a major factor in thrombus formation, by producing a marked
decrease in blood volume in the lower legs, accompanied by a corresponding increasein blood velocity. Pressures in excess of 30 mmHg do not result in a further increase inblood velocity in the large veins or the microcirculation as at this pressure the vesselsare maximally emptied and venous volume cannot be reduced any further6.
In the upright position, the pressure in the lower leg fluctuates during walking,
between 20-100 mmHg, and therefore much higher levels of compression (e.g. 40-50mmHg) are required to exert a marked effect upon blood flow.
Figure 2 | Compression of
the leg veins leads to a
Although it is accepted that compression should never be allowed to impede arterial
shift in blood volume with
inflow, there is currently no convincing clinical evidence to indicate what levels of
an increase in the preload
compression may safely be applied to a limb, particularly if there is a risk of arterial
of the heart
A systolic ankle pressure below 50-80 mmHg is commonly regarded as a
contradiction for high compression therapy, as is an ankle-brachial pressure index(ABPI) of less than 0.8. Intermittent pneumatic compression systems that exertpressures of 30-80 mmHg aid venous return, reduce oedema and may even help toincrease arterial flow (by a type of reactive hyperaemic response)7.
The function of the lymphatic system is to remove fluid from the interstitial tissues
and return it to the venous system. In patients with venous insufficiency, isotopic
lymphography shows that prefascial lymphatic drainage is intact or even increased.
Subfascial lymph transport is reduced or absent in patients with deep vein thrombosis
and deep venous incompetence due to a post-thrombotic syndrome8.
Short-stretch compression bandages and walking exercises can improve the
diminished subfascial lymph transport, but prefascial lymph transport may bedecreased due to the reduction of filtration8. The morphological changes of thelymphatics in lipodermatosclerotic skin, such as fragmentation and extravasation ofthe contrast medium (dermal back-flow), can be normalised with long-termcompression9.
The dramatic reduction of oedema by compression therapy can be explained by the
reduction of lymphatic fluid in the tissue, rather than by an improvement of lymphatictransport10.
Ambulatory venous hypertension in patients with chronic venous insufficiency is the
trigger for functional alterations in the endothelium. These alterations are complex and
only partially understood. One possibility is that neutrophils become activated, adhere
to the endothelial cells and, mediated by the surface exposure of adhesion molecules,
produce endothelial injury by releasing cytokines, oxygen free radicals, proteolytic
enzymes and platelet activating factors11. Dermal tissue fibrosis (lipodermatosclerosis) is
always be used beforeapplying compression with
associated with increased transforming growth factor (TGF)-beta(1) gene expression12;
the loss of tissue compliance caused by the fibrosis can lead to reduced skin perfusion
and ulceration13. Capillary microthrombosis also contributes to tissue necrosis14.
Compression accelerates blood flow in the microcirculation, favours white cell
detachment from the endothelium and prevents further adhesion15. Capillary filtration is
also reduced and reabsorption is increased due to enhanced tissue pressure14. In
lipodermatosclerotic areas where skin perfusion may be reduced due to the strain
40-50 mmHg) are required toproduce beneficial
associated with high tissue pressure13, the use of compression therapy can increase this
gradient and improve blood flow. This leads to softened skin16.
Effects on mediators involved in the local inflammatory response may explain both
the immediate pain relief that occurs with good compression and subsequent ulcer
healing. It has recently been demonstrated, for example, that compression therapy is
able to reduce elevated levels of vascular endothelial growth factor and tumour necrosis
factor (alpha) in patients with venous ulcers and that this reduction of serum cytokinelevels parallels ulcer healing17. The influence of compression on the tissue injury causedby free radicals, including nitric oxide, requires further investigation18.
The application of external compression initiates a variety of complex physiological and biochemical effects involving the venous, arterial and lymphatic systems. Providedthat the level of compression does not adversely affect arterial flow and the rightapplication technique and materials are used, the effects of compression can bedramatic, reducing oedema and pain while promoting healing of ulcers caused byvenous insufficiency.
1. Landis EM, Pappenheimer JR. Exchange of substances through the capillary
intermittent pneumatic compression on both leg lymphedema volume and on
wall. In: Handbook of Physiology Circulation.
Washington: Am Physiol Soc 1963
lymph transport as semi-quantitatively evaluated by lymphoscintigraphy.
2. Partsch H, Mostbeck A, Leitner G. Eperimental investigations on the effect of
11. Smith PD. The microcirculation in venous hypertension. Cardiovasc Res
intermittent pneumatic compression (Lymphapress) in lymphoedema. Phlebol u
12. Pappas PJ, You R, Rameshwar P, Gorti R, et al. Dermal tissue fibrosis in
3. Partsch H, Rabe E, Stemmer R. Compression Therapy of the Extremities
patients with chronic venous insufficiency is associated with increased
Editions Phlébologiques Francaises, 2000.
transforming growth factor-beta1 gene expression and protein production. J
4. Christopoulos DC, Nicolaides AN, Belcaro G, Kalodiki E. Venous hypertensive
microangiopathy in relation to clinical severity and effect of elastic compression.
13. Chant A. The biomechanics of leg ulceration. Ann R Coll Surg Engl
J Dermatol Surg Oncol
5. Mostbeck A, Partsch H, Peschl L. (Alteration of blood volume distribution
14. Bollinger A, Fagrell B. Clinical Capillaroscopy
. New York: Hofgrefe & Huber 1991.
throughout the body resulting from physical and pharmacological interventions.)
15. Abu-Own A, Shami SK, Chittenden SJ, et al. Microangiopathy of the skin and
the effect of leg compression in patients with chronic venous insufficiency. J
6. Partsch H, Menzinger G, Mostbeck A. Inelastic leg compression is more
effective to reduce deep venous refluxes than elastic bandages. Dermatol Surg
16. Gniadecka M. Dermal oedema in lipodermatosclerosis: distribution, effects of
posture and compressive therapy evaluated by high frequency ultrasonography.
7. Mayrovitz HN, Larsen PB. Effects of compression bandaging on leg pulsatile
Acta Derm Venereol
1995; 75: 120-24.
blood flow. Clin Physiol
17. Murphy MA, Joyce WP, Condron C, Bouchier-Hayes D. A reduction in serum
8. Lofferer O, Mostbeck A, Partsch H. (Nuclear medicine diagnosis of lymphatic
cytokine levels parallels healing of venous ulcers in patients undergoing
transport disorders of the lower extremities.) Vasa
1972; 1: 94-102.
compression therapy. Eur J Endovasc Surg
2002; 23: 349-52.
9. Partsch H. Compression therapy of the legs. A review. Dermatol Surg Oncol
18. Dai G, Tsukurov O, Chen M, Gertler JP, Kamm RD. Endothelial nitric oxide
production during in-vitro simulation of external limb compression. Am J Physiol
10. Miranda F Jr, Perez MC, Castiglioni ML, Juliano Y, et al. Effect of sequential
Heart Circ Physiol
2002; 282: H2066-75.
Compression bandages: principles
The degree of compression produced by any bandage system over a period of time
is determined by complex interactions between four principle factors – the
physical structure and elastomeric properties of the bandage, the size and shape of
the limb to which it is applied, the skill and technique of the bandager and the
nature of any physical activity undertaken by the patient. This paper describes the
mechanisms by which compression is achieved and maintained, and discusses some
of the practical problems involved in measuring sub-bandage pressure.
The pressure generated by a bandage immediately following application is determined
principally by the tension in the fabric, the number of layers applied, and the degree of
curvature of the limb. The relationship between these factors is governed by Laplace’sLaw (see Box). The use of this law to calculate or predict sub-bandage pressure has beendescribed by Thomas1, although this remains a controversial issue2.
in a bandage is determined initially by the amount of force applied to the
fabric during application. The ability of a bandage to sustain
a particular degree of
tension (and therefore sub-bandage pressure) is determined by its elastomeric
properties, and these in turn are a function of the composition of the yarns and the
The ability of a bandage to increase in length in response to an applied force is described as
(ability to stretch) and it has become common practice across Europe to use
terms such as short-stretch
(minimally extensible, inelastic, passive) and long-stretch
(highly extensible, elastic, active) to describe this aspect of a bandage’s performance.
to the tension in abandage but inversely
At some point, the physical structure of a bandage will prevent further stretching
once a certain degree of extension is achieved. This condition is called ‘lock-out’.
Stemmer and colleagues3 suggested that short-stretch bandages should lock-out at up
is applied (P
increases with T
to 70% extension (and ideally at 30 to 40% extension), with long-stretch bandages
decreases as R
only locking out at over 140% extension. Unfortunately, they did not suggest whattension should be applied to the bandages in order to achieve these levels of extension,since different bandages may achieve similar extensions when very different extensionforces are applied4. Without some form of ‘reference’ tension, definitions such as long-
or short-stretch are relatively meaningless and it is preferable to use the terms elastic or
With elastic bandages a small change in extension (as might occur during walking) will
result in minor fluctuations in sub-bandage pressure. These bandages are also able to
accommodate changes in limb circumference, as occurs when oedema is reduced, with
minimal effects on sub-bandage pressure. Conversely, with inelastic bandages large changes
Elastic bandages producesustained compression with
in sub-bandage pressure may result from minor changes in calf geometry. These bandages
may produce high compression during walking, but low resting pressures (see Box).
The amount of force required to cause a specific increase in the length of an elastic
bandage is an indicator of the bandage’s power
5; this characteristic determines the
amount of pressure a bandage will produce at a predetermined extension.
of a bandage determines its ability to return to its original (unstretched)
of Wales College of Medicine,Cardiff, UK.
Table 1 | Comparison of British and German bandage pressures
e British standard
Pressure German standard
Currently there are no international or European standards relating to the performance
of compression bandages. An on-line search of 20 European national standards bodies,conducted in December 2002, identified three national standards related to bandagesused to apply limb compression, two of which, British Standard (BS) 7505:19956 andRAL-GZ 387 (Germany)7, will be used to illustrate the lack of European agreement onthe classification of compression bandage systems. The third standard, fromSwitzerland, dates back to 1975.
The standards set out test methods for establishing the different aspects of the
performance of non-adhesive, fabric-based compression bandages. Of note is thatdifferent test methods are used in different countries across Europe.
Bandages are classified within the standard into one of six categories. Type 1 refers to
retention, lightweight, elastic bandages. Type 2 are support bandages (inelastic, short-
1. Pressure sensors
stretch) and type 3A to 3D are compression bandages (elastic, long-stretch). The four
classes of compression bandage are defined according to their ability to apply a
specified sub-bandage pressure to a known ankle circumference (23 cm) where the
bandage is applied with a 50% overlap between successive layers.
surface area and so do notreport peak pressures.
Inflexible sensors may record
The German standard also classifies compression bandages into four groups. However
the thresholds used in the BS and German standards differ (see Table 1). This may be
due to differences in the required level of pressure and the use of different test methods.
This highlights a need for wider European agreement on the classification of
2. Site of sensor application
compression bandages8 and the introduction of a standard similar to that in preparation
A sensor placed over a softtissue (calf) may return lower
pressure readings than asimilar sensor placed over a
Achieving adequate pressure
On a normal leg the circumference of the ankle is generally substantially smaller than
3. Method of application
that of the calf, and it follows from Laplace’s Law that if a bandage is applied with
constant tension and overlap, the pressures achieved at the gaiter and the calf will be
lower than those applied at the ankle. As the circumference of the leg progressively
number of layers applied andthe degree of overlap between
increases, a compression gradient is produced with the highest pressure on the most
distal part of the limb (i.e. the ankle). The consistent formation of this ideal pressure
gradient has been difficult to demonstrate practically10. The failure to demonstrate
4. Position of limb
graduated compression may reflect poor operator technique, the practical problems of
maintaining constant tension throughout the bandage during the application process
and poor measurement technique. Factors affecting the measurement of sub-bandage
UNDERSTANDING COMPRESSION THERAPY
Some of the practical problems associated with bandage application have been addressed by
manufacturers who have included various visual guides to help operators achieve the
required tension within the bandage. Advances in textile technology may also help to
reduce both inter- and intra-bandager variability. One very promising concept is the
development of an elastomeric yarn which enables a bandage to achieve relatively constant
sub-bandage pressures regardless of minor variations in extension12.
Compression of the lower leg aids the healing of venous leg ulcers. Much is made of sub-bandage pressures in the presentation and evaluation of compression bandages – the valuescited (for example 40 mmHg at the ankle) are typically given as single values with noapparent variation within and between subjects. In reality, sub-bandage pressures are greatlyinfluenced by several factors including posture, locomotion and bandage applicationtechniques.
The current standards classify individual products, but do not define the ways in which
these bandages work clinically. In addition, simplistic descriptions of short-stretch(inelastic) and long-stretch (elastic) bandages fail to take account of the huge variationswithin these two groups and, more importantly, the development of multi-layercompression systems that combine materials with different performance characteristics.
Multi-layer bandage development is based upon the fact that multiple layers of weak
elastic bandages can be used in combination to achieve optimum compression withoutthe inherent risk of using ‘high power’ elastic bandages capable of excessive pressure.
Multi-layer bandages are complex with some incorporating both elastic and inelasticmaterials, which provide advantages of both systems: the elastic element providessustained pressure and the inelastic element provides high pressures during walking andlow resting pressures.
At the heart of any new classification must be the ability to translate the technical details
about systems into a clinical decision. Optimal levels of compression and best methods ofapplication remain to be determined across Europe, perhaps within the framework ofdeveloping a European-wide standard for the testing and classification of bandage systems.
1. Characteristics of extensibility, power and elasticity affect the amount of pressure a bandage will apply and
2. The current classification system refers to individual bandages and does not adequately reflect the
physiological effects of multi-layer bandaging systems.
3. A European-wide standard for the testing and classification of bandage systems is required.
1. Thomas S. The use of the Laplace equation in the calculation of sub-bandage
Kompressionsstrümpfe RAL-GZ 387. Berlin: Beuth-Verlag, 1987.
8. Pokrovsky AV, Sapelkin SP. Compression therapy and united Europe: new
2. Melhuish JM, Clark M, Williams RJ, Harding KG. The physics of sub-bandage
standards in new realias [sic]. J Ang Vasc Surg
2002; 8(2): 58-63.
pressure measurement. J Wound Care
9. CEN/Technical Committee 205/WG 2. Medical Compression Hosiery. Draft for
3. Stemmer R, Marescaux J, Furderer C. (Compression therapy of the lower
Development DD ENV 12718:2001 Available from National Standards Agencies
extremities particularly with compression stockings.) Hautarzt
1980; 31: 355-
10. Nelson EA. Compression bandaging in the treatment of venous leg ulcers. J
4. Thomas S. Bandages and bandaging. The science behind the art. Care
1996; 5(9): 415-18.
Science and Practice
1990; 8(2); 57-60.
11. Sockalingham S, Barbenel JC, Queen D. Ambulatory monitoring of the
5. Thomas S, Nelson AE. Graduated external compression in the treatment of
pressures beneath compression bandages. Care Science and Practice
venous disease. J Wound Care
1998; 78 (Suppl): 1-4.
6. British Standards Institute. Specification for the elastic properties of flat, non-
12. Moffatt C. Oral presentation: Lo stato dell’arte della terapia compressiva (Vari-
adhesive, extensible fabric bandages. BS 7505:1995. London: British
stetchTM compression). La terapia elastocompressiva nella gestione delle ulcere
dell’arto inferiore: domande e risposte. III Congresso Nazionale AIUC, Italy,
7. Deutsches Institut für Gütesicherung und Kennzeichnung Medizinische
Cost-effectiveness of compression
A recent systematic review of the literature on compression therapy for venous leg
ulcers concluded that treatment with compression improves healing compared with
no compression and that high, multi-layer compression is more effective than low
compression or single-layer compression1. The most clinically effective treatment,
however, is not always the most cost-effective. This article looks at the meaning of
cost-effectiveness in relation to the treatment of patients with a venous leg ulcer.
Cost-effectiveness is about ensuring that available resources are used in the most efficientway to improve the health-related quality of life of patients as a whole. When budgets areconstrained, it may be more efficient to treat 30 patients with a less effective therapy thanto treat 25 patients with the best. The choice of treatment will depend on the balancebetween the additional costs involved in implementing one option and the extent of theadditional benefits generated (see Box) (Figure 1).
The Cochrane review on compression in venous ulceration concluded that there is
insufficient evidence in the literature to draw conclusions about the relative cost-effectiveness of different treatment regimens1. In the absence of evidence from publishedstudies, it is necessary to use a modelling approach to illustrate the principles involved.
There are a number of methods for assessing cost in relation to the outcomes of
treatment including: cost minimisation
(if outcomes are identical the least cost option isselected); cost utility analysis
(in which outcomes are measured by the value placed bypatients on alternative health states, such as living with an infected ulcer); cost-effectivenessanalysis
(in which outcomes are measured in clinical terms, such as time to heal a wound)and cost benefit analysis
(in which outcomes are valued in money terms)2. A cost-effectivenessapproach has been chosen because it is the most relevant, given available information.
First, for the purposes of this analysis, two treatment options were compared, that of a
systematic treatment regimen using high compression bandaging (4-layer) for all patients
as appropriate (option A
), against the usual care provided by nurses in the community
). With usual care there is no systematic approach to the delivery or use of high
compression. The next stage was to estimate expected outcomes and costs for the two
groups of patients treated over a period of at least 52 weeks. The time period is important
as differences between treatment costs and outcomes usually depend on the time at which
the difference is measured. Fifty-two weeks is chosen as it corresponds to an annual
budgetary cycle and is meaningful to decision-makers.
In this example the viewpoint of the analysis is the health services (UK) and costs
included are those that impact directly on healthcare providers. When further information isavailable it may be appropriate to adopt a societal perspective that includes costs falling onpatients, their families and other private and public sector organisations.
Information has been abstracted from published clinical audits and randomised clinical
trials of treatment regimens published during the 1990s and cited in Medline. ‘Usual’ carerefers to evidence where the costs and outcomes relate to treatment provided by nursesprior to the introduction of a systematic approach to care. Key costs include frequency ofcare, site of care delivery and use of wound care products including bandages, dressings
and topical agents. The studies chosen provide evidence of both clinical effectiveness and
appropriate cost data on the same patients3-7. Readers may wish to examine the original
Research and Implementation ofClinical Practice, Thames Valley
articles for definitions and descriptions of usual care.
University, London, UK. 2. Professor of Health
The study by Simon et al
3 reports on a baseline comparison of outcomes in two health
York, UK; and Head of HealthEconomics, Smith and Nephew
authorities in the UK in 1993 and a before-and-after study comparing outcomes after the
introduction of community leg ulcer clinics in 1994. The 12-week healing rates (20%,
UNDERSTANDING COMPRESSION THERAPY
23% and 26%) in the before-arm of this study provide an estimate of the healing rates
which might be expected from the usual care provided by community nurses in the UK.
The Morrell4 and Taylor5 studies show similar healing rates at 12 weeks for a usual care
The Morrell study4 and the before-and-after study by Simon et al
3 evaluate the impact of
the introduction of community leg ulcer clinics (i.e. sytematic treatment regimen) and the
use of high compression bandaging where appropriate. Healing rates are improved in both
studies and are reasonably consistent at 12 weeks (42% Simon3, 34% Morrell4). The healing
rates with high compression reported in the Taylor5, Marston6 and Moffatt7 studies are
higher than those observed in other studies (72-75%) and this is probably a result of
differences in the risk factors for healing, principally ulcer size and duration of the ulcers.
The probabilities of healing and recurrence used in the cost-effectiveness model were
imputed from the 12, 24 and 52-week healing rates and annual rates of recurrence reported
by Morrell et al
4. The Morrell study was chosen for this illustration as it is one of very few
Option A costs more thanoption D and produces better
studies that measured healing rates up to 52 weeks. In addition, the healing rates with high
compression are quite conservative relative to other studies; this means that our estimate of
the relative cost-effectiveness of compression will also be conservative.
Weekly costs of treatment
Cost per patient
The two main determinants of the weekly costs of treatment are the setting of care and thefrequency of dressing changes. The care setting is important: providing care in a specialistoutpatient clinic is more costly than a home visit by a community nurse, which in turn is
more costly than a visit to a practice nurse8. In order to abstract from the impact of caresetting on costs and to focus on the cost impact of treatment alone, the cost-effectiveness
model assumes patients in both groups are treated by a community nurse at home (Table 1).
Table 1 | Weekly cost (unhealed)
NOTE ON COSTS
Systematic care with
high compression (%)
Figure 1 | Relationship
between cost and
community nurse visit (including traveltime)8
=based on Morrell study4 2.2 (2.4 Freak10and Simon3). High compression = based
The cost-effectiveness model was run for a cohort of 100 patients over 52 weeks, using a
Markov (decision) model. The results are shown in Table 2.
The model predicts the number of first ulcers healed and the number of
recurrences associated with treatment for both groups. The predictions of the model are the
same as the results reported in the Morrell study4.
The average annual cost per patient and the average cost per first ulcer healed are
both lower using a systematic treatment approach. The average cost per healed ulcer is
higher than the cost per patient. This is because not all ulcers are healed within the 52-week
period. More than one patient needs to be treated to achieve one healed ulcer.
Table 2 | Expected costs and outcomes
Systematic care with
high compression (option A)
that high compression is thesingle most effective means of
treatment is also the mostexpensive, other factors such
key clinical outcome,systematic treatment with high
Cost per first ulcer healed (excluding recurrences)
cost-effective method oftreating patients with venous
This illustration shows that, based on the assumptions used in this example, option A
option B: outcomes are better and costs are lower. Despite the fact that the
global perspective on therelative costs of high
compression bandage (4-layer) is four times more expensive than the typical dressings
used in a usual care regimen, the cost per week is lower with a systematic approach using
high compression because of the lower frequency of dressing changes. Even if the
effectiveness of the two treatment options is the same, a systematic regimen using highcompression (option A) is more cost-effective due to its lower weekly cost. With option Amore patients are expected to respond to treatment and fewer remain unhealed after 52weeks of treatment. This would suggest that a systematic approach using highcompression (4-layer) is unambiguously more cost-effective than usual care (option B) inthe treatment of venous leg ulcers.
The implications for efficiency are straightforward: with the same annual budget
(€ 2,135) it would be possible to treat 100 patients with option B or 177 patients withoption A. Alternatively, it would be possible to treat 100 patients with option A at a costthat is 44% lower.
In the past, decisions on reimbursement have been made principally on the basis ofclinical evidence alone. With the demand for higher efficiency in using scarce resourcesthere is likely to be an ever greater demand for evidence of cost-effectiveness beforetreatments are reimbursed. There is a clear need to provide more evidence on differenttreatment modalities, and for evidence from other countries and healthcare systems toprovide a global perspective on the relative cost-effectiveness of systematic use of highcompression and other therapies used in the management of patients with chronic venousulceration.
1. Cullum N, Nelson EA, Fletcher AW, Sheldon TA. Compression for venous leg
6. Marston WA, Carlin RE, Passman MA, Farber MA, Keagy BA. Healing
ulcers (Cochrane Review). In: The Cochrane Library. Oxford: Update software,
rates and cost efficacy of outpatient compression treatment for leg
ulcers associated with venous insufficiency. J Vasc Surg
2. Drummond MF, Stoddart GL, Torrance GW. Methods for the Economic Evaluation
of Healthcare Programmes
. Oxford: Oxford Medical Publications, 1994.
7. Moffatt CJ, Simon DA, Franks PJ, Connolly MF, et al. Randomised trial
3. Simon DA, Freak L, Kinsella A, Walsh J, et al. Community leg ulcer clinics: a
comparing two four-layer bandage systems in the management of chronic leg
comparative study in two health authorities. BMJ
1996; 312: 1648-51.
1999; 14: 139-42.
4. Morrell CJ, Walters SJ, Dixon S, Collins K, et al. Cost effectiveness of community
8. Netten A, Curtis L. Unit Costs of Health and Social Care 2000. Personal
leg ulcer clinics: randomised controlled trial. BMJ
1998. 316: 1487-91.
Social Services Research Unit, University of Kent.
5. Taylor AD, Taylor RJ, Marcuson RW. Prospective comparison of healing rates and
9. Drug Tariff. London: The Stationery Office, 2002.
therapy costs for conventional and four-layer high-compression bandaging
10. Freak L, Simon D, Kinsella A, McCollum C, et al. Leg ulcer care: an audit of
treatments for venous leg ulcers. Phlebology
1998; 13: 20-24.
cost-effectiveness. Health Trends
1995; 27: 133-36.
Compression therapy: a guide to safe
Compression has been successfully applied to the management of leg ulceration since
the time of Hippocrates1. As yet, however, there is little international agreement on the
optimal mode of compression. Recently, the International Leg Ulcer Advisory Board
was commissioned to provide guidance on the use of various treatment techniques for
leg ulcer management. The result of this collaboration was the development of a
recommended treatment pathway, which highlights the central role of compression in
the treatment of venous leg ulceration2 (Figure 1). This pathway is based on a
combination of Cochrane systematic reviews, published guidelines and a review of
approximately 150 published papers. Expert opinion was used to address issues where
no reliable research data were available. In this paper, the treatment pathway will be
discussed and the rationale behind the recommendations explored.
Assessment is the key to effective leg ulcer treatment. Chronic venous insufficiency, diabeticcomplications and arterial insufficiency, when taken together, are responsible for over 90% ofleg ulcers. It has been reported that patients with venous leg ulcers often have other complexpathologies, which may impact on treatment3. A detailed patient history provides clues as tothe differential diagnosis, and physical examination is important to evaluate the size and
Patient presents with
characteristics of the wound and should highlight any associated medical conditions. The
process of assessing a patient with lower limb ulceration is set out in a number of
publications and features widely in the European and UK guidelines4-6. This should alsoinclude an evaluation of the patient’s social circumstances as these may impact on both careand healing7.
Failure to recognise arterial disease will result in the unsafe application of high compression
therapy. Arterial perfusion should be evaluated using the hand-held Doppler to calculate the
ankle-brachial pressure index (ABPI)8. Training and experience increases the accuracy of this
assessment9. Pedal pulses should also be palpated, although this alone is an inadequate
method of assessment10. Opinion would suggest that an ABPI <0.8 is usually taken toindicate that the patient is unsuitable for high compression bandaging. Evidence for thechoice of 0.8 is lacking, yet most expert practitioners use this as a guide for the safeapplication of high compression11. However, an ABPI >0.8 does not always indicate thathigh compression bandaging can be undertaken safely and other factors may need to beconsidered before applying compression.
Factors to be considered before applying compression
– delicate friable skin can be damaged by high levels of pressure
Shape of the limb
– the sub-bandage pressure and the pressure gradient will be altered by the limb shape in
accordance with Laplace’s Law. Skin overlying exposed bony prominences may be subject to pressure damage
Presence of neuropathy
– the absence of a protective response increases the risk of sub-bandage pressure
Presence of cardiac failure
– rapid fluid shifts can be dangerous as it increases the preload of the heart
Medical Director, University ofNorth Carolina WoundManagement Clinic, University of
The ABPI may not always be reliable, particularly in patients with diabetes where
vascular calcification can prevent arterial compression and falsely elevate arterial systolic
pressure and therefore the ABPI. In these patients, Doppler waveforms and toe pressure
analysis have been found to be more reliable12. Other modalities that may be useful
Consultant (Acute and ChronicWounds), Bradford Royal
include transcutaneous P
O and laser Doppler measurement of skin perfusion pressure13,14.
Arterial perfusion should be re-evaluated on a regular basis in all patients receiving
RECOMMENDATIONS FOR TREATMENT
Patient presents with
Multi-layer (elastic or
Immobile/fixed ankle patient
• Medical/surgical treatment
Ulcer fails to heal
• Appropriate dressing
Refer to vascular
selection according to:
Wound and surrounding
Mixed arterial and
Reasons for referral
Refer to vascular
specialist particularly if
continuing rest pain
• No reduction in ulcer size in one month• Ulcer duration >6 months• Cellulitis unresponsive to
Mixed arterial and
Refer to vascular
for oedema control
based on ABPI
Figure 1 | A recommended
compression therapy, in particular in the elderly, in whom arterial disease is more
common and may progress more rapidly15.
developed by the Leg
The recommended treatment pathway also emphasises the importance of confirming
Ulcer Advisory Board for
the presence of venous disease. Factors other than chronic venous insufficiency, such as
the use of compression
congestive heart failure, renal insufficiency, and morbid obesity may be responsible for
therapy in venous leg
limb oedema and chronic ulceration. The presence of venous disease may be confirmedusing venous Duplex ultrasound or plethysmography16,17.
Following assessment, a leg ulcer can be assigned as follows:
● Uncomplicated venous ulceration
– an ulcer occurring in the presence of venous
disease in a limb with an ABPI >0.8 and no other significant medical diseases thatwould prevent the use of high compression therapy
International Leg Ulcer
: C Allegra
Complicated venous ulceration
– an ulcer occurring in the presence of venous disease
in a limb with an ABPI <0.8 or with other significant medical diseases that would
prevent the use of high compression bandages or may complicate management.
– Mixed arterial and venous ulcer
(moderate arterial insufficiency with an ABPI
S Meaume (France); C Moffatt(UK); HAM Neuman (The
0.5-0.8). In a normotensive individual an ABPI 0.5 equates to an ankle systolic
pressure of 65-75 mmHg and at such pressures high compression bandaging is
– Mixed arterial and venous ulcer
(severe arterial insufficiency with an ABPI<0.5)
● Arterial ulceration
JE Torra i Bou (Spain); W Vanscheidt (Germany).
● Other causes of ulceration
UNDERSTANDING COMPRESSION THERAPY
High compression elastic bandages
These elastic, highly extensible (long-stretch) bandages expand or contract to
accommodate changes in leg geometry during walking with the result that pressurechanges over the calf are fairly small. They also sustain applied pressures for extendedperiods, even when the patient is at rest.
High compression inelastic bandages
These inelastic, minimally extensible (short-stretch) cotton bandages, when firmly applied,
cannot accommodate changes in limb circumference. As a result, the pressures beneath
such bandages tend to increase during the walking cycle as the calf muscle attempts to
expand against the relatively rigid and inextensible fabric covering. The bandage therefore
reinforces or supports the action of the calf muscle pump18.
These bandages tend to have lower residual or resting pressures than more elastic
bandages, making them inappropriate for use in immobile patients19. However, this maymake them safer when the arterial supply is moderately impaired. They also require morefrequent replacement20 as they do not ‘follow in’ as the oedema is reduced and the legdimensions decrease.
It is suggested that such bandages have a significant effect on deep venous
haemodynamics when compared with elastic compression stockings, which exert theirprimary effect on the superficial venous system. Inelastic bandages may therefore be moreeffective in patients with extensive deep vein reflux (see page 3
There are a variety of multi-layer systems available. They all tend to have 3-4 layers and
include either elastic or inelastic compression bandages, cohesive/adhesive bandages, crepe
bandages and/or padding layers. The components in each system are different and have
different extensibilities, powers and elasticities. It is possible that the success of elastic multi-
layer compression systems is due to the fact that these generally contain a combination of
bandages. The elastic bandage provides sustained compression and the cohesive/adhesive
inelastic bandage offers rigidity and enhances the calf muscle pump function. The concept
of multi-layer is that pressure is applied in layers, giving an accumulation of pressure.
The role of dynamic compression or intermittent pneumatic compression (IPC) in the
management of lower limb venous ulcer disease has been reviewed21. Although much of
the medical literature relates to the use of IPC in the prevention of deep vein thrombosis,
there is some evidence that improvements in venous return due to the use of IPC may
facilitate healing of venous leg ulcers. Eight small studies have been undertaken, which
conclude that IPC may be of benefit, particularly when used in conjunction with
compression bandaging, but as yet there is no statistically significant evidence for its
routine use22,23. Theoretical analysis of the benefits of IPC, however, do suggest that it may
be advantageous in the immobile patient with a slow or non-healing ulcer21.
Cullum et al
performed an extensive literature search yielding 22 trials evaluating
compression techniques24. From this it was concluded that these trials supported the use of compression therapy, with higher healing rates compared to no compression. Highcompression (ankle compression 35-45 mmHg) was more effective than low (reduced)compression (ankle compression 15-25 mmHg), and elastic or inelastic multi-layer systemswere more effective than single-layer compression. There was no evidence of differencesbetween hosiery, Unna’s boot (paste bandage with either an elastic or inelastic overlay),inelastic and elastic multi-layer high compression bandaging24.
To date, there appear to be few studies that have effectively compared the results
obtained with elastic multi-layer and inelastic multi-layer high compression25.
Based on the results of these randomised clinical trials, expert opinion and patient-related
factors, the treatment pathway recommends a preference for multi-layer high compressionsystems for venous leg ulcers. In order to optimise care, the International Leg UlcerAdvisory Board has based decisions on both the physiological effects of bandaging onmobile and immobile patients and the differences in outcome between these two groups (i.e.
immobile patients in whom healing is often difficult to achieve26).
Active and mobile patients
For active patients, either elastic or inelastic multi-layer compression is recommended. For
patients who prefer the self-care option, elastic compression hosiery can be used as an
alternative, particularly in those with smaller ulcers who do not need a bulky primary dressing.
Elastic multi-layer compression is recommended for immobile patients or those with a fixed
Immobile/fixed ankle patient
ankle joint. Compression with inelastic bandages is not recommended as these bandages
cannot perform properly if the calf muscle pump is weak or ineffective as they will fail to
generate adequate levels of compression. IPC may be used as an adjunct to elastic multi-
layer compression when the ulcer is not healing as expected with compression bandaging
alone, although the supporting evidence for this is limited21,23.
Choosing an ideal compression system
In putting together this document, which draws upon current evidence and expert opinion,
a number of criteria are proposed that should be considered as benchmarks for the ideal
compression system in patients with uncomplicated venous ulcers.
Benchmarks for an ideal compression system
– evidence-based treatment
– ability to provide and maintain clinically effective levels of compression for at least
one week during walking and at rest
Enhances calf muscle pump function
– account needs to be taken of known and likely allergens (e.g. latex hypersensitivity)
Ease of application and ease of training
Conformable and comfortable (non-slip)
selection according to:
Wound and surrounding
Appropriate dressing selection
A Cochrane systematic review recommends that for the majority of venous ulcers, a
simple non-adherent, absorbent dressing offers sufficient ulcer protection under thecompression system24. However, clinicians must choose an appropriate dressing according
Reasons for referral
to the characteristics of the wound and surrounding skin, taking into account issues such
• Unable to tolerate compression• Uncontrolled pain• No reduction in ulcer size in
Other treatment considerations
In patients who fail to progress with high compression bandaging, who have venous ulcers
• Ulcer duration >6 months• Cellulitis unresponsive to
complicated by co-existing arterial disease (ABPI<0.8), or who develop complications such
as cellulitis, allergy, uncontrolled pain or who fail to tolerate compression therapy, referral to
a specialist is necessary for further assessment and management.
UNDERSTANDING COMPRESSION THERAPY
MIXED ARTERIAL AND
For patients with an ABPI <0.5, compression therapy is not indicated and referral to a
vascular specialist is recommended. Many of these patients may benefit from either arterialsurgery or interventional radiology.
If the ulcer is classified as mixed, the ABPI is 0.5-0.8, and there is access to expert
bandagers and teams with immediate access to vascular services, the patient may be treatedwith reduced compression of 15-25 mmHg. This has been proved to be an effective methodof care27,28. An inelastic, short-stretch system may also be used which has a lower restingpressure, although this form of compression is less effective in the immobile patient.
Ischaemic rest pain is an absolute contraindication for compression therapy and an
indication for urgent referral to a vascular specialist.
Other conditions such as rheumatoid arthritis, diabetes, renal failure, anaemia, infection,oedema, autoimmune disorders, pyoderma gangrenousum and malignancy are less commoncauses of leg ulceration. These patients require disease-specific treatments; compression,providing the ABPI is adequate, may also have a major part to play in the management ofoedema in these conditions.
The effectiveness of treatment should be evaluated continually by the multidisciplinaryteam in order to maximise the healing potential. The degree of improvement at four weekshas been related to eventual ulcer healing29,30. If the wound shows progress, with ameasurable decrease in size at this time, it is reasonable to continue the initial therapy.
However, if no measurable progress has been made, or there is a change in the patient’sunderlying medical status, a complete re-assessment should be performed. This shouldinclude reassessment of the venous and arterial systems and the appearance of the ulcer.
Where indicated, bacterial culture and biopsy should be taken.
A reassessment of the patient’s lifestyle and suitability of the chosen therapy should be
undertaken. This may result in the use of an alternate form of compression or referral to aspecialist for the consideration of venous surgery, or for patients with a reduced ABPI,arterial investigation.
Those patients with ulcers that show slow progress in the first 3-4 weeks of treatment or
that fail to heal may benefit from the addition of adjunctive therapies to accelerate healingonce other correctable causes of delayed healing have been investigated. It is, however,beyond the scope of this article to discuss these in detail, although it is worth mentioningthat treatment with oxypentifylline has been shown to improve ulcer healing31.
Delayed healing of venous leg ulcers
Much work is still needed to identify the clinical, social and psychological effects ofcompression on healing. Several studies have evaluated risk factors associated with delayedhealing of venous leg ulcers treated with compression therapy32,33. Using multivariateanalysis, Franks et al
7 identified three major factors that can delay ulcer healing: ulcer size,ulcer pre-treatment duration and limb mobility. Margolis et al
34 also examined factorsaffecting healing and suggested a simple scoring system to predict ulcer healing. Whilesome authors propose a role for popliteal vein reflux as an independent risk factor35-37,others such as Guest38 suggest that this is not an important factor in delayed ulcer healing.
It has also been suggested that socio-economic factors, through an association with
general health, nutritional status and adherence to treatment, may adversely affect healingrates39. The study by Franks et al
7 showed an association between social factors (socialclass, central heating, being male and being single) and venous ulcer healing, althoughfurther investigation is required to understand the precise mechanisms of theseassociations.
Patient participation with treatment
• Prevention of recurrence
It is important for practitioners to encourage patients to participate actively in their
treatment. This may improve concordance and aid healing40. The use of education and a
holistic approach to care is important, as is an effective interaction between the healthcare
professional and the patient if best outcomes are to be achieved. Adherence with treatment is
also dependent upon patient motivation, which can be affected by factors such as socialisolation or treatment discomfort41. Pain management is an often underestimated aspect ofleg ulcer management. Effective symptom control either with dressings or analgesia can
Ulcer fails to heal
Definition: no reduction in size
improve quality of life and patient tolerance of compression therapy42.
• Re-evaluation including diagnosis and re-assessment
Unfortunately ulcer recurrence is common43-45 with many patients experiencing multiple
episodes of ulceration46. Moffatt and Dorman47 identified factors that lead to re-ulceration.
These include a history of a deep vein thrombosis, previous ulcer size and arterialhypertension. The mainstay of preventative treatment is hosiery48 providing compression of35-45 mmHg at the ankle. For patients who find it difficult to apply their garments, a lowerlevel of compression (25-35 mmHg) or a combination of low compression hosiery may beused. Alternatives include the use of long-term elastic or inelastic bandaging. Sustained useof these techniques to prevent recurrent oedema results in a lower incidence of ulcerrecurrence49. The higher the level of compression the patient can tolerate the lower theincidence of recurrence50. This does, however, depend on the regular use and replacement ofprescribed hosiery.
The role of surgery in both the healing and prevention of venous leg ulceration is yet to
be established; results published to date would suggest that surgery reduces ulcerrecurrence51,52 although further work, including randomised controlled studies, is required.
Multi-layer high compression bandaging has been shown unequivocally to provide a safeand highly effective treatment for the majority of patients with uncomplicated lower limbvenous ulceration. Healing rates of up to 70% at 12 weeks can be obtained and whencombined with a programme to prevent ulcer recurrence can dramatically improve patients’quality of life and reduce the burden of venous ulcer disease on healthcare systems.
Further work is needed to validate the benchmarking criteria used to define the ideal
compression system proposed in this document. This will be helped by the development ofan international classification system which is required to standardise terminology andensure that the physical attributes of bandages are reflected in a common language.
The recommended treatment pathway developed by the International Leg Ulcer
Advisory Board highlights the association between accurate assessment, detailed diagnosisand effective compression therapy in the management of uncomplicated venous leg ulcers.
Using the recommended treatment pathway described, healthcare professionals can, byworking together, develop their practice and ensure the highest standards of care for patientswith lower leg ulceration.
1. High compression therapy is the cornerstone of management of venous leg ulcers.
2. The recommended treatment pathway highlights the importance of effective compression therapy, as well
the need for accurate assessment and detailed diagnosis.
3. In patients with uncomplicated venous leg ulcers, decisions about which compression system to use
should be based on whether the patient is mobile or immobile.
4. Criteria for an ideal compression system have been proposed and require validation.
5. To prevent ulcer recurrence patients require life-long compression therapy.
6. Patient-related and social factors, which may include treatment costs, must be taken into consideration
when recommending compression therapy to achieve the best healing rates.
UNDERSTANDING COMPRESSION THERAPY
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2. Stacey MC, Falanga V, Marston W, Moffatt C, et al. The use of compression
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8. Vowden KR, Goulding V, Vowden P. Hand-held Doppler assessment for
35. Barwell JR, Ghauri ASK, Taylor M, et al. Risk factors for healing and recurrence
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Biscayne Building 19 West Flagler Street, Suite 220 The Honorable Dr. Barbara Carey-Shuler, Chair and Members of the Board of County Commissioners OIG Investigation of Fraud Against the MDHA and Housing Recipients. Attached please find the Office of the Inspector General’s (OIG) Press Release regarding an OIG investigation of fraud perpetrated on the Miami-Dade Housing Agency (MDHA) and its
Page 1 sur 3 Questions Questions/Réponses Les contraceptifs oraux combinés (appelés le plus souvent « pilules »). 1. Qu’est-ce qu’un contraceptif oral combiné ? 2. Qu’est-ce qu’une thrombose veineuse ? 3. Qu’est ce qu’une thrombose artérielle ? 4. Quels sont les signes cliniques évocateurs de thrombose qui doivent amener à consulter en 5. Le risque de thromb