Cases & Commentaries

An Ounce of Prevention

Spotlight Case
Commentary By Nils Kucher, MD

Case Objectives

  • Assess risk for venous thromboembolism
    (VTE) in hospitalized patients
  • List recommended strategies for VTE
    prevention for various risk groups
  • Identify patients who qualify for
    extended-duration prophylaxis
  • Appreciate interventions that may
    increase system-wide use of VTE prophylaxis

Case & Commentary: Part 1

A 47-year-old woman was admitted to the
plastic surgery service after a motor vehicle collision with major
trauma to her right hand, which required repair with use of an
abdominal flap. On the second postoperative day, the patient
suffered a sudden cardiopulmonary arrest. After successful
resuscitation, a chest CT revealed a massive pulmonary
embolism.

Venous thromboembolism (VTE) is a common
condition, with an incidence of 1.5/1000 per year in all U.S.
adults and at least 1% of hospitalized patients.(1) Deep vein
thrombosis (DVT) is associated with a 30-day mortality rate of less
than 2% (in fact, many cases go undiagnosed and undetected), but
pulmonary embolism (PE) is far more serious, with an overall 30-day
mortality of approximately 10%.(2) Most early
PE deaths are due to acute right ventricular failure, whereas late
PE mortality often is caused by the underlying conditions that
predisposed to the clot. In the United States, more than 100,000
patients per year die from PE.(3)

The most common VTE risk factors include surgery,
trauma, cancer, congestive heart failure, chronic lung disease, age
older than 70 years, obesity, bed rest, prior VTE, thrombophilic
disorders, and acute respiratory failure. Recurrences are common:
more than 50% of surgical patients with a previous history of VTE
who do not receive prophylaxis will develop postoperative
DVT.(4) Nearly one
in five surgeries (even in the absence of additional risk factors)
results in VTE if neither pharmacologic nor mechanical prophylaxis
is applied.(5) That number
skyrockets to more than 50% in patients undergoing total hip and
total knee replacement who fail to receive prophylaxis.(6) Spinal
surgery, pelvic surgery, and neurosurgery also place patients at
particularly high risk of VTE.

Trauma, particularly of the lower extremities and
pelvis, increases the risk of VTE. PE has been identified at
autopsy in as many as 60% of patients with lower-extremity
fractures (7), and
mortality has been attributed to PE in as many as 50% of patients
dying after hip fracture.(8) The
incidence of VTE increases with time after the traumatic event.
Autopsy-confirmed PE in patients surviving less than 24 hours after
trauma has been demonstrated in 3.3%, increasing to 5.5% in those
surviving up to 7 days. PE was found in 18.6% of those surviving a
longer period.(9) The risk of
VTE after major trauma to the upper extremity is less clear. In
this setting, lower-extremity DVT often is caused by prolonged bed
rest; the risk increases when surgery and general anesthesia are
required. Upper-extremity trauma enhances the risk of
upper-extremity DVT.(10) The risk of
symptomatic PE in patients with lower-extremity DVT ranges between
15% and 30% (11), and it
occurs less often (3%) in patients with upper-extremity
DVT.(10)

Case & Commentary: Part 2

Review of the patient's chart revealed no pre-
or postoperative DVT prophylaxis.

Without knowing the full extent of this
patient’s trauma and the presence of additional risk factors,
it is impossible to say if prophylaxis should have been
administered. The critical point for clinicians is to consider this
risk and make appropriate, evidence-based decisions about
prophylaxis in all hospitalized patients.

Despite detailed North American guidelines, VTE
prophylaxis continues to be underutilized. In a registry of 5,451
consecutive patients with ultrasound-confirmed DVT from 183 United
States institutions, only 42% of inpatients had received
prophylaxis within 30 days prior to developing acute DVT.(12) In this
registry, compliance with guidelines was better in surgical than in
medical patients.

VTE prophylaxis recommendations differ for the
various surgical settings (Table).
According to current consensus guidelines from the American College
of Chest Physicians (ACCP) (13),
prophylaxis should be administered in all trauma patients with at
least one additional risk factor. Low-molecular-weight heparin
(LMWH) is recommended as pharmacologic prophylaxis. In some
patients, however, the use of LMWH may be precluded, usually
because of the risk of bleeding. In such patients, mechanical
prophylaxis, including graduated compression stockings or
intermittent pneumatic compression devices, should be considered.
Ultrasound surveillance, seeking evidence of DVT that would tip the
scales toward anticoagulation (or, if that is too risky, placement
of an inferior vena cava [IVC] filter), is recommended in high-risk
trauma patients not receiving pharmacologic prophylaxis. The ACCP
recommends against the routine (ie, prophylactic) use of IVC
filters in trauma patients. Newer retrievable IVC filters may be
useful for patients with transiently increased risk of both
clotting and bleeding complications, and many institutions now use
them in this setting. Although permanent IVC filters reduce the
risk of PE, there is a tradeoff: the risk of DVT at 1 year,
particularly due to filter thrombosis (Figure 1), is
double that of patients without filters.(14)

Case & Commentary: Part 3

The patient was aggressively resuscitated and
started on systemic anticoagulation with heparin, and then
warfarin. After a 3-day stay in the intensive care unit, the
patient was transferred to the floor. Ultimately, she was
discharged to home without any evidence of anoxic brain injury or
permanent pulmonary sequelae from her PE.

In 2003, the American Public Health Association
(APHA) created a national coalition to advocate for greater
awareness of DVT and PE among health care providers and the general
public.(15) The Joint
Commission on Accreditation of Healthcare Organizations (JCAHO) has
been encouraged by the APHA to make adherence to DVT prevention
guidelines part of its accreditation process. As of now, specific
actions from JCAHO have not been undertaken, and DVT prophylaxis
still is not part of ratings for hospital performance.

Continuing medical education (16) and
computerized electronic alerts (17,18) can
increase physician utilization of VTE prophylaxis. In a randomized
controlled trial of 2506 high-risk patients who did not receive
prophylaxis, a single computer alert to the responsible physician
doubled the prophylaxis rate and reduced the VTE rate at 90 days by
41%.(19) The
computer program used eight common risk factors to determine each
hospitalized patient's risk profile for VTE on a daily basis. Each
risk factor was weighted according to a point scale: the major risk
factors of cancer, prior VTE, and hypercoagulability were assigned
a score of 3; the intermediate risk factor of major surgery was
assigned a score of 2; and the minor risk factors of advanced age,
obesity, bed rest, and the use of hormone-replacement therapy or
oral contraceptives were assigned a score of 1. An increased risk
of VTE was defined as a cumulative risk score of at least 4. In
patients with a VTE risk score greater than or equal to 4, the
computer program used medical record numbers to randomly assign
1255 eligible patients to an intervention group, in which the
responsible physician was alerted to a patient's risk of DVT, and
1251 patients to a control group, in which no alert was issued. The
alert was sent once for each patient (Figure 2). The
physician was required to acknowledge the alert and could then
withhold or order prophylaxis, including graduated compression
stockings, pneumatic compression boots, unfractionated heparin,
LMWH, or warfarin. The results of this trial suggest that hospitals
with adequate information system resources should consider
implementation of electronic alerts to increase the awareness of
VTE risk, to improve the utilization of prophylaxis, and to reduce
the rates of DVT and PE.

Take-Home Points

  • Know the common VTE risk factors.
  • Assess VTE risk for each hospitalized
    patient individually.
  • Become familiar with the various VTE
    prophylaxis regimens for different patient groups at risk.
  • Apply the current ACCP guidelines to
    prevent VTE in hospitalized patients.
  • Use hospital information systems to
    increase awareness of VTE and implement adequate prophylaxis in
    patients at risk.

Nils
Kucher, MD
Staff Interventional Cardiologist
Department of Medicine, Cardiovascular Division
University Hospital Zurich
Switzerland

Faculty Disclosure: Dr. Kucher has
declared that neither he, nor any immediate member of his family,
has a financial arrangement or other relationship with the
manufacturers of any commercial products discussed in this
continuing medical education activity. In addition, his commentary
does not include information regarding investigational or off-label
use of pharmaceutical products or medical devices.

References

1. Tsai AW, Cushman M, Rosamond WD, Heckbert SR,
Polak JF, Folsom AR. Cardiovascular risk factors and venous
thromboembolism incidence: the longitudinal investigation of
thromboembolism etiology. Arch Intern Med. 2002;162:1182-1189.
[
go to PubMed
]

2. Goldhaber SZ, Visani L, De Rosa M. Acute
pulmonary embolism: clinical outcomes in the International
Cooperative Pulmonary Embolism Registry (ICOPER). Lancet.
1999;353:1386-1389.
[
go to PubMed
]

3. Goldhaber SZ. Pulmonary embolism. Lancet.
2004;363:1295-1305.
[
go to PubMed
]

4. Kakkar VV, Howe CT, Nicolaides AN, Renney JT,
Clarke MB. Deep vein thrombosis of the leg: Is there a "high risk"
group? Am J Surg. 1970;120:527-530.
[
go to PubMed
]

5. Clagett GP, Reisch JS. Prevention of venous
thromboembolism in general surgical patients: results of
meta-analysis. Ann Surg. 1988;208:227-240.
[
go to PubMed
]

6. Clagett GP, Anderson FA Jr, Geerts W, et al.
Prevention of venous thromboembolism. Chest. 1998;114(suppl
5):531S-560S.
[
go to PubMed
]

7. Fisher M, Michele A, McCann W.
Thrombophlebitis and pulmonary infarction associated with fractured
hip. Clin Res. 1963;11:407.

8. Fitts, WT Jr, Lehr HB, Bitner RL, Spellman JW.
An analysis of 950 fatal injuries. Surgery. 1964;56:663-668.
[
go to PubMed
]

9. Coon WW. Risk factors in pulmonary embolism.
Surg Gynecol Obstet. 1976;143:385-390.
[
go to PubMed
]

10. Joffe HV, Kucher N, Tapson VF, Goldhaber SZ,
for the Deep Vein Thrombosis (DVT) FREE Steering Committee.
Upper-extremity deep vein thrombosis: a prospective registry of 592
patients. Circulation. 2004;110:1605-1611.
[
go to PubMed
]

11. Kucher N, Tapson VF, Goldhaber SZ, for the
DVT FREE Steering Committee. Risk factors associated with
symptomatic pulmonary embolism in a large cohort of DVT patients.
Thromb Haemost. 2005;93:494-498.
[
go to PubMed
]

12. Goldhaber SZ, Tapson VF, for the DVT FREE
Steering Committee. A prospective registry of 5,451 patients with
ultrasound-confirmed deep vein thrombosis. Am J Cardiol.
2004;93:259-262.
[
go to PubMed
]

13. 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.
[
go to PubMed
]

14. Decousus H, Leizorovicz A, Parent F, et al,
for the Prévention du Risque d'Embolie Pulmonaire par
Interruption Cave Study Group. A clinical trial of vena caval
filters in the prevention of pulmonary embolism in patients with
proximal deep-vein thrombosis. N Engl J Med. 1998;338:409-415.
[
go to PubMed
]

15. Public Health Leadership Conference on
Deep-Vein Thrombosis. Deep-vein thrombosis: advancing awareness to
protect patient lives. Washington, DC: American Public Health
Association; 2003. Available at: http://www.apha.org/ppp/DVT_White_Paper.pdf.
Accessed December 13, 2005.

16. Anderson FA Jr, Wheeler HB, Goldberg RJ,
Hosmer DW, Forcier A, Patwardhan NA. Changing clinical practice.
Prospective study of the impact of continuing medical education and
quality assurance programs on use of prophylaxis for venous
thromboembolism. Arch Intern Med. 1994;154:669-677.
[
go to PubMed
]

17. Dexter PR, Perkins S, Overhage JM, Maharry K,
Kohler RB, McDonald CJ. A computerized reminder system to increase
the use of preventive care for hospitalized patients. N Engl J Med.
2001;345:965-970.
[
go to PubMed
]

18. Durieux P, Nizard R, Ravaud P, Mounier N,
Lepage E. A clinical decision support system for prevention of
venous thromboembolism: effect on physician behavior. JAMA.
2000;283:2816-2821.
[
go to PubMed
]

19. Kucher N, Koo S, Quiroz R, et al. Electronic
alerts to prevent venous thromboembolism among hospitalized
patients. N Engl J Med. 2005;352:969-977. [
go to PubMed
]

Table

Table. VTE Prophylaxis Modalities for Common
Surgical Settings

Indication

Prevention Strategy

General surgery UFH 5,000 units q 8h, 1st dose 2h
preoperatively, continued for 7 days or LMWH once daily.
Cancer surgery Enoxaparin 40 mg daily, 1st dose 10-14h
preoperatively if possible, for 28 days.
Total hip replacement Enoxaparin 40 mg daily, beginning preoperative
evening, continuing out-of-hospital for 21-28 days.
Enoxaparin 30 mg BID, 1st dose 12-24h
postoperatively, until hospital discharge.
Dalteparin 2,500 units ≥ postoperatively,
then 5,000 units daily until hospital discharge or for 35
days.
Fondaparinux 2.5 mg 4-8h postoperatively, then
≥ 12h after 1st dose, then daily for 5-9
days.
Warfarin daily, 1st dose 7.5 mg 24-48h
preoperatively, adjusted to target INR of 2.0-3.0.
Warfarin daily, 1st dose 5 mg
preoperative evening, adjusted to target INR of 2.0-3.0 and
continued 4-6 weeks.
Total knee replacement Enoxaparin 30 mg BID, beginning 12-24h
postoperatively, continued for an average of 9 days.
Fondaparinux 2.5 mg, 1st dose 4-8h
postoperatively, 2nd dose ≥ 12h after 1st dose,
then daily for 5-9 days.
Hip fracture surgery Fondaparinux 2.5 mg, 1st dose 4-8h
postoperatively, 2nd dose ≥ 12h after 1st dose,
then daily for 5-9 days. If surgery is delayed > 24-48h after
admission, give 1st dose 10-14h preoperatively. Continue
prophylaxis for 28-35 days after surgery.
Neurosurgery Enoxaparin 40 mg daily, 1st dose
≤ 24h postoperatively, continued until hospital discharge,
plus GCS.
Craniotomy for brain tumor Enoxaparin 40 mg daily or UFH 5,000 units BID,
1st dose on 1st postoperative morning,
continued until hospital discharge, plus GCS/IPC, plus predischarge
venous ultrasonography.
UFH = unfractionated heparin, LMWH =
low-molecular-weight heparin, GCS = graduated compression
stockings, IPC = intermittent pneumatic compression devices

Figures

Figure 1. CT Scan in a Patient with Inferior
Vena Cava (IVC) Filter Thrombosis, Causing 50% Obstruction of the
IVC


Figure 2. Example Electronic VTE Alert System
(Brigham and Women's Hospital)