The risk of VTE, mainly PEs and fatal PEs, is the impetus for administration of anticoagulation agents after TJA [2, 5-8, 10, 13, 16, 18-21, 24, 26, 30, 44]. Unfortunately, the administration of chemical prophylaxis is associated with many complications such as increased hematoma formation, wound-related problems, and infection [31, 32, 36]. Sharrock et al.  reported that all-cause mortality is greater in patients who received aggressive anticoagulation after TJA. It therefore would be appealing to have a strategy that allows for individualization of postoperative anticoagulation for patients undergoing TJAs based on their risk for the development of PE. To develop such a strategy, we must identify the factors that place patients at the greatest risk for PE. We have provided identification of such risk factors in patients who received routine warfarin or aspirin prophylaxis.
Our study has some limitations. First, this study was limited to the evaluation of symptomatic PEs. We may have missed subclinical PEs in asymptomatic patients. However, we felt that it would have not been possible or medically appropriate to screen all patients for PE. Second, comorbidities were identified using ICD-9 coding data from discharge records at one institution. These records are assumed to be complete and accurate because they generally report known preoperative diagnoses, but underreporting of diagnoses can occur. Third, another shortcoming is that the study design only identifies patients who had their PE diagnosed at this institution and, therefore, misses those who had a PE identified elsewhere. Nonetheless it is reasonable that nearly all of the PEs that occurred were captured, especially given that the majority of PEs occur during the immediate postoperative period [1, 12]. Fourth, 90-day mortality was determined using the Social Security Death Index. Of the 86 patients who died during the postoperative period, we were able to confirm only who four died owing to PE, and no death was directly attributable to PE prophylaxis. However, it was not possible to identify cause of death if the patient died after discharge. Although our rate of documented fatal postoperative PEs is low at 0.02%, a recent meta-analysis by Poultsides et al. showed that non-PE cardiac causes were the leading cause of death after TJA, with PE as the second leading cause at a 0.1% rate of fatal postoperative PEs with pharmacologic prophylaxis . Fifth, in 2008, a new PE screening protocol was instituted at our institution to avoid overdiagnosis of subclinical PEs, and we gradually began to transition from warfarin to aspirin for VTE prophylaxis. It is unclear how these changes affected the risk of PE, but we did not see any increase in the risk of symptomatic PE with use of aspirin for VTE prophylaxis.
A major strength of this study was that all PEs were identified and verified by reviewing radiologic reports and not simply by relying on ICD-9 coding data. When only ICD-9 coding data (ICD-9 codes 415, 415.11, 415.19, 451, 451.0, 451.11, 451.19, 451.2, 451.81, 453, and 453.9) were reviewed, only 205 of the total 283 postoperative PE events were identified. This highlights the potential significant underreporting of adverse events when only ICD-9 coding from databases is used.
Patients with greater BMI, multiple medical comorbidities (as reflected by an elevated Charlson Comorbidity Index), chronic obstructive pulmonary disease, hypertension, and history of atrial fibrillation were more likely to have a PE develop after TJA. There are theoretical bases for the associations between some of these conditions and VTE. Patients with chronic obstructive pulmonary disease, for example, are more likely to have inflammation of the pulmonary vessels and/or experience pulmonary hypertension that leads to stagnation of blood in the inflamed or damaged vessels and subsequent thrombus formation . Patients with arrhythmia such as atrial fibrillation have a high risk of thrombi developing in cardiac atria leading to elevated rates of PE and stroke . Patients with postoperative deep vein thrombosis formation are, as expected, at higher risk for PEs. This is likely the result of the contribution of deep vein thrombosis to embolic phenomena such as PE. Obesity and elevated comorbidity index have been shown to be associated with an increased risk of VTE [9, 14, 17, 40]. This may be secondary to an inflammatory state in these patients that may contribute to increased thrombus formation and subsequent embolization [9, 40]. Simultaneous bilateral TJAs also have been suggested as a higher risk for the development of PE when compared with unilateral TJA . This may be the result of multiple factors, including the difficulty of early mobilization and a higher embolic load from intramedullary debris from bilateral surgery. Other risk factors for PE development such as preoperative anemia and depression are not as easily explained. Subsets of anemia including sickle cell, hemolytic, and even iron deficiency anemia have been associated with PEs [27, 28, 42]. Despite this, it is unclear whether anemia has a direct mechanism to lead to increased risk of PE. Depression has been suggested to be associated with PE. Schulte et al. found depression to be an independent risk factor of PE after spinal surgery . Furthermore, in the psychiatric literature, studies have suggested an association between the lack of physical activity in patients in catatonic and depressive states to development of VTE [15, 23]. Patients with depression may experience self-neglect, which may have resulted in noncompliance with anticoagulation prophylaxis or lack of mobility, both of which may have increased the risk of PE.
Although a goal of our study was to identify risk factors associated with postoperative symptomatic PE development in patients who have undergone TJA, the ultimate purpose of this study is to use this information in making clinical choices regarding patients undergoing TJAs. Therefore, using a logistic regression model, the risk factors identified in this study have been ranked according to their relative risk (Table 4). Using these scoring criteria, three clinically significant risk groups (low, medium, and high) have been created. The application of these relative risk criteria to individual patients may help to determine the type of postoperative anticoagulation that best balances the overall risk of the development of PE with that of postsurgical bleeding.
We found that patients who have an elevated BMI, Charlson Comorbidity Index, chronic obstructive pulmonary disease, atrial fibrillation, postoperative deep vein thrombosis, or anemia, and patients who undergo knee surgery (particularly bilateral knee surgery), are at greater risk of having a postoperative PE develop. These risks should be considered when deciding on postoperative anticoagulation prophylaxis. Further studies must be done to validate the PE risk stratification criteria presented here. These criteria, together with similar risk stratification for postoperative bleeding risk, ultimately can help to determine the appropriate postoperative PE prophylaxis on an individualized basis for patients undergoing TJAs.
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