0
Clinical Investigations: PULMONARY VASCULATURE |

New Onset of Venous Thromboembolism Among Hospitalized Patients at Brigham and Women’s Hospital Is Caused More Often by Prophylaxis Failure Than by Withholding Treatment* FREE TO VIEW

Samuel Z. Goldhaber, MD, FCCP; Kelly Dunn, BA; Regina C. MacDougall, RN, BSN, CVN
Author and Funding Information

*From the Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA.

Correspondence to: Samuel Z. Goldhaber, MD, FCCP, Brigham and Women’s Hospital, 75 Francis St, Boston, MA 02115; e-mail: sgoldhaber@partners.org



Chest. 2000;118(6):1680-1684. doi:10.1378/chest.118.6.1680
Text Size: A A A
Published online

Context: Guidelines to prevent venous thromboembolism (VTE) have been widely distributed and generally have been assumed to be effective. Therefore, among hospitalized patients, the development of VTE is thought to occur in the context of omitted prophylaxis.

Objectives: To describe hospitalized patients who develop VTE and to determine whether they received antecedent prophylaxis.

Design: Case series.

Setting: Brigham and Women’s Hospital.

Patients: Three hundred eighty-four patients who developed in-hospital deep venous thrombosis or pulmonary embolism or who developed VTE within 30 days of prior hospital discharge.

Main outcome measures: The relationship of developing new-onset VTE to the use or omission of antecedent in-hospital prophylaxis.

Results: Of the 384 identified patients, 272 had deep venous thrombosis alone, 62 had pulmonary embolism alone, and 50 had deep venous thrombosis and pulmonary embolism. Most were medical service patients; fewer than one fourth were general or orthopedic surgery patients. Overall, 52% had received antecedent VTE prophylaxis. Thirteen deaths (3.4%) were ascribed to pulmonary embolism, and prophylaxis was omitted in only 1 of those 13 patients.

Conclusions: Most deaths from pulmonary embolism among patients hospitalized for other conditions occurred in the setting of failed prophylaxis rather than omitted prophylaxis. High-risk patients, especially medical service patients, warrant intensive VTE prophylaxis and close follow-up to ensure successful outcomes.

Figures in this Article

During the past 2 decades, prevention of venous thromboembolism (VTE) has become widely accepted as an effective and worthwhile strategy. North American1and European2guidelines have provided detailed recommendations for prophylaxis among virtually all groups of hospitalized patients. Nevertheless, despite favorable outcomes with preventive measures, some patients have not received routine prophylaxis.3

“Primary” VTE occurs outside of the hospital and without predisposing cancer, trauma, or surgery. In contrast, “secondary” VTE occurs during or soon after hospitalization and is precipitated by concomitant illness. Hospitalization provides an opportunity to institute universal prophylaxis against VTE, thus minimizing the occurrence of secondary VTE. In this article, we evaluate those patients who developed secondary VTE at Brigham and Women’s Hospital (BWH). We hypothesized that most patients who developed secondary VTE would have received no in-hospital prophylaxis.

We searched our hospital database for all discharge diagnoses of secondary deep vein thrombosis (DVT) and pulmonary embolism (PE), except for neurosurgical patients,4from January 1995 through December 1996. We also searched the database for a principal diagnosis of DVT or PE among patients previously discharged from BWH within 30 days. We then reviewed each chart to confirm the diagnosis of VTE. PE was diagnosed primarily by high-probability lung scan (38 patients), intermediate lung scan with high clinical suspicion (50 patients) using revised criteria of the Prospective Investigation of Pulmonary Embolism Diagnosis,5or positive pulmonary angiography (33 patients). DVT was diagnosed primarily by venous leg ultrasound (309 patients). The results of 155 ultrasound examinations showed proximal leg DVT, 108 showed isolated calf DVT, and 46 showed both proximal and calf DVT. We previously validated the accuracy of our ultrasound laboratory for detecting calf DVT against contrast venography.6Software programs were used to analyze demographic and clinical data (SPSS Inc; Chicago, IL)7and statistical calculations (StatCalc, Epi Info version 501b; Centers for Disease Control and Prevention; Atlanta, GA).8

We identified 384 patients with VTE: 180 men (46.9%) and 204 women (53.1%). Overall, 272 patients had DVT alone, 62 had PE alone, and 50 had concomitant PE and DVT. The ages of the patients spanned a wide range (Fig 1 ).

Secondary VTE developed during the initial hospitalization in 211 of 384 patients (55%) and resulted in rehospitalization at BWH within 30 days of a previous BWH discharge among 173 of the 384 patients (45%). Of the 173 who were rehospitalized, 69 were men (40%) and 104 were women (60%). Thus, a higher proportion of women (104 of 204; 51%) than men (69 of 180; 38%) were rehospitalized with VTE (p = 0.02).

The majority of patients whom we identified were receiving general medicine or medical oncology services (Table 1 ). General surgery and orthopedic surgery patients accounted for less than one fourth of the overall hospital population with secondary VTE.

Most patients who developed secondary VTE had multiple risk factors for venous thrombosis (Table 2 ). One hundred four patients (27%) had at least four predisposing risk factors. Specific predispositions for VTE are listed in Table 3 . Overall, 11 patients developed upper-extremity DVT, 10 cases of which occurred in association with a central venous catheter.

With respect to our principal hypothesis, we found that fewer than half of patients (n = 183; 48%) had received no prophylaxis prior to developing secondary VTE (Table 4 ). Of these 183 patients who did not receive prophylaxis, 110 were admitted to medical services (general medicine and medical oncology) and 73 were admitted to surgical services (general surgery, orthopedics, thoracic surgery, cardiac surgery, gynecology, obstetrics, surgical gastroenterology, and renal transplant). Of the 201 patients whose prophylaxis treatment against VTE was unsuccessful (52%), 112 received an anticoagulant (including 68 patients who received unfractionated heparin alone), 31 received mechanical prophylaxis, and 58 received a combination of pharmacologic and mechanical prophylaxis (Table 5 ).

After the diagnosis of VTE was established, all but 26 of 384 patients (93%) received specific therapy for DVT or PE. Three hundred forty-two patients received full heparin or warfarin treatment. Eighty-six patients (25%) underwent placement of a vena caval filter, usually in combination with anticoagulation. Only 17 of these 86 patients received an inferior vena caval filter alone. Five patients received thrombolysis, two patients underwent suction catheter embolectomy, and one patient underwent open surgical embolectomy.

Secondary VTE caused considerable morbidity from anticoagulation and mortality from hemodynamically important PE. Nineteen patients had GI bleeding, and 1 patient sustained a nonfatal intracranial hemorrhage. Overall, 33 patients died; PE was a major contributor to 13 deaths (seven men, six women; Table 6 ). Thus, in our series, the death rate from secondary pulmonary embolism was 3.4%. Of these 13 patients, prophylaxis was omitted in 1 patient and failed in 12 patients; 11 patients were receiving medical services, and 2 were thoracic surgery patients. An additional 11 patients (five men, six women) had PE considered incidental to death. Nine other patients with secondary VTE died of noncardiovascular causes.

Surprisingly, the majority of secondary VTE occurred in the setting of failed prophylaxis rather than omitted prophylaxis. This was especially apparent in 12 of the 13 patients who died of PE despite receiving prophylaxis. Secondary VTE affected both genders similarly and occurred in a wide age range of patients. Almost half of the cohort was readmitted to BWH after discharge from BWH within the prior 30 days. In addition to its impact on morbidity, mortality, and rehospitalization, secondary VTE was associated with a high frequency of filter placement and other cost-intensive therapies such as thrombolysis and embolectomy.

Previous clinical trials of VTE prophylaxis have yielded successful outcomes in the vast majority of patients.12 Thus, we had hypothesized that most cases of secondary VTE would have been due to omitted prophylaxis. Certain groups, such as medical ICU patients, appear to be at especially high risk even when standard prophylaxis is administered.9 Compared with prior reports, most patients in our current series are medical patients. However, some patients were initially admitted to a nonsurgical service and subsequently underwent surgery. Our evaluation also tracks rehospitalizations within 30 days of discharge. This approach, combined with the population of high-risk patients (most of whom had three or more high risk factors), contributes to the high failure rate of prophylaxis that we observed.

Undoubtedly, many more patients than we identified actually had secondary VTE, due to the silent nature of DVT and PE. It is possible that the ratio of failed to omitted prophylaxis might change if we could identify definitively the entire cohort of patients with secondary VTE. However, this is not feasible because even if we had undertaken routine VTE screening of the entire hospitalized population, noninvasive imaging tests such as venous ultrasonography are often insensitive in asymptomatic patients.1011 Screening blood tests such as the plasma D-dimer enzyme-linked immunosorbent assay lack specificity, especially among hospitalized patients with cancer, myocardial infarction, pneumonia, sepsis, and the postoperative state.12

Our findings should not be misconstrued as endorsing a nihilistic policy of abandoning VTE prophylaxis. Indeed, since the patients we describe represented less than 0.5% of BWH admissions, it is quite possible that, overall, VTE prophylaxis was almost always successful. Based on our findings, we hope that quality improvement committees will emphasize the importance of implementing more intensive prophylaxis among high-risk patients as well as meticulous follow-up of these patients to ensure successful outcomes. In the future, this goal may be achieved with more frequent use of low-molecular-weight heparin prophylaxis, especially among medical patients,13or pneumatic compression boots,14 or both.

Abbreviations: BWH = Brigham and Women’s Hospital; DVT = deep vein thrombosis; PE = pulmonary embolism; VTE = venous thromboembolism

Figure Jump LinkFigure 1. The relationship between age and VTE.Grahic Jump Location
Table Graphic Jump Location
Table 1. VTE According to Hospital Service
Table Graphic Jump Location
Table 2. Risk Factors for VTE in Study Population
Table Graphic Jump Location
Table 3. Risk Factors According to Gender*
* 

IVC = inferior vena caval.

Table Graphic Jump Location
Table 4. Patients Who Did Not Receive Prophylaxis According to Service*
* 

Data are presented as No.

Table Graphic Jump Location
Table 5. Prophylaxis Modality in Patients Who Nevertheless Developed VTE
Table Graphic Jump Location
Table 6. PE as a Major Contributor to Death*
* 

UFH = unfractionated heparin; LMWH = low-molecular-weight heparin; IPC = intermittent pneumatic compression boots; U/S = venous ultrasound of the deep leg veins; GCS = graduated compression stockings; ECHO = echocardiography showing right ventricular dysfunction.

Clagett, GP, Anderson, FA, Jr, Geerts, W, et al (1998) Prevention of venous thromboembolism.Chest114(5 suppl),531S-560S
 
Prevention of venous thromboembolism: international consensus statement (guidelines according to scientific evidence). Int Angiol 1997; 16:3–38.
 
Keane, MG, Ingenito, EP, Goldhaber, SZ Utilization of venous thromboembolism prophylaxis in the medical intensive care unit.Chest1994;106,13-14. [CrossRef] [PubMed]
 
Chan, AT, Atiemo, A, Diran, LL, et al Venous thromboembolism occurs frequently in patients undergoing brain tumor surgery despite prophylaxis.J Thromb Thrombolysis1999;8,139-142. [CrossRef] [PubMed]
 
Gottschalk, A, Sostman, HD, Coleman, RE, et al Ventilation-perfusion scintigraphy in the PIOPED study: Part II. Evaluation of the scintigraphic criteria and interpretations.J Nucl Med1993;34,1119-1126. [PubMed]
 
Simons, GR, Skibo, LK, Polak, JF, et al Utility of ultrasonography in suspected symptomatic isolated calf deep vein thrombosis.Am J Med1995;99,1-5. [CrossRef] [PubMed]
 
SPSS, Base 10.0. Chicago, IL: SPSS, Inc; 1999.
 
Epi Info, version 5.01b. Atlanta, GA: Centers for Disease Control and Prevention, Epidemiology Program Office, 1991.
 
Hirsch, DR, Ingenito, EP, Goldhaber, SZ Prevalence of deep vein thrombosis among patients in medical intensive care.JAMA1995;274,335-337. [CrossRef] [PubMed]
 
Jongbloets, LMM, Lensing, AWA, Koopman, MMW, et al Limitations of compression ultrasound for the detection of symptomless postoperative deep vein thrombosis.Lancet1994;343,1142-1144. [CrossRef] [PubMed]
 
Lensing, AWA, Doris, CI, McGrath, FP, et al A comparison of compression ultrasound with color Doppler ultrasound for the diagnosis of symptomless postoperative deep vein thrombosis.Arch Intern Med1997;157,765-768. [CrossRef] [PubMed]
 
de Moerloose, P, Michiels, JJ, Bounameaux, H The place of D-dimer testing in an integrated approach of patients suspected of pulmonary embolism.Semin Thromb Hemost1998;24,409-412. [CrossRef] [PubMed]
 
Samama, MM, Cohen, AT, Darmon, JY, et al A comparison of enoxaparin with placebo for the prevention of venous thromboembolism in acutely ill medical patients.N Engl J Med1999;341,793-800. [CrossRef] [PubMed]
 
Ramos, R, Salem, BI, De Pawlikowski, MP, et al The efficacy of pneumatic compression stockings in the prevention of pulmonary embolism after cardiac surgery.Chest1996;109,82-85. [CrossRef] [PubMed]
 

Figures

Figure Jump LinkFigure 1. The relationship between age and VTE.Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1. VTE According to Hospital Service
Table Graphic Jump Location
Table 2. Risk Factors for VTE in Study Population
Table Graphic Jump Location
Table 3. Risk Factors According to Gender*
* 

IVC = inferior vena caval.

Table Graphic Jump Location
Table 4. Patients Who Did Not Receive Prophylaxis According to Service*
* 

Data are presented as No.

Table Graphic Jump Location
Table 5. Prophylaxis Modality in Patients Who Nevertheless Developed VTE
Table Graphic Jump Location
Table 6. PE as a Major Contributor to Death*
* 

UFH = unfractionated heparin; LMWH = low-molecular-weight heparin; IPC = intermittent pneumatic compression boots; U/S = venous ultrasound of the deep leg veins; GCS = graduated compression stockings; ECHO = echocardiography showing right ventricular dysfunction.

References

Clagett, GP, Anderson, FA, Jr, Geerts, W, et al (1998) Prevention of venous thromboembolism.Chest114(5 suppl),531S-560S
 
Prevention of venous thromboembolism: international consensus statement (guidelines according to scientific evidence). Int Angiol 1997; 16:3–38.
 
Keane, MG, Ingenito, EP, Goldhaber, SZ Utilization of venous thromboembolism prophylaxis in the medical intensive care unit.Chest1994;106,13-14. [CrossRef] [PubMed]
 
Chan, AT, Atiemo, A, Diran, LL, et al Venous thromboembolism occurs frequently in patients undergoing brain tumor surgery despite prophylaxis.J Thromb Thrombolysis1999;8,139-142. [CrossRef] [PubMed]
 
Gottschalk, A, Sostman, HD, Coleman, RE, et al Ventilation-perfusion scintigraphy in the PIOPED study: Part II. Evaluation of the scintigraphic criteria and interpretations.J Nucl Med1993;34,1119-1126. [PubMed]
 
Simons, GR, Skibo, LK, Polak, JF, et al Utility of ultrasonography in suspected symptomatic isolated calf deep vein thrombosis.Am J Med1995;99,1-5. [CrossRef] [PubMed]
 
SPSS, Base 10.0. Chicago, IL: SPSS, Inc; 1999.
 
Epi Info, version 5.01b. Atlanta, GA: Centers for Disease Control and Prevention, Epidemiology Program Office, 1991.
 
Hirsch, DR, Ingenito, EP, Goldhaber, SZ Prevalence of deep vein thrombosis among patients in medical intensive care.JAMA1995;274,335-337. [CrossRef] [PubMed]
 
Jongbloets, LMM, Lensing, AWA, Koopman, MMW, et al Limitations of compression ultrasound for the detection of symptomless postoperative deep vein thrombosis.Lancet1994;343,1142-1144. [CrossRef] [PubMed]
 
Lensing, AWA, Doris, CI, McGrath, FP, et al A comparison of compression ultrasound with color Doppler ultrasound for the diagnosis of symptomless postoperative deep vein thrombosis.Arch Intern Med1997;157,765-768. [CrossRef] [PubMed]
 
de Moerloose, P, Michiels, JJ, Bounameaux, H The place of D-dimer testing in an integrated approach of patients suspected of pulmonary embolism.Semin Thromb Hemost1998;24,409-412. [CrossRef] [PubMed]
 
Samama, MM, Cohen, AT, Darmon, JY, et al A comparison of enoxaparin with placebo for the prevention of venous thromboembolism in acutely ill medical patients.N Engl J Med1999;341,793-800. [CrossRef] [PubMed]
 
Ramos, R, Salem, BI, De Pawlikowski, MP, et al The efficacy of pneumatic compression stockings in the prevention of pulmonary embolism after cardiac surgery.Chest1996;109,82-85. [CrossRef] [PubMed]
 
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

Find Similar Articles
CHEST Journal Articles
PubMed Articles
  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543