Development Of Symptomatic Venous Thromboembolism Research Articles

466 Development of Machine Learning Algorithms to Predict Symptomatic VTE at Time of Admission and Time of Discharge after Severe Traumatic Injury

OBJECTIVES/GOALS: Clinical indicators predictive of venous thromboembolism (VTE) in trauma patients at multiple time points are not well outlined, particularly at time of discharge. We aimed to describe and predict inpatient and post-discharge risk factors of VTE after trauma using a multi-variate regression model and best of class machine learning (ML) models. METHODS/STUDY POPULATION: In a prospective, case-cohort study, all trauma patients (pts) who arrived as level 1 or 2 trauma activations, from June 2018 to February 2020 were considered for study inclusion. A subset of pts who developed incident, first time, VTE and those who did not develop VTE within 90 days of discharge were identified. VTE were confirmed either by imaging or at autopsy during inpatient stay or post-discharge. Outcomes were defined as the development of symptomatic VTE (DVT and/or PE) within 90 days of discharge.A multi-variate Cox regression model and a best in class of a set of 5 different ML models (support-vector machine, random-forest, naives Bayes, logistic regression, neural network]) were used to predict VTE using models applied a) at 24 hours of injury date or b) on day of patient discharge. RESULTS/ANTICIPATED RESULTS: Among 393 trauma pts (ISS=12.0, hospital LOS=4.0 days, age=48 years, 71% male, 96% with blunt mechanism, mortality 2.8%), 36 developed inpatient VTE and 36 developed VTE after discharge. In a weighted, multivariate Cox model, any type of surgery by day 1, increased age per 10 years, and BMI per 5 points were predictors of overall symptomatic VTE (C-stat 0.738). Prophylactic IVC filter placement (4.40), increased patient age per 10 years, and BMI per 5 points were predictors of post-discharge symptomatic VTE (C-stat= 0.698). A neural network ML model predicted VTE by day 1 with accuracy and AUC of 0.82 and 0.76, with performance exceeding those of a Cox model. A naīve Bayesian ML model predicted VTE at discharge, with accuracy and AUC of 0.81 and 0.77 at time of discharge, with performance exceeding those of a Cox model. DISCUSSION/SIGNIFICANCE: The rate of inpatient and post-discharge VTEs remain high. Limitations: single institution study, limited number of patients, internal validation only, with the use of limited number of ML models. We developed and internally validated a ML based tool.Future work will focus on external validation and expansion of ML techniques.

Aspirin Is an Effective Prophylaxis for Venous Thromboembolism in Ambulatory Patients with Femoral Neck Fracture Undergoing Hip Arthroplasty.

Although aspirin has been adopted as an effective and safe prophylaxis against venous thromboembolism (VTE) by the arthroplasty community, the role of aspirin in the prevention of VTE in the setting of arthroplasty for trauma remains insufficiently known. Therefore, the present multicenter study investigated the efficacy of aspirin as VTE prophylaxis for patients with femoral neck fracture undergoing total hip arthroplasty or hemiarthroplasty. We reviewed the medical records of 1,141 patients with femoral neck fracture who underwent total hip arthroplasty or hemiarthroplasty from 2008 to 2018 at 3 different institutions. Data on patient demographic characteristics, body mass index, history of VTE, and comorbidities were obtained from an electronic chart query and were confirmed by reviewing the medical records manually. Patients were allocated to cohorts based on the type of prophylaxis administered: aspirin (n = 454) and other anticoagulants (n = 687). Patients were then propensity score-matched on the basis of the risk score calculated using a previously validated tool and the remaining confounding variables. The primary outcome was the development of symptomatic VTE, namely deep vein thrombosis (DVT) or pulmonary embolism (PE) confirmed by appropriate imaging, within 90 days after the surgical procedure. A bivariable analysis was performed. The overall VTE rate was 1.98% for patients who received aspirin compared with 6.7% for patients who received other anticoagulants (p < 0.001). After propensity score matching and regression modeling, aspirin was found to be noninferior to more potent anticoagulation in preventing VTE after both total hip arthroplasty and hemiarthroplasty. Aspirin is an effective option for VTE prophylaxis in patients with femoral neck fracture who undergo hip arthroplasty. Based on the patient management benefits of aspirin for elective arthroplasty and the present study, we suggest its use in standard-risk ambulatory patients. Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.

Association of Perioperative Red Blood Cell Transfusion With Symptomatic Venous Thromboembolism Following Total Hip and Knee Arthroplasty

BackgroundPrior registry data suggest that perioperative red blood cell (RBC) transfusion may increase the incidence of venous thromboembolism (VTE) in patients status post surgery. However, there are limited data that explore VTE risk after perioperative transfusion in the setting of primary total joint arthroplasty (TJA). Our aim is to investigate the association between perioperative RBC transfusion and the development of symptomatic VTE after adjusting for confounding variables. MethodsWe retrospectively reviewed all patients undergoing primary TJA at a single institution from 2001 to 2016. The primary outcome was development of symptomatic VTE (deep vein thrombosis or pulmonary embolism) up to 90 days following primary TJA. To identify the association between RBC transfusion and development of VTE, univariate and multivariate analyses were used, as well as a sensitivity analysis using propensity score matching based on patient comorbidities. ResultsOf the 29,003 patients who underwent TJA, 2500 (8.62%) received RBC transfusion perioperatively and 302 (1.04%) developed a postoperative VTE within 90 days of surgery. While univariate analysis did suggest a slightly increased incidence of VTE in association with RBC transfusion (odds ratio [OR], 1.53; 95% confidence interval [CI], 1.09-2.16), this difference was eliminated when multivariate analysis (OR, 0.42; 95% CI, 0.12-1.39) and propensity score matching (propensity-matched OR, 1.2; 95% CI, 0.7-1.8) were employed. ConclusionPerioperative RBC transfusion does not significantly increase the incidence of symptomatic VTE following primary TJA in the 90-day postoperative period after adjustment for host VTE risk scores and other confounding variables. Perioperative RBC transfusion may be safely administered if indicated following total hip and knee arthroplasty.

Venous thromboembolism in emergency general surgery patients: a single-centre retrospective cohort study

There is limited literature on the risk of venous thromboembolism (VTE) in emergency general surgery (EGS) patients. We undertook this study to identify the rate of symptomatic VTE for patients undergoing EGS operations. We conducted a retrospective cohort study evaluating EGS patients who underwent operative intervention between March and December 2014. Data collected included patient demographics, type of procedure, risk of VTE, VTE prophylaxis, development of symptomatic VTE, and mortality. We included 767 patients in our analysis. The mean age was 53 ± 19.7 years, and 52.2% of patients were female. Eighteen patients (2.3%) experienced VTE in hospital and 12 (1.6%) experienced VTE after discharge. Only 66% of patients received appropriate VTE prophylaxis. High-risk patients had a higher VTE rate (7.4% v. 2.3%, p < 0.001) and higher mortality (17.6% v. 4.0%, p < 0.001) than lowto moderate-risk patients. The risk of VTE in patients requiring EGS is significant and persists after hospital discharge. Further studies on quality improvement with VTE prophylaxis are warranted.

TPA Use for Central Line De-Occlusion and Its Relationship to Symptomatic Venous Thromboembolism in Pediatric Leukemia Patients

Introduction: Venous thromboembolism (VTE) is a known complication of pediatric leukemia with reported incidence ranging widely from 1.5-40%. It is associated with significant morbidity including loss of venous access, post thrombotic syndrome, and thrombosis recurrence or embolization. Increased risk of VTE in these patients is often multifactorial. There are currently no standard guidelines for VTE prophylaxis in pediatric leukemia patients, and it is unclear which patients are at highest risk. Identifying potential markers for patients at risk for VTE could be helpful for guiding prophylaxis practices and ultimately decreasing rates of VTE in these children. Thrombolytic agents are commonly used to treat catheter obstruction by breaking down fibrin that forms within the catheter. Therefore, we hypothesize that patients requiring more tissue plasminogen activator (TPA) for treatment of catheter obstruction may be at higher risk of developing fulminant thromboses. Therefore, the primary objectiveof this study is to determine the association between central line clearance with TPA and development of symptomatic VTE (sVTE) in pediatric leukemia patients. Methods: This is a multi-center,retrospective cohort study of patients under 21 years old with a central line (CVC), including peripherally inserted central catheters (PICC), who began treatment at Weill Cornell Medicine (WCM) or Memorial Sloan Kettering Cancer Center (MSKCC) from January 2012-December 2015 for newly diagnosed or relapsed leukemia. Patients were excluded if they had a prior VTE, or an incidental VTE was identified. Transplant and CAR-T -cell patients were excluded, as were those who transferred into the institution over 30 days from start of treatment. Data collected included demographics, disease-specific information (including type of leukemia, treatment regimen, and CVC details), dates of TPA administration, and details of sVTE. Data analysis was performed with Fisher's exact test andWilcoxon rank-sum test. Results: A total of 96 patients with leukemia were included. The median age was 6.5 years (Q1, Q3: 3.15-15.05 years), and 55% (n=53) were male. 78% (n=75) were new diagnoses. Acute lymphoblastic leukemia (ALL; 72%, n=69) was most common, followed by acute myelogenous leukemia (AML; 25%, n=24), and mixed lineage leukemias (3%, n=3). There were no significant differences between gender, age, type of leukemia, or TPA use between the two centers. The overall incidence of sVTE over the 4-year period in this cohort was 6% (6/96). At the time of thrombosis, five of the six patients had a PICC line in place and one patient had a mediport (Table 1). Four sVTE patients were diagnosed with ALL. Four of the thromboses were line-associated, one was a sinus venous thrombosis, and one was an inferior vena cava thrombus. Five of the six sVTEs were diagnosed at WCM. There was no association found between use of TPA for line de-occlusion and development of sVTE (OR 0.55, CI 0.07-6.57, p=0.61) or between number of TPA doses needed and development of sVTE (p=0.830). The patients who developed sVTE were significantly older than those who did not develop sVTE (Figure 1, p=0.048). There was no significant difference between gender and development of sVTE. A significant difference (p &lt;0.05) was seen when analyzing the association between PICC line and development of sVTE, however the sample size was too small to draw formal conclusions. Conclusions: In our cohort, neither TPA use for line occlusion nor the number of TPA doses was predictive of sVTE development. This may be due to the small sample size and low number of sVTE events. Single center analysis of data from WCM, however, previously indicated a significant association between TPA use and development of thrombosis in their patients. Given the increased use of PICC lines at WCM, this raises the question of whether TPA use may be predictive in patients who have PICC lines. Our data are consistent with previous pediatric studies, which found older age to be a risk factor for thrombosis. Analysis of a larger cohort of patients is necessary to further investigate our hypothesis. Given the importance of preventing sVTE in pediatric leukemia patients, further prospective studies are needed to investigate potential predictors of thrombosis in this population. Disclosures Cooley: off-label: Other: drug use.

High Risk of Venous Thromboembolism After Surgery for Long Bone Metastases: A Retrospective Study of 682 Patients.

Previous studies have shown that venous thromboembolism (VTE) is a complication associated with neoplastic disease and major orthopaedic surgery. However, many potential risk factors remain undefined. (1) What proportion of patients develop symptomatic VTE after surgery for long bone metastases? (2) What factors are associated with the development of symptomatic VTE among patients receiving surgery for long bone metastases? (3) Is there an association between the development of symptomatic VTE and 1-year survival among patients undergoing surgery for long bone metastases? (4) Does chemoprophylaxis increase the risk of wound complications among patients undergoing surgery for long bone metastases? A retrospective study identified 682 patients undergoing surgical treatment of long bone metastases between 2002 and 2013 at the Massachusetts General Hospital and Brigham and Women's Hospital. We included patients 18 years of age or older who had a surgical procedure for impending or pathologic metastatic long bone fracture. We considered the humerus, radius, ulna, femur, tibia, and fibula as long bones; metastatic disease was defined as metastases from solid organs, multiple myeloma, or lymphoma. In general, we used 40 mg enoxaparin daily for lower extremity surgery and 325 mg aspirin daily for lower or upper extremity surgery. The primary outcome was a VTE defined as any symptomatic pulmonary embolism (PE) or symptomatic deep vein thrombosis (DVT; proximal and distal) within 90 days of surgery as determined by chart review. The tertiary outcome was defined as any documented wound complication that might be attributable to chemoprophylaxis within 90 days of surgery. At followup after 90 days and 1 year, respectively, 4% (25 of 682) and 8% (53 of 682) were lost to followup. Statistical analysis was performed using multivariable logistic and Cox regression and Kaplan-Meier. Overall, 6% (44 of 682) of patients had symptomatic VTE; 22 patients sustained a DVT, and 22 developed a PE. After controlling for relevant confounding variables, higher preoperative hemoglobin level was independently associated (odds ratio [OR], 0.75; 95% confidence interval [CI], 0.60-0.93; p = 0.011) with decreased symptomatic VTE risk, the presence of symptomatic VTE was associated with a worse 1-year survival rate (VTE: 27% [95% CI, 14%-40%] and non-VTE: 39% [95% CI, 35%-43%]; p = 0.041), and no association was found between wound complications and the use of chemoprophylaxis (OR, 3.29; 95% CI, 0.43-25.17; p = 0.252). The risk of symptomatic 90-day VTE is high in patients undergoing surgery for long bone metastases. Further study would be needed to determine the VTE prevention strategy that best balances risks and benefits to address this complication. Level III, therapeutic study.

Preoperative Incidence of Deep Venous Thrombosis in Patients With Bladder Cancer Undergoing Radical Cystectomy

To determine the preoperative incidence of subclinical lower-extremity deep vein thrombosis (DVT), as well as to evaluate the utility of preoperative DVT screening in patients with bladder cancer before undergoing radical cystectomy. Beginning in 2014, we prospectively instituted a policy of obtaining a screening lower-extremity duplex ultrasound on all patients within 7 days before undergoing radical cystectomy. We reviewed the electronic medical records of all patients at our institution who underwent radical cystectomy for bladder cancer from January 2012 through December 2015. The screened group (n = 65) underwent preoperative screening; the historical control group (n = 78) did not. Primary outcome was a lower-extremity duplex ultrasound positive screening. Secondary outcome measures included the development of symptomatic venous thromboembolism (VTE) postoperatively, and the rate and severity of complications. DVT was identified in 13.9% of patients before undergoing cystectomy. Univariate analysis demonstrated an increased risk of subclinical DVT in patients who were exposed to neoadjuvant chemotherapy (35.3% vs 5.1%, P = .008). Postoperatively, there was a nonsignificant trend of lower DVT rate in the screened group compared to historical control. Overall complication rate and severity were similar between the groups. Subclinical DVT is present in a significant number of pre-cystectomy patients, especially those exposed to neoadjuvant chemotherapy. Ultrasound screening in patients before undergoing radical cystectomy may identify opportunities for early intervention to reduce morbidity and mortality associated with perioperative DVT or venous thromboembolism in the cystectomy population.

ABO Blood Group Is a Predictor for the Development of Venous Thromboembolism After Total Joint Arthroplasty

BackgroundThe study's purpose was to determine if there is an association between ABO blood group and the development of symptomatic venous thromboembolism (VTE) after total joint arthroplasty (TJA). MethodsA total of 28,025 patients who underwent primary TJA at a single health care system from 2000 to 2014 were retrospectively reviewed from electronic records. Patients who experienced a symptomatic VTE were identified. A multivariate regression model adjusted for known potential risk factors, including age, gender, body mass index, surgery type, previous VTE, smokers, rheumatologic diseases, malignancy, hypercoagulable state, and VTE prophylaxis, was developed to test the association of ABO blood group and postoperative VTE. Separate multivariate regressions were performed for total knee arthroplasty and total hip arthroplasty, specifically looking at pulmonary embolism. ResultsThe risk of symptomatic VTE after TJA was increased in AB blood group patients (odds ratio = 1.4; P = .03). Furthermore, the risk of pulmonary embolism was increased after total knee arthroplasty in AB blood group patients (odds ratio = 2.24; P = .001) but not after total hip arthroplasty (P = .742). ConclusionAB blood group increased the risk of VTE after TJA. Patient's ABO blood group should be considered in terms of risk stratification and selection of appropriate postoperative VTE prophylaxis.

Mechanical and suboptimal pharmacologic prophylaxis and delayed mobilization but not morbid obesity are associated with venous thromboembolism after total knee arthroplasty: A case‐control study

The FDA-approved dose of low-molecular-weight heparin (LMWH) may not provide adequate thromboprophylaxis in morbidly obese patients after total knee arthroplasty (TKA). Suboptimal dosing, delayed initiation, and overreliance on mechanical methods may also limit the effectiveness of thromboprophylaxis. We explored the associations between the type of thromboprophylaxis, obesity, time of mobilization, and undergoing bilateral TKA on development of symptomatic venous thromboembolism (VTE) after TKA. This was a case-control study of patients undergoing TKA in 15 teaching hospitals between October 2008 and March 2010. Cases were screened using the Agency for Healthcare Research and Quality's Patient Safety Indicator 12 and had objectively documented acute VTE within 9 days of surgery; controls were randomly selected from the same hospital. Multivariable logistic regression was used to analyze risk factors for postoperative VTE, adjusted for age and gender. Among 130 cases with and 463 controls without acute VTE, body mass index (BMI) ranged from 17 to 61 (median = 34). Thromboprophylaxis was LMWH in 284 (48%), warfarin in 189 (32%), both in 55 (10%), and mechanical prophylaxis alone in 120 (20%). Overall, 77% ambulated on day 1 or 2 after surgery. Factors significantly associated with VTE were bilateral simultaneous TKA (odds ratio [OR] = 4.2; 95% confidence interval [CI]: 1.9-9.1), receipt of FDA-approved pharmacological prophylaxis (OR = 0.5; 95% CI: 0.3-0.8), and ambulation by postoperative day 2 (OR = 0.3; 95% CI: 0.1-0.9). Obesity was neither a significant confounder nor a modifier of these effects. Severe obesity was not a significant independent predictor for VTE and did not modify the beneficial effect of FDA-approved pharmacological thromboprophylaxis. Bilateral TKA and failure to ambulate by the second day after surgery were significant risk factors.

Incidence of Symptomatic Venous Thromboembolism in Oncologic Patients Undergoing Lower-Extremity Endoprosthetic Arthroplasty

As both cancer and major orthopaedic surgery are risk factors for venous thromboembolism, patients undergoing lower-extremity oncologic endoprosthetic arthroplasty for neoplastic processes are at substantial risk of the development of symptomatic venous thromboembolism. Therefore, the primary purpose of this study was to determine the incidence of symptomatic venous thromboembolism in patients undergoing lower-extremity oncologic endoprosthetic arthroplasty. Secondary purposes were to assess whether chemoprophylaxis influenced the incidence of venous thromboembolism, surgical complications, or the incidence of local sarcoma recurrence. We also sought to determine whether any known risk factors for venous thromboembolism could be identified in this patient population. We performed a retrospective comparative review of 423 patients who had undergone mega-endoprosthetic reconstruction following cancer resection. Univariate analysis was used to assess the association between chemoprophylaxis and the incidence of venous thromboembolism, to postulate the surgical complications associated with chemoprophylaxis, and to assess the rate of recurrence of local sarcoma as well the association between risk factors and venous thromboembolism. Seventeen patients (4.0%) (95% confidence interval: 2.5% to 6.3%) had a venous thromboembolic event, ten with deep venous thrombosis and seven with nonfatal pulmonary embolism. Risk factors and chemoprophylactic regimens were not statistically associated with the occurrence of venous thromboembolism. The incidence of symptomatic venous thromboembolism in our group of cancer patients who underwent lower-extremity endoprosthetic arthroplasty was lower than anticipated. A significant difference was not identified between the use of any or no chemoprophylactic agent and the incidence of venous thromboembolism or complication rates. No risk factors were associated with the incidence of symptomatic venous thromboembolism.

Patients Admitted with Acute Abdominal Conditions are at High Risk for Venous Thromboembolism but Often Fail to Receive Adequate Prophylaxis

IntroductionThe aim was to determine the frequency with which thromboprophylaxis is prescribed, factors predicting its prescription, and the frequency of symptomatic venous thromboembolism in patients admitted with acute abdominal conditions. MethodsCharts of patients admitted with acute abdominal conditions that did not have surgery for at least 24 h following admission were audited to identify if thromboprophylaxis was prescribed, if it was prescribed appropriately, factors affecting its prescription, and the rate of symptomatic venous thromboembolism. ResultsOf 350 patients (176 females, mean age 64.9 ± 18.6), 194 (55.4%) were admitted for bowel obstruction, 113 (32.3%) for biliary conditions, 14 (4.0%) for diverticulitis, 8 (2.3%) for pancreatitis, and 21 (6.0%) for other conditions. One hundred forty-two (40.6%) underwent surgery. Two hundred fifty-two (72.0%, 95% CI 67.3–76.7%) received thromboprophylaxis although only 199 (56.9%, 95% CI 51.7–62.1%) received adequate thromboprophylaxis. Hospital site and having surgery were associated with prescription of thromboprophylaxis. Twelve patients (3.4%, 95% CI 1.5–4.3%) developed symptomatic venous thromboembolism (nine deep venous thrombosis, three pulmonary embolism). ConclusionsDespite patients admitted with acute abdominal conditions being at high risk for development of symptomatic venous thromboembolism, many do not receive adequate thromboprophylaxis. Further work is required to decrease this gap in care.

427 Patients Admitted With Acute Abdominal Conditions are at High Risk for Development of Symptomatic Venous Thromboembolism (VTE) but Often Fail to Receive Adequate Prophylaxis

427 Patients Admitted With Acute Abdominal Conditions are at High Risk for Development of Symptomatic Venous Thromboembolism (VTE) but Often Fail to Receive Adequate Prophylaxis

The Value of Four-Detector Row Spiral Computed Tomography for the Diagnosis of Pulmonary Embolism

Although spiral computed tomography (CT) is being used increasingly as the first-line imaging procedure in the diagnostic workup of patients with clinically suspected pulmonary embolism (PE), the diagnostic value of negative findings, at least when using the four-detector row scanners, is still controversial. A total of 702 consecutive patients with clinical symptoms suggestive of PE underwent four-slice CT. Patients with negative findings received the determination of D-dimer. Those with positive D-dimer underwent further diagnostic workup to confirm or rule out the diagnosis of PE. Those with negative D-dimer were followed-up to 6 months to detect the development of symptomatic venous thromboembolism (VTE). The CT test was interpreted as negative in 536 patients (76.3%). These patients had the D-dimer determination, which was positive in 279 and negative in the remaining 257 patients. Of the former, PE subsequently was documented in 55 patients (19.7%). Of the latter, symptomatic VTE in the follow-up period developed in three patients (1.17%; 95% confidence interval, 0.24 to 3.38%). In conclusion, when using the four-detector row, the negative predictive value of CT findings in patients with clinically suspected PE and positive D-dimer is low. In contrast, it is safe to withhold anticoagulation from patients with negative findings and negative D-dimer.

Catheter-Associated Thrombosis: Thromboprophylaxis or Not?

Long-term indwelling central venous catheters are commonlyusedincancerpatientsfortheadministrationof chemotherapy, parenteral nutrition, and blood products and for the facilitation of the drawing of blood. Despite their important role in the delivery of quality patient care, central venous catheters can be associated with morbidity. One of the most common complications is catheter-related venous thrombosis. The extent of thrombosis associated with a central vein catheter can involve the catheter tip (ball-valve clot), the length of the catheter (fibrin sheath), orthecatheterizedvesselintheupperlimb,withorwithout the central vasculature of the neck or mediastinum. 1 In the 1990s, with the increasing use of central venous catheters in cancer patients, there was a clinical impression that catheter thrombosis was a common occurrence, associated with considerable morbidity. The results of two randomized trials provided evidence to support the use of prophylactic antithrombotic agents to prevent catheterassociated thrombosis. In a trial conducted by Monreal et al, 2 patients with a long-term subclavian venous catheter were randomly assigned either to 2,500 U of dalteparin low molecular weight heparin subcutaneously once daily for 90 days or to no prophylaxis. Upper limb venography was performed at 90 days or sooner if symptoms appeared. The trial was stopped early, after upper extremity thrombosis developed in one (6%) of 16 patients treated with low molecularweightheparincomparedwitheight(62%)of13 control patients (P.002). Six of the 29 thrombotic events were symptomatic. There was no increased risk of bleeding associated with the low molecular weight heparin. Bern et al 3 randomly assigned cancer patients with indwelling central venous catheters to either 1 mg of warfarin for 90 days or no treatment. This dosage regimen was based on the demonstrated efficacy of postoperative prophylaxis with 1 mg of warfarin in patients undergoing gynecologic surgery. 4 Venography was performed at 90 days. Onehundredtwenty-onepatientswererandomlyassigned, but only 80 patients completed the trial. Fifteen (37.5%) of 40 control patients developed thrombosis compared with four (9.5%) of 42 patients on warfarin (P .001). Seventeenofthethromboticepisodesweresymptomatic.Inmost cases, the prothrombin time was not prolonged, and there was no increase in bleeding associated with warfarin. After the publication of these studies, although there was lack of consensus on whether patients with central vein catheters should routinely receive thromboprophylaxis, low-dose warfarin was used in some clinical practices. In some patients, the prothrombin time was prolonged excessively because of interactions with chemotherapy drugs. 5 This issue contains two well-conducted randomized controlledtrialsbyVersoetal 6 andCoubanetal 7 evaluating thromboprophylaxis in cancer patients with central venous catheters. Both of these trials were double blind and, hence, provide higher quality evidence than the earlier published randomized trials that were not double blind. The two trials in this issue used different approaches in the choice of outcome for their studies. Verso et al 6 used mandatory venography of the upper limb at 42 days, whether the patient had symptoms or not. The use of this screening technique for venous thrombosis was adopted from prophylactic studies in patients undergoing orthopedic surgery, 8 with venography of the lower limbs at 7 to 10 days after surgery as the standard outcome measure used in clinical trials evaluating antithrombotics in this setting. Asymptomatic thrombosis in the deep veins of the lower limbs is considered a reasonable surrogate for the development of symptomatic venous thromboembolism because 20% of thrombi in the calf veins extend to the proximal deep veins and 50% of patients with proximal deep vein thrombosis have associated pulmonary embolism. Unfortunately, the natural history of catheter-associated thrombosis is not nearly as well defined as postoperative

Predictors of Rehospitalization for Symptomatic Venous Thromboembolism After Total Hip Arthroplasty: A Case-Contol Study

PURPOSE: Recent studies have shown that symptomatic venous thromboembolism (VTE) frequently develops after hospital discharge following total hip arthroplasty (THA). Risk factors associated with the development of symptomatic VTE, and the efficacy of extended medical prophylaxis to prevent late VTE, are not well defined. METHODS: Using California Medicare discharge data from 1995 through 1997, we identified 298 individuals ≥65 years who were re-hospitalized for symptomatic VTE <91 days after elective unilateral THA. We compared these cases with 599 unmatched controls. Hospital records of the surgical admission were carefully abstracted to obtain information about demographic, surgical and medical variables potentially associated with the development of VTE. Outcomes were confirmed by review of the hospitalization for VTE. RESULTS: Alone or in combination, 70% of control patients were treated with pneumatic compression, 43% with warfarin, 28% with enoxaparin and 6% with unfractionated heparin. Warfarin was given to 29% after discharge. In bivariate analysis, a body mass index (BMI) of ≥25 was strongly associated with rehospitalization for VTE [OR = 2.5, CI 1.8–3.5]. In a risk-adjusted model, independent predictors of VTE included: age over 85 years (vs 65–74) [OR = 2.3, CI 1.2–4.5], female sex [OR = 1.4, CI 1.0–1.9], ambulating before the second post-operative day [OR = 0.7, CI 0.5–0.9], and prior VTE [OR = 3.7, CI 1.8–8.0]. Using patients with a BMI <25 who received no form of prophylaxis (except TED stockings) as the referent group, the only patients who had significantly lower odds of VTE were patients with a BMI <25 who received the following forms of prophylaxis: pneumatic compression alone [OR = 0.4, CI 0.1–1.0], pneumatic compression with enoxaparin [OR = 0.35, CI 0.1–0.9] and pneumatic compression with warfarin [OR = 0.19, CI 0.1–0.5]. Similarly, warfarin use after hospital discharge was associated with absence of VTE, but this was significant only among patients with a BMI <25 [OR = 0.5, CI 0.2–0.8]; for BMI> 25 [OR = 0.7, CI 0.5–1.1]. CONCLUSION: Higher BMI was strongly associated with rehospitalization for symptomatic VTE after total hip arthroplasty. Pneumatic compression and oral anticoagulation after hospital discharge were both associated with significantly lower odds of developing VTE, but only among patients with a BMI <25. Further studies are clearly needed to confirm our findings. In order to further reduce the incidence of symptomatic VTE after THA, efforts should focus on improving the effectiveness of in-hospital as well as extended medical prophylaxis among overweight and obese patients.