Thrombosis Risk Assessment as a

Guide to Quality Patient Care

Joseph A. Caprini, MD
Background
Venous thromboembolism (VTE) is a serious complication that is
frequently encountered in medical and surgical practice. Approximately 2 million people each year will suffer from a deep vein
thrombosis (DVT), and approximately 600,000 of these individuals
will suffer a pulmonary embolism (PE), which is fatal in about
200,000 patients annually.1 Pulmonary hypertension can be expected
to develop in approximately 30,000 patients who survive their PE. The
postthrombotic syndrome (PTS) will be seen in approximately
800,000 patients annually in the United States; 7% of these individuals
will have a severe form of the problem and become permanently
disabled.2 One of the most troubling statistics is the fact that 50% of
the 2 million cases of DVT yearly are silent. Occasionally, the first
sign or symptom of the disease is a fatal PE.3 Furthermore, it has been
estimated that approximately 1 of 20 hospitalized medical patients will
suffer a fatal PE if they have not received appropriate thrombosis
prophylaxis.4
Another serious complication of DVT is nonhemorrhagic stroke that
may occur in a patient with a patent foramen ovale.5 A clot in the deep
venous system of the leg can break off and travel to the right atrium,
dilating that heart chamber. If the patient is one of the 25 or 30% who
have a nonfunctioning patent foramen ovale, this atrial dilatation can
open the patent foramen and allow the clot to enter the left side of the
heart and proceed to the brain, producing a stroke.6 The diagnosis of
this problem is difficult because once the right atrium returns to
normal size, the patent foramen ovale may be difficult to detect. Often
when the clot breaks off from the leg, it does so cleanly without
residual damage that can be detected on subsequent duplex examination.6
Table 1 shows some of the commonly seen problems that at first glance
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TABLE 1. Common manifestations of venous thromboembolism including required investigations to

uncover all instances of the disease

Leg pain
Leg tenderness
Leg swelling
Chest pain
Shortness of breath
Transient or orthostatic hypotension
Transient hypoxemia
Unexplained decrease in level of consciousness
Suspected narcotic excess
Suspected postoperative myocardial infarction
Postoperative nonhemorrhagic stroke
Postoperative pneumonia
Unexplained sudden death
Unexplained cardiovascular collapse
Postoperative death without autopsy
90-day follow-up for death, readmission, outpatient treatment of VTE
5-year follow-up looking for signs of the postthrombotic syndrome

may not seem to be associated with a DVT. We recommend keeping a

high level of suspicion for patients who exhibit these clinical manifestations. Not all of these problems will result in a fatal or serious outcome.
They may predispose the patient to later develop the postthrombotic
syndrome or have a higher incidence of DVT if they have a subsequent
operative procedure.
The problem of long-term follow-up of patients is not easy to solve
and many DVT events occur several weeks or longer after discharge.
Readmissions, deaths, and outpatient treatment of DVT using low
molecular weight heparin (LMWH) may be very difficult data for the
surgeon to obtain. The average busy clinician may not associate a
stroke or a variety of other postoperative symptoms as being caused by
a postoperative DVT. It is no wonder that many feel that VTE is not
a problem in their clinical practice.

Risk Assessment
The process of providing appropriate thrombosis prophylaxis to medical
and surgical patients is a complex issue because many times the
administration of powerful anticoagulants may carry the risk of side
effects, most notably bleeding. The seventh American College of Chest
Physicians Consensus on antithrombotic and thrombolytic therapy has
recently published a thorough evaluation of the literature that has been
translated into evidence-based guidelines for thrombosis prophylaxis and
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TABLE 2. Prophylaxis regimen

Total Risk
Factor
Score

Incidence of DVT

Risk Level

01

10%

Low

2
34

1020%
2040%

Moderate
High

5 or more

4080% 15%
mortality

Highest

Prophylaxis Regimen
No specific measures; early
ambulation
ES or IPC or LDUH, or LWMH
IPC or LDUH, or LMWH alone or in
combination with ES or IPC
Pharmacological: LDUH, LMWH,*
Warfarin,* or Fac Xa* alone or
in combination with ES or IPC

Based on Geerts WH, Pineo GF, Heit JA, et al: Prevention of venous thromboembolism. Chest
2001; 119:132S75S; Nicolaides AN, Breddin HK, Fareed J, et al: 2001 International
consensus statement: prevention of venous thromboembolism guidelines according to
scientific evidence; Caprini JA, Arcelus JI, et al: State-of-the-art venous thromboembolism
prophylaxis. Scope 2001;8:228 240; Oger E: incidence of venous thromboembolism: a
community-based study in western France. Thromb Haemost 2000; 657 660. Turpie AG,
Bauer KA, Eriksson Bl, et al: Fondaparinux vs. enoxaparin for the prevention of venous
thromboembolism in major orthopedic surgery: a meta-analysis of 4 randomized double-blind
studies. Arch Intern Med 2002;162(16):1833 40. ES, elastic stockings; IPC, intermittent
pneumatic compression; LDUH, low-dose unfractionated heparin; LMWH, low molecular weight
heparin; Fac Xa, Factor X Inhibitor.

treatment.1 It is an excellent compilation of relevant medical literature as

interpreted by some of the foremost authorities in the field. This document
endorses the concept of thrombosis risk assessment, although they point
out that individual formal risk assessment models have not been adequately validated, are cumbersome, and are infrequently used by the
physician. They recommend a simplification of the process by assigning
patients to one of four VTE risk levels based on type of operation, age,
and the presence of additional risk factors (Table 2). Some of us feel that
this approach leaves certain gaps in the implementation of prophylaxis
and calculation of degree of risk. In certain cases the number of risk
factors is so great that the patients decision to have a quality-of-life
procedure may be affected.7 We feel that all possible risk factors need to
be queried to identify the extent of risk for each individual patient.
Thrombosis prophylaxis then needs to be individualized on the basis of
the results of this analysis. If one misses any of these factors, the patients
thrombosis risk may not be properly estimated. In those with a doubledigit point score, the risk may be extremely high and, although this has
not been subjected to rigorous clinical trial to determine the degree of
increased risk, still needs to be considered. Some patients may want to
forgo elective quality-of-life procedures when the point score indicates an
extremely high chance of VTE.
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Interpretation of Risk Assessment Guidelines

Our group has been performing detailed individual risk assessment on
medical and surgical patients since the late 1980s.8 The latest version of
this model is seen in Table 3. We use a hybrid approach which begins
with evidence-based guidelines and consensus statements, combined with
logic, emotion, and the experience of the interviewer. This approach was
selected because it is the approach used by physicians when dealing with
patients and their illnesses. If there is no available level 1 data or if the
patients circumstances would have resulted in them being excluded from
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a randomized trial, they still need to be treated in the best manner possible
using a combination of science, logic, emotion, and experience.9

Case Study
One practical example of this principle would be a 62-year-old
morbidly obese male requiring arthroscopic knee surgery on the left leg.
The patient has a past history of venous thrombosis after cholecystectomy
20 years ago, and 4 years ago had successful surgical treatment for
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prostate cancer. The point score for this patient using our model is 9 and
includes 2 each for surgery, cancer, and age over 60 years, and 3 for past
history of DVT.10 There is no specific trial that would address this clinical
situation. If one looks at the Chest Guidelines, thrombosis prophylaxis for
outpatient arthroscopic surgery is not recommended unless additional risk
factors are present. There are no specific guidelines regarding the
intensity or duration of prophylaxis. The Consensus Guidelines are based
on clinical trial data and many clinical trials would exclude patients with
a past history of venous thrombosis, such as the individual in this
example. The question is what this patients risk is and what prophylaxis,
if any, should be used. According to our risk scoring system, the patients
point total is 9 and we know, according to Chest Consensus Guidelines,
that patients with more than five risk factors are in the very high-risk
group and have a 40 to 80% chance of developing a venous thrombosis
with up to 5% mortality.1

Length of Prophylaxis
Furthermore, we know that abdominal surgery cancer patients, who
are also in this very high-risk group, when given 30 days of LMWH,
have a statistically significantly lower incidence of thrombosis than
when 7 days of prophylaxis are used.11 If one were to apply the
Caprini score to the average patient in this trial, the following
calculations would be done. We would assign 2 points each for
abdominal surgery, cancer, and age over 60 years for a total score of
6. Since our hypothetical arthroscopic surgical patient has a score of
9, we could extrapolate that he should receive at least 30 days of
LMWH prophylaxis postoperatively. This regime significantly reduced the incidence of DVT in abdominal surgery patients who had an
estimated score of 6 as noted above. The all cause fatality rate in this
trial for those receiving 30 days of the drug was 0.3%. Quite an
improvement compared to the up to 5% fatal PE death rate in those in
the highest risk group not receiving prophylaxis as quoted in the
Consensus Guidelines.

Personal or Family History of VTE

One of the most frequently missed risk factors is a past history or
family history of VTE. In our practice 56% of patients with a past
history of thrombosis were found to have a positive marker for
thrombophilia, while 42% of patients with a family history of
thrombosis were found to have a positive marker.12 We feel that a
history or family history of VTE in combination with patients having
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a major operation is sufficient to classify an individual in the very

high-risk group.13

Obstetrical History
Another important and frequently overlooked risk factor occurs in
women with a past history of an obstetrical complication including a
stillborn, miscarriage in any trimester, premature birth with toxemia, or
growth-restricted infant. These past events may be the clinical manifestation of a serious thrombophilia defect known as anticardiolipin antibodies, which includes the lupus anticoagulant.14-19 We also are careful
to question patients about a history or family history of stroke, since, in
some of these individuals, elevated levels of homocysteine have been
found and this is easily treated with vitamin prophylaxis.20-22

Long-Term Prophylaxis
The length of prophylaxis in postoperative patients is important. Except
for certain orthopedic and general surgical populations, not many studies
have been done to show the benefit of long-term prophylaxis. In the
above-mentioned groups we know that statistically significant lowering of
the venographic incidence of venous thrombosis has been achieved with
4 to 6 weeks of postoperative prophylaxis using various pharmacologic
agents.23,24 One thing to keep in mind when deciding about long-term
prophylaxis is the mobility of the patient. Seriously ill patients are
discharged with fistulas, draining wounds, or intravenous catheters for
nutritional support or antibiotic treatment. These individuals spend most
of the time in a recliner, which is not early ambulation but rather early
angulation.

Efcacy versus Safety

One of the most important considerations regarding the choice of
thrombosis prophylaxis is to balance efficacy and safety concerns. Many
times clinicians use inadequate prophylaxis because of a concern for
bleeding despite the fact that some of these patients are already at
enormously high risk. It is natural for a surgeon to consider bleeding to
be a surgical problem and thrombosis to be an act of God. We would like
to suggest a different philosophy. Depending upon the patients level of
risk, one may require a type or intensity of prophylaxis that may increase
their chances of bleeding. These increased risks, however, can be justified
by the very high incidence of fatal PE or disabling stroke. We feel it is
important to have a preoperative discussion with patients and their
families regarding the relative risks and benefits of a particular thrombo76

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sis prophylaxis strategy. This should include a realistic evaluation of the

risk of serious venous thromboembolic complications. One must also
remember that if the patient is at very high risk and thrombosis
prophylaxis has to be discontinued in the early postoperative period due
to bleeding, the chances of a serious event are magnified. Patients
undergoing quality-of-life procedures must weigh the risks and benefits of
such procedures if they are in this very high-risk group.
Finally, we feel that a careful individual assessment of thrombosis risk
must be done in every patient to minimize the morbidity and mortality of
venous thromboembolic events. As a part of this analysis, the length of
prophylaxis needs to be determined based on the patients individual
circumstances.

REFERENCES
1.

2.

3.
4.
5.

6.

7.
8.
9.

10.

11.

Geerts WH, Pineo GF, Heit JA, et al. Prevention of venous thromboembolism: the
Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest
2004;126(suppl 3):338S-400S.
Heit JA, Rooke TW, Silverstein M, et al. Trends in the incidence of venous stasis
syndrome and venous ulcer: a 25-year population-based study. J Vasc Surg
2001;33(5):1022-7.
Stein PD, Henry JW. Prevalence of acute pulmonary embolism among patients in
a general hospital and at autopsy. Chest 1995;108(4):978-81.
Baglin TP, White K, Charles A. Fatal pulmonary embolism in hospitalised medical
patients. J Clin Pathol 1997;50(7):609-10.
Bridges ND, Hellenbrand W, Latson L, et al. Transcatheter closure of patent
foramen ovale after presumed paradoxical embolism. Circulation 1992;86(6):
1902-8.
Messe SR, Silverman IE, Kizar JR, et al. Practice parameter: recurrent stroke with
patent foramen ovale and atrial septal aneurysm: report of the Quality Standards
Subcommittee of the American Academy of Neurology. Neurology 2004;62(7):
1042-50.
Arcelus JI, Caprini JA, Traverso CI. International perspective on venous thromboembolism prophylaxis in surgery. Semin Thromb Hemost 1991;17(4):322-5.
Caprini JA, Arcelus I, Traverso CI, et al. Clinical assessment of venous thromboembolic risk in surgical patients. Semin Thromb Hemost 1991;17(suppl 3):304-12.
Motykie GD, Zebala LP, Caprini JA, et al. Risk factor assessment in the
management of patients with suspected deep venous thrombosis. Int Angiol
2000;19(1):47-51.
Caprini JA, Arcelus JI, Reyna JJ. Effective risk stratification of surgical and
nonsurgical patients for venous thromboembolic disease. Semin Hematol 2001;
38(2 suppl 5):12-9.
Bergqvist D, Agnelli G, Cohen AT, et al. Duration of prophylaxis against venous
thromboembolism with enoxaparin after surgery for cancer. N Engl J Med
2002;346(13):975-80.

DM, February/March 2005

77

12.
13.
14.
15.
16.
17.
18.
19.
20.

21.

22.

23.
24.

78

Caprini JA, Glase CJ, Anderson CB, et al. Laboratory markers in the diagnosis of
venous thromboembolism. Circulation 2004;109(12 suppl 1):I4-8.
Baglin T. Thrombophilia testing: what do we think the tests mean and what should
we do with the results? [see comment]. J Clin Pathol 2000;53(3):167-70.
Greer IA. Thrombophilia: implications for pregnancy outcome. Thromb Res
2003;109(2-3):73-81.
Greer IA. Prevention of venous thromboembolism in pregnancy. Best Pract Res
Clin Haematol 2003;16(2):261-78.
Greer IA. Hypercoagulable states and pregnancy. Curr Hematol Rep
2002;1(1):56-62.
Greer IA. Endothelial cell microparticles and antiphospholipid syndrome: pathologic
explanations and diagnostic opportunities. Thromb Haemost 2004;91(4):636-8.
Rodie VA, Freeman DJ, Sattar N, et al. Pre-eclampsia and cardiovascular disease:
metabolic syndrome of pregnancy? Atherosclerosis 2004;175(2):189-202.
Robertson L, Wu O, Greer I. Thrombophilia and adverse pregnancy outcome. Curr
Opin Obstet Gynecol 2004;16(6):453-8.
Stam F, Vanguldener C, TerWee, PM, et al. Effect of folic acid on methionine and
homocysteine metabolism in end-stage renal disease. Kidney Int 2005;67(1):25964.
Hankey GJ, Eikelboom JW, Loh K, et al. Sustained homocysteine-lowering effect
over time of folic acid-based multivitamin therapy in stroke patients despite
increasing folate status in the population. Cerebrovasc Dis 2004;19(2):110-6.
Ikegaya N, Yanagisawa C, Kumagai H. Relationship between plasma homocysteine
concentration and urinary markers of tubulointerstitial injury. Kidney Int
2005;67(1):375.
Bergqvist D, Lowe GD, Berstad A, et al. Prevention of venous thromboembolism
after surgery: a review of enoxaparin. Br J Surg 1992;79(6):495-8.
Bergqvist D, Efsing HO, Halbook T, et al. Thromboembolism after elective and
post-traumatic hip surgerya controlled prophylactic trial with dextran 70 and
low-dose heparin. Acta Chir Scand 1979;145(4):213-8.

DM, February/March 2005