Venous thromboembolism
BMJ 2006; 332 doi: https://doi.org/10.1136/bmj.332.7535.215 (Published 26 January 2006) Cite this as: BMJ 2006;332:215All rapid responses
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A shortcoming of this otherwise excellent review is that it did not
draw sufficient attention to those diagnostic pitfalls which are an almost
inevitable consequence of the reliance that many frontline medical staff
place on diagnostic tests when differentiating between three of the most
life-threatening chest pain syndromes(what I would call the three ugly
sisters), namely, pulmonary embolism(PE), dissecting aortic aneurysm, and
myocardial infarction. Dissecting aneutysm simulates pulmonary embolism
when it presents with chest pain and/or collapse in association with an
elevation in D-dimer levels of the order of > 0.5 mcg/ml(1), so much so
that, according to one study "testing for d-dimer should be part of the
initial assessment of patients with chest pain, especially if aortic
dissection is suspected"(1). When PE presents with chest pain and an
elevation in serum cardiac troponin(2) a mistaken diagnosis of myocardial
infarction might lead not only to inappropriate thrombolysis, but also to
a false sense of security given the likelihood that in that context,
thrombolytic therapy will not be followed by a course of oral
anticoagulation lasting at least three months as recommended by the
authors(3).
The reality is that, such is the overlap in the symptomatology of the
three "ugly sisters" that, if I were to paraphrase the authors of a recent
study evaluating the limitations of the chest pain history, none of the
elements of the chest pain history, alone or in combination, identify a
group of patients that can be safely categorised without further
diagnostic testing(4). If, as in the real world, the patient with chest
pain enters the diagnostic algorithm on the basis of the D-dimer test,
even where PE is deemed unlikely(5), or on the basis of troponinosis, even
where myocardial infarction is deemed unlikely, the consequences will be
incalculable unless these diagnostic pitfalls are highlighted.
OMP Jolobe
References
(1)Weber T., Hogler S., Auer J., et al
D-dimer in Acute Aortic Dissection
Chest 2003:123:1375-8
(2) Francis GS and Tang WHW
Cardiac troponins in renal insufficiency and other non-ischemic cardiac
conditions
(3) Blann AD and Lip GYH
Venous thromboembolism
British Medical Journal 2006:332:215-9
(4) Swap CJ and Nagurney JT
Value and limitations of chest pain history in the evaluation of patients
with suspected acute coronary syndromes
Journal of the American Medical Association 2005:294:2623-9
(5) Writing Group for the Christopher Study Investigators
Effectiveness of managing suspected pulmonary embolism using an algorithm
combining clinical probability, D-Dimer testing, and computer tomography
Journal of the American Medical Association 2006:295:172-9
Competing interests:
None declared
Competing interests: No competing interests
This article and last week's on pulmonary embolus made no mention of
the porcine origin of heparins which is an important issue for some
religions, for example, muslims. Many doctors and nurses are unaware of
this and therefore cannot fully inform patients when giving advice about
prophylaxis or treatment with heparin (unfractionated or low molecular
weight). However, according to our trust's muslim chaplain when there is
no alternative non-porcine treatment available and there is a risk to
life, then it is allowable for muslims to receive a drug of porcine origin
under these circumstances. Even so, some muslims may choose not to receive
treatment or prophylaxis with heparin because of its porcine origin and
patients do have the right to make the decision for themselves.
Fondaparinux is a synthetic alternative for some of the indications
for which heparins are currently used and I was interested to read that it
may have advantages over low molecular weight heparin both in efficacy and
cost effectiveness. Ethically, it should be available for use by muslim
patients and others who object to the use of medicines of porcine origin.
Competing interests:
None declared
Competing interests: No competing interests
Editor: It was a delight to read in total nine pages worth of
information on Venous thromboembolism (VTE) in the BMJ over the past two
weeks 1,2. What did strike me amiss is that out of these nine pages only
fifteen words refer to the use of compression stockings and pneumatic
compression devices. I feel that these cheap and completely non-invasive
means of thromboembolic deterrent should have a more marked place.
The evidence behind compression stockings and pneumatic device use is
well known. As long as twenty years ago there was controlled trial
evidence showing the efficacy of graduated compression stockings compared
to low dose heparin 3. More recently a meta-analysis showed that graduated
compression stockings are a useful adjunct to Low Molecular Weight
Heparins and reduce the incidence of VTE in colorectal surgery 4.
Whilst I am sure everyone knows about the use of stockings in
prophylaxis against VTE, I believe it important to give more space to
these devices which are often used as a direct alternative to Heparins
especially when the consequences of bleeding are dire.
1)Robinson GV. Pulmonary embolism in hospital practice. BMJ 2006;
332: 156-160
2)Blann AD, Lip GYH. Venous thromboembolism. BMJ 2006; 332: 215-219
3)Fasting H, Andersen K, Kraemmer Nielsen H et al. Prevention of
postoperative deep venous thrombosis. Low-dose heparin versus graded
pressure stockings. Acta Chir Scand. 1985; 151(3): 245-8
4)Wille-Jorgensen P, Rasmussen MS, Andersen BR et al. Heparins and
mechanical methods for thromboprophylaxis in colorectal surgery. Cochrane
Database Syst Rev. 2003; (4): CD001217
Competing interests:
None declared
Competing interests: No competing interests
Blan and Lip’s review of venous thromboembolism places patients
undergoing elective joint replacement of the hip or knee in groups such as
“strong risk factors”, or at “very high risk”.
This is however highly misleading. Their statement that lower limb
deep vein thrombosis has been documented in half of all major orthopaedic
operations is correct, although they provide no reference for this except
a link to the National Institute for Health and Clinical Excellence (NICE)
and Scottish Intercollegiate Guidelines Network (SIGN) websites. These
thromboses are, in the vast majority, of no clinical significance
whatsoever.
Unfortunately, further examination of these sites quote Warwick et
al1 and Fender et al2 demonstrating the risk of symptomatic DVT at only
1.1-2.8% for hip replacements and 7-11% for knee replacements, even in
patients with no thromboprophylaxis. In addition the risk of non-fatal PE
is only 0.6-3%, and the risk of fatal PE is a mere 0.1-1.1%, hardly what I
would call a high risk.
To date not a single trial has been able to conclusively prove that
any chemical thromboprophylaxis has been able to prevent a single death
from PE in elective hip and knee joint replacement.
According to the National Joint Registry, over 2400 joint
replacements are carried out each week in the England, well above 120000
per annum, and many more in Scotland and Wales. Despite this large number,
the incidence of fatal PE remains so low, that a change in its incidence
due to a particular intervention remains undetectable. This is not
necessarily the case in patients undergoing emergency orthopaedic surgery,
however, and there is a role for thromboprophylaxis here. These views are
similar to the conclusions drawn by the PEP trial3 regarding the use of
aspirin in patients undergoing elective and emergency orthopaedic surgery.
I would hesitate to generalise about the use of thromboprophylaxis in
these groups, let alone make them into a homogenous entity. The risks of
anticoagulation include persistent wound ooze and haematoma formation
among others, both of which are factors in developing deep infection. As a
group of patients for whom deep infection remains a problem with more
serious consequences, I think it would be wise to take careful
consideration before the routine use of chemical prophylaxis is applied.
The BOA published its own best practice guide in 1999, in which it
recommended that hip and knee replacement be regarded as moderate risk for
death from pulmonary embolism. Let us not overstate its significance as an
indication for the use of anticoagulant agents.
Reference List
(1) Warwick D, Williams MH, Bannister GC. Death and thromboembolic
disease after total hip replacement. A series of 1162 cases with no
routine chemical prophylaxis. J Bone Joint Surg Br 1995; 77(1):6-10.
(2) Fender D, Harper WM, Thompson JR, Gregg PJ. Mortality and fatal
pulmonary embolism after primary total hip replacement. Results from a
regional hip register. J Bone Joint Surg Br 1997; 79(6):896-899.
(3) Prevention of pulmonary embolism and deep vein thrombosis with
low dose aspirin: Pulmonary Embolism Prevention (PEP) trial. Lancet 2000;
355(9212):1295-1302.
Competing interests:
None declared
Competing interests: No competing interests
Role of venometry: An omission
Role of venometry: An omission
Andrew D Blann et al review article on Venous thromboembolism was
informative and exhaustive but not without few omissions of information
regarding the diagnosis and the management of VTE.
It is curious that the role of venometry (Strain gauge
plethysmography ) which is well established and supported in the diagnosis
of DVT was not mentioned and needless to say it is cost effective when
combined with D Dimers, in evaluation of DVT in a district general
hospital set up. (1)
Plasma D-dimers is an end product derived from plasmin mediated
degradation of cross-linked fibrin clots, and a sensitive marker for VTE
but lack specificity. Therefore it cannot be used to make a positive
diagnosis of VTE; however, d dimers generally have high negative
predictive value and are useful as an exclusionary test, a potentially
important role given that VTE is eventually ruled out in most patients
investigated. (2)
Flanagan et al and Robinson et al reported that computed strain gauge
plethysmography can be used as a satisfactory first line investigation for
the diagnosis of DVT, with a negative predictive value of 97 %.( 3, 4)
As both venometry and D dimers are highly sensitive (75-95%) with a
high negative predictive value ranging between 90 and 100%, they make a
safer diagnostic test in ruling out a DVT with a low probability score,
which obviates the need for the ultra sound, which is the current gold
standard investigation. It is also known that the prevalence of DVT in
patients with low clinical probability on the predictive score is around 5
%.( 5).
And it had been predicted that plethysmography, together with pre-
test probability scoring and a modern D-dimer test, would approach a
negative predictive value of 100%, providing a cost effective strategy in
the district general hospitals, where the Doppler ultrasound is still an
elusive, time-consuming test and not readily available after hours. (6, 7)
But the only point of contention being that Venometry though
sensitive to proximal DVT, may miss out a calf DVT. A negative venometry
with positive D-dimer may indicate calf DVT. Therefore these patients
should undergo repeat imaging in few days time to detect extension of
thrombus. (7)
Treatment of DVT with LMWH in patients with renal impairment is
currently not clear, though few would use a cut off of 30ml of creatinine
clearance, before halving the dose.(8)
The following criteria will be useful in the investigation of low
probability DVT, while using the adaptation from Ho et al (8), for a high
probability predictive score.
.High probability of DVT:Ho et al guidelines
.Low probability of DVT: Venometry & Dimer
.Negative venometry& Normal D Dimer: No DVT
.Negative venometry& High D Dimer: repeat venometry in 7 days and
following
venometry negative: No DVT
venometry positive: Doppler
References
1. R Sinharay, G Strang and D Bird (2002). Cost effective strategy
for a safe diagnosis of deep vein thrombosis at a district general
hospital. Postgraduate Medical Journal 2003; 79:363
2. Kelly J, Rudd A, Lewis RR, Hunt BJ. Plasma D-dimers in the
diagnosis of venous thromboembolism. Arch Intern Med 2002 Apr 8;
162(7):747-56.
3. Flanagan DEH, Creasy T, Thomas P, et al. Computed assisted venous
occlusion plethysmography in the diagnosis of acute deep vein thrombosis.
Q J Med 2000; 93:277–82.
4. Robinson, Brian J., Kesteven, Patrick J. L. & Elliott, Simon
T. (2002)
The role of strain gauge plethysmography in the assessment of patients
with suspected deep vein thrombosis. British Journal of Haematology 118
(2), 600-603.
5. Wells PS, Owen C, Doucette S, Fergusson D, and Tran H. JAMA: Does
this patient have deep vein thrombosis? The Journal of the American
Medical Association [NLM - MEDLINE]. Jan 11 2006.Vol.295, Iss. 2; pg. 199
6. Sinharay R. Pleuritic chest pain and hypoxia—a diagnostic dilemma.
Br J Cardiol 2002; 9:589.
7. D.M. Collas, J. Brooks, P. Jacob Venometry And D-Dimer Levels In
The Investigation Of Deep Venous Thrombosis - A Means Of Selecting
Patients Who Do Not Require Imaging – DVT Age and Ageing, July, 2001
8. Jeff Nagge, Mark Crowther et al. Is impaired Renal function a
contraindication to the Use of LMW heparin?. Arch Intern Med 2002;162:2605
-2609
9. Ho WK, Hankey GJ, Lee CH, Eikelboom JW. Venous thromboembolism:
diagnosis and management of deep vein thrombosis. Med J Aust 2005;182: 476
-81.[ISI][Medline]
Competing interests:
None declared
Competing interests: No competing interests