APPENDIX 4
Memorandum by Tyco Healthcare (UK) (VT
7)
1. EXECUTIVE
SUMMARY
1.1 Tyco Healthcare is pleased to be able
to have an opportunity to submit evidence to this inquiry by the
Healthcare Select Committee into the prevention of thromboembolism
in the hospitalised patient. Media attention over recent years
has focused on the risk associated with travel related thrombosis
and this matter has also been raised in the House of Lords. However
the actual risk of Deep Vein thrombosis developing in the hospitalised
patient is considerably greater. This memorandum will focus on
the clinical evidence showing the risk of patients developing
venous thromboembolism and more specifically of the development
of thrombosis located in the deep veins of the lower limbs commonly
known as Deep Vein Thrombosis (abbreviated to DVT). The evidence
supporting strategies to prevent DVT in hospitalised patients
with a focus on mechanical measures will also be presented drawing
on evidence from clinical trials and recommendations form consensus
groups and government bodies such as the National Institute for
Health NIH (USA).
2. ABOUT TYCO
HEALTHCARE
2.1 Tyco Healthcare is a leading manufacturer,
distributor and servicer of medical devices worldwide. The company's
portfolio includes disposable medical supplies, monitoring equipment,
medical instruments and bulk analgesic pharmaceuticals and chemicals.
2.2 The author of this memorandum is the
Vascular UK Product Manager, Nicholas Tiller, who is responsible
for the marketing activities within the UK associated with the
prevention of Deep Vein Thrombosis. This is namely in the form
of Anti-Embolism Stockings and Intermittent Pneumatic Compression
Devices.
2.3 Position Statement: Tyco Healthcare
aims to provide world-class expertise both in technology and clinical
support to enable clinicians and healthcare professionals to provide
evidence based DVT prophylaxis to all risk categories of patients.
Clinical evidence emphasises that to maximise potential DVT reduction
all appropriate measures should be incorporated into an integrated
package of DVT prophylaxis, including anticoagulation and mechanical
measures both IPC and Antiembolism Stockings. Our approach includes
consultation with leading independent clinical professionals.
We offer a program of clinical symposia where the evidence platform
is reviewed; these symposia are open to all both within the NHS
and private hospital groups.
2.4 Please note that Tyco Healthcare would
pleased if requested to supply oral evidence during the session
planned for the 9 December, if attendance is required please make
contact using the information at the end of this memorandum.
3. SUBMISSION
TO THE
COMMITTEE
3.1 The severity of the problem: Incidents
of DVT in the hospitalised patient
3.1.1 As outlined in the introduction, considerable
media attention has focused on the incidence of travel thrombosis
and in particular a number of high profile deaths from Pulmonary
Embolism (PE) associated with long haul plane travel. It is of
note however that the incidence of DVT in hospitalised patients
is much greater. This can be confirmed by reviewing the following
studies; The Lonflit 4 study showed that asymptomatic DVT in the
long-haul flight passenger is in the region 4-6% Belcaro et al
(1). In-contrast the International Consensus (2) study entitled
"Prevention of venous thromboembolism guidelines according
to clinical evidence" (2002) concluded that the incidence
in hospitalised cases could be as high as 55% if no preventative
measures were taken. In the afore mentioned study it was concluded
that DVT incidence calculated by summarising published clinical
studies, without preventative measures, was as follows:
3.1.2 Stroke patients 51 to 61%; Elective
Hip Replacement 48 to 54%; Neurosurgery 17 to 24%. Patients groups
undergoing minimal invasive surgical procedures were still shown
to be significantly at risk for example patients undergoing transurethral
resection of the prostate 5 to 15% (2).
3.2 Costs associated with the treatment
of Deep Vein thrombosis and associated secondary diseases
3.2.1 The office for Healthcare Economics
(3) estimated in 1993, that the annual costs in the UK of treating
patients that developed post-surgical DVT and PE was in the region
of 204.7 to 222.8 million pounds. The International Consensus
Statement (2) also stated that approximately 25% of patients that
have in the past suffered from deep vein thrombosis will later
in life develop the debilitating condition of venous leg ulceration.
They also estimated that the annual costs of the treating venous
leg ulcers in the UK was in the region of 400 million pounds.
3.3 The asymptomatic nature of DVT development
in the hospitalised patient
3.3.1 Studies have shown that prophylactic
measures are still not practiced with the full proportion of patients
that are at risk of DVT development. (4,5,6,7) A possible reason
why DVT preventative measures are under-utilised is the asymptomatic
nature of DVT this could cause medical professionals to consider
that it is not a problem effecting patients under their care.
A hospitalised patient who has developed a DVT will often have
no outward signs that show that they have developed the condition.
For this reason DVT has sometimes been referred to as the "silent
killer" as the first indication may be a symptomatic or fatal
pulmonary embolism PE. The clinically silent nature of DVT has
been confirmed in several clinical studies. Sandler and Martin
(8) reviewed the autopsy records of patients who had died from
PE. They showed that less than 19% of patients showed clinical
symptoms of a DVT prior to their death. Patients with non-fatal
but symptomatic pulmonary embolism have also been shown to have
an underlying asymptomatic DVT. This was shown in a study published
in 1999 by Girard (9) in which the authors used venography to
confirm that 68% of patients with a symptomatic PE had an undiagnosed
underlying asymptomatic DVT.
3.3.2 Due to the asymptomatic nature of DVT
development, preventative strategies have focused on risk assessment
in order to assign appropriate interventions to maximise the opportunities
to reduce the incidence of DVT according to the patients individual
level of risk.
3.4 Risk Assessment strategies for the prevention
of DVT
3.4.1 It has been recognised for many years
that hospitalised patients are at significant risk of developing
this condition, especially if inadequate preventative measures
are taken, for example in 1968 Morrell (10) commented "Pulmonary
embolism remains the most common preventable death in hospital".
3.4.2 Measures to reduce the risk of DVT
development in the hospitalised patient have focused on the design
and implementation of patient focused DVT risk assessment tools.
These are designed to assess individual patients of risk of DVT
development and implement appropriate levels of preventative measures.
Many authors have published risk assessment tools with recent
examples including Autar (11) and Caprini (12). These tools assess
factors such as: patient mobility; age; complexity of surgery;
and predisposing underlying medical conditions such as cancer
and haematological or blood clotting disorders.
3.4.3 The theory behind risk stratification
for DVT preventions takes into account the underlying pre-disposing
factors that can trigger DVT. These factors and their reduction
also underpin the prevention strategies that the risk assessment
models propose. The following section will therefore briefly review
some of these factors as defined by the 19th Century researcher
Virchow (13).
3.5 Trigger Factors for DVT development:
Virchow's identified three main trigger factors or mechanism that
caused DVT to develop: Venous Stasis; Endothelial Damage and Alterations
in the blood clotting mechanism.
3.5.1 Venous Stasis: When patients are immobile
during surgery or in the immediate post-operative period there
is a reduction in the efficiency of blood return from the lower
limbs. Primarily this is caused by a reduced muscular activity,
specifically the contraction of the calf muscle that in healthy
mobile adults has a natural "blood pumping" action that
assists with blood return to the heart. This reduction in blood
flow or venous return to the heart results in blood becoming stagnant
in the lower limb. It should be noted that the three factors strongly
interact with each other, venous stasis as a result of reduced
blood flow results in the accumulation of trigger factors that
would otherwise be dispersed by normal blood flow.
3.5.2 Endothelial damage to the vein wall:
A result of the immobility discussed above the veins of lower
limb dilates this can be especially pronounced in valves that
are found within the deep veins and superficial veins of the lower
limb. The function of these valves is to prevent backflow of blood
towards the distal extremity (feet). Dilation of these valves
as a result of venous stasis if not prevented eventually may lead
to tearing of the delicate cell layer (endothelium) lining the
veins. This effect and the increased risk of Deep Vein thrombosis
that it can cause has been shown in studies by Coleridge (14)
and Comerata (15). The damage to vein wall can release factors
that activate the clotting cascade as discussed in more detail
in the following section.
3.5.3 Alterations in the blood clotting mechanism:
The third factor identified by Virchow was inherited or acquired
factors that increase the tendency for blood to clot. Certain
individual patients may have inherited blood-clotting disorders
that pre-dispose them to an increased risk of DVT formation. However
after surgery there are generalised factors that affect many patients
increasing the likelihood of DVT formation. As mentioned above
one of these is endothelial damage particularly within the valve
pocket that results in the triggering of the clotting cascade
due to the exposure of sub-endothelial collagen, which is strongly
thrombogenic.
3.5.4 Virchow (13) emphasised in his seminal
study in the 19th centaury that the interaction between the different
factors that cause DVT is critical to the formation of deep vein
thrombosis and that each factor multiplies the risks caused by
the other factors. It is important to address all factors to reduce
the risk of DVT development to a minimum.
3.6 Evidence Supporting the Prevention of
Deep Vein Thrombosis with a focus on mechanical interventions.
3.6.1 Prophylaxis to prevent DVT aims to
reduce the effect of the above-mentioned three factors and thereby
reducing the likelihood of a patient developing a DVT. The clinical
evidence that mechanical measures can reduce the clinical evidence
of DVT will be discussed in more detail in section 3.8.
3.6.2 Venous Stasis: The use of Antiembolism
Stockings has been shown to be significantly reduce the development
of venous stasis. Studies have shown increased blood flow velocity
when antiembolism stockings are warn as well as faster clearance
of blood from the areas such as the valve cusps where venous stasis
has the most pronounced effect Lewis (16) Benko (17).
3.6.3 In Higher risk Patients intermittent
pneumatic compression systems such as the SCD system supplied
by Tyco Healthcare have been shown to be effective. The SCD system
is designed to increase blood flow velocity in the lower limb.
The sequential action of the system is designed to collapse the
veins in a distal to proximal manner ie starting at the ankle
and progressing upwards. The system is also graduated applying
greatest pressure at the ankle. The combination of this technology
has been designed to cause a progressive collapse of the veins
from the ankle upwards to ensure that not only is blood velocity
is increased, but also to ensure that the pockets of stagnant
blood in the vein valve pockets are reduced as far as possible.
Evidence that SCD Systems are effective Scurr (18) Janson (19)
Kamm (20).
3.6.4 Endothelial damage: Venous dilation
that can cause endothelial damage has also been shown in a number
of studies to be prevented by Antiembolism Stockings, Colerdige.
(14) It has also been shown that the combination of the use of
intermittent pneumatic compression together with Antiembolism
Stockings has been shown to be more effective than either measure
used alone, Scurr. (18)
3.6.5 Alterations in the blood clotting mechanism:
Anticoagulants are often used to reduce the risk of thrombus formation
and to compensate for the reduction in the body's natural fibrinolytic
activity. Interestingly recent evidence has shown that intermittent
pneumatic compression can also reduce this risk by increasing
localised fibrinolysis within the lower limb. Hartman (21) et
al 1982 commented, "In patients who are to have an operation
on the hip, therefore, it would theoretically be more beneficial
to use thigh-length sleeves, as in the present study, than to
use knee-length sleeves. The longer sleeves compress a greater
muscle mass and they do not interfere with the surgical incisions
for operations on the hip. Fitting the cyclic sequential-compression
sleeves to the patient on the evening before the operation would
also have the beneficial effect of `gearing up' the patient's
fibrinolytic capacity and thereby reducing the magnitude of the
fibrinolytic shutdown." A more recent study by Hoppenstadt
(22) has also shown similar results.
3.7 Combined methods of prophylaxis It is
emphasised in the above references that combined methods of prophylaxis
are required to effectively address the risk of DVT development.
A number of studies have shown the effectiveness of such regimes
of patient care.
3.7.1 It is logical that by preventing DVT
the incidence of pulmonary embolism will also be reduced. A recent
study by Ramos (23) showed that the addition of IPC to a regime
of subcutaneous heparin further reduced the incidence of PE by
62%. Over 2,500 patients were included in this trial and it showed
clearly the effectiveness of the SCD Sequel Compression System
to reduce the incidence of Pulmonary Embolism. A study by Hooker
(24) in orthopaedic patients showed that when anticoagulants are
not chosen for prophylaxis the SCD Sequel System has been shown
to be as effective as anticoagulants used alone.
3.8 Clinical evidence showing the effectiveness
of Antiembolism Stockings in a clinical setting.
3.8.1 As well as individual clinical studies
describing the effectiveness of antiembolic stockings in the prevention
of Deep Vein thrombosis there have been a number of meta-analysis
that have overviewed the effectiveness of this intervention in
the prevention of Deep Vein Thrombosis.
3.8.2 A meta-analysis by Wells Lensing et
al (25) 1994, which included many of the above papers, this showed
an overall reduction in DVT incidence of 72.5%. This meta-analysis
by Wells Lensing and Hirsch was reviewed by Rumano Dickson of
the centre for health economics at York University in 1996 and
the following conclusions were drawn. "This review provides
an excellent opportunity to translate statistical analysis into
implications for clinical practice. . .this means treating nine
patients with graduated compression stockings will prevent the
development of one DVT"
3.8.3 A review of the effectiveness of Antiembolism
stockings in the prevention of Deep Vein Thrombosis published
by the Cochrane Library 2003 authored by Amaragiri. (26) This
review by the Cochrane Library is one of the most recent overviews
or meta-analysis relating to the prevention of DVT using Antiembolism
stockings. The authors of this report again included the "core"
TED studies that had previously been quoted in the 1984 review
by Wells et al. This again emphasises the validity of these studies
and the unique quality of this research supporting the efficacy
of TED. Antiembolism stockings.
3.9 Recommendation of National and International
consensus panels on the prevention of Deep Vein Thrombosis in
relation to the use of Antiembolic Stockings.
3.9.1 Many National and International panels
have published evidence-based guidelines concerning the reduction
in the incidence of Deep Vein Thrombosis. These guidelines make
recommendations according to levels of clinical evidence; the
more substantial the evidence base the stronger the clinical recommendation
or practice implication stated within the guideline, the following
are recent examples:
3.9.2 International Consensus Statement (27)
(Guidelines According to Clinical Evidence 2002);
3.9.3 Prevention of Thromboembolism (28)
(Sixth Consensus Conference on Antithrombotic Therapy American
College of Chest Physicians CHEST2001);
3.9.4 Prophylaxis of Venous Thromboembolism
A National Clinical Guideline Scottish Intercollegiate Guidelines
Network (SIGN Guideline 2002)
3.9.5 The authors of the SIGN guideline made
the following overall conclusion about the use of Antiembolic
Stockings "GECS are effective in prophylaxis of Asymptomatic
DVT and symptomatic PE in surgical patients page 5 SIGN Guidelines"
the authors also made the following comment about the length or
style of antiembolic stocking that should be used "Above
Knee GECS are preferred to below knee stockings for the prophylaxis
of DVT"
3.9.6 Note in the above study the authors
of the SIGN guidelines refer to Antiembolic stockings using the
generic term abbreviation "GECS" this is more commonly
used to describe therapeutic compression hosiery. In general terms
the included studies within the sign guidelines are similar to
the selection identified by Wells et al and by the International
Consensus Statement and also the Cochrane review.
3.9.7 In the above clinical reviews no distinction
is made between the manufactures of included studies however many
of the included studies used the TED brand from Tyco Healthcare.
Attention has however been drawn to this point in a clinical study
published in 1995 by Wille-Jorgenson (29) "Two methods
of compression prophylaxis have gained wide acceptance- intermittent
pneumatic compression (IPC) and graduated compression stockings
(TED). `TED' is a Kendall Company trademark, but the term has
become generally used for all kinds of compression stockings.
This is unfortunate, as it is only the original TED stocking which
has been thoroughly investigated in prospective clinical trials."
It should be noted that Kendall is a trading division of Tyco
Healthcare.
3.9.8 The above summary is not totally exhaustive
list of evidence that Tyco healthcare (UK) is aware of supporting
the use of antiembolic stockings and intermittent pneumatic compression
for the prevention of DVT in the hospitalised patient. If further
clinical information is required the company would be pleased
to submit this at a later date.
3.10 Conclusions and recommendations:
3.10.1 In order to prevent DVT adequately
within the context of the hospitalised patient it is important
that a combination of interventions are used in order to maximally
reduce the incidence of Deep Vein Thrombosis. This should include
the use of pharmacological measures and mechanical measures both
antiembolic stockings and intermittent pneumatic compression.
3.10.2 The use of clinically based risk assessment
tools to stratify patients according to their risk levels should
become more widespread. Prevention options based on such tools
should be firmly evidenced based to ensure that interventions
will have the maximum clinical impact.
3.10.3 The increased deployment of DVT Nurse
Specialists to encourage the dissemination and implementation
of Risk assessment based strategies could lead to significantly
improved patient care.
3.10.4 Cost pressures within the healthcare
system could lead to the selection of the lowest cost available
mechanical interventions and not necessarily those that are strongly
supported by clinical evidence.
REFERENCES 1 Belcaro
Lonflit 4.
2 Int cons statement.
3 Office of Healthcare economics
4 Morris GK. Prevention of venous thromboembolism:
A survey of methods used by orthopaedic and general surgeons.
Lancet 1980: ii: 572-574.
5 Brenkel IJ et al. Total Hip replacement
and antithrombotic prophylaxis. Br J Hosp Med 1989; 42:282-284.
6 Bergqvist D. Prophylaxis against postoperative
venous thromboembolism a survey of surveys. Thromb Haemorrh Disorders
1990.
7 Laverick MD et al. Orthopaedic surgeons
and thromboprophylaxis. Br Med J 1991; 303:549-550.
8 Sandler DA and Martin et al; Autopsy proven
pulmonary embolism in hospital patients: are we detecting enough
deep vein thrombosis? J Ryl Soc. Med April 1989 Vol 82.
9 Girard Phillip et al High prevalence of
detectable venous thrombosis in patients with acute pulmonary
embolism; Chest Oct 1999 vol. 116 No 4 pge 903-908.
10 Morrell MT The post-mortem incidence of pulmonary
embolism in a hospital population. Br J Surg. May 1968 Vol 55
No 5 Pge 347-52.
11 Autar R. Calculating patients' risk of deep
vein thrombosis; Br J Nursing 1998 Vol. 7 No 1 pge 7-12.
12 Caprini Joseph A et al Effective Risk Stratification
of surgical and nonsurgical patients for venous thrombembolic
disease. Semin Hematol 38 (Suppl 5): 12-19. Copyright 2001 by
W.B.. Saunders Company.
13 Virchow R. Die Celluarpathologie in ihrer
begrunung auf physiologische und pathologische gewebelehre. A.
Hirschwald, berlin, 1858. cited in Bergquivist D et al 1988 The
economics of general surgery thromboembolic prophylaxis.
14 Coleridge-Smith PD. Venous Stasis and Vein
Lumen Changes During Surgery Br J Surg 1990 Vol. 77, 1055-1059.
15 Comerata AJ: Operative venodilation; A previously
unsuspected factor in the cause of postoperative deep vein thrombosis:
Surgery Aug 1989 Vol 106 No 2.
16 Lewis CE Elastic Compression in the Prevention
of Venous Stasis: A Critical Reevaluation The American Journal
of Surgery 1976 Vol. 132, 739-743.
17 Benko T. The physiological effect of graded
compression stockings on blood flow in the lower Limb; An assesment
with colour duplex doppler ultrasound. Phebology 1999 Vol 14;
17-20.
18 Scurr JH. Regimen for improved effectiveness
of intermittent pneumatic compression in deep venous thrombosis
prophylaxis Surgery Vol. 102, No. 5, 816-820, November 1987
19 Janson HF. The role of venous Blood flow in
the prevention of Deep vein Thrombosis 38th Annual meeting, orthopaedic
research Society, Feb 17th 1992.
20 Kamm J. Bioengineering Studies of Periodic
External Compression as Prophylaxis Against Deep Vein Thrombosis
Part I: Numerical Studies, Part II: Experimental Studies on a
Simulated Leg Journal of Biomechanical Engineering Vol. 104, 87-95,
May 1982.
21 Hartman .T. Cyclic Sequential compression
of the Lower limb in prevention of Deep Venous Thrombosis The
Journal of Bone and Joint Surgery Vol. 64-A, No. 7, 1059-1062,
September 1982.
22 Hoppensteadt DA. The Role of tissue factor
pathway inhibitor in the mediation of the antithrombotic actions
of heparin and low-molecular-weight heparin. Blood coagulation
and Fibrinolysis 1995 Pt 1 Vol 6; S57-S64.
23 Ramos R. the efficacy of Pneumatic Compression
stockings in the prevention of pulmonary embolism after cardiac
surgery Chest Jan 1996 Vol 109 Pge 82-85.
24 Hooker J. A. Efficacy of prophylaxis against
thromboembolism with intermittent pneumatic compression after
primary and revision total hip arthroplasty. May 1999 Jnl Bone
& joint Surg Vol. 81-A No 5 Pge 690-696.
25 Wells P.S. et al Application of a Diagnostic
Clinical Model for the Management of Hospitalised patients with
Suspected Deep-Vein Thrombosis Thromb Haemost 1999 Pt 81;486-492.
26 Cochrane Library: Amaragiri SV, & Lees
TA. Elastic Compression Stockings for Prevention of Deep Vein
Thrombosis 2003.
27 Nicolaides Editor AN "Prevention of Venous
Thromboebolism" International Consensus Statement Guidelines
according to clinical evidence, Int Angio 2001 Vol20 No 1-37.
28 Jack Hirsch. The Sixth (2000) ACCP Guidelines
for Antithrombotic Therapy for Prevention and Treatment of Thrombosis
CHEST 2001; 119:1S-2S).
29 Prophylaxis of Venous Thromboembolism, A National
Clinical Guideline. Scottish Intercollegiate guidelines network
(SIGN). 2003 www.sign.ac.uk
30 Wille-Jorgenson P: Prophylaxis of postoperative
thromboembolism with a combination of heparin and graduated compression
stockings Sept 1996 Int. Angio Vol 15 supl 1 to No 3 pge 15-20.
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