Brief Reports

Thrombolytic therapy for venous thromboembolism: Current clinical practice

Abstract

Abstract

BACKGROUND:

Venous thromboembolism (VTE) is a life‐threatening condition for which thrombolytic therapy may be beneficial. The appropriate setting for the use of thrombolytic therapy remains controversial. More than 10 years ago we described the case‐based practice patterns for the use of thrombolytics in VTE, and now, in the context of recent studies and guidelines, we sought to reevaluate the use of thrombolytics and to determine whether beliefs have changed.

METHODS:

Active pulmonologists in 11 southeastern states were selected to complete a web‐based questionnaire that included background questions and hypothetical case scenarios involving VTE and potential treatment with thrombolytics.

RESULTS:

Eighty‐one physicians completed the survey and 84% reported using thrombolytic therapy for VTE within the last 2 years. In the absence of absolute contraindications, 99% of respondents would strongly consider using systemic thrombolytic therapy for massive pulmonary embolism (PE) with hypotension, 83% would strongly consider thrombolysis for a large PE with severe hypoxemia, and 62% would strongly consider thrombolysis for PE with echocardiographic evidence of right ventricular dysfunction. In a patient with massive PE and hypotension with certain contraindications, 91% of respondents would still strongly consider thrombolysis.

CONCLUSIONS:

Most practicing pulmonologists would strongly consider administering thrombolytic therapy for massive PE with hypotension or hypoxemia, and a majority favor thrombolysis for PE in the setting of echocardiographic evidence of right heart dysfunction. Despite the evolving data and guidelines for the management of VTE, our findings are similar to prior survey results, emphasizing the need for further physician education and future randomized trials to clarify the therapy for this potentially deadly condition. Journal of Hospital Medicine 2009;4:313–316. © 2009 Society of Hospital Medicine.

Copyright © 2009 Society of Hospital Medicine

More than a decade ago, we surveyed a group of practicing pulmonologists to determine their attitudes regarding the use of thrombolytic therapy in various settings of acute venous thromboembolism (VTE).1 Since that time, the literature regarding the treatment of acute VTE has grown dramatically.214 However, despite the available evidence, there remains considerable controversy regarding the appropriate setting for thrombolysis in acute pulmonary embolism (PE) or deep‐vein thrombosis (DVT). We therefore sought to better describe the current patterns of thrombolytic use among practicing pulmonologists and to determine if these patterns have changed over the last decade.

Methods

Five‐hundred and ten physicians in the southeastern US were selected from the American Thoracic Society (ATS) membership roster and were e‐mailed a link to an online questionnaire. The roster was searched for physicians who described their subspecialty as pulmonary disease or pulmonary and critical care.

Participants were asked background information and questions regarding hypothetical clinical scenarios. All participants were offered a $50 stipend, and to further improve the response rate, 2 reminder e‐mail messages were sent 30 days and 45 days after the initial request.

Baseline findings of the survey were summarized using descriptive statistics. Differences among participants and their responses were determined by Fisher's exact test. Analyses were performed using SAS E‐Guide Version 3.0 for Windows (SAS Institute, Cary, NC) with 2‐sided P values at the standard 0.05 level used to determine statistical significance.

Results

Baseline Characteristics

Eighty‐one physicians completed the questionnaire; their baseline characteristics are shown in Table 1. During the previous 2 years, all physicians surveyed had treated at least 1 patient with acute PE and all but 1 had treated at least 1 patient with DVT. Also, 68 respondents reported that they had used thrombolytic therapy in at least 1 case of PE in the past 2 years.

Background Information of 81 Physician Survey Participants
  • Abbreviations: DVT, deep vein thrombosis; PE, pulmonary embolism.

Age, mean (years) 45.6
Training completed, n (%)
1980‐1989 28 (34.5)
1990‐1999 25 (31.0)
2000‐2007 28 (34.5)
Practice type n (%)
Academic 35 (43)
Private practice 37 (46)
Private practice with academic appointment 6 (7)
Other 3 (4)
Practice setting, n (%)
Predominantly outpatient 8 (10)
Predominantly inpatient 29 (36)
Equal inpatient and outpatient 44 (54)
Hospital size (beds), n (%)
<50 1 (1)
50‐100 1 (1)
100‐300 20 (25)
300‐500 22 (27)
>500 37 (46)
Number of patients treated with PE in the past 2 years, n (%)
0 0 (0)
1‐5 3 (4)
6‐10 14 (17)
11‐15 12 (15)
16‐20 17 (21)
>20 35 (43)
Number of patients treated with DVT in the past 2 years, n (%)
0 1 (1)
1‐5 3 (4)
6‐10 7 (9)
11‐15 16 (20)
16‐20 11 (14)
>20 43 (53)
Number of patients with PE treated with thrombolysis, n (%)
0 13 (16)
1‐5 53 (65)
6‐10 11 (14)
11‐15 1 (1)
16‐20 2 (2)
>20 1 (1)

Use of Thrombolytic Therapy in Various Scenarios

The responses for the 8 clinical scenarios are shown in Table 2. Approximately equal numbers of academic and private practice physicians completed the questionnaire, and comparison between these groups showed no significant differences in decision‐making for each of the case scenarios. Less experienced physicians (>10 cases treated versus 10 cases treated) were more likely to consider thrombolytic therapy in a patient with a smaller PE but with poor cardiopulmonary reserve (P = 0.001), and with proximal symptomatic DVT of any size present less than 7 days (P = 0.047).

Use of Thrombolytic Therapy in Various Clinical Scenarios in the Current Survey and Compared with Our Prior Study
Scenario Current Study (%) Previous Study1 (%) P
  • Abbreviations: DVT, deep vein thrombosis; NS, not significant; PE, pulmonary embolism; RV, right ventricular.

Massive PE with hypotension 80 (99) 56 (100) NS
Large PE with hypoxemia 67 (83) 41 (73) NS
PE with RV strain or failure 50 (62) 31 (55) NS
Large PE without hypotension, hypoxemia, or RV strain 9 (11) 6 (11) NS
Smaller PE in a patient with poor cardiopulmonary reserve 11 (14)
Massive symptomatic DVT, <7 days 41 (51) 33 (59) NS
Massive symptomatic DVT, >7 days 14 (17)
Proximal DVT, any size, <7 days 6 (7) 7 (13) NS

Use of Thrombolytic Therapy When Contraindications Exist

The vast majority of respondents reported that they would consider giving thrombolytic therapy to a patient with massive PE and hypotension requiring vasopressor therapy despite having a traditional contraindication (relative or absolute) to thrombolysis (Table 3). Most respondents would consider giving thrombolytic therapy to postoperative orthopedic, abdominal, or thoracic surgery patients if they were more than 2 weeks postoperation, and very few would give thrombolytic therapy to patients who were less than 2 days postoperation. Many respondents would also consider giving thrombolytic therapy to a patient with a massive PE and with a history of major gastrointestinal (GI) bleeding (requiring blood transfusion) if the bleed was more than 4 weeks prior to the embolism (Figure 1).

Figure 1

In a patient with massive PE and hypotension, the percentage of physician respondents who would strongly consider systemic thrombolytic therapy at various time points following an operation or gastrointestinal (GI) bleed. GI bleed (light gray); orthopedic surgery (white); thoracic or abdominal surgery (dark gray).

Strong Consideration of Thrombolytic Therapy for Hemodynamically Significant PE in the Context of Absolute or Relative Contraindications
Condition Number of Physicians (%)
  • Abbreviations: CPR, cardiopulmonary resuscitation; ICH, intracranial hemorrhage.

Age >75 years 58 (72)
Guaiac + stool 54 (67)
CPR in past 10 days 39 (48)
History of ischemic stroke 37 (46)
Recent venipuncture of a noncompressible vessel 33 (41)
History of ICH 6 (7)
Brain tumor 6 (7)
Would never use thrombolytics in these scenarios 7 (9)

Discussion

Given the paucity of data from randomized controlled trials, there remains considerable controversy regarding the indications for thrombolytic therapy. It may be difficult to define those patients in whom the benefit of a rapid reduction in clot burden outweighs the increased hemorrhagic risk. The case for thrombolysis is the strongest in patients with massive PE complicated by hypotension, in whom the mortality rate may be 30%.15 Our survey confirms that the vast majority of practicing pulmonologists would strongly consider systemic thrombolysis in this clinical setting, which is in accordance with current guidelines and with our previous survey results.1, 5, 10, 12

No clinical trial has specifically evaluated thrombolytic therapy in patients with large PE and hypoxemia but without hypotension, and it is interesting that so many physicians would consider thrombolytic therapy in this scenario. As right heart failure is the cause of death in PE, the absence of significant hypotension would imply less cardiovascular risk and thrombolytic use would seemingly be less justifiable from a physiologic point of view. It may be that further study and education is warranted in this area.

Many patients who present with acute, life‐threatening PE have contraindications or relative contraindications to systemic thrombolysis. Our study suggests that most practicing pulmonologists would consider giving thrombolytic therapy in some of these situations, such as if the patient was more than 2 weeks postoperative from major thoracic or abdominal surgery (or even a few days following orthopedic surgery), or in the setting of advanced age or guaiac positive stools. Physicians were appropriately very reluctant to use thrombolytic therapy in the setting of a brain tumor or prior intracranial hemorrhage. These scenarios emphasize the vagaries of the current guidelines and real‐world complexities of considering thrombolytic therapy in clinical practice, in which the risks and benefits must be weighed on a case‐by‐case basis.

One major difference between our current and past findings is the general experience with thrombolytic therapy in acute PE. In our first study, only 54% of physicians queried had employed systemic thrombolysis for acute PE. Our current findings were that 84% of physicians had used thrombolysis for acute PE within the last 2 years, perhaps suggesting a greater comfort with this therapy.

Response bias is a major limitation of our study. We sought to keep questions short and clear, and offered a small stipend to improve the return rate. Despite these measures, only 81 of 510 questionnaires were completed. We selected our list of participants from the ATS roster and by geographic location. As suggested by our findings, the results may have been different had we focused solely on VTE experts or those treating large numbers of VTE patients. One strength of this study is that our sample had approximately even numbers of academic and private practice physicians, and that we could compare current results with our prior findings.

In conclusion, practicing pulmonologists generally agreed that in the absence of contraindications, thrombolytic therapy should be considered in patients with massive PE and hypotension, which is in accordance with current guidelines. Furthermore, a majority would still consider thrombolytic therapy in this scenario even if certain contraindications were present. Although there is less agreement in other scenarios, a majority of physicians would consider using thrombolytics in patients with PE and severe hypoxemia or right ventricular (RV) dysfunction. Despite the evolving data and guidelines, our findings are similar to prior survey results, with the notable exception that more physicians reported thrombolytic therapy use in acute PE in the current study. This emphasizes the need for further physician education and future randomized clinical trials to delineate and unify therapeutic strategies in cases of VTE.

References

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