Original Article
Predictors of Rehospitalization for Symptomatic Venous Thromboembolism after Total Hip Arthroplasty
N Engl J Med 2000; 343:1758-1764December 14, 2000
- Abstract
Background
Recent studies have shown that symptomatic venous thromboembolism after total hip arthroplasty most commonly develops after the patient is discharged from the hospital. Risk factors associated with these symptomatic thromboembolic events are not well defined.
Methods
Using administrative data from the California Medicare records for 1993 through 1996, we identified 297 patients 65 years of age or older who were rehospitalized for thromboembolism within three months after total hip arthroplasty. We compared demographic, surgical, and medical variables potentially associated with the development of thromboembolism in these patients and 592 unmatched controls.
Results
A total of 89.6 percent of patients with thromboembolism and 93.8 percent of control patients were treated with pneumatic compression, warfarin, enoxaparin, or unfractionated heparin, alone or in combination. In addition, 22.2 percent and 29.7 percent, respectively, received warfarin after discharge. A body-mass index (the weight in kilograms divided by the square of the height in meters) of 25 or greater was associated with rehospitalization for thromboembolism, with an odds ratio of 2.5 (95 percent confidence interval, 1.8 to 3.4). In a multivariate model, the only prophylactic regimens associated with a reduced risk of thromboembolism were pneumatic compression in patients with body-mass indexes of less than 25 (odds ratio, 0.3; 95 percent confidence interval, 0.2 to 0.6) and warfarin treatment after discharge (odds ratio, 0.6; 95 percent confidence interval, 0.4 to 1.0).
Conclusions
In patients who underwent total hip arthroplasty, a body-mass index of 25 or greater was associated with subsequent hospitalization for thromboembolism. Pneumatic compression in patients with a body-mass index of less than 25 and prophylaxis with warfarin after discharge were independently protective against thromboembolism.
Media in This Article
Figure 2
Time of Readmission for Thromboembolism in the 297 Patients with Thromboembolism.Figure 1
Odds Ratios for Readmission for Thromboembolism in Patients with Various Body-Mass Indexes.Article Activity
- Article
Early studies of venous thromboembolism after total hip arthroplasty documented a high frequency of symptomatic complications.1,2 Subsequent studies documented the efficacy of low-dose standard heparin,3 pneumatic compression,4,5 warfarin,6,7 and low-molecular-weight heparin6,8 in reducing the incidence of asymptomatic venous thrombosis, a surrogate measure of clinical thromboembolism. The use of asymptomatic venous thrombosis as the standard to define thromboembolism improves statistical power and dramatically decreases the number of subjects required in a clinical trial,9 but it may not accurately reflect symptomatic outcomes.
The three-month incidence of symptomatic thromboembolism after elective hip arthroplasty is approximately 3 to 4 percent among patients given prophylaxis with warfarin or enoxaparin during their hospital stay.10 Over 75 percent of these events are diagnosed after the patient is discharged from the hospital.10,11 Although prophylactic treatment with enoxaparin for three weeks after discharge reduces the incidence of venographically documented thrombosis,12,13 it is not clear whether extended prophylaxis reduces the incidence of symptomatic thromboembolism.14,15
We sought to identify risk factors associated with the development of symptomatic thromboembolism after hip arthroplasty and to determine whether extended prophylaxis reduces the incidence of symptomatic thromboembolism. Therefore, we designed a large case–control study of patients who underwent total hip arthroplasty and in whom symptomatic thromboembolism developed after they were discharged from the hospital.
Methods
Study Design
Assuming that approximately 32 percent of patients who undergo hip arthroplasty are treated with warfarin after discharge,11 we estimated that 250 patients with thromboembolism and 500 controls would be needed to detect a clinically meaningful 40 percent reduction in the odds of warfarin use in patients with thromboembolism as compared with controls (with a beta level of 80 percent and an alpha level of 0.05). To ensure that our study had adequate power, we decided to review the cases of approximately 300 patients with thromboembolism and 600 unmatched controls.
Definition of Patients with Thromboembolism and Controls
We selected subjects using the Medicare inpatient claims of 25,388 fee-for-service patients 65 years of age or older who underwent unilateral total hip arthroplasty (code 81.51 in the International Classification of Diseases, 9th Revision, Clinical Modification [ICD-9-CM])16 in a California acute care hospital between January 1, 1993, and December 31, 1996. We excluded patients with hip fracture and patients likely to require long-term therapy with warfarin because of atrial fibrillation, a prosthetic heart valve, or venous thromboembolism during the index hospitalization or a prior hospitalization (within six months before hip surgery). We also excluded all patients who were rehospitalized and underwent surgery within 91 days after arthroplasty, unless there was an intervening admission associated with thromboembolism (ICD-9-CM codes 451.11, 451.18, 451.2, 451.81, 451.9, 453.1, 453.2, 453.8, 453.9, and 415.1). A total of 21,718 patients were eligible for selection as subjects. We defined patients with thromboembolism as eligible patients who were readmitted within 91 days after surgery with a primary or secondary diagnosis of venous thromboembolism.
We requested the records of all 436 patients with venous thromboembolism who met our case definition. Of the remaining 21,282 records, we requested a random sample of 1308 for use as controls. After three months and one or two follow-up mailings, we received 429 of the case records (98.4 percent) and 1269 of the control records (97.0 percent). We randomly selected 305 case records and 611 control records for abstraction. We excluded 7 patients with thromboembolism and 12 control patients because of incomplete records. One patient with thromboembolism and 7 control patients who received rarely used or experimental prophylactic agents were also excluded, leaving 297 patients with thromboembolism and 592 control patients.
Data Abstraction
Trained physicians, who were unaware of the study hypotheses, used a computerized tool to abstract independently the hospital records regarding surgery and thromboembolism. This tool was pretested, and sources of potential variation in responses were identified, in an initial subsample of 28 records. The items or their definitions were modified as needed. The records of 44 patients with thromboembolism and 89 control patients were reabstracted; no error was detected in 99.1 percent of the data elements.
Table 1Table 1
Results of Bivariate Analysis of Clinical Variables. and Table 2Table 2
Results of Bivariate Analysis of Thromboprophylactic Variables at the Time of Surgery. summarize the abstracted information. All nurses' notes and physicians' orders were reviewed to determine whether elastic stockings or pneumatic compression had been prescribed. The types and durations of surgery were determined from the anesthesia records. The first day after surgery that the patient was ambulatory was ascertained from the physical-therapy notes. The anticipated duration of medical prophylaxis was determined from the physicians' orders, progress notes, and pharmacy records. Objective documentation of thromboembolism required positive findings on pulmonary arteriography, ventilation–perfusion lung scanning, venography of the legs, venous ultrasonography, or impedance plethysmography.Statistical Analysis
We categorized the body-mass index (the weight in kilograms divided by the square of the height in meters) as less than 25 or 25 or greater, the cutoff used to define overweight and obesity.17 We categorized in-hospital prophylaxis as warfarin, unfractionated heparin, or low-molecular-weight heparin, either alone or in combination with pneumatic compression. Seven patients with thromboembolism and 26 controls who were treated with warfarin plus either unfractionated heparin or enoxaparin during the index hospitalization were categorized as having received in-hospital prophylaxis with heparin. All patients treated with warfarin after discharge were considered to have received postdischarge prophylaxis. We did not classify continued use of heparin or enoxaparin as postdischarge prophylaxis, because the average total duration of treatment with standard and low-molecular-weight heparin was less than seven days. Moreover, extended use of low-molecular-weight heparin was uncommon in 1995 and 1996. Because there is no evidence that aspirin provides effective prophylaxis against thromboembolism,18,19 and because bivariate analysis showed no association between aspirin use and the risk of thromboembolism, patients who received aspirin were considered to have received no prophylaxis. Patients who used elastic stockings alone were also considered to have received no prophylaxis.
For continuous variables, bivariate comparisons were made with the use of Student's t-test. For categorical variables, the unadjusted odds ratio and Cornfield's 95 percent confidence interval were determined.
Multivariate models were developed with the use of logistic regression. Age was categorized as 65 to 74, 75 to 84, or 85 or more years. Body-mass index was categorized as less than 25 or 25 or greater, because the odds of thromboembolism among patients with body-mass-index values of 25 or greater were relatively uniform (Figure 1Figure 1
Odds Ratios for Readmission for Thromboembolism in Patients with Various Body-Mass Indexes.). Other potential risk factors included race (categorized as white or nonwhite); sex; type of anesthesia (general or regional); presence or absence of prior venous thromboembolism, estrogen-replacement therapy, cancer, or rheumatoid arthritis; number of days after surgery until the patient was ambulatory; and discharge destination (home or other). In-hospital prophylaxis and postdischarge prophylaxis (with warfarin) were included in the model as main effects. Potential risk factors forced into the model on the basis of prior studies included age, sex, race, type of in-hospital prophylaxis, and presence or absence of rheumatoid arthritis.20 Other terms were entered in a stepwise fashion (with cutoffs of P≥0.1 to be included and P>0.05 to be excluded). Two-way interactions involving treatment methods and key risk factors were tested. Statistical analyses were performed using the SAS-PC program (SAS Institute, Cary, N.C.). The study was approved by the human subjects committee of the University of California, Davis.Results
Hospitalization for Thromboembolism
Among the 297 patients who were hospitalized with a diagnosis of postoperative venous thromboembolism, 203 (68.4 percent) had venous thrombosis alone and 94 (31.6 percent) had pulmonary embolism. Symptoms were recorded for 284 (95.6 percent) of the patients, a report or note indicated that thromboembolism was objectively confirmed in 285 (96.0 percent), and anticoagulant treatment was administered to 293 (98.7 percent). Of the four untreated patients, one died of acute pulmonary embolism (discovered at autopsy), and the remaining three had active bleeding.
At the time of admission for venous thromboembolism, 49 patients were receiving warfarin and 19 were receiving standard heparin or enoxaparin. An international normalized ratio was recorded at the time of admission in 45 of the 49 patients treated with warfarin. The median international normalized ratio was 1.4, and 29 of the 45 patients (64 percent) had a ratio of less than 2.0. Figure 2Figure 2
Time of Readmission for Thromboembolism in the 297 Patients with Thromboembolism. shows the cumulative incidence of readmissions for thromboembolism.Hospitalization for Surgery
Table 1 shows the results of bivariate analysis of clinical risk factors. A body-mass index of 25 or greater was associated with an odds ratio of 2.5 for thromboembolism (95 percent confidence interval, 1.8 to 3.4). In a multivariate analysis the odds ratio was 1.8 (95 percent confidence interval, 1.1 to 2.9; P=0.03). The relation between body-mass index and the odds of thromboembolism is shown in Figure 1, with a body-mass index of less than 21 as the reference category.
The mean (±SD) dose of standard heparin was 10,422±4490 IU per day in patients with thromboembolism and 11,000±2260 IU per day in controls (P=0.6). The mean dose of enoxaparin was 59±4.5 mg per day in patients with thromboembolism and 60±2.4 mg per day in controls (P=0.3). The expected total durations of heparin therapy were also similar: 6.6±3.2 days in patients with thromboembolism and 6.8±5.4 days in controls (P=0.9).
Bivariate analysis revealed that the use of pneumatic compression significantly reduced the risk of thromboembolism (odds ratio, 0.7; 95 percent confidence interval, 0.5 to 0.9). Table 2 shows the results of bivariate analysis of in-hospital thromboprophylaxis stratified according to the use or nonuse of pneumatic compression.
The results of risk-adjusted multivariate modeling are shown in Table 3Table 3
Results of Multivariate Analysis of Variables Associated with Thromboembolism.. Independent predictors of thromboembolism included an age of at least 85 years (as compared with an age of 65 to 74 years), female sex, a history of thromboembolism, and a body-mass index of 25 or greater. Factors associated with protection against thromboembolism were initial ambulation before day 2 after surgery, use of pneumatic compression (among patients with a body-mass index of <25), and use of warfarin after discharge. A significant interaction was found between pneumatic compression and body-mass index (P<0.03). Among patients treated with pneumatic compression, there was a significant reduction in the odds of thromboembolism only among those with a body-mass index of less than 25 (odds ratio, 0.3; 95 percent confidence interval, 0.2 to 0.6). Medical prophylaxis with standard heparin, enoxaparin, or warfarin during the index hospitalization was not associated with a reduced risk of rehospitalization due to thromboembolism. This was true regardless of the use of pneumatic compression or body-mass index. Interactions between body-mass index and types of medical prophylaxis were not significant.Discussion
The use of longitudinal California Medicare data allowed us to identify risk factors associated with symptomatic thromboembolism in a large, representative sample of patients who underwent hip arthroplasty. We found that the use of pneumatic compression was associated with a significant reduction in the risk of symptomatic thromboembolism; however, this effect was found only in patients with a body-mass index of less than 25. Also noteworthy were the findings that female sex and a higher body-mass index were each associated with a significantly higher risk of symptomatic thromboembolism. Protective factors included ambulation before day 2 after surgery and use of warfarin after discharge from the hospital.
Given that immobilization is a well-known risk factor associated with venous thrombosis,9,21 the finding that early ambulation was associated with a lower risk of thromboembolism is not surprising. Other studies have noted a trend over time toward earlier mobilization of patients,22 and delayed weight bearing is known to be associated with an increased risk of venous thrombosis.23
Most clinical studies that have assessed the efficacy of pneumatic compression either have not analyzed the effect of weight or body-mass index5,24-28 or have restricted the analysis to patients with a body-mass index of 30 or greater.29 Further studies are needed to confirm the finding that pneumatic compression is significantly more effective in patients with a lower body-mass index.
A higher body-mass index was an independent predictor of symptomatic thromboembolism. Obesity is generally acknowledged as a risk factor for venous thrombosis, and two recent studies of patients undergoing hip arthroplasty reported associations between a body-mass index of greater than 30 and the development of symptomatic10 or venographically detected thromboembolism.30 It is tempting to speculate that obesity is associated with inflammation, which may be the primary stimulus for the development of thromboembolism.31-34
Obesity is also associated with reduced fibrinolysis,35 and the effectiveness of pneumatic compression appears to be due to an enhancement of systemic fibrinolysis.36 Taken together, these observations provide a plausible explanation for our findings. In overweight or obese patients, the stimulation of fibrinolysis associated with pneumatic compression may not be sufficient to overcome the enhancement of blood coagulation associated with surgery and immobilization.
The failure of in-hospital prophylaxis with standard heparin, enoxaparin, or warfarin to be associated with a significant reduction in the risk of thromboembolism was not expected. This finding may in part reflect a type II error, given the relatively small number of patients who received each type of medical prophylaxis. In addition, a short course of medical prophylaxis may simply be insufficient to prevent late symptomatic thromboembolism. It should be stressed that we analyzed only symptomatic thromboembolism that was diagnosed after discharge from the hospital. Medical prophylaxis may reduce the incidence of symptomatic thromboembolism that develops during the initial hospitalization, which accounts for approximately 20 to 25 percent of all cases of symptomatic thromboembolism.10,11 The apparent benefit of postdischarge prophylaxis with warfarin could have been underestimated if a greater proportion of the patients with thromboembolism than of the controls received inadequate anticoagulant therapy.37 Unfortunately, comparative data specifying the adequacy of warfarin therapy could not be obtained.
Potential sources of bias in this case–control study include diagnostic bias and selection bias. Because it may be difficult to determine whether compression of a vein is complete in the leg of an extremely obese person,38 the incidence of false positive ultrasonographic findings may be increased in very large patients. If only high-risk patients were treated with warfarin after discharge from the hospital, the observed effect of postdischarge prophylaxis with warfarin might have been reduced. Because of these potential biases, our findings should be corroborated in randomized trials or by careful meta-analysis of existing data.
Our findings are likely to apply to the majority of patients undergoing elective hip-replacement surgery, since most hip-arthroplasty surgery is performed in patients over the age of 65.39 The prevalence of prophylaxis against thromboembolism in the control group, 93.8 percent, was similar to the prevalence of 93 percent reported by orthopedic surgeons in Massachusetts.40 The 2.1 percent incidence of symptomatic thromboembolism that we observed over a period of three months is in accord with the rates reported in other large studies.10,41 Finally, the time course of postdischarge events (Figure 2) is similar to that previously reported.11 To further reduce the incidence of symptomatic thromboembolism, efforts need to focus on improving the effectiveness of in-hospital as well as postdischarge thromboprophylaxis in overweight patients.
Supported by a contract (500-96-P535, “Utilization and Quality Control Peer Review Organization for the State of California”) with the Health Care Financing Administration, Department of Health and Human Services. The content of this article does not necessarily reflect the views or policies of the Department of Health and Human Services.
Source Information
From the Division of General Medicine, Department of Medicine (R.H.W., P.S.R.), and the Department of Orthopaedic Surgery (K.B.T.), University of California, Davis, Sacramento; and California Medical Review, Inc., San Francisco (S.G., J.M.N.).
Address reprint requests to Dr. White at the Division of General Medicine, Suite 2400, PSSB, 4150 V St., Sacramento, CA 95817, or at rhwhite@ucdavis.edu.
- References
References
1
Johnson R ,Green JR ,Charnley J . Pulmonary embolism and its prophylaxis following the Charnley total hip replacement. Clin Orthop 1977;127:123-132
Web of Science | Medline2
Coventry MB ,Beckenbaugh RD ,Nolan DR ,Ilstrup DM . 2,012 Total hip arthroplasties: a study of postoperative course and early complications. J Bone Joint Surg Am 1974;56:273-284
Web of Science | Medline3
Collins R ,Scrimgeour A ,Yusuf S ,Peto R . Reduction in fatal pulmonary embolism and venous thrombosis by perioperative administration of subcutaneous heparin: overview of results of randomized trials in general, orthopedic, and urologic surgery. N Engl J Med 1988;318:1162-1173
Full Text | Web of Science | Medline4
Hull RD ,Raskob GE ,Gent M , et al. Effectiveness of intermittent pneumatic leg compression for preventing deep vein thrombosis after total hip replacement. JAMA 1990;263:2313-2317
CrossRef | Web of Science | Medline5
Francis CW ,Pellegrini VD Jr ,Marder VJ , et al. Comparison of warfarin and external pneumatic compression in prevention of venous thrombosis after total hip replacement. JAMA 1992;267:2911-2915
CrossRef | Web of Science | Medline6
Hull R ,Raskob G ,Pineo G , et al. A comparison of subcutaneous low-molecular-weight heparin with warfarin sodium for prophylaxis against deep-vein thrombosis after hip or knee implantation. N Engl J Med 1993;329:1370-1376
Full Text | Web of Science | Medline7
Paiement GD ,Schutzer SF ,Wessinger SJ ,Harris WH . Influence of prophylaxis on proximal venous thrombus formation after total hip arthroplasty. J Arthroplasty 1992;7:471-475
CrossRef | Medline8
Levine MN ,Hirsh J ,Gent M , et al. Prevention of deep vein thrombosis after elective hip surgery: a randomized trial comparing low molecular weight heparin with standard unfractionated heparin. Ann Intern Med 1991;114:545-551
Web of Science | Medline9
Clagett GP ,Anderson FA Jr ,Geerts W , et al. Prevention of venous thromboembolism. Chest 1998;114:Suppl:531S-560S
CrossRef | Web of Science | Medline10
Colwell CW Jr ,Collis DK ,Paulson R , et al. Comparison of enoxaparin and warfarin for the prevention of venous thromboembolic disease after total hip arthroplasty: evaluation during hospitalization and three months after discharge. J Bone Joint Surg Am 1999;81:932-940
CrossRef | Web of Science | Medline11
White RH ,Romano PS ,Zhou H ,Rodrigo J ,Bargar W . Incidence and time course of thromboembolic outcomes following total hip or knee arthroplasty. Arch Intern Med 1998;158:1525-1531
CrossRef | Web of Science | Medline12
Bergqvist D ,Benoni G ,Bjorgell O , et al. Low-molecular-weight heparin (enoxaparin) as prophylaxis against venous thromboembolism after total hip replacement. N Engl J Med 1996;335:696-700
Full Text | Web of Science | Medline13
Planes A ,Vochelle N ,Darmon JY ,Fagola M ,Bellaud M ,Huet Y . Risk of deep-venous thrombosis after hospital discharge in patients having undergone total hip replacement: double-blind randomised comparison of enoxaparin versus placebo. Lancet 1996;348:224-228
CrossRef | Web of Science | Medline14
Heit JA ,Elliott CG ,Trowbridge AA ,Morrey BF ,Gent M ,Hirsh J . Ardeparin sodium for extended out-of-hospital prophylaxis against venous thromboembolism after total hip or knee replacement: a randomized, double-blind, placebo-controlled trial. Ann Intern Med 2000;132:853-861
Web of Science | Medline15
Hirsh J . Evidence for the needs of out-of-hospital thrombosis prophylaxis: introduction. Chest 1998;114:Suppl:113S-114S
CrossRef | Medline16
Department of Health and Human Services. The international classification of diseases, 9th rev., clinical modification: ICD-9-CM. Vol. 1. Diseases: tabular list. Washington, D.C.: Government Printing Office, 1980. (DHHS publication no. (PHS) 80-1260.)
17
Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults: the evidence report. Bethesda, Md.: National Heart, Lung, and Blood Institute, 1998. (NIH publication no. 98-4083.)
18
Imperiale TF ,Speroff T . A meta-analysis of methods to prevent venous thromboembolism following total hip replacement. JAMA 1994;271:1780-1785[Erratum, JAMA 1995;273:288.]
CrossRef | Web of Science | Medline19
Pulmonary Embolism Prevention (PEP) Trial Collaborative Group
CrossRef | Web of Science | Medline20
Buchanan RR ,Kraag G . Is there a lower incidence of deep venous thrombosis after joint replacement in rheumatoid arthritis? J Rheumatol 1980;7:551-554
Web of Science | Medline21
Lassen MR ,Borris LC . Mobilisation after hip surgery and efficacy of thromboprophylaxis. Lancet 1991;337:618-618
CrossRef | Web of Science | Medline22
Munin MC ,Rudy TE ,Glynn NW ,Crossett LS ,Rubash HE . Early inpatient rehabilitation after elective hip and knee arthroplasty. JAMA 1998;279:847-852
CrossRef | Web of Science | Medline23
Buehler KO ,D'Lima DD ,Petersilge WJ ,Colwell CW Jr ,Walker RH . Late deep venous thrombosis and delayed weightbearing after total hip arthroplasty. Clin Orthop 1999;361:123-130
CrossRef | Web of Science | Medline24
Grady-Benson JC ,Oishi CS ,Hanson PB ,Colwell CW Jr ,Otis SM ,Walker RH . Routine postoperative duplex ultrasonography screening and monitoring for the detection of deep vein thrombosis: a survey of 110 total hip arthroplasties. Clin Orthop 1994;307:130-141
Web of Science | Medline25
Lieberman JR ,Huo MM ,Hanway J ,Salvati EA ,Sculco TP ,Sharrock NE . The prevalence of deep venous thrombosis after total hip arthroplasty with hypotensive epidural anesthesia. J Bone Joint Surg Am 1994;76:341-348
Web of Science | Medline26
Woolson ST . Intermittent pneumatic compression prophylaxis for proximal deep venous thrombosis after total hip replacement. J Bone Joint Surg Am 1996;78:1735-1740
Web of Science | Medline27
Kaempffe FA ,Lifeso RM ,Meinking C . Intermittent pneumatic compression versus coumadin: prevention of deep vein thrombosis in lower-extremity total joint arthroplasty. Clin Orthop 1991;269:89-97
Web of Science | Medline28
Salvati EA ,Pellegrini VD Jr ,Sharrock NE , et al. Recent advances in venous thromboembolic prophylaxis during and after total hip replacement. J Bone Joint Surg Am 2000;82:252-270
Web of Science | Medline29
Hooker JA ,Lachiewicz PF ,Kelley SS . Efficacy of prophylaxis against thromboembolism with intermittent pneumatic compression after primary and revision total hip arthroplasty. J Bone Joint Surg Am 1999;81:690-696
Web of Science | Medline30
Lowe GD ,Haverkate F ,Thompson SG , et al. Prediction of deep vein thrombosis after elective hip replacement surgery by preoperative clinical and haemostatic variables: the ECAT DVT Study: European Concerted Action on Thrombosis. Thromb Haemost 1999;81:879-886
Web of Science | Medline31
Mohamed-Ali V ,Goodrick S ,Rawesh A , et al. Subcutaneous adipose tissue releases interleukin-6, but not tumor necrosis factor-alpha, in vivo. J Clin Endocrinol Metab 1997;82:4196-4200
CrossRef | Web of Science | Medline32
Danesh J ,Collins R ,Appleby P ,Peto R . Association of fibrinogen, C-reactive protein, albumin, or leukocyte count with coronary heart disease: meta-analyses of prospective studies. JAMA 1998;279:1477-1482
CrossRef | Web of Science | Medline33
Visser M ,Bouter LM ,McQuillan GM ,Wener MH ,Harris TB . Elevated C-reactive protein levels in overweight and obese adults. JAMA 1999;282:2131-2135
CrossRef | Web of Science | Medline34
Cermak J ,Key NS ,Bach RR ,Balla J ,Jacob HS ,Vercellotti GM . C-reactive protein induces human peripheral blood monocytes to synthesize tissue factor. Blood 1993;82:513-520
Web of Science | Medline35
Lundgren CH ,Brown SL ,Nordt TK ,Sobel BE ,Fujii S . Elaboration of type-1 plasminogen activator inhibitor from adipocytes: a potential pathogenetic link between obesity and cardiovascular disease. Circulation 1996;93:106-110
Web of Science | Medline36
Comerota AJ ,Chouhan V ,Harada RN , et al. The fibrinolytic effects of intermittent pneumatic compression: mechanism of enhanced fibrinolysis. Ann Surg 1997;226:306-314
CrossRef | Web of Science | Medline37
Caprini JA ,Arcelus JI ,Motykie G ,Kudrna JC ,Mokhtee D ,Reyna JJ . The influence of oral anticoagulation therapy on deep vein thrombosis rates four weeks after total hip replacement. J Vasc Surg 1999;30:813-820
CrossRef | Web of Science | Medline38
White RH ,McGahan JP ,Daschbach MM ,Hartling RP . Diagnosis of deep-vein thrombosis using duplex ultrasound. Ann Intern Med 1989;111:297-304
Web of Science | Medline39
Lawrence L, Hall MJ. 1997 Summary: National Hospital Discharge Survey. Advance data from vital and health statistics. No. 308. Hyattsville, Md.: National Center for Health Statistics, 1999:13.
40
Anderson FA Jr ,Audet AM . Physician practices in the prevention of deep vein thrombosis: the MassPRO DVT Study. Orthopedics 1996;19:Suppl:9-11
Web of Science | Medline41
Robinson KS ,Anderson DR ,Gross M , et al. Ultrasonographic screening before hospital discharge for deep venous thrombosis after arthroplasty: the post-arthroplasty screening study: a randomized, controlled trial. Ann Intern Med 1997;127:439-445
Web of Science | Medline
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Mathieu Emily, Pierre Casez, Olivier François. (2009) Risk Assessment for Hospital-Acquired Diseases: A Risk-Theory Approach. Risk Analysis 29:4, 565-575
CrossRef18
Javier Granero Xiberta, José María Soler Minoves, Laura Garcia Nuño. (2008) Enfermedad tromboembólica en pacientes de cirugía ortopédica. Medicina Clínica 131, 18-24
CrossRef19
Juan Carlos Villalba, Manuel Monreal. (2008) Enfermedad tromboembólica venosa e inmovilización de causa médica. Medicina Clínica 131, 10-17
CrossRef20
Naomi P. O’Grady, Philip S. Barie, John G. Bartlett, Thomas Bleck, Karen Carroll, Andre C. Kalil, Peter Linden, Dennis G. Maki, David Nierman, William Pasculle, Henry Masur. (2008) Guidelines for evaluation of new fever in critically ill adult patients: 2008 update from the American College of Critical Care Medicine and the Infectious Diseases Society of America. Critical Care Medicine 36:4, 1330-1349
CrossRef21
C. Vielpeau, J. Barre, M.-T. Barrellier, A. Borel-Derlon, N. Rosencher, C.M. Samama, M.-M. Samama, P. Zufferey. (2008) Profilaxis de los accidentes tromboemb
licos venosos en cirug
CrossRef22
Clifford W Colwell, Mary E Hardwick. (2008) Thromboprophylaxis in Elderly Patients Undergoing Major Orthopaedic Surgery. Drugs & Aging 25:7, 551-558
CrossRef23
Katharine He Xing, Gareth Morrison, Wendy Lim, James Douketis, Adefowope Odueyungbo, Mark Crowther. (2008) Has the incidence of deep vein thrombosis in patients undergoing total hip/knee arthroplasty changed over time? A systematic review of randomized controlled trials. Thrombosis Research 123:1, 24-34
CrossRef24
Aldo L. Brasileiro, Fausto Miranda, João E. M. T. M. Ettinger, Aldemar A. Castro, Guilherme B. B. Pitta, Liberato K. Moura, Euler Ázaro, Marcelo L. Moura, Carlos A. B. Mello, Edvaldo Fahel, Luiz F. P. Figueiredo. (2008) Incidence of Lower Limbs Deep Vein Thrombosis After Open and Laparoscopic Gastric Bypass: A Prospective Study. Obesity Surgery 18:1, 52-57
CrossRef25
C.-M. SAMAMA, P. RAVAUD, F. PARENT, J. BARRÉ, P. MERTL, P. MISMETTI, . (2007) Epidemiology of venous thromboembolism after lower limb arthroplasty: the FOTO study. Journal of Thrombosis and Haemostasis 5:12, 2360-2367
CrossRef26
Elisabeth R. Pomp, Saskia le Cessie, Frits R. Rosendaal, Carine J. M. Doggen. (2007) Risk of venous thrombosis: obesity and its joint effect with oral contraceptive use and prothrombotic mutations. British Journal of Haematology 139:2, 289-296
CrossRef27
Thomas J. Semrad, Robert O'Donnell, Ted Wun, Helen Chew, Danielle Harvey, Hong Zhou, Richard H. White. (2007) Epidemiology of venous thromboembolism in 9489 patients with malignant glioma. Journal of Neurosurgery 106:4, 601-608
CrossRef28
Cary P. Gross, Deron H. Galusha, Harlan M. Krumholz. (2007) The Impact of Venous Thromboembolism on Risk of Death or Hemorrhage in Older Cancer Patients. Journal of General Internal Medicine 22:3, 321-326
CrossRef29
Chethan Gangireddy, John R. Rectenwald, Gilbert R. Upchurch, Thomas W. Wakefield, Shukri Khuri, William G. Henderson, Peter K. Henke. (2007) Risk factors and clinical impact of postoperative symptomatic venous thromboembolism. Journal of Vascular Surgery 45:2, 335-342.e1
CrossRef30
Richard H. White, Helen Chew, Ted Wun. (2007) Targeting patients for anticoagulant prophylaxis trials in patients with cancer: Who is at highest risk?. Thrombosis Research 120, S29-S40
CrossRef31
Matthew L. Ortman, Todd E.H. Hecht. 2007. Prevention of Venous Thromboembolism in the Surgical Patient. , 151-222.
CrossRef32
Sergio Coccheri. (2007) Approaches to Prevention of Cardiovascular Complications and Events in Diabetes Mellitus. Drugs 67:7, 997-1026
CrossRef33
John A. Heit. 2007. Thrombophilia: Clinical and Laboratory Assessment and Management. , 211-244.
CrossRef34
Burak Beksa??, Alejandro Gonz??lez Della Valle, Eduardo A Salvati. (2006) Thromboembolic Disease after Total Hip Arthroplasty. Clinical Orthopaedics and Related Research 453, 211-224
CrossRef35
Gregory Piazza, Samuel Z. Goldhaber. (2006) Venous Thromboembolism Guidebook. Critical Pathways in Cardiology: A Journal of Evidence-Based Medicine 5:4, 211-227
CrossRef36
John A. Heit. (2006) The Epidemiology of Venous Thromboembolism in the Community: Implications for Prevention and Management. Journal of Thrombosis and Thrombolysis 21:1, 23-29
CrossRef37
Eduardo A Salvati, Alejandro Gonz??lez Della Valle, Geoffrey H Westrich, Adam J Rana, Lawrence Specht, Babette B Weksler, Ping Wang, Charles J Glueck. (2005) THE JOHN CHARNLEY AWARD: Heritable Thrombophilia and Development of Thromboembolic Disease after Total Hip Arthroplasty. Clinical Orthopaedics and Related Research 441:&NA;, 40-55
CrossRef38
David Garcia, Walter Ageno, Edward Libby. (2005) Update on the diagnosis and management of pulmonary embolism. British Journal of Haematology 131:3, 301-312
CrossRef39
Craig R Keenan, Richard H White. (2005) Age as a risk factor for venous thromboembolism after major surgery. Current Opinion in Pulmonary Medicine 11:5, 398-402
CrossRef40
J. A. HEIT. (2005) Venous thromboembolism: disease burden, outcomes and risk factors. Journal of Thrombosis and Haemostasis 3:8, 1611-1617
CrossRef41
(2005) Electronic Alerts to Prevent Venous Thromboembolism. New England Journal of Medicine 352:22, 2349-2350
Full Text42
Paul A Kyrle, Sabine Eichinger. (2005) Deep vein thrombosis. The Lancet 365:9465, 1163-1174
CrossRef43
Clifford W. Colwell. (2004) Length of Thrombosis Prophylaxis After Orthopaedic Surgery of the Lower Extremity. Techniques in Orthopaedics 19:4, 300-302
CrossRef44
R. H. White, H. Zhou, B. F. Gage. (2004) Effect of age on the incidence of venous thromboembolism after major surgery. Journal of Thrombosis and Haemostasis 2:8, 1327-1333
CrossRef45
Samuel Z Goldhaber. (2004) Pulmonary embolism. The Lancet 363:9417, 1295-1305
CrossRef46
Carlos B. Mantilla, Terese T. Horlocker, Darrell R. Schroeder, Daniel J. Berry, David L. Brown. (2003) Risk Factors for Clinically Relevant Pulmonary Embolism and Deep Venous Thrombosis in Patients Undergoing Primary Hip or Knee Arthroplasty. Anesthesiology 99:3, 552-560
CrossRef47
John A Heit. (2003) Risk factors for venous thromboembolism. Clinics in Chest Medicine 24:1, 1-12
CrossRef48
Peter Kaboli, Mark C Henderson, Richard H White. (2003) DVT prophylaxis and anticoagulation in the surgical patient. Medical Clinics of North America 87:1, 77-110
CrossRef49
J. E. Morley. (2003) Editorial: Hot Topics in Geriatrics. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 58:1, M30-M36
CrossRef50
Patrick S. Romano, Benjamin K. Chan, Michael E. Schembri, Julie A. Rainwater. (2002) Can Administrative Data Be Used to Compare Postoperative Complication Rates Across Hospitals?. Medical Care 40:10, 856-867
CrossRef51
Jane M. Geraci. (2002) The Demise of Comparative Provider Complication Rates Derived from ICD-9-CM Code Diagnoses. Medical Care 40:10, 847-850
CrossRef52
Richard H. White, Mark C. Henderson. (2002) Risk factors for venous thromboembolism after total hip and knee replacement surgery. Current Opinion in Pulmonary Medicine 8:5, 365-371
CrossRef53
Graham F. Pineo, Russell D. Hull. (2002) Pulmonary vascular disease. Current Opinion in Pulmonary Medicine 8:5, 357-359
CrossRef54
Margaret Wood, Carlos B. Mantilla, Terese T. Horlocker, Darrell R. Schroeder, Daniel J. Berry, David L. Brown. (2002) Frequency of Myocardial Infarction, Pulmonary Embolism, Deep Venous Thrombosis, and Death following Primary Hip or Knee Arthroplasty. Anesthesiology 96:5, 1140-1146
CrossRef55
(2001) Thrombophilia. New England Journal of Medicine 345:9, 697-699
Full Text56
Russell D Hull, Graham F Pineo. (2001) Dalteparin sodium. Expert Opinion on Pharmacotherapy 2:8, 1325-1337
CrossRef57
John W Eikelboom, Daniel J Quinlan, James D Douketis. (2001) Extended-duration prophylaxis against venous thromboembolism after total hip or knee replacement: a meta-analysis of the randomised trials. The Lancet 358:9275, 9-15
CrossRef
