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Logo of nihpaAbout Author manuscriptsSubmit a manuscriptHHS Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
 
Arch Intern Med. Author manuscript; available in PMC 2009 October 16.
Published in final edited form as:
PMCID: PMC2762787
NIHMSID: NIHMS97812

Venous Thromboembolism in the Outpatient Setting

Abstract

Background

There has been great interest in optimizing prophylaxis against venous thromboembolism (VTE) in the hospital setting. However, data from earlier studies suggest that the majority of VTE events occur in the outpatient setting. The purpose of this observational study was to describe the frequency of VTE events occurring in the outpatient setting, characterize the prevalence of previously identified risk factors for VTE, and to identify prior utilization of VTE prophylaxis.

Methods

The medical records of residents from the Worcester (MA) metropolitan area diagnosed with ICD-9 codes consistent with possible VTE during 1999, 2001, and 2003 were independently validated and reviewed by trained abstractors.

Results

A total of 1,897 subjects had a confirmed episode of VTE. Approximately 74% of patients developed VTE in the outpatient setting – a substantial proportion of these patients had undergone surgery (23%) or hospitalization (37%) in the preceding 3 months. Among these patients, more than 50% experienced VTE within one month of the preceding hospital encounter. Other major risk factors for VTE in the outpatient setting included active malignancy (29%) or prior VTE (20%). Among patients with a recent hospitalization who subsequently developed VTE, less than 50% had received anticoagulant prophylaxis for VTE during that visit.

Conclusions

More VTE events were diagnosed in the 3 months following hospitalization than during hospitalization. Efforts to improve in-hospital utilization of VTE prophylaxis may help decrease the incidence of outpatient VTE. However, given shortening lengths of hospital stay, studies of extended VTE prophylaxis following hospital discharge are warranted.

Keywords: venous thromboembolism, deep vein thrombosis, pulmonary embolism, population-health

Introduction

Data from the population-based Worcester DVT Study in the mid to late 1980s suggested that the vast majority of episodes of venous thromboembolism that occur in a community take place in the outpatient setting [1]. Nevertheless, data from another population-based study (Olmsted County) suggests that factors associated with hospitalization accounted for nearly 50% of the attributable risk of VTE [2]. The risk factor profile of outpatients suffering VTE, particularly with respect to recent hospitalizations and surgeries, has not been well described. The objectives of this observational study are to identify the proportion of patients with VTE in a community who experience their events in the outpatient setting, characterize the prevalence of previously identified risk factors for VTE, and identify use (or non-use) of VTE prophylaxis prior to the occurrence of VTE.

Methods

Computerized printouts of all Worcester residents with healthcare system encounters in which any of 34 ICD-9 diagnosis codes possibly consistent with the occurrence of VTE (see Appendix A) had been listed in 1999, 2001, and 2003 were obtained from each of 12 hospitals serving residents of the Worcester Standard Metropolitan Statistical Area (SMSA). These data queries were not limited to discharge diagnoses, but also encompassed all outpatient, emergency department, radiology, and laboratory encounters. For the first study cohort, the logs and/or computerized billing lists of patients evaluated in area ultrasound departments for potential deep vein thrombosis were also screened. This was done to identify potential cases of VTE in greater Worcester residents that may have been missed due to coding errors and to identify patients referred directly from outside physicians' offices, rehabilitation facilities, and nursing homes for testing who then returned directly to these outside settings for treatment. Since this additional screen identified only a few additional cases of VTE, and in only 1 of 11 hospitals, this screening process was not performed in the other 10 hospitals in 2001 and 2003.

The medical records of all identified patients meeting the geographic inclusion criteria (residents of the Worcester SMSA, 2000 census = 477,800) were reviewed. Trained abstractors using pre-specified criteria performed validation and characterization of each case of VTE as definite, probable, possible, or absent. These criteria were based on a modification of a classification schema proposed by Silverstein et al [3] (see Appendix B). Each case and its classification were also validated by the study project coordinator (CE). If the classification of VTE was not immediately clear using the criteria specified, the medical record was reviewed by the principal investigator (FS). Incident cases of VTE were defined as those occurring in patients without any prior history of upper or lower extremity deep vein thrombosis or pulmonary embolism. Potential cases of recurrent VTE were classified using similar criteria as that employed for incident cases – however, the development of a definite or probable recurrence of VTE required the new occurrence of thrombosis in a previously uninvolved venous or pulmonary segment.

The medical records of each patient's current as well as previous hospitalizations and/or outpatient visits were reviewed to identify whether the index VTE event represented an incident (initial) or a recurrent case. Ambulatory patients presenting to the hospital with signs and symptoms consistent with VTE, or diagnosed with VTE within 24 hours of hospital presentation, were considered to have developed VTE in the outpatient setting.

Data collection

Information was collected about patients' demographic characteristics, medical history, clinical characteristics, diagnostic test results, and hospital management practices. Only medical history variables documented in patients' medical records by a physician were abstracted. For variables in which a number of medical record entries were possible, data abstractors were instructed to record only entries matching those on a pre-specified list. For example, cardiac procedures were defined to include only electrophysiology studies, percutaneous coronary interventions, pacemaker implantation, and implantable cardiac defibrillator placement. For purposes of analysis, infections were limited to those involving the blood (laboratory confirmed clinical bacteremia, sepsis), bone and joint, central nervous system, cardiovascular system, gastrointestinal system, respiratory system (pneumonia only), surgical sites, or the skin. Only infections considered serious enough to be documented in the medical record were included.

The variable surgery included major operations where general or epidural anesthesia lasted 30 minutes or longer. Medical history variables defined as “recent” were those occurring or active in the 3 months prior to the diagnosis of VTE.

Although information about recent hospitalizations and or surgery was usually available in the index medical record, prior medical records were also searched for hospitalizations and/or surgeries occurring in the 3 months prior to the index VTE diagnosis. A focus of our data abstraction efforts was to identify the proportion of patients experiencing VTE in the outpatient setting who had recently been hospitalized or undergone surgery and the timing of prior hospitalizations/surgeries relative to the VTE event. Using the index and prior medical records, utilization of VTE prophylaxis during prior hospitalizations (at any time until discharge) or following surgery (any time until hospital discharge) was also recorded.

Data Analysis

Differences in the distribution of various demographic and clinical characteristics between patients who presented with VTE from the outpatient setting, as compared to those who were diagnosed with VTE during hospitalization, were examined using chi-square tests of statistical significance for categorical variables and t tests for continuous variables. Based on their prevalence, as well as clinical importance, we described the proportion of outpatients who had 0, any 1, any 2-3, or any 4 or all 5 of the following VTE risk factors: recent hospitalization, recent surgery, active malignancy, recent infection, or prior documented episode of VTE. In order to better understand the temporal relationship between prior hospital encounters and development of subsequent VTE, we stratified outpatients with VTE following hospitalization or surgery into 1 of 3 groups –onset of VTE within 1 month (e.g. ≤ 29 days) of a hospital encounter, between 1 and 2 months (e.g. 30-59 days) of an encounter, and more than 2 months (e.g., ≥60 days) after a recent hospitalization or surgery.

Since we were particularly interested in examining missed opportunities for prevention in outpatients who developed VTE, we also described the utilization of VTE prophylaxis during prior hospitalization in the subset of outpatients with VTE who had been hospitalized in the preceding 3 months. This was carried out in the overall study sample and in patients further stratified according to the presence of several predefined major risk factors for VTE (recent surgery, active malignancy, recent infection, or prior VTE).

Results

A total of 7,222 medical records were identified using predefined ICD-9 codes in which cases of VTE might have been diagnosed (2,333 for 1999, 2,462 for 2001, and 2,427 for 2003). All of these records were reviewed for validation of VTE. A total of 1,897 Worcester residents experienced an independently validated episode of DVT (n = 1348), PE (n = 285), or both (n = 264) during the 3 study years of 1999, 2001, and 2003. Approximately 96% of cases of DVT were classified as definite, <1% as probable, and 3% as possible. Of the validated cases of PE, 50% were classified as definite, 23% were classified as probable, and 27% were classified as possible. All remaining cases of potential VTE were classified as negative for acute VTE after medical record review.

Of these 1,897 validated cases of VTE, 1,399 (74%) presented from the outpatient setting with signs and symptoms consistent with VTE and/or had VTE diagnosed within 1 day of hospital admission.

Medical Characteristics of Outpatients with Venous Thromboembolism

A large proportion of patients presenting with VTE from the outpatient setting had recently been hospitalized (37%) or had undergone major surgery (23%) during the past 3 months. Approximately 30% had a recent or active diagnosis of malignancy, one quarter had experienced a recent infection, and approximately one fifth had previously had a VTE event (Table 1). Among outpatients with VTE, 27% had none, 31% had only one, 38% had any 2-3, and 4% had any 4 or all 5 of the previously described risk factors for VTE. For comparative purposes, the prevalence of these characteristics in patients who developed and were diagnosed with VTE during hospitalization is also provided in Table 1. Patients developing VTE in the outpatient setting tended to be younger; were less likely to have been previously hospitalized, admitted to an intensive care unit, have had a central venous catheter placed, or have undergone surgery; and were less likely to have had a recent fracture, heart failure, or infection than patients who developed VTE in the inpatient setting. These patients were also more likely to have a prior history of DVT or PE or to have been taking hormonal therapy.

Table 1
Demographic and Clinical Characteristics of Patients According to Setting of Venous Thromboembolism (Outpatient vs. Inpatient)

Timing of Venous Thromboembolism Relative to Prior Hospitalization or Surgery

Of VTE episodes occurring within 3 months of a prior hospitalization, 67% occurred within the 1st month following hospital discharge. The median and mean lengths of the prior hospital stay for patients developing VTE within 3 months of the present hospitalization were 4.0 and 7.4 days, respectively.

Among patients who had recently been hospitalized, but had not undergone surgery, 67% were diagnosed with VTE within 1 month after hospital discharge, 20% between 1 and 2 months after hospital discharge, and the remainder (13%) between 2 and 3 months from the time of hospital discharge. Among patients who had been hospitalized, and had undergone recent surgery, 66% had been diagnosed with VTE within 1 month after surgery, 18% between 1 and 2 months after hospital discharge, and 15% between 2 and 3 months after hospital discharge (see figure 2).

History of VTE prophylaxis

We examined the utilization of prophylaxis for VTE during the preceding hospitalization overall and for different categories of outpatients with VTE who had been hospitalized in the prior 3 months: 1) those with none of the other major risk factors for VTE (surgery, malignancy, infection, prior VTE); 2) those with recent surgery; 3) those with active malignancy; 4) those with prior VTE, 5) those with recent infection; and 6) those with any 2 or 3 or more of these major risk factors (see Table 2). Approximately 3 out of 5 previously hospitalized patients received any form of VTE prophylaxis during their hospitalization - 43% received anticoagulant prophylaxis (with or without mechanical prophylaxis) and an additional 17% received only mechanical prophylaxis. Similar utilization patterns of therapies for the prevention of VTE were seen in each of our pre-specified patient subsets with the exception of patients with a history of prior VTE or 3 or more risk factors in which slightly higher rates of VTE prophylaxis were observed.

Table 2
Utilization of Prophylaxis for Venous Thromboembolism during Prior Hospitalization in Outpatients with Venous Thromboembolism According to Existing Risk Factors

Discussion

Almost two decades ago, findings from the initial Worcester DVT study suggested that VTE was an “outpatient disease” [1]. In our contemporary population-based study of greater Worcester residents, this remains the case - the vast majority (74%) of patients diagnosed with VTE presented from the outpatient setting. Nevertheless, almost half of these patients had been hospitalized or undergone surgery in the prior 3 months. While reducing the risk of VTE in hospitalized patients is important, our findings suggest that decreasing the occurrence of VTE after hospital discharge may have even more of an impact on the overall VTE burden. Although we cannot assess the magnitude of VTE risk associated with specific surgery types, hospital diagnoses, or co-morbidities, we characterized the profile of outpatients experiencing VTE in the community, the temporal relationship between VTE and prior hospital encounters, and whether VTE prophylaxis was provided during these encounters.

Approximately 40% of outpatients presenting with VTE had been hospitalized in the preceding 3 months – half of these for medical reasons only and half had also undergone surgery during hospitalization. These data are consistent with the findings from the Olmsted County study in which the attributable risk associated with VTE for a number of different risk factors was examined [2]. In this study of greater Rochester (MN) residents, factors associated with hospitalization were estimated to have accounted for nearly half (46%) of all cases of VTE occurring in the community setting. Similar to the results of our study, hospitalization for surgery and for medical illness accounted for a similar proportion of independently validated cases of VTE.

Interestingly, the utilization of VTE prophylaxis during a prior hospitalization in patients with subsequent VTE in the outpatient setting was far from optimal. Only 60% of patients had received any form of prophylaxis and only 43% had received anticoagulant prophylaxis during their preceding hospital stay. Since the majority of cases of VTE occurred with 28 days of hospital discharge (and 41% occurred within 14 days), it is not unreasonable to assume that some of these cases may have been prevented simply by increased utilization of appropriate in-hospital DVT prophylaxis (e.g., compression stockings, pneumatic compression devices, and in high-risk patients, anticoagulants).

Approximately one half of the outpatients who experienced VTE following hospitalization had a length of stay ≤4 days. These data suggest that omission of VTE prophylaxis in patients with anticipated short lengths of hospital stay may not be appropriate. It is also important to recognize that due to decreasing lengths of hospital stay, the duration of in-hospital DVT prophylaxis has been shortened and there may be increased periods of immobilization among outpatients. During the study time period (1999-2003), prescription of DVT prophylaxis following hospital discharge was not an accepted practice (except in a small proportion of patients undergoing hip or knee surgery). One could speculate that even more cases of VTE may be prevented by the judicious application of DVT prophylaxis following hospital discharge. Prior studies have documented that symptomatic VTE often occurs in orthopedic surgery patients after hospital discharge, that “silent” thrombus present early after surgery can extend after DVT prophylaxis is discontinued, and that post-discharge prophylaxis in these patients is efficacious and cost-effective [4-8]. Studies evaluating the efficacy, as well as cost-effectiveness, of outpatient DVT prophylaxis following hospital discharge in other high-risk populations (including those with serious medical conditions) are needed.

Finally, patients with malignancy constituted approximately one third of all cases of outpatient VTE in our study. Previous studies have suggested that patients with cancer have up to a 6-fold increased risk of VTE compared to those without cancer [9]. Among patients undergoing similar surgical procedures, those with active malignancy have a 2-3 fold increased risk of VTE compared to those without cancer [10-12]. Patients with cancer are also more likely to experience VTE after surgery, despite provision of VTE prophylaxis [13, 14]. Given their extraordinarily high risk, the American College of Chest Physicians (ACCP) guidelines strongly recommends (Grade 1A) VTE prophylaxis in patients with cancer who are undergoing surgery or hospitalization [15]. In our study sample, patients with malignancy who suffered outpatient VTE received suboptimal DVT prophylaxis during prior recent hospitalizations or surgeries.

Interestingly, approximately one half of patients with malignancy and outpatient VTE had neither a recent hospitalization or prior surgery. Unfortunately, data on the utility and/or cost-effectiveness of DVT prophylaxis in cancer patients without another indication is limited. Study of this population has been difficult due to the heterogeneity of cancer types and treatments. Although the use of low dose warfarin or low-molecular weight heparin therapy has been associated with a decreased incidence of VTE in some earlier studies of patients with advanced cancer or those receiving chemotherapy, other studies have not been able to demonstrate a benefit from long-term DVT prophylaxis in cancer patients with indwelling central venous catheters [16-19]. Accordingly, the ACCP guidelines recommend against the use of anticoagulant prophylaxis in cancer patients without a traditional indication for DVT prophylaxis [15]. Since these patients made up a sizable proportion of all VTE events occurring in the greater Worcester community, further study of DVT prophylaxis in ambulatory patients with cancer are clearly needed.

Study limitations

Similar to the design and conduct of any observational study, the present investigation has several limitations. Although we conducted a broad screening for possible cases of VTE which may have occurred in greater Worcester residents using multiple databases, validated each potential case of VTE, and performed regular audits of randomly selected charts, it is likely that we may have missed some cases of VTE – in particular, cases of VTE occurring in Worcester residents who sought care at outside hospitals and cases of pulmonary embolism resulting in out of hospital death. Another potential study limitation is that while our data abstracters were provided with pre-specified definitions of medical history variables of interest, they still had to rely on documentation of these conditions in the medical record. As such, the possibility of over or underestimation of the prevalence of specific risk factors for VTE cannot be excluded.

Since we collect data on only the most recent hospitalization or surgery that may have occurred in the 3 months prior to VTE, we cannot comment on the proportion or characteristics of patients with VTE who had multiple hospitalizations during this period. Finally, since the Worcester VTE study does not capture data on a control population of outpatients without VTE, we cannot directly assess the magnitude of VTE risk associated with prior hospitalizations, surgery type, or malignancy. Similarly, we cannot comment on the impact of use, or non-use, of DVT prophylaxis during these high-risk scenarios.

Conclusions

Our study provides insights into the profile of patients who suffer outpatient VTE within this well-defined, large, and representative Northeast community. These patients ultimately represent a significant proportion of our failures in VTE prevention. The results of our descriptive epidemiologic investigation provide insights into the characteristics of potentially high-risk patient subsets that may benefit from the use of outpatient prophylaxis for the prevention of VTE. Further characterization of this high risk patient profile in additional observational studies will generate further testable hypotheses and subsequent investigations that will result in a decrease in the number of these failures.

Figure 1
Timing of diagnosis of VTE relative to prior hospital discharge among patients developing VTE as an outpatient.

Acknowledgments

This study was funded by a grant from the National Heart, Lung, and Blood Institute (R01-HL70283). The principal investigator of this study had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. This study was made possible by the cooperation of administrators, physicians, and medical records personnel in 12 central Massachusetts hospitals. The medical records analyzed in this study were reviewed by Colleen Toronto, Rebecca Poxon, Kathleen Barrett, and Elizabeth Mills.

Supported by a grant from the National Heart, Lung, and Blood Institute (R01-HL70283)

Appendix A: Venous thrombosis ICD-9 codes

415.1(1,9)-pulmonary embolism and infarction
451- phlebitis and thrombophlebitis
451.11- femoral vein
451.19- other deep vein
451.2- lower extremities, unspecified
451.81-iliac vein
451.83-deep veins of upper extremities
451.84-upper extremity, unspecified
451.89-other (axillary, jugular, subclavian)
451.9-unspecified site
453.1-thrombophlebitis migrans
453.2-vena cava
453.8-of other specified veins
453.9–of unspecified site
671.3 (0,1,3)-deep phlebothrombosis, antepartum
671.4 (0, 2, 4)-deep phlebothrombosis, postpartum
671.9 (0-4)-unspecified venous complication of puerperium
673.2 (0-4)-obstetrical blood clot embolism
996.73-Complication due to renal dialysis device, implant, and graft
996.74-Complication due to other vascular device, implant, and graft
997.2-phlebitis or thrombophlebitis during or resulting from a procedure

Appendix B: Criteria for classification of VTE events*

Deep vein thrombosis

Definite - if confirmed by venography, compression/Duplex ultrasound, CT scan, MRI scan, or at autopsy.

Probable - if the above tests were not performed, or were indeterminate, but impedance plethysomography, radionuclide venography, or radiolabelled fibrinogen scan test results were reported as positive.

Possible - if all of these confirmatory tests were not performed, or were indeterminate, and two of the following criteria were satisfied - medical record indicates the physician made a diagnosis of DVT, signs and/or symptoms of DVT were documented, and the patient underwent therapy with anticoagulants or an IVC filter was placed.

Pulmonary embolism

Definite - if confirmed by pulmonary angiography, spiral CT scan, MRI scan, or pathology.

Probable - if the above tests were not performed, or were indeterminate, but ventilation-perfusion scan findings were of high probability.

Possible - if all of the above confirmatory tests were not performed, or were indeterminate, and two of the following criteria were satisfied - medical record indicates the physician made a diagnosis of PE, signs and/or symptoms of PE were documented, and the patient underwent therapy with anticoagulants or an IVC filter was placed.

Footnotes

*Modification of criteria previously used by Silverstein et al in the Olmstead County study of venous thromboembolism [3]. Given increasing acceptance over the last decade of compression/Duplex ultrasound as a single diagnostic modality for DVT, we have classified patients with DVT confirmed by compression/Duplex ultrasound as definite whereas these patients would be classified as probable by Silverstein's criteria.

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