SUPPLEMENT ARTICLE
Treatment and Complications in Orthopaedic Trauma Patients With Symptomatic Pulmonary Embolism Yelena Bogdan, MD,* Paul Tornetta, III, MD,* Ross Leighton, MD,† Uwe Dahn, MD,† Henry Sagi, MD,‡ Charles Nalley, MD,‡ David Sanders, MD,§ Jodi Siegel, MD,k Brian Mullis, MD,¶ Thomas Bemenderfer, MS,¶ Heather Vallier, MD,** Alysse Boyd, MS,** Andrew Schmidt, MD,†† J. R. Westberg, BA,†† Kenneth A. Egol, MD,‡‡ Stephen Kottmeier, MD,§§ and Cory Collinge, MDkk
Objectives: The purpose of this study is to characterize the presentation, size, treatment, and complications of pulmonary embolism (PE) in a large series of orthopaedic trauma patients who developed PE after injury.
Methods: We reviewed the records of orthopaedic trauma patients who developed a PE within 6 months of injury at 9 trauma centers and 2 tertiary care facilities. Results: There were 312 patients, 186 men and 126 women, average age 58 years. Average body mass index was 29.6, and average Injury Severity Score was 18. Seventeen percent received anticoagulation before injury, and 5% had a history of PE. After injury, 87% were placed on prophylactic anticoagulation and 68% with low-molecular weight heparin. Fifty-three percent of patients exhibited shortness of breath or chest pain. Average heart rate and O2 saturation before PE diagnosis were 110 and 94%, respectively. Thirty-nine percent had abnormal arterial blood gas, and 30% had abnormal electrocardiogram findings. Eighty-nine percent had computed tomography pulmonary angiography for diagnosis. Most clots were segmental (63%), followed by subsegmental (21%), lobar (9%), and central (7%). The most common treatment was unfractionated heparin and Coumadin (25%). Complications of anticoagulation were common: 10% had bleeding at the surgical site. Other complications of anticoagulation included gastrointestinal bleed, anemia, wound complications, death, and com-
Accepted for publication December 18, 2013. From the *Boston Medical Center, Boston, MA; †Dalhousie University, Nova Scotia, Canada; ‡Tampa General Hospital, Tampa, FL; §London Health Science Center, Ontario, Canada; kUniversity of Massachusetts, Boston, MA; ¶Indiana University-Purdue, Indianapolis, IN; **MetroHealth Medical Center, Cleveland, OH; ††HCMC, Minneapolis, MN; ‡‡NYU Hospital for Joint Diseases, New York, NY; §§Stony Brook University Health Sciences Center, Stony Brook, NY; and kkTexas Health Fort Worth, Fort Worth, TX. P. Tornetta serves as a consultant for Smith and Nephew and Exploramed; R. Leighton, for Zimmer, Depuy, Synthes, Biomet, and Stryker; H. Sagi, for Smith and Nephew, Stryker, and Synthes; B. Mullis, for Synthes, Amgen, Wyeth, Smith and Nephew, and Medtronic; H. Vallier, for OTA; A. Schmidt, for OTA, Medtronic, DGIMed, Twinstar, and METRC; K.A. Egol, for Exactech, OREF, OTA, Synthes, Omega, and J+J; C. Collinge, for Smith and Nephew, Biomet, and Advanced Orthopaedic Systems. The remaining authors report no conflicts of interest. Reprints: Yelena Bogdan, MD, Department of Orthopaedics, 850 Harrison Avenue, Dowling 2 North, Boston Medical Center, Boston, MA (e-mail: [email protected]). Copyright © 2014 by Lippincott Williams & Wilkins
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partment syndrome. PE recurred in 1% of patients. Four percent died of PE within 6 months.
Conclusions: This is the first large data set to evaluate the course of PE in an orthopaedic trauma population. The complications of anticoagulation are significant and were as common in patients with lower risk clots as those with higher risk clots. Key Words: pulmonary embolism, orthopaedic trauma, anticoagulation
Level of Evidence: III (retrospective). See Instructions for Authors for a complete description of levels of evidence. (J Orthop Trauma 2014;28:S6–S9)
INTRODUCTION Orthopaedic patients, both in the pre- and postoperative settings, have a significant risk of pulmonary embolism (PE).1 Concurrently, they also have a high risk of bleeding. The balance between therapeutic anticoagulation and the sequelae of undertreated or untreated PE is important to understand. The American Academy of Orthopaedic Surgeons has a guideline for deep vein thrombosis prevention in arthroplasty patients that recommends prophylactic anticoagulation to prevent PE.2 However, there are no set algorithms for proceeding once an orthopaedic patient has been diagnosed with a PE. There are also no guidelines regarding orthopaedic trauma patients who are at an increased risk for bleeding from therapeutic anticoagulation. Moreover, there is evidence that PE exists on a spectrum and that small clots may not necessarily possess the same clinical relevance as larger clots. The term “overdiagnosis”3 has been used to describe the increasing diagnosis of potentially irrelevant small PEs with sensitive tests, such as computed tomography pulmonary angiography (CTPA). This raises questions about whether all clots should be treated the same way. The purpose of this study is to characterize the presentation, size, treatment, and complications of PE in a large series of orthopaedic trauma patients who developed PE after injury. We also aimed to record the complications of anticoagulation treatment in these patients. To our knowledge, this is the first study of its type.
J Orthop Trauma Volume 28, Number 4 Supplement, April 2014
J Orthop Trauma Volume 28, Number 4 Supplement, April 2014
MATERIALS AND METHODS This retrospective study was approved by our institutional review board as a retrospective review. All participating institutions received either IRB approval or a waiver given the retrospective nature of the study. The total number of participating institutions, 9 of which were level 1 trauma centers, was 11. At each site, the primary investigator and trained assistants reviewed the records of orthopaedic trauma patients who sustained their index injury between January 1999 and March 1, 2012. The inclusion criterion was patients with a fracture who developed a PE within 6 months of their index injury. The exclusion criteria were nonfracture patients, patients with deep vein thrombosis only, patients whose PE developed greater than 6 months after injury, and patients with spinal fractures as their only orthopaedic injury. All data collection met patient privacy regulations. Patients were identified through morbidity and mortality lists, patient lists, and institutional databases at the various institutions. Once a patient was identified as having had a PE and met the inclusion criterion, his/her chart, outpatient records, and imaging were reviewed. For each patient, the investigator gathered and recorded the data points seen in Table 1. All data sheets from each participating site were reviewed by the primary investigator at our institution and combined into a master spreadsheet, which was then used for data analysis. Percentages of all variables were calculated using the mathematical functions within Excel. Because of the limited number of patients, the large number of data points required for each patient, and the low numbers of TABLE 1. Data Points Collected for Each Patient Category Demographics/history
Triggers for obtaining a test for the diagnosis of PE
Type and findings of the diagnostic test PE treatment
Treatment complications
Outcomes
Data Points Age, height, weight, body mass index, sex, previous PE or DVT, pre-injury anticoagulation, OTA fracture type, Injury Severity Score Heart rate 24 h before diagnosis and at diagnosis, oxygen saturation 24 h before diagnosis, presence of electrocardiogram changes, presence of arterial blood gas changes, Wells score, presence of symptoms such as chest pain or shortness of breath CTPA, V/Q (ventilation–perfusion) scan, size and location of PE, presence of concurrent DVT Type of anticoagulation, INR and PTT goals of treatment, peak INR/PTT, inferior vena cava filter placement Bleeding at the surgical site, bleeding at another site, death as a result of anticoagulation, return to the operating room as a result of bleeding, changes in anticoagulation, and other complications (as free-text entry) Improvement in vitals or symptoms at discharge, discharge date, death from PE, repeat PE or DVT
DVT, deep vein thrombosis; PTT, partial thromboplastin time.
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PE in Orthopaedic Trauma Patients
complications, we felt it was important not to exclude patients from the analysis if some of the data points were missing. Particular attention was placed on bleeding complications, which were calculated both as a percentage of the total cohort and as a percentage of only those patients for whom data on clot size were available. The percentages for data points other than complications were calculated only if data were available for that patient; in other words, the denominator included only those patients with available data, if different from the total cohort. No external funding source was used for this study.
RESULTS There were 312 patients, 186 men and 126 women, average age 58 (15–101) years. Average body mass index was 29.6 (16–81), and average Injury Severity Score was 18 (4–66). Seventeen percent of patients were on anticoagulation before injury (primarily aspirin, with 73% of patients taking this medication), and 5% had a history of PE. After injury, 87% were placed on prophylactic anticoagulation with various combinations of medications (Fig. 1); most (68%) were treated with low-molecular weight heparin. With regard to the clinical triggers for PE testing, average heart rate and O2 saturation before PE diagnosis were 110 and 94%, respectively. Thirty-nine percent had an abnormal arterial blood gas (below normal arterial oxygen levels), and 30% had abnormal electrocardiogram findings. Fifty-three percent complained of shortness of breath and/or chest pain. The average Wells score4 was 5 (0–11.5). The diagnostic modalities used for PE testing were CTPA (89%), ventilation–perfusion scan (7%), and other (pulmonary angiogram, etc.) (4%). Forty-nine percent of the PEs were single lobe and 51% multilobar. Most were segmental (63%), followed by subsegmental (21%), lobar (9%), and central (7%), with central being the largest in size. The most common treatment regimens were unfractionated heparin (UFH) in conjunction with Coumadin (17%) or low-molecular weight heparin with Coumadin (17%), with multiple other treatment combinations comprising the remainder. Fifty-four percent of those who received UFH were bolused. Interestingly, neither the treatment regimen nor an initial bolus of UFH correlated with bleeding complications. Thirty-nine percent of all patients received an inferior vena cava filter, with 88% of those also concurrently receiving anticoagulation. Complications of anticoagulation were common: 30 patients (10% of total cohort) had bleeding at the surgical site, with 5 of these patients returning to the operating room (OR) to address the bleeding. Twelve percent experienced bleeding at another site. Other complications of anticoagulation included persistent hematoma (7), gastrointestinal bleed (5), anemia requiring transfusion (5), wound complications (3), death related to anticoagulation (3), hemoptysis (3), intracranial hemorrhage (3), compartment syndrome (2), infection (2), sciatic nerve injury because of hematoma (1), disseminated intravascular coagulation (1), heparin induced thrombocytopenia (1), pericardial effusion (1), myocardial infarction (1), and hypotension (1). The causes of death were listed as hypotension, intraparenchymal bleed, and multiorgan failure; all 3 were stated by the site investigators to be related to anticoagulation treatment. www.jorthotrauma.com |
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FIGURE 1. Postinjury prophylaxis. LMWH, low-molecular weight heparin.
With regard to PE outcomes, PE recurred in 3 patients (1% of total cohort) and 12 (4%) died as a result of PE within 6 months. These deaths were separate from the 3 patients who died as a result of anticoagulation treatment. Data on clot size were available for 247 patients, of whom 28 (11%) had bleeding at the surgical site; 5 of these patients returned to the OR. Twelve percent (29 patients) experienced bleeding at another site. One percent of patients with small clots (segmental or subsegmental) died as a result of anticoagulation treatment, compared with 2.5% of patients with larger clots (lobar or central). On the other hand, 1.4% of patients with small clots died as a result of PE, compared with 10% of patients with larger clots (Table 2).
DISCUSSION
The American College of Chest Physicians5 has been very clear in their standpoint: therapeutic anticoagulation should be instituted once a PE diagnosis is verified. However, this approach may result in severe complications, including death, in patients with a high bleeding risk, such as orthopaedic trauma patients. Also, PE seems to be a spectrum of disease, ranging from large central clots to small subsegmental clots that are of questionable clinical significance.6–9 However, despite attempts to characterize the likelihood of having a PE (eg, the Wells criteria4), PE is notoriously labile in its
presentation and even asymptomatic in as high as 2.6% of cases.10 An argument can thus be made that once a PE is diagnosed, it should be treated to prevent death.11 But if small clots often have good outcomes without treatment,12 should they be treated the same way as large ones in patients with a high bleeding risk? This is the first large data set to evaluate the course and complications of PE in an orthopaedic trauma population. The treatments were varied but similar for small and large clots. The complications of anticoagulation are significant and were as common in patients with lower risk clots as those with higher risk clots. These data are compatible with the reports of multiple authors13–15 who have cautioned against instituting therapeutic anticoagulation in the first postoperative week given the high rate of bleeding complications, longer hospitalizations, and higher transfusion requirements. In our study, very low-risk clots (subsegmental) comprised 21% and lower risk clots (segmental) 63% of those seen, as opposed to central clots (7%), which have a high PE mortality and morbidity risks. This supports recent literature, which suggests that the advent of increasingly sensitive diagnostic tests, such as CTPA, has resulted in higher PE diagnosis without a decrease in mortality from PE.3,16,17 For example, a 2009 study16 showed an almost 2-fold increase in PE from 1998 to 2005, but fatal PE rates dropped from 12.3% to 8.2%. These changes are attributed to the increased diagnosis of small PEs with sensitive testing. Our primary limitation is that this is a retrospective trial, which attempts to provide a snapshot of current management and complications of PE. Even after multiple attempts at data collection and assessment of radiology reports on clot size, the data set was not fully complete for every patient. The calculated percentages for each data point were only obtained if a patient had the data point available; however, we do not know whether patients without data were different from those with data. Final clot size data were available for 247 out of 312 patients, and our conclusions are limited by this. Additionally, regarding outcomes, because all PEs were treated, we do not know what the rate of death and PE recurrence would have been if they were untreated. This study presents an initial look at where we are in terms of management of PE in trauma patients. It reveals a modest but important complication rate for anticoagulation,
TABLE 2. Bleeding Complications by Clot Size From Smallest (Subsegmental) to Largest (Central) PE Clot Type, N = 247
Subsegmental, n = 52
Bleeding—surgical site Return to operating room Bleeding—other site Death (anticoagulation) PE recurrence Death from PE Total results Death (anticoagulation) Death from PE
10% (5) 0% (0) 6% (3) 2% (1) 0% (0) 0% (0) Small clots (n = 208) 1% (2) 1.4% (3)
Segmental, n = 156 10% 1% 12% 1% 0% 2%
(16) (2) (19) (1) (0) (3)
Lobar, n = 21 19% (4) 10% (2) 14% (3) 0% (0) 5% (1) 5% (1) Large clots (n = 39) 2.5% (1) 10% (4)
Central, n = 18 17% 6% 22% 6% 0% 17%
(3) (1) (4) (1) (0) (3)
Of note, data on clot size available for 247 out of 312 total patients. Number of patients in parentheses.
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including death. We may wish to modify treatment algorithms based on the risk and size of the clot. However, we must still be aware of the risk of untreated PE. Further work is needed to define these competing risks and benefits prospectively. REFERENCES 1. Montgomery KD, Geerts WH, Potter HG, et al. Thromboembolic complications in patients with pelvic trauma. Clin Orthop Relat Res. 1996; 329:68–87. 2. American Academy of Orthopaedic Surgeons. Preventing venous thromboembolic disease in patients undergoing elective hip and knee arthroplasty: evidence-based guideline and evidence report. Available at: http:// www.aaos.org/Research/guidelines/VTE/VTE_full_guideline.pdf. Accessed December 1, 2012. 3. Wiener RS, Schwartz LM, Woloshin S. Time trends in pulmonary embolism in the United States: evidence of overdiagnosis. Arch Intern Med. 2011;171:831–837. 4. Wells PS, Anderson DR, Rodger M, et al. Derivation of a simple clinical model to categorize patients probability of pulmonary embolism: increasing the model’s utility with the simpliRed d-dimer. J Thromb Haemost. 2000;83:416–420. 5. Kearon C, Akl EA, Comerota AJ, et al. Antithrombotic therapy for VTE disease: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(suppl 2):e419S–e494S. 6. Auer RC, Schulman AR, Tuorto S, et al. Use of helical CT is associated with an increased incidence of postoperative pulmonary emboli in cancer patients with no change in the number of fatal pulmonary emboli. J Am Coll Surg. 2009;208:871–878. 7. Le Gal G, Righini M, Parent F, et al. Diagnosis and management of subsegmental pulmonary embolism. J Thromb Haemost. 2006;4:724–731.
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8. Carrier M, Righini M, Wells PS, et al. Subsegmental pulmonary embolism diagnosed by computed tomography: incidence and clinical implications. A systematic review and meta-analysis of the management outcome studies. J Thromb Haemost. 2010;8:1716–1722. 9. PIOPED Investigators. Value of the ventilation/perfusion scan in acute pulmonary embolism. Results of the prospective investigation of pulmonary embolism diagnosis (PIOPED). JAMA. 1990;263:2753–2759. 10. Dentali F, Ageno W, Becattini C, et al. Prevalence and clinical history of incidental, asymptomatic pulmonary embolism: a meta-analysis. Thromb Res. 2010;125:518–522. 11. Barritt DW, Jordan SC. Anticoagulant drugs in the treatment of pulmonary embolism: a controlled trial. Lancet. 1960 1:1309–1312. 12. Stein PD, Henry JW, Relyea B. Untreated patients with pulmonary embolism: outcome, clinical, and laboratory assessment. Chest. 1995; 107:931–935. 13. Patterson BM, Marchand R, Ranawat C. Complications of heparin therapy after total joint arthroplasty. J Bone Joint Surg Am. 1989;71: 1130–1134. 14. Zidane M, Schram MT, Planken EW, et al. Frequency of major hemorrhage in patients treated with unfractionated intravenous heparin for deep venous thrombosis or pulmonary embolism: a study in routine clinical practice. Arch Intern Med. 2000;160:2369–2373. 15. Neviaser AS, Chang C, Lyman S, et al. High incidence of complications from enoxaparin treatment after arthroplasty. Clin Orthop Relat Res. 2010;468:115–119. 16. Park B, Messina L, Dargon P, et al. Recent trends in clinical outcomes and resource utilization for pulmonary embolism in the United States: findings from the nationwide inpatient sample. Chest. 2009;136: 983–990. 17. Burge AJ, Freeman KD, Klapper PJ, et al. Increased diagnosis of pulmonary embolism without a corresponding decline in mortality during the CT era. Clin Radiol. 2008;63:381–386.
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Treatment and Complications in Orthopaedic Trauma Patients With Symptomatic Pulmonary Embolism Yelena Bogdan, MD,* Paul Tornetta, III, MD,* Ross Leighton, MD,† Uwe Dahn, MD,† Henry Sagi, MD,‡ Charles Nalley, MD,‡ David Sanders, MD,§ Jodi Siegel, MD,k Brian Mullis, MD,¶ Thomas Bemenderfer, MS,¶ Heather Vallier, MD,** Alysse Boyd, MS,** Andrew Schmidt, MD,†† J. R. Westberg, BA,†† Kenneth A. Egol, MD,‡‡ Stephen Kottmeier, MD,§§ and Cory Collinge, MDkk
Objectives: The purpose of this study is to characterize the presentation, size, treatment, and complications of pulmonary embolism (PE) in a large series of orthopaedic trauma patients who developed PE after injury.
Methods: We reviewed the records of orthopaedic trauma patients who developed a PE within 6 months of injury at 9 trauma centers and 2 tertiary care facilities. Results: There were 312 patients, 186 men and 126 women, average age 58 years. Average body mass index was 29.6, and average Injury Severity Score was 18. Seventeen percent received anticoagulation before injury, and 5% had a history of PE. After injury, 87% were placed on prophylactic anticoagulation and 68% with low-molecular weight heparin. Fifty-three percent of patients exhibited shortness of breath or chest pain. Average heart rate and O2 saturation before PE diagnosis were 110 and 94%, respectively. Thirty-nine percent had abnormal arterial blood gas, and 30% had abnormal electrocardiogram findings. Eighty-nine percent had computed tomography pulmonary angiography for diagnosis. Most clots were segmental (63%), followed by subsegmental (21%), lobar (9%), and central (7%). The most common treatment was unfractionated heparin and Coumadin (25%). Complications of anticoagulation were common: 10% had bleeding at the surgical site. Other complications of anticoagulation included gastrointestinal bleed, anemia, wound complications, death, and com-
Accepted for publication December 18, 2013. From the *Boston Medical Center, Boston, MA; †Dalhousie University, Nova Scotia, Canada; ‡Tampa General Hospital, Tampa, FL; §London Health Science Center, Ontario, Canada; kUniversity of Massachusetts, Boston, MA; ¶Indiana University-Purdue, Indianapolis, IN; **MetroHealth Medical Center, Cleveland, OH; ††HCMC, Minneapolis, MN; ‡‡NYU Hospital for Joint Diseases, New York, NY; §§Stony Brook University Health Sciences Center, Stony Brook, NY; and kkTexas Health Fort Worth, Fort Worth, TX. P. Tornetta serves as a consultant for Smith and Nephew and Exploramed; R. Leighton, for Zimmer, Depuy, Synthes, Biomet, and Stryker; H. Sagi, for Smith and Nephew, Stryker, and Synthes; B. Mullis, for Synthes, Amgen, Wyeth, Smith and Nephew, and Medtronic; H. Vallier, for OTA; A. Schmidt, for OTA, Medtronic, DGIMed, Twinstar, and METRC; K.A. Egol, for Exactech, OREF, OTA, Synthes, Omega, and J+J; C. Collinge, for Smith and Nephew, Biomet, and Advanced Orthopaedic Systems. The remaining authors report no conflicts of interest. Reprints: Yelena Bogdan, MD, Department of Orthopaedics, 850 Harrison Avenue, Dowling 2 North, Boston Medical Center, Boston, MA (e-mail: [email protected]). Copyright © 2014 by Lippincott Williams & Wilkins
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partment syndrome. PE recurred in 1% of patients. Four percent died of PE within 6 months.
Conclusions: This is the first large data set to evaluate the course of PE in an orthopaedic trauma population. The complications of anticoagulation are significant and were as common in patients with lower risk clots as those with higher risk clots. Key Words: pulmonary embolism, orthopaedic trauma, anticoagulation
Level of Evidence: III (retrospective). See Instructions for Authors for a complete description of levels of evidence. (J Orthop Trauma 2014;28:S6–S9)
INTRODUCTION Orthopaedic patients, both in the pre- and postoperative settings, have a significant risk of pulmonary embolism (PE).1 Concurrently, they also have a high risk of bleeding. The balance between therapeutic anticoagulation and the sequelae of undertreated or untreated PE is important to understand. The American Academy of Orthopaedic Surgeons has a guideline for deep vein thrombosis prevention in arthroplasty patients that recommends prophylactic anticoagulation to prevent PE.2 However, there are no set algorithms for proceeding once an orthopaedic patient has been diagnosed with a PE. There are also no guidelines regarding orthopaedic trauma patients who are at an increased risk for bleeding from therapeutic anticoagulation. Moreover, there is evidence that PE exists on a spectrum and that small clots may not necessarily possess the same clinical relevance as larger clots. The term “overdiagnosis”3 has been used to describe the increasing diagnosis of potentially irrelevant small PEs with sensitive tests, such as computed tomography pulmonary angiography (CTPA). This raises questions about whether all clots should be treated the same way. The purpose of this study is to characterize the presentation, size, treatment, and complications of PE in a large series of orthopaedic trauma patients who developed PE after injury. We also aimed to record the complications of anticoagulation treatment in these patients. To our knowledge, this is the first study of its type.
J Orthop Trauma Volume 28, Number 4 Supplement, April 2014
J Orthop Trauma Volume 28, Number 4 Supplement, April 2014
MATERIALS AND METHODS This retrospective study was approved by our institutional review board as a retrospective review. All participating institutions received either IRB approval or a waiver given the retrospective nature of the study. The total number of participating institutions, 9 of which were level 1 trauma centers, was 11. At each site, the primary investigator and trained assistants reviewed the records of orthopaedic trauma patients who sustained their index injury between January 1999 and March 1, 2012. The inclusion criterion was patients with a fracture who developed a PE within 6 months of their index injury. The exclusion criteria were nonfracture patients, patients with deep vein thrombosis only, patients whose PE developed greater than 6 months after injury, and patients with spinal fractures as their only orthopaedic injury. All data collection met patient privacy regulations. Patients were identified through morbidity and mortality lists, patient lists, and institutional databases at the various institutions. Once a patient was identified as having had a PE and met the inclusion criterion, his/her chart, outpatient records, and imaging were reviewed. For each patient, the investigator gathered and recorded the data points seen in Table 1. All data sheets from each participating site were reviewed by the primary investigator at our institution and combined into a master spreadsheet, which was then used for data analysis. Percentages of all variables were calculated using the mathematical functions within Excel. Because of the limited number of patients, the large number of data points required for each patient, and the low numbers of TABLE 1. Data Points Collected for Each Patient Category Demographics/history
Triggers for obtaining a test for the diagnosis of PE
Type and findings of the diagnostic test PE treatment
Treatment complications
Outcomes
Data Points Age, height, weight, body mass index, sex, previous PE or DVT, pre-injury anticoagulation, OTA fracture type, Injury Severity Score Heart rate 24 h before diagnosis and at diagnosis, oxygen saturation 24 h before diagnosis, presence of electrocardiogram changes, presence of arterial blood gas changes, Wells score, presence of symptoms such as chest pain or shortness of breath CTPA, V/Q (ventilation–perfusion) scan, size and location of PE, presence of concurrent DVT Type of anticoagulation, INR and PTT goals of treatment, peak INR/PTT, inferior vena cava filter placement Bleeding at the surgical site, bleeding at another site, death as a result of anticoagulation, return to the operating room as a result of bleeding, changes in anticoagulation, and other complications (as free-text entry) Improvement in vitals or symptoms at discharge, discharge date, death from PE, repeat PE or DVT
DVT, deep vein thrombosis; PTT, partial thromboplastin time.
Ó 2014 Lippincott Williams & Wilkins
PE in Orthopaedic Trauma Patients
complications, we felt it was important not to exclude patients from the analysis if some of the data points were missing. Particular attention was placed on bleeding complications, which were calculated both as a percentage of the total cohort and as a percentage of only those patients for whom data on clot size were available. The percentages for data points other than complications were calculated only if data were available for that patient; in other words, the denominator included only those patients with available data, if different from the total cohort. No external funding source was used for this study.
RESULTS There were 312 patients, 186 men and 126 women, average age 58 (15–101) years. Average body mass index was 29.6 (16–81), and average Injury Severity Score was 18 (4–66). Seventeen percent of patients were on anticoagulation before injury (primarily aspirin, with 73% of patients taking this medication), and 5% had a history of PE. After injury, 87% were placed on prophylactic anticoagulation with various combinations of medications (Fig. 1); most (68%) were treated with low-molecular weight heparin. With regard to the clinical triggers for PE testing, average heart rate and O2 saturation before PE diagnosis were 110 and 94%, respectively. Thirty-nine percent had an abnormal arterial blood gas (below normal arterial oxygen levels), and 30% had abnormal electrocardiogram findings. Fifty-three percent complained of shortness of breath and/or chest pain. The average Wells score4 was 5 (0–11.5). The diagnostic modalities used for PE testing were CTPA (89%), ventilation–perfusion scan (7%), and other (pulmonary angiogram, etc.) (4%). Forty-nine percent of the PEs were single lobe and 51% multilobar. Most were segmental (63%), followed by subsegmental (21%), lobar (9%), and central (7%), with central being the largest in size. The most common treatment regimens were unfractionated heparin (UFH) in conjunction with Coumadin (17%) or low-molecular weight heparin with Coumadin (17%), with multiple other treatment combinations comprising the remainder. Fifty-four percent of those who received UFH were bolused. Interestingly, neither the treatment regimen nor an initial bolus of UFH correlated with bleeding complications. Thirty-nine percent of all patients received an inferior vena cava filter, with 88% of those also concurrently receiving anticoagulation. Complications of anticoagulation were common: 30 patients (10% of total cohort) had bleeding at the surgical site, with 5 of these patients returning to the operating room (OR) to address the bleeding. Twelve percent experienced bleeding at another site. Other complications of anticoagulation included persistent hematoma (7), gastrointestinal bleed (5), anemia requiring transfusion (5), wound complications (3), death related to anticoagulation (3), hemoptysis (3), intracranial hemorrhage (3), compartment syndrome (2), infection (2), sciatic nerve injury because of hematoma (1), disseminated intravascular coagulation (1), heparin induced thrombocytopenia (1), pericardial effusion (1), myocardial infarction (1), and hypotension (1). The causes of death were listed as hypotension, intraparenchymal bleed, and multiorgan failure; all 3 were stated by the site investigators to be related to anticoagulation treatment. www.jorthotrauma.com |
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FIGURE 1. Postinjury prophylaxis. LMWH, low-molecular weight heparin.
With regard to PE outcomes, PE recurred in 3 patients (1% of total cohort) and 12 (4%) died as a result of PE within 6 months. These deaths were separate from the 3 patients who died as a result of anticoagulation treatment. Data on clot size were available for 247 patients, of whom 28 (11%) had bleeding at the surgical site; 5 of these patients returned to the OR. Twelve percent (29 patients) experienced bleeding at another site. One percent of patients with small clots (segmental or subsegmental) died as a result of anticoagulation treatment, compared with 2.5% of patients with larger clots (lobar or central). On the other hand, 1.4% of patients with small clots died as a result of PE, compared with 10% of patients with larger clots (Table 2).
DISCUSSION
The American College of Chest Physicians5 has been very clear in their standpoint: therapeutic anticoagulation should be instituted once a PE diagnosis is verified. However, this approach may result in severe complications, including death, in patients with a high bleeding risk, such as orthopaedic trauma patients. Also, PE seems to be a spectrum of disease, ranging from large central clots to small subsegmental clots that are of questionable clinical significance.6–9 However, despite attempts to characterize the likelihood of having a PE (eg, the Wells criteria4), PE is notoriously labile in its
presentation and even asymptomatic in as high as 2.6% of cases.10 An argument can thus be made that once a PE is diagnosed, it should be treated to prevent death.11 But if small clots often have good outcomes without treatment,12 should they be treated the same way as large ones in patients with a high bleeding risk? This is the first large data set to evaluate the course and complications of PE in an orthopaedic trauma population. The treatments were varied but similar for small and large clots. The complications of anticoagulation are significant and were as common in patients with lower risk clots as those with higher risk clots. These data are compatible with the reports of multiple authors13–15 who have cautioned against instituting therapeutic anticoagulation in the first postoperative week given the high rate of bleeding complications, longer hospitalizations, and higher transfusion requirements. In our study, very low-risk clots (subsegmental) comprised 21% and lower risk clots (segmental) 63% of those seen, as opposed to central clots (7%), which have a high PE mortality and morbidity risks. This supports recent literature, which suggests that the advent of increasingly sensitive diagnostic tests, such as CTPA, has resulted in higher PE diagnosis without a decrease in mortality from PE.3,16,17 For example, a 2009 study16 showed an almost 2-fold increase in PE from 1998 to 2005, but fatal PE rates dropped from 12.3% to 8.2%. These changes are attributed to the increased diagnosis of small PEs with sensitive testing. Our primary limitation is that this is a retrospective trial, which attempts to provide a snapshot of current management and complications of PE. Even after multiple attempts at data collection and assessment of radiology reports on clot size, the data set was not fully complete for every patient. The calculated percentages for each data point were only obtained if a patient had the data point available; however, we do not know whether patients without data were different from those with data. Final clot size data were available for 247 out of 312 patients, and our conclusions are limited by this. Additionally, regarding outcomes, because all PEs were treated, we do not know what the rate of death and PE recurrence would have been if they were untreated. This study presents an initial look at where we are in terms of management of PE in trauma patients. It reveals a modest but important complication rate for anticoagulation,
TABLE 2. Bleeding Complications by Clot Size From Smallest (Subsegmental) to Largest (Central) PE Clot Type, N = 247
Subsegmental, n = 52
Bleeding—surgical site Return to operating room Bleeding—other site Death (anticoagulation) PE recurrence Death from PE Total results Death (anticoagulation) Death from PE
10% (5) 0% (0) 6% (3) 2% (1) 0% (0) 0% (0) Small clots (n = 208) 1% (2) 1.4% (3)
Segmental, n = 156 10% 1% 12% 1% 0% 2%
(16) (2) (19) (1) (0) (3)
Lobar, n = 21 19% (4) 10% (2) 14% (3) 0% (0) 5% (1) 5% (1) Large clots (n = 39) 2.5% (1) 10% (4)
Central, n = 18 17% 6% 22% 6% 0% 17%
(3) (1) (4) (1) (0) (3)
Of note, data on clot size available for 247 out of 312 total patients. Number of patients in parentheses.
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including death. We may wish to modify treatment algorithms based on the risk and size of the clot. However, we must still be aware of the risk of untreated PE. Further work is needed to define these competing risks and benefits prospectively. REFERENCES 1. Montgomery KD, Geerts WH, Potter HG, et al. Thromboembolic complications in patients with pelvic trauma. Clin Orthop Relat Res. 1996; 329:68–87. 2. American Academy of Orthopaedic Surgeons. Preventing venous thromboembolic disease in patients undergoing elective hip and knee arthroplasty: evidence-based guideline and evidence report. Available at: http:// www.aaos.org/Research/guidelines/VTE/VTE_full_guideline.pdf. Accessed December 1, 2012. 3. Wiener RS, Schwartz LM, Woloshin S. Time trends in pulmonary embolism in the United States: evidence of overdiagnosis. Arch Intern Med. 2011;171:831–837. 4. Wells PS, Anderson DR, Rodger M, et al. Derivation of a simple clinical model to categorize patients probability of pulmonary embolism: increasing the model’s utility with the simpliRed d-dimer. J Thromb Haemost. 2000;83:416–420. 5. Kearon C, Akl EA, Comerota AJ, et al. Antithrombotic therapy for VTE disease: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(suppl 2):e419S–e494S. 6. Auer RC, Schulman AR, Tuorto S, et al. Use of helical CT is associated with an increased incidence of postoperative pulmonary emboli in cancer patients with no change in the number of fatal pulmonary emboli. J Am Coll Surg. 2009;208:871–878. 7. Le Gal G, Righini M, Parent F, et al. Diagnosis and management of subsegmental pulmonary embolism. J Thromb Haemost. 2006;4:724–731.
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PE in Orthopaedic Trauma Patients
8. Carrier M, Righini M, Wells PS, et al. Subsegmental pulmonary embolism diagnosed by computed tomography: incidence and clinical implications. A systematic review and meta-analysis of the management outcome studies. J Thromb Haemost. 2010;8:1716–1722. 9. PIOPED Investigators. Value of the ventilation/perfusion scan in acute pulmonary embolism. Results of the prospective investigation of pulmonary embolism diagnosis (PIOPED). JAMA. 1990;263:2753–2759. 10. Dentali F, Ageno W, Becattini C, et al. Prevalence and clinical history of incidental, asymptomatic pulmonary embolism: a meta-analysis. Thromb Res. 2010;125:518–522. 11. Barritt DW, Jordan SC. Anticoagulant drugs in the treatment of pulmonary embolism: a controlled trial. Lancet. 1960 1:1309–1312. 12. Stein PD, Henry JW, Relyea B. Untreated patients with pulmonary embolism: outcome, clinical, and laboratory assessment. Chest. 1995; 107:931–935. 13. Patterson BM, Marchand R, Ranawat C. Complications of heparin therapy after total joint arthroplasty. J Bone Joint Surg Am. 1989;71: 1130–1134. 14. Zidane M, Schram MT, Planken EW, et al. Frequency of major hemorrhage in patients treated with unfractionated intravenous heparin for deep venous thrombosis or pulmonary embolism: a study in routine clinical practice. Arch Intern Med. 2000;160:2369–2373. 15. Neviaser AS, Chang C, Lyman S, et al. High incidence of complications from enoxaparin treatment after arthroplasty. Clin Orthop Relat Res. 2010;468:115–119. 16. Park B, Messina L, Dargon P, et al. Recent trends in clinical outcomes and resource utilization for pulmonary embolism in the United States: findings from the nationwide inpatient sample. Chest. 2009;136: 983–990. 17. Burge AJ, Freeman KD, Klapper PJ, et al. Increased diagnosis of pulmonary embolism without a corresponding decline in mortality during the CT era. Clin Radiol. 2008;63:381–386.
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