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CHAPTER
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40
Diagnosis of Deep Vein Thrombosis
WARNER P. BUNDENS
BACKGROUND
Patients with one or more of Virchow’s triad of stasis,
hypercoagulability, or vein wall abnormalities are susceptible to thrombosis.1 Lower limb deep venous thrombosis
(DVT) is a common and potentially serious problem. Over
fi ve million occur in the United States annually, and approximately 10% become pulmonary emboli.
pulmonary emboli originate from lower limb DVTs.
can also result in permanent venous obstruction (i.e., chronic
DVT) and/or damage to venous valves leading to postphlebitic chronic venous insuffi ciency. Timely and accurate
diagnosis can aid signifi cantly in the reduction of morbidity
and mortality.
The clinical presentation of DVT can range from silent,
with no symptoms or physical fi ndings, to phlegmasia cerula
dolens and venous gangrene. The sensitivity and specifi city
of symptoms and physical fi ndings such as pain, tenderness,
swelling, redness, or a positive Homan’s sign range from 30
to 80%. The clinical diagnosis of DVT is not reliable with
an overall accuracy of only approximately 50%.
when DVT is suspected or part of a differential diagnosis an
accurate, objective test that can rule in or rule out DVT is
indicated.
Though this chapter is devoted to the diagnosis of thrombosis in the deep leg veins, one should keep DVT in mind
when seeing a patient with superfi cial thrombophlebitis. The
clinical diagnosis of thrombophlebitis of a superfi cial vein
is accurate. One should be aware, however, that multiple
studies have shown that approximately 20% of patients will
also have an occult DVT.
superfi cial veins usually extends further than is evident clinically and in up to one third of cases the thrombus eventually
11–16
The extent of thrombus in
2,3
Ninety percent of
4,5
6–10
Thus,
DVT
will extend into the deep system via the saphenofemoral
junction or communicating veins.
The traditional gold standard of objective DVT testing is
ascending contrast phlebography. Compared to autopsy
fi ndings it has a 97% sensitivity and 95% specifi city.20
The test, however, is costly, invasive, uncomfortable, and
associated with defi nite risks. One of the “particularly
unwelcome” complications is a 2 to 3% risk of the contrast
agents actually causing DVT.9 For decades the trend has
been to less invasive and, in the case of ultrasound, less
expensive methods of studying patients suspected of having
DVT. For years radioactive fi brinogen scanning and impedance plethysmography were widely used have been supplanted by duplex ultrasonography as scanners became
widely available and multiple studies showed acceptable
accuracy. Currently duplex ultrasonography is still the most
commonly used method of testing for lower limb DVT
though other methodologies are being used increasingly in
selected settings.
17–19
DUPLEX ULTRASONOGRAPHY
The combination of B-mode imaging and the pulse
Doppler into one instrument, the duplex, was originally done
as an aid to arterial diagnosis. It soon became evident that
it also could be used for venous investigations of both
obstruction and refl ux. Over the past 25 years the hardware
technology has improved the quality of the B-mode imaging
dramatically. Color-coded fl ow displays as well as “power
Doppler” are now available in most instruments. These two
modes are often helpful for locating veins, and outlining
intraluminal defects.
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353
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354 Chapter 40/Diagnosis of Deep Vein Thrombosis
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TABLE 40.1 Duplex Findings of Lower Limb DVT
Mode Finding Implication
B-Mode Image Unable to coapt vein Intraluminal thrombus
walls with probe
pressure
Visible thrombus Thrombus, possibly old
Vein enlarged Acute thrombus
Pulse Doppler No spontaneous fl ow Occlusive thrombus
No augmentation
of fl ow with distal Obstruction distal to probe
limb compression
No fl ow variation Obstruction proximal to
with respiration probe
Color Flow Intraluminal defect Nonocclusive thrombus
or Power
Doppler
Combined Increased fl ow Being used as collaterals
velocity and size of
surrounding veins
FIGURE 40.1 Duplex of normal femoral vein. Vein can be completely
collapsed with probe pressure.
The possible duplex fi ndings of a lower limb DVT are
listed in Table 40.1. Virtually all vascular labs use the fi rst
criteria, the inability to collapse a vein with probe pressure
(Figures 40.1 and 40.2), as the primary diagnostic method.
21
Some use only this fi nding.
Meta-analysis has shown this
sign to be 95% sensitive and 98% specifi c for proximal leg
DVTs. When all the criteria of Table 40.1 are used the sensitivity is 98% and specifi city 94%.
22
Though the accuracy of this noninvasive, readily available, and relatively low-cost test is impressive one should
realize most data refl ect fi ndings in patients with femoral
and/or popliteal vein disease. The majority of patients with
symptomatic DVTs have thrombus in these veins.
23,24
In
some cases the thrombus also may involve the iliac or calf
veins. Duplex examination may not detect the full extent of
thrombosis in these instances but at least the diagnosis of
FIGURE 40.2 Duplex of acute femoral vein DVT. Vein cannot be col-
lapsed with probe pressure. Also note, vein is enlarged and thrombus
is echolucent and partially compressible, which are signs of acute
thrombus.
DVT will be made and presumably appropriate treatment
given. One must realize, however, that isolated calf vein
DVTs are common, and isolated iliac thrombi do occur.
Duplex is not as accurate in these instances. In a study of
postoperative orthopedic patients, 24% of the symptomatic
and 88% of the asymptomatic patients had isolated calf
thrombi. In the symptomatic group duplex was 85% sensitive and 86% specifi c, but in the asymptomatic group sensitivity was 16% and specifi city 99%.
Isolated iliac vein thrombosis often is reported as being
rare. However, most series from which data come do not
include patients who are at increased risk for this problem,
such as those who are pregnant, or have pelvic conditions
such as tumors, trauma, or recent surgery. The true incidence
of isolated pelvic vein thrombosis is unknown but probably
higher than previous estimates. Most vascular labs do not
routinely scan iliac veins as part of a lower extremity DVT
study. Those that do fi nd the study unsatisfactory because of
excessive bowel gas in 20% of patients.
used in the leg, the ability to coapt vein walls with probe
pressure, is usually not possible. Many labs use indirect
signs such as lack of fl ow variation with respiration in the
proximal femoral (“common femoral”) vein, or a 50%
increase in proximal femoral vein diameter with the Valsalva
maneuver. The accuracy of these methods varies greatly in
the literature.
27–30
reliable diagnostic modality in these patients (see later).
In addition to the ability to diagnose the presence of a
deep vein thrombosis, duplex ultrasonography usually provides information as whether the thrombus is acute or
chronic. Criteria are listed in Table 40.2. The fi nding of a
partially compressible thrombus is the most common reliable sign of an acute DVT. A “free fl oating” thrombus; that
is, thrombus that appear to be moving within the vein lumen
25
26
The primary sign
Magnetic resonance venography is a more
Magnetic Resonance Venography 355
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TABLE 40.2 Duplex Criteria for Differentiating Acute versus
Chronic Thrombus (Modifi ed from Karkow, Ruoff, and
Cranley. B-Mode Imaging, in Practical noninvasive vascular
diagnosis. 1982.)
Characteristic Acute Chronic
Degree of Occlusion Total ++ Partial ++
Free Floating Free ++++ Stationary +
Clot Compressibility Soft ++++ Firm +
Surface Character Smooth ++ Irregular ++
Echogenicity Faint or ++ Bright ++
None
Homogeneity Homogen. ++ Heterogen. ++
Collaterals Absent + Present ++
Recanalization Absent + Present ++++
++++ = Diagnostic, +++ = Good, ++ = Fair, + = Poor
are seen only occasionally. Many clinicians use the criteria
of the degree of echogenicity of a thrombus to determine
age. Although the echogenicity of thrombus does increase
with time, it is also dependant on the duplex settings and is
only a fair indication of age.
31–34
Determination of the thrombus age is particularly important when a clinician is faced with the presentation of a
patient with a past history of DVT who presents with the
complaint of new or increasing leg pain and/or swelling with
no past studies available for comparison. Because 10 to 20%
of acute DVTs may become chronic, determining if the
patient has a new thrombus, or new thrombus in addition to
chronic thrombus or some other cause of the leg symptoms
such as chronic venous insuffi ciency can be challenging.
When thrombus is found, application of the age criteria in
Table 40.2 are reliable but one should realize there may be
both acute and chronic thrombi in conjunction—that is,
“new on old.” In these cases one should look for partially
compressible thrombus (i.e., acute) at either the proximal or
distal ends of the old DVT.
Duplex examination also can be used to help determine
the cause of leg pain and/or swelling when a DVT is not
found. Intramuscular hematomas (sometimes with associated muscle tears), ruptured and unruptured Baker’s cysts,
and venous refl ux disease are common causes of symptoms
that may mimic DVT and often can be identifi ed by duplex
ultrasound if one keeps them in mind.
TABLE 40.3 Sensitivity and Specifi city of Different D-dimer
Tests (Figures represent averages from the literature.
results include subjects with both possible pulmonary
embolism and/or DVT.)
Method Sensitivity (%) Specifi city (%)
ELISA 96 39
Red Blood Cell 88 64
Agglutination
Latex Agglutination 87 60
35–38
The
blood clotting. Unfortunately numerous conditions other
than DVT can give positive D-dimer test results.
Several laboratory methods are currently available for
D-dimer testing (see Table 40.3). Though the enzyme-linked
immunosorbent assay (ELISA) is the most sensitive it is also
the most expensive and time consuming. The others are less
expensive and much quicker, taking minutes as opposed to
hours, and are thus more attractive as clinical tools for management of patients with suspected DVT. As can be seen
from the table, however, the low specifi city makes a positive
test virtually useless for ruling in DVT. Infection, infl ammation, vasculitis, pregnancy, trauma, hemorrhage, and postsurgical states can cause a positive D-dimer test.
A negative test may be a useful aid in ruling out DVT.
Numerous studies have reported sensitivities of D-dimer but
different methodologies are used, populations tested vary,
and many studies combine patients with pulmonary emboli
and/or DVT. Other studies have shown varying sensitivity
in relation to the timing of testing and to the location and or
extent of DVT.
35–38
Though Wells et al. showed that anticoagulation could
safely be withheld in patients with a low clinical suspicion
of DVT and a negative D-dimer test these results should not
be generalized unless one knows the methodology and accuracy of the laboratory used.39 Until there is standardization
of D-dimer testing and better information on the negative
predictive value of the test in heterogenous populations one
should not rely solely on a negative D-dimer result to rule
out DVT.
MAGNETIC RESONANCE
VENOGRAPHY
The use of a blood test to rule in or rule out DVT, and
negate the need for more complicated and expensive testing,
has received considerable attention in the last decade as
monoclonal antibody tests have become available to detect
circulating D-dimer. D-dimers are degradation products that
result from the action of plasmin on cross-linked fi brin. Thus
the presence of D-dimer is an indication of the initiation of
D-DIMER
The quality of magnetic resonance venography (MRV)
has steadily improved since its introduction in the early
1990s. It is now a powerful technology that often is used as
a problem solver. Various techniques are used, including
spin echo and gradient recalled echo. Intravenous gadolinium can be used to enhance images and can aid in determination of the age of the thrombus. Absence of imaging of a
vein or an intraluminal fi lling defect indicate the presence
of DVT. Examiners must be cognizant, however, of known
356 Chapter 40/Diagnosis of Deep Vein Thrombosis
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fl ow artifacts that can be mistaken for thrombus. Images can
be viewed in axial, coronal, or sagittal planes and postprocessing techniques are available that can be used to
produce 3D images with removal of background structures
for improved ease of viewing.
MRV has been shown to be highly accurate. Sensitivities of 97% and specifi cities of 100% have been demonstrated along with excellent interobserver variability for
iliac, femoral, and below knee DVT.
40,41
Several authors
now consider MRV to be the study of choice for pelvic vein
DVT. Compared to conventional contrast venography it is
not only noninvasive and avoids the use of ionizing radiation,
but it also has demonstrated better ability to show the proximal extent of femoral and iliac vein thrombi. An added
advantage is that it may show underlying pathology that
contributed to the formation of the DVT such as pelvic
masses or left iliac vein compression by the right common
iliac artery.
42
The limitations of MRV include expense, lack of portability, and in some cases, availability. Also, some patients
with implanted metal devices, claustrophobia, and inability
to remain still are not suitable for this exam.
COMPUTERIZED TOMOGRAPHIC
VENOGRAPHY
Computerized tomographic venography has many of the
same advantages as MRV when compared to duplex ultrasound. It does involve, however, the use ionizing radiation
and for imaging peripheral veins the use of intravenous
iodinated contrast agents. In imaging peripheral and pelvic
veins the accurate timing of image acquisition in relation to
contrast injection is often diffi cult and multiple runs may be
necessary to acquire all the desired veins. In larger veins one
can also be faced with the infl ow of noncontrast blood from
a branch vein into a vein with blood containing contrast,
which creates a “wash in” artifact that can be mistaken for
thrombus. For these reasons MRV usually is considered a
more appropriate modality when duplex testing is felt to be
inadequate. However, some do employ a technique known
as combined computerized tomographic venography and
pulmonary arteriography (CCTVPA). Computerized tomographic pulmonary arteriography (CTPA) has become the
test of choice in many centers for suspected pulmonary
emboli. Katz et al. has reported that by waiting for 3 to 3.5
minutes after the injection of contrast that is used for CTPA,
one can then scan the veins from the diaphragm to the
calves. The scanning can be a survey with cuts taken every
4 cm or as a continual helical imaging. This test does involve
considerably more radiation to the subject, however.
with this technique, one study can not only answer the question of whether or not there is a pulmonary embolus and its
extent, but also often fi nd the source of the embolus and the
43
Thus,
amount of residual thrombus in the veins. Ninety-seven
percent sensitivity and 100% specifi city has been reported
in comparison to ultrasound and a large study has shown
that in patients with lower limb DVT, 23% extended into
the iliac veins or the inferior vena cava.
44
SUMMARY
It is well documented that the clinical diagnosis of lower
limb DVT is unreliable. Fortunately there are a number of
methodologies available that can objectively rule in or rule
out the presence of DVT with accuracies very close to the
gold standard of conventional contrast phlebography. They
are also less invasive, safer, and usually less costly. This
chapter has presented a brief overview of the currently available technologies that continue to evolve and improve. The
limitations and shortcomings of the present day testing
methods should be viewed as challenges and not barriers to
improving patient care.
References
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Medicine, 2e. 1994. 653. Philadelphia: WB Saunders Co.
3. Anderson FA Jr, Wheeler HB, Goldberg RJ et al. A population-based
perspective of the hospital incidence and case-fatality rates of deep
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4. Matzdorff A, Green D. Deep vein thrombosis and pulmonary embo-
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5. Sperry K, Key C, Anderson R. Toward a population-based assessment
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6. Diamond P, Macciocchi S. Predictive power of clinical symptoms in
patients with presumptive deep venous thrombosis, Am J Phys Med
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incidence, risk factors, and symptoms and signs, Arch Intern Med.
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8. Robinson K, Anderson D, Gross M. Accuracy of screening compres-
sion ultrasonography and clinical examination for the diagnosis of deep
vein thrombosis after total hip or knee arthroplasty, Can J Surg. 1998.
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9. Weinmann E, Salzman E. Deep-vein thrombosis, N Engl J Med. 1994.
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10. Oudega R, Moons K, Hoes A, Arno W. Limited value of patient history
and physical examination in diagnosing deep vein thrombosis in
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11. Jorgensen J, Hanel K, Morgan A, Hunt J. The incidence of deep venous
thrombosis in patients with superfi cial thrombophlebitis of the lower
limbs, J Vasc Surg. 1993. 18: 70–73.
12. Prountjos P, Bastounis E, Hadjinikolaou L, Felekuras E, Bala P. Super-
fi cial venous thrombosis of the lower extremities co-existing with deep
venous thrombosis, Int Angiol. 1991. 10: 63–65.
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Superfi cial thrombophlebitis diagnosed by duplex scanning, Surgery.
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14. Skillman J, Kent K, Porter D, Kim D. Simultaneous occurrence of
superfi cial and deep thrombophlebitis in the lower extremity, J Vasc
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15. Bergqvist D, Jaroszewski H. Deep vein thrombosis in patients with
superfi cial thrombophlebitis of the leg, Brit Med J. 1986. 292:
658–659.
16. Guex J. Thrombotic complications of varicose veins. A literature
review of the role of superfi cial venous thrombosis, Dermatol Surg.
1996. 22: 378–382.
17. Markovic M, Lotina S, Davidovic L et al. Acute superfi cial thrombophlebitis—Modern diagnosis and therapy, Srp Arh Celok Lek. 1997.
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18. Salzman E. Venous thrombosis made easy, N Engl J Med. 1986. 314:
847–848.
19. Mattos M, Londrey G, Leutz D et al. Color-fl ow duplex scanning for
the surveillance and diagnosis of acute deep venous thrombosis, J Vasc
Surg. 1992. 15: 366–376.
20. Lund F, Diener L, Ericsson J. Postmortem intraosseous phlebography
as an aid in studies of venous thromboembolism, Angiology. 1969. 20:
155.
21. Lensing A, Preandoni P, Brandjes D et al. Detection of deep-vein
thrombosis by real-time B-mode ultrasonography, N Engl J Med. 1989.
320: 342–345.
22. Wheeler H, Anderson F. Use of noninvasive tests as the basis for
treatment of deep vein thrombosis. In: Bernstein EF, ed. Vascular
Diagnosis, 4e. 867. St Louis: Mosby.
23. Markel A, Manzo R, Bergelin R, Strandness D. Acute deep vein thrombosis: Diagnosis, localization, and risk factors, J Vasc Med Biol. 1991.
3: 432–439.
24. Markel A, Manzo R, Bergelin R, Strandness D. Pattern and distribution
of thrombi in acute venous thrombosis, Arch Surg. 1992. 127:
305–309.
25. Sumner D, Mattos M. Diagnosis of deep vein thrombosis with realtime color and duplex scanning. In: Bernstein EF, ed. Vascular Diagnosis, 4e. 794–795. St. Louis: Mosby.
26. Messina L, Sarpa M, Smith M, Greenfi eld L. Clinical signifi cance of
routine imaging of iliac and calf veins by color fl ow duplex scanning
in patients suspected of having lower extremity deep venous thrombosis, Surgery. 1993. 114: 921–927.
27. Polak J, O’Leary D. Deep venous thrombosis in pregnancy: Noninvasive diagnosis, Radiology. 1988. 166: 377–379.
28. Effeney D, Friedman M, Gooding G. Iliofemoral venous thrombosis:
Real-time ultrasound diagnosis, normal criteria, and clinical application, Radiology. 1984. 150: 787–792.
29. Duddy M, McHugo J. Duplex ultrasound of the common femoral vein
in pregnancy and puerperium, Brit J Radiol. 1991. 64: 785–791.
30. Bach A, Hann L. When the common femoral vein is revealed as fl attened on spectral Doppler sonography: Is it a reliable sign for the
diagnosis of proximal venous obstruction, Am J Roentgenol. 1997.
168: 733–736.
31. Wright D, Shepard A, McPharlin M, Ernst B. Pitfalls in lower extremity venous duplex scanning, J Vasc Surg. 1990. 11: 675–679.
32. Van Gemmeren D, Fobbe F, Ruhnke-Trautmann M et al. Diagnostik
tiefer Beinvenenthrombosen mit der farbcodierten Duplexsonographie
und sonographische Altersbestimmung der Thrombose, Arch Kardiol.
1991. 80: 523–528.
33. Salles-Cuhna S, Fowlkes J, Wakefi eld T. B-mode quantifi cation of deep
vein thrombi, J Vasc Tech. 1994. 18: 207–209.
34. Fowlkes J, Streiter R, Downing L et al. Ultrasound echogenicity in
experimental venous thrombosis, Ultrasound Med Biol. 1998. 24:
1175–1182.
35. Turkstra F, van Beek E, Buller H. Observer and biological variation of
a rapid whole blood D-dimer test, Thromb Haemost. 1998. 79:
91–93.
36. Bounameaux H, Cirafi ci P, de Moerloose P et al. Measurement of Ddimer in plasma as diagnostic aid in suspected pulmonary embolism,
Lancet. 1991. 337: 196–200.
37. Quinn D, Fogel R, Smoth C et al. D-dimers in the diagnosis of pulmonary embolism, Am J Respir Crit Care. 1999. 159: 1445–1449.
38. Chapman C, Akhtar N, Campbell S et al. The use of D-dimer assay by
enzyme imunnoassay and latex agglutination techniques in the diagnosis of deep vein thrombosis, Clin Lab Haematol. 1990. 12: 37–42.
39. Wells P, Anderson D, Rodger M et al. Evaluation of D-dimer in the
diagnosis of suspected deep vein thrombosis, N Engl J Med. 2003. 349:
1227–1235.
40. Fraser D, Moody A, Morgan P et al. Diagnosis of lower limb deep
venous thrombosis: A prospective blinded study of magnetic resonance
direct thrombus imaging, Ann Intern Med. 2002. 136: 89–98.
41. Spritzer C, Arata M, Freed K. Isolated pelvic deep vein thrombosis:
Relative frequency as detected with MR imaging, Radiology. 2001.
219: 521–525.
42. Fraser D, Moody A, Martel A, Morgan P. Re-evaluation of iliac compression syndrome using magnetic resonance imaging in patients with
acute deep venous thromboses, J Vasc Surg. 2004. 40: 604–611.
43. Katz D, Hon M. Current DVT imaging, Tech in Vasc Intervent Radiol.
2004. 7: 55–62.
44. Cham D, Yankelevitz D, Shaham D et al. Distribution of suspected
pulmonary embolism, Radiology. 2002. 225: 384 (abstract).
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CHAPTER
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41
Thrombotic Risk Assessment: A Hybrid Approach
JOSEPH A. CAPRINI
INTRODUCTION
Venous thromboembolism (VTE) is one of the most
common, yet highly preventable causes of in-hospital death.
In response to this problem, the implementation of an appropriate, targeted thromboprophylaxis strategy has been
described as the most important single factor for improving
patient safety.1 Both medical and surgical patients are at risk
of VTE. It has been calculated that without prophylaxis, the
incidence of hospital-acquired deep vein thrombosis (DVT)
is approximately 10 to 40% among medical or general
surgery patients, and 40 to 60% following major orthopedic
surgery.2 Approximately 10% of all deaths in the hospital
subjected to autopsy are attributed to pulmonary embolism
(PE),3 with most patients who suffer a fatal embolus dying
within the initial 30-minute period. This small window for
effective treatment, combined with its frequently asymptomatic nature, explains the high fatality rate associated with
this condition.4 VTE is also responsible for a signifi cant
number of long-term health problems: 30% of patients with
symptomatic DVT will suffer recurrent VTE in the following eight years,
of patients who suffer a DVT will go on to develop longterm venous insuffi ciency complications in the lower leg,
also known as postthrombotic syndrome (PTS). This condition may result in chronic leg swelling, discomfort, dermatitis, and leg ulcers, which can reduce the patient’s quality
of life and have an economic impact frequently overlooked
in DVT cost assessment.
Clinically proven methods of prophylaxis have been
shown to prevent a signifi cant proportion of clinically
signifi cant VTEs. Yet despite the publication of regularly
updated consensus guidelines,
under- or inappropriately prescribed in a high proportion of
5
and Prandoni has shown that almost a third
6
2,7–10
VTE prophylaxis is still
patients, leaving them at signifi cant risk of serious complication due to PE or DVT.
Effective VTE risk assessment is therefore critical in
targeting and optimizing prophylaxis, and for the subsequent
improvement in patient outcomes. There is an urgent need
for a clear, easy-to-use risk assessment model based on
information in the patient’s medical history and clinical
examination. Although there has been, and continues to be,
a great deal of clinical research into VTE, it is unlikely that
there will ever be suffi cient high-quality clinical evidence to
guide decisions on prophylaxis in every group of patients—
medical and surgical. With each patient representing a
unique clinical situation with their own combination of risk
factors, it can be diffi cult to determine the level of VTE risk,
and the appropriate intensity of thromboprophylaxis. This
review considers the reasons contributing to underuse of
prophylaxis, and discusses a hybrid approach, combining
risk assessment scoring with the application of current treatment guidelines. The results of an audit from the author’s
hospital and a real-world case study are also detailed to
illustrate key issues.
11,12
POOR ADHERENCE TO
PROPHYLAXIS GUIDELINES
Consensus groups such as the American College of Chest
Physicians (ACCP) and the THRIFT Consensus Group regularly publish guidelines on the prevention and treatment of
VTE in both surgical and nonsurgical patients.
the recommendations from these groups are based on clinical evidence from trials and meta-analyses that are stratifi ed
clearly according to patient risk, VTE prophylaxis is still
2,7–10
Although
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360 Chapter 41/Thrombotic Risk Assessment: A Hybrid Approach
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suboptimal in many patients,
11–17
and the rates of total and
proximal DVT remain high.
US surveys of prophylaxis use indicate that the percentage of surgical patients receiving prophylaxis ranges from
38 to 94% according to the type of procedure.
11,15,18,19
One
particular study documenting adherence to the 1995 ACCP
guidelines in surgical patients found that 25% of patients
undergoing high-risk major abdominal surgery did not
receive any form of VTE prophylaxis.11 Furthermore, in a
retrospective analysis by Arnold et al. looking at cases of
VTE in a US cohort of surgical and medical patients, it was
found that one out of six VTE events could have been prevented if physicians had followed the ACCP guidelines.12
Inadequate prophylaxis was most often due to the fact that
no prophylactic measures were prescribed.
Surprisingly, a tendency has been reported for prophylaxis to be administered less frequently with increasing risk
level.20 Why this occurs is unknown, although it may refl ect
physician concerns that the risk of complications due to
anticoagulant therapy may be greater in very high-risk
patients.
SUBOPTIMAL PROPHYLAXIS
IN ACTION
assessment, and the type and duration of prophylaxis prescribed to each patient was recorded and compared with
their individual risk score. In-hospital outcomes for all
patients were carefully monitored, and patients were followed up by telephone after a month.
The study found that 19% (30 of 157) of patients were
not prescribed any prophylactic measures despite the existence of several risk factors. This was even more surprising
considering that the majority of patients were in the highest
risk category, and therefore at greatest need of prophylaxis.
Clinically overt VTE appeared in two out of 73 (2.7%)
patients in the highest risk category, both of whom had not
received appropriate prophylaxis, and a total 57% of patients
were shown to have received inadequate prophylaxis according to the ACCP guidelines.2 Comparison of these results
with our previous thromboprophylaxis audit performed
in 1991 (see Table 41.1) indicates no improvement in compliance with treatment guidelines; indeed, in the group at
highest risk of VTE, only 30% of patients received appropriate prophylaxis in 2002 compared with 70% in the same
category in 1991.
UNDERUSE OF PROPHYLAXIS—WHY
IS THERE A PROBLEM?
The extent of the prophylaxis problem was highlighted
in a recent study by the author’s group.14 Carried out to test
the performance of current VTE risk assessment, the primary
objective was to determine the percentage of a surgical
patient population falling into one of three risk categories
(moderate, high, and highest risk; see Table 41.1). The study
also sought to identify whether patients were receiving
appropriate prophylaxis based on their risk level, and to
compare the degree of compliance with prophylaxis guidelines with that found and reported for the same hospital in
1991. A total of 157 patients undergoing neurosurgery, cardiovascular surgery, general, gynecological, or orthopedic
surgery (other than arthroplasty) were included in the
study. Each patient had a detailed preoperative VTE risk
TABLE 41.1 Adherence with ACCP Consensus Guidelines: An Audit of Hospital Practice
Highest risk
Moderate risk (2 risk factors) High risk (3–4 risk factors) (5 or more risk factors)
Total (2002) 9/157 (6%) 43/157 (27%) 105/157 (67%)
Prophylaxis guidelines followed 7/9 (78%) 28/43 (65%) 32/105 (30%)
Prophylaxis guidelines not followed 2/9 (22%) 15/43 (35%) 73/105 (70%)
High risk
Low (0–1 risk factors) Moderate (2–4 risk factors) (more than 4 risk factors)
Total (1991) 185/538 (34%) 261/538 (49%) 92/538 (17%)
Prophylaxis guidelines followed 18/185 (10%) 110/261 (42%) 70/92 (76%)
Prophylaxis guidelines not followed 167/185 (90%) 151/261 (58%) 22/92 (24%)
Modifi ed with permission from Blackwell Publishing.
14
Although the serious implications to health are now well
accepted—both in the short and long term—a large part of
the problem can be attributed to its clinically silent nature.
For surgical patients there is a low incidence of clinically
apparent VTE in the perioperative period, thus it is rare for
an individual surgeon to witness an acute PE or major DVT
event in one of their patients. Studies have shown that a
signifi cant proportion of symptomatic thromboembolic
complications occur after discharge from hospital,
a survey of California orthopedic surgeons fi nding that 76%
of VTE events were diagnosed following discharge from
hospital after total hip replacement (THR), and 48% after
Misconception of Risk
21–23
with
Underuse of Prophylaxis—Why Is There a Problem? 361
https://t.me/med1917
total knee replacement (TKR).24 The current trend toward
shorter hospital stays serves to accentuate this problem,
whereby the need for and benefi ts of thromboprophylaxis
can be diffi cult to appreciate for a physician who rarely sees
the problem. Extended prophylaxis not only has value in
preventing sudden death but in prevention of all the other
complications of VTE responsible for signifi cant morbidity
and mortality.
Although the majority of trials in VTE have studied surgical patients, medical patients are also at signifi cant risk of
thrombotic disease.2 Fewer than a third of patients who
suffer a fatal PE recently have undergone surgery,25 and as
many as one in 20 hospitalized patients with multiple clinical conditions go on to develop PE.26 The average overall
incidence of DVT in medical patients is 10 to 20%,2 but this
rises in certain patient groups. For example, stroke is associated with a 20 to 50% risk of VTE complications without
prophylaxis,2 whereas VTE is thought to occur in 20 to 40%
of patients with an acute myocardial infarction.27 Cancer is
also a well-known thrombotic risk factor due to the hypercoagulable state induced by the malignancy, with treatments
for the disease, such as surgery and chemotherapy, only
serving to further compound the risk.
2,28
Despite current
guidelines stating that medical patients can be at signifi cant
risk of VTE and should receive thromboprophylaxis, a
survey from the International Medical Prophylaxis Registry
On Venous Thromboembolism (IMPROVE) of acutely ill
medical patients recently revealed that fewer than 40% of
patients enrolled in the registry received prophylaxis.
13
Safety Concerns
Another factor underlying the suboptimal use of pharmacological prophylaxis is the overestimation of bleeding risk
associated with anticoagulant prophylaxis. For example, a
survey of orthopedic surgeons in the United Kingdom found
that almost half (48%) had discontinued the use of low
molecular weight heparin (LMWH) for TKR or THR due to
concern over bleeding complications.29 However, numerous
randomized, placebo-controlled, double-blind trials and
further meta-analyses of prophylaxis with LMWH and
unfractionated heparin (UFH) during major surgery have
demonstrated that both types of heparin prophylaxes are
extremely effective in preventing VTE at the expense of no,
or a very small, increase in the rate of major bleeding.
Although LMWH and UFH are associated with an increased
risk of wound hematomas,
30,33,34
major bleeding complications are extremely uncommon, and the consequences of
VTE are potentially much more severe—thereby outweighing any justifi cation for withholding heparin prophylaxis.
LMWH is at least as safe and effective as UFH.
LMWH has been associated with a lower risk of major
bleeding complications; one particular study of patients
undergoing abdominal surgery reported a 23% reduction in
30–35
31,34,54
the frequency of major bleeding events in patients who
received LMWH compared with UFH, although this difference was not signifi cant. The study also observed signifi cantly fewer severe bleeds and wound hematomas.
exhibits minimal binding with plasma proteins, endothelial
cells, and platelet factor IV, providing a more predictable
clinical response than UFH and reduced likelihood of
causing heparin-induced thrombocytopenia (HIT).
an incidence of 1 to 5%, immune HIT is an uncommon but
serious complication of heparin therapy, and often is cited
as a reason for caution in prescribing heparin prophylaxis.
Of 665 patients who received prophylaxis with either UFH
or LMWH during elective THR, 18 patients developed HIT,
and the majority of these patients were in the UFH group
(4.8% versus 0.6%; p < 0.001).
37
Although the benefi ts of LMWH thromboprophylaxis
have been shown in numerous studies, suboptimal use may
arise from additional safety fears combined with a misconception of risk. Clinical issues remain unanswered and may
contribute to physician hesitation to pharmacologic prophylaxis; for example, optimal dosing and need for monitoring
in patients with severe obesity or renal insuffi ciency.
Lack of Awareness of the Problem
Physicians frequently cite informal, retrospective surveys
of their own clinical service, or personal experience as to
why they believe the rate of VTE is low.38 There also appears
to be poor awareness of the diverse range of clinical signs
and symptoms that can be attributed to thrombosis and the
fact that these relatively minor symptoms can be extremely
common (see Table 41.2). Many physicians fail to realize
that what they are seeing may be an indicator of an otherwise
TABLE 41.2 Clinical Signs, Symptoms, or Events
That May Be Associated with Venous Thromboembolism in
Clinical Practice
• Leg pain
• Leg swelling
• Chest pain
• Shortness of breath
• Transient orthostatic hypotension
• Decreased level of consciousness presumed to be narcotic excess
• Fainting spell
• Hypoxia
• Follow-up of patient for readmission or death 90 days
postoperatively
• Sudden death
• Death without autopsy
• Postoperative stroke due to patent foramen ovale
• Suspected myocardial infarction
• Failure to thrive, sinking spell or “the dwindles”
• Postthrombotic syndrome during physical examination of the legs
(standing) 5 years postoperatively
• Postoperative pneumonia
30
LMWH
36,37
With
2
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