Low-molecular-weight heparin (LMWH) is as effective as unfractionated heparin for treatment of venous thromboembolism (VTE) in adults. Recently it has been shown that once-daily (q24h) or twice-daily (q12h) administration of enoxaparin for treatment of VTE in adults yields similar safety (bleeding rate) and efficacy (rethrombosis rate) results. Whether enoxaparin can be administered q24h or q12h in children remains unclear.

In this open-label pilot safety study, 80 children (non-neonates) at 2 study centers received enoxaparin adjusted to a target 2- to 4-hour anti-Xa level of 0.4 IU/mL to 0.8 IU/mL. After acute thrombotic onset, during which enoxaparin was administered q12h for a median of 7 days (range 1 to 14 days), patients were stratified into 2 treatment groups: 1 mg/kg enoxaparin q12h (n = 30) and 1.5 mg/kg q24h (n = 50). Enoxaparin was administered regardless of age at onset of deep vein thrombosis (DVT), thrombus burden, underlying basic diseases, or presence of prothrombotic risk factors. There was no difference in treatment parameters. Median dose administered q24h or q12h in children with DVT was 1.2 mg/kg (range 0.5 to 3.0 mg/kg); median treatment duration was 5 months (range 1 to 13 months). Clinical end points included rethrombosis, bleeding, and therapy-related death. Median follow-up time was 24 months.
 
There were no significant differences between the 2 patient groups with respect to anti-Xa activity, efficacy, or safety. Rethrombosis occurred in 2 patients in each of the study groups (P = 0.62). Minor bleeding occurred in 1 patient on 1.5 mg/kg q24h and in 2 patients on 1 mg/kg q12h (P = 0.65). No major bleeding or therapy-related death was observed during the follow-up period. These data suggest that, within the reported target anti-Xa activity, long-term enoxaparin administration for treatment of childhood VTE has a good efficacy and safety profile. A large-scale randomized controlled trial will be performed to further assess the safety and efficacy of childhood VTE treatment with both 1.5 mg/kg enoxaparin q24h and 1 mg/kg enoxaparin q12h.

Reference
Nowak-Gottl U, During C, Bidlingmaier C, Merkel N, Schobess R. Long-term safety and efficacy data on childhood venous thrombosis treated with enoxaparin: an open label survey of once-daily versus twice-daily administration. Blood. 2005;106(11). Abstract 549.

Activated factor X (FXa) is a pivotal coagulation factor, positioned at the crossroads of the extrinsic and intrinsic coagulation cascade. Hence, anticoagulants that inhibit FXa might be effective in the prevention and treatment of thrombosis and VTE. The aim of this study was to evaluate dosing of YM150, a once-daily, orally active FXa inhibitor.

A randomized, enoxaparin-controlled, dose-escalation study was performed to assess the safety and efficacy of 7 to 10 days of treatment with oral doses of YM150 (3, 10, 30, or 60 mg qd, starting 6 to 10 hours after surgery) or SC enoxaparin (40 mg qd, starting 12 hours before surgery). The study included 178 patients undergoing elective primary hip-replacement surgery. Safety end points included major and/or clinically relevant non-major bleeding, and efficacy end points included VTE detected by bilateral venography on the last treatment day and/or symptomatic VTE. The study was open-label with blinded evaluation of outcomes.

There were no major bleeds. Three clinically relevant non-major bleeds were reported; 1 (2.9%; 95% confidence interval [CI]: 0% to 16%) in a patient receiving 3 mg YM150 and 2 (5.7%; 95% CI: 1% to 19%) in patients receiving 10 mg YM150. No trend was observed in the incidence of minor bleeding as a function of YM150 dosing in the range of 10 to 60 mg daily. The proportion of patients with minor bleeding events in the enoxaparin group was similar to that in patients receiving 60 mg YM150 (22% versus 24%, respectively). Evaluable venograms were available for 147 patients (84%). The incidences of VTE were 52% (95% CI: 31% to 72%), 39% (22% to 57%), 23% (9% to 40%), and 19% (7% to 37%) for the 3, 10, 30, and 60 mg YM150 dose groups, respectively, compared with 39% (22% to 57%) for enoxaparin. Logistic regression analysis demonstrated a statistically significant dose-related trend (P = 0.006) for patients with VTE during YM150 treatment. No trend in any of the safety parameters was observed with study treatment (YM150 or enoxaparin) or dose of YM150. 

The authors of this study conclude that oral, once-daily dosing of YM150 (10 to 60 mg), administered 6 to 10 hours after primary hip-replacement surgery, is safe, well tolerated, and effective.
 
Reference
Eriksson BI, Turpie AGG, Lassen MR, et al. YM150, an oral direct factor Xa inhibitor, as prophylaxis for venous thromboembolism in patients with elective primary hip replacement surgery: a dose escalation study. Blood. 2005;106(11). Abstract 1865. 

Studies suggest that thrombosis may play an important etiologic role in adults who develop idiopathic osteonecrosis. Thrombotic occlusion in the bone results in increased intraosseus venous pressure, reduced arterial flow, and ultimately hypoxic bone death. The majority of untreated patients with idiopathic osteonecrosis progress to significant degenerative disease, for which total joint arthroplasty is standard therapy. This study reports the results from 5 consecutive patients treated with anticoagulant therapy instead of surgical intervention.
 
Five adult patients (median age 38 years; range 28 to 49 years) were evaluated for knee or hip pain, with the diagnosis of osteonecrosis confirmed by magnetic resonance imaging (MRI). Osteonecrosis was identified as idiopathic after eliminating other known associated factors. Response to treatment was measured by pain relief, stability or improvement on bone imaging, and subsequent need for surgical intervention. Four patients were treated with warfarin (target international normalized ratio [INR], 2 to 3), and 1 patient was treated with enoxaparin (1 mg/kg bid). Patients were followed up every 3 months, and MRI evaluation was performed at 3-month intervals for 1 year or if symptoms worsened. 

Three out of 4 patients receiving warfarin and the patient receiving enoxaparin reported pain reduction within 3 months of initiating therapy. MRI revealed disease stability in these patients within 3 months, and radiographic signs of improvement were observed at 9 months. All 5 patients reported a reduction of pain at a median of 7.5 months (range, 6 to 9 months). Complete resolution of imaging abnormalities was observed after 5 years in 1 patient. Overall, therapy was well tolerated without any major toxicity, and all patients elected to continue anticoagulation therapy. One patient who preferred to discontinue therapy after 4.5 years continued to be asymptomatic 10 months later. 

The fifth patient, who had bilateral distal femoral and proximal tibial osteonecrosis, eventually underwent right knee arthroplasty for severe degenerative joint disease involving the right knee secondary to an automobile accident. Warfarin therapy was resumed postoperatively, with stability of imaging abnormalities on the left side after 3.5 years of continuous therapy. Warfarin was replaced by aspirin, and the patient continued to be asymptomatic with stable imaging abnormalities of the left leg after 18 months of follow-up. 

These findings suggest that anticoagulation therapy may benefit patients with early stage idiopathic osteonecrosis, and may delay or eliminate the need for surgical intervention.

Reference
Shehadat SA, Bociek GR, Haire W. Anticoagulant therapy for the treatment of idiopathic osteonecrosis. Blood. 2005;106(11). Abstract 919.

Atrial fibrillation (AF) patients treated with coumadin receive LMWH as “bridging” therapy until their INRs achieve therapeutic levels, but the benefit for this remains unclear. This study compared a cohort of patients over 65 years of age discharged with a diagnosis of AF (index date) who had been bridged (n = 201) with a cohort of patients over 65 years of age who were not bridged on discharge but who achieved a therapeutic INR within 30 days of coumadin initiation (nonbridged and early INR [NB-E], n = 1376). Log-rank Mantel Haenszel 2-group comparisons were used to test for differences in time to event rate for admission for cardiovascular accident (CVA) or hemorrhage, and number of laboratory INRs in therapeutic range (NLTR).
 
The incidence of CVA admissions in the bridged group at 15, 30, 60, 90, 180, and 365 days was 0%, 0%, 0%, 0%, 0.5%, and 1.2%, compared with 0.1%, 0.3%, 0.8%, 1.3%, 1.8%, and 2.8% for the NB-E group (P = 0.19). No significant difference was noted in the time to admission for hemorrhage. When NLTRs were expressed as dichotomous variables (INR < 1.9 = bad, 2-3.5 = good, 3.6-20 = bad) and assessed for 1 year from index date, there was no significant difference (55.3% of bridged NLTRs were in the good range compared with 52.3% for NB-E). When either of these groups was compared with patients with AF who did not achieve therapeutic INRs until after 30 days (but less than 1 year [NB-L], n = 2061), there was a statistically significant difference in the incidence of admissions for CVA (0.2%, 0.7%, 1.1%, 1.2%, 2.5%, and 4.8% at days 15, 30, 60, 90, 180, and 365, respectively; P = 0.025 versus bridged; P = 0.048 versus NB-E) and NLTR (45.2%), but not in the incidence of admission for hemorrhage at 90 days.

Because risk factors prompting the decision to bridge patients were not examined, the nonsignificantly decreased incidence of CVA admissions in bridged patients may be important insofar as patients who were bridged may have been at higher risk for stroke than those who were not bridged (early or late). These data indicate no significant additional hemorrhagic risk for patients with AF who are bridged with LMWH, and suggest a potential benefit to early effective anticoagulation.

Reference
Billett HH, Madsen EM, Giannattasio E. Event rate for patients with atrial fibrillation with and without low molecular weight heparin bridging. Blood. 2005;106(11). Abstract 916.

Decreased bone mineral density (BMD) is a serious complication of long-term heparin use. To date, there have not been adequate clinical trials addressing its risk in association with long-term use of LMWH. A substudy of the Thrombophilia in Pregnancy Prophylaxis Study (TIPPS) was planned to assess the effect of LMWH on BMD. TIPPS is an ongoing randomized controlled trial comparing the effect of LMWH prophylaxis on pregnancy outcomes in thrombophilic pregnant women.

Sixty-two pregnant women (< 20 weeks gestation) with confirmed thrombophilia who were at moderate risk of venous thrombosis or had a history of pregnancy complications were randomized to either LMWH (dalteparin 5000 U qd until 20 weeks and then 5000 U q12h to term) or control. Thirty-four patients received dalteparin and 28 did not; all patients received dalteparin postpartum (5000 U qd from postpartum day 1 to 42). BMD (hip and lumbar spine) was measured at 6 weeks postpartum. Primary outcome was absolute spine BMD compared using an unpaired t-test. 

Treatment duration was 214.5 ± 41.9 days for patients in the dalteparin group versus 47.0 ± 38.6 days for control (P < 0.001). One case of osteoporosis and 7 cases of osteopenia were documented in the dalteparin group compared with 0 cases and 3 cases, respectively, in the control group. Results of post hoc logistic regression analysis examining the odds of obtaining an abnormal (osteoporosis, osteopenia) spine or hip BMD result in both treatment groups were not significant (crude odds ratio [OR]: 2.59; 95% CI: 0.61 to 10.97; P = 0.20; adjusted OR: 6.83; 95% CI: 0.17 to 272.33; P = 0.307), as were results of post hoc multiple linear regression to predict changes in BMD and T-scores.

The investigators conclude from these data that use of long-term prophylactic dalteparin in pregnancy is not associated with a significant decrease in BMD.

Reference
Rodger MA, Lazo-Langner A, Kahn S, et al. Prophylactic low molecular weight heparin (LMWH) during pregnancy is not associated with a decrease in bone mineral density (BMD): the TIPPS (Thrombophilia in Pregnancy Prophylaxis Study) BMD substudy. Blood. 2005;106(11). Abstract 548.  

Uncertainty remains as to the effectiveness of anticoagulants in either preventing VTE or prolonging survival in cancer patients. The recently completed WARP trial showed no apparent benefit for low-dose warfarin. To help put the results of WARP into context, meta-analyses of other randomized controlled clinical trials were performed to evaluate the effect of warfarin and LMWH on VTE rates and cancer mortality.

Computerized searches for trials were performed using various databases, including MedLine, Embase, National Cancer Institute trials register, and meeting abstracts (American Society of Hematology, American Society of Clinical Oncology). Standard methods of meta-analysis were used and results presented as OR and 95% CI, with heterogeneity of treatment effect between trials examined using tests for interaction. In 5 trials (N = 1353 patients) comparing warfarin with no warfarin, there was no clear evidence of a decrease in VTE (OR: 0.75; 95% CI: 0.50 to 1.13; P = 0.2). When mortality data were assessed for warfarin versus no warfarin in 7 randomized trials (N = 2033), no decrease in mortality was observed in patients receiving warfarin (OR: 0.92; 95% CI: 0.82 to 1.03).

In 4 trials (N = 1667) comparing LMWH with no LMWH, the rate of VTE was significantly reduced in patients receiving LMWH (OR: 0.64; 95% CI: 0.44 to 0.94; P = 0.02). Four trials (N = 772) contained survival data showing a significant reduction in mortality with LMWH compared with no LMWH (OR: 0.77; 95% CI: 0.66 to 0.90; P = 0.001).

In 5 trials (N = 985) of LMWH versus oral anticoagulation (mainly with warfarin), VTE rates were significantly lower with LMWH compared with warfarin (OR: 0.50; 95% CI: 0.35 to 0.72; P = 0.0001), although no mortality benefit was observed (OR: 0.89; 95% CI: 0.74 to 1.10, P = 0.3).

The results from these meta-analyses suggest that LMWH is the preferred form of prophylaxis for VTE in cancer patients. Moreover, there may be an antitumor effect, leading to an overall survival benefit.

Reference
Wheatley K, Gross LE, Hills RK, Young AM. Meta-analyses of randomised controlled trials (RCT) of warfarin and low molecular weight heparin (LMWH) for the prevention of venous thromboembolism (VTE) and death in cancer patients. Blood. 2005;106(11). Abstract 909.

There is a substantial clinical need for alternatives to vitamin K antagonists for treatment of DVT. Use of long-term, weight-adjusted LMWH avoids anticoagulant monitoring and may be associated with less bleeding. In accordance with CONSORT (Consolidated Standards of Reporting Trials), this study presents a harm analysis of hemorrhagic complications from the LITE trial.

In this multicenter study, patients (N = 737) with acute symptomatic proximal-vein thrombosis were randomized to receive subcutaneous tinzaparin qd (n = 369) or usual-care (n = 368) intravenous unfractionated heparin/vitamin K antagonists for 3 months. Benefit was assessed as the frequency of symptomatic, objectively documented recurrent VTE, and harm was assessed by objectively documented hemorrhagic complications.

Among patients receiving tinzaparin, 4.9% suffered recurrent VTE at 3 months compared with 5.7% receiving usual-care (absolute difference: –0.9%; 95% CI: –4.1 to 2.4). Hemorrhagic complications occurred less frequently in the LMWH group (13.0%) versus usual-care (19.8%) (absolute difference: –6.8%; P = 0.011; risk ratio = 0.66). The prevalence of major bleeding favored therapy with LMWH. Major bleeding persisted throughout study treatment for patients in the usual-care group receiving warfarin but ceased early (by day 23) in the LMWH group (P = 0.034). Mortality in the LMWH group was 6.8% compared with 6.5% in patients receiving usual-care (absolute difference: 0.3%; 95% CI: –3.4 to 3.9).

These data demonstrate that self-management with subcutaneous tinzaparin was at least as effective as usual-care therapy and offers a safety advantage with less harm as a result of bleeding. The authors underscore the clinical importance and relevance of these results in offering clinicians an alternative to vitamin K antagonist therapy in a wide range of patients with proximal venous thrombosis that does not require anticoagulant monitoring.

Reference
Hull RD, Pineo GF, Brant RF, for the LITE Trial Investigators. Self-managed long-term low-molecular-weight heparin therapy compared with usual-care anticoagulation for the treatment of patients with proximal venous thrombosis: harm associated with thrombocytopenia. Blood. 2005;106(11). Abstract 4142.  

While consensus guidelines regarding VTE prophylaxis for hospital inpatients have been available for more than 15 years, the number of inpatients who are potentially eligible for prophylaxis in the United States is unknown. These data are required to estimate potential costs and benefits of prophylaxis in reducing the incidence of VTE.

To estimate the actual number of eligible patients, the authors of this study applied current guidelines from the American College of Chest Physicians (ACCP) Conference on VTE prophylaxis to US acute-care hospital inpatients (2002) with hospital discharge International Classification of Diseases (ICD-9) codes for major surgery or medical illness identified from the Healthcare Utilization and Cost Database (HCUP). Of a total of 37.8 million inpatients discharged from US acute-care hospitals in 2002, 13.4 million (35%) met ACCP guidelines for VTE prophylaxis. Of these, 7.6 million met ACCP criteria for VTE prophylaxis based on medical illness risk factors, while 7.7 million were defined by HCUP criteria as having had a major operative procedure. When ACCP surgical risk criteria were applied to this population, 1.9 million (25%) were at low VTE risk, while 5.8 million were at moderate (26%), high (39%), or highest (10%) VTE risk.

Almost 60% of all VTE events that occur in the community are related to recent acute-care hospitalization; hence, providing universal, safe, and effective VTE prophylaxis to this population affords an important opportunity to significantly reduce the incidence of VTE. Data from this study provide support for developing and monitoring compliance with hospital guidelines for VTE prevention.

Reference
Anderson FA Jr, Zayaruzny M, Heit JA, Cohen AT, on behalf of the VTE Impact Assessment Group. Estimated annual number of US acute-care hospital inpatients meeting ACCP criteria for venous thromboembolism (VTE) prophylaxis. Blood. 2005;106(11). Abstract 903.

LMWH is a safe and effective treatment for DVT and pulmonary embolism (PE). Furthermore, outpatient treatment of DVT at home has been demonstrated as a feasible alternative. The present study (phase 2) is a follow-up to a previously published study (phase 1) suggesting that outpatient management of PE is feasible and safe for the majority of patients.

In phase 1, 44% of patients fulfilled criteria for outpatient management. Absence of bleeding or thromboembolic complications in the LMWH treatment phase suggested that these patients could have been safely discharged early. In the present phase 2 of the study, all patients with a confirmed PE were entered into an early discharge scheme (within 72 hours of presentation) if they fulfilled criteria validated in phase 1. Patients were treated with 175 IU/kg tinzaparin qd for a minimum of 6 days and oral anticoagulant therapy. Exclusion criteria included any of the following: age < 18 years, admission for additional monitoring or treatment, active bleeding or bleeding disorder, poor compliance or morbidity, pregnancy, previous PE, coexisting major DVT, and patient preference. Outcomes data, including mortality, thromboembolic events, and bleeding events, were collected at 3 months. Patients were asked to complete a 10-point visual analogue satisfaction scale at the end of the LMWH treatment phase and to indicate their preference for inpatient or outpatient management for any future episodes of PE.

A total of 107 patients with confirmed PE were discharged early, while receiving LMWH. All patients completed the acute treatment phase; 3-month outcomes data were available in 106 out of 107 patients. There were no bleeding, thromboembolic complications, deaths, or related readmissions in the early treatment phase. Patients received a mean of 7.6 days of tinzaparin, continued for a mean of 5.5 days after discharge, indicating that outpatient management of PE saved up to 5.5 inpatient bed days. Among the 87 out of 107 patients who completed the satisfaction scale, the mean score was 9.3, showing that patients were highly satisfied with outpatient treatment; 94% of patients expressed a preference for outpatient management.

These data indicate that selected patients with confirmed PE can be safely managed as outpatients in schemes similar to outpatient management of DVT and that this is highly acceptable to patients.

Reference
Rhodes S, Bond S, Green S, et al. Outpatient management of pulmonary embolism: results from the National Multicentre PE Study. Blood. 2005;106(11). Abstract 911.

The presence of residual vein thrombosis (RVT) at the third month following an episode of DVT of the lower limbs has been demonstrated to be an independent risk factor for recurrent VTE. Detection of RVT, therefore, may represent a simple and reproducible method for establishing individual risk of recurrence and for tailoring the optimal duration of treatment with oral anticoagulants. At present, it is unknown whether RVT may also identify patients at increased risk for cancer and/or cardiovascular disease (CD).

To answer this question, the investigators conducted a prospective study to evaluate the correlation between RVT and the risk of new overt cancer and/or CD in patients with DVT of the lower limbs. Consecutive patients, with an episode of idiopathic or provoked DVT, were treated with oral anticoagulants and evaluated after 3 months from the index DVT for presence or absence of RVT; 1 group of patients with RVT at 3 months was also randomized to receive anticoagulation for 12 months following the index DVT. The incidence of VTE recurrence, overt cancer, and new CD was evaluated over a period of 3 years from the index DVT.

A total of 345 patients were included in the analysis. Regardless of whether the index DVT was idiopathic or provoked, the incidence of recurrent VTE and new overt cancer was statistically lower in patients without RVT than in those with RVT; no significant differences were found in the incidence of new CD. In patients with RVT, the advantage of prolonging anticoagulation for 12 months was lost at the end of the treatment period.

These data demonstrate that presence of RVT at 3 months from the index DVT is an independent risk factor for recurrent VTE and indicates patients at risk for new overt cancer. This risk remains over a period of 3 years, independent of whether the index DVT was idiopathic or provoked. The authors conclude that the benefit of indefinite anticoagulation in these patients should be assessed in a properly designed study.

Reference  
Siragusa S, Malato A, Anastasio R, et al. The persistence of residual vein thrombosis, after an episode of deep vein thrombosis, and the risk of new overt cancer and cardiovascular disease. Blood. 2005;106(11). Abstract 262.

Bilateral, centrally adjudicated venography is currently required for diagnosis of DVT in confirmatory trials of new antithrombotic agents. Noninvasive and less cumbersome methods would be welcomed by both patients and investigators. Centrally adjudicated complete compression ultrasound (CCUS) of all leg veins is a potential alternative to venography. However, CCUS needs to be externally validated against the current gold standard to gain general acceptance and regulatory approval.

A substudy of 2 recent phase IIb trials of a novel, oral anticoagulant (BAY 59-7939) for the prevention of VTE in patients undergoing elective hip or knee surgery was undertaken to validate CCUS against venography. Both studies had similar designs to allow pooling of data. Mandatory bilateral venography was performed 7 ± 2 days after surgery; CCUS was performed later the same day, with the sonographers blinded to the venography result. Venograms and CCUS videos were adjudicated centrally by 2 independent readers; discrepancies were resolved by consensus reading.

From the 1347 patients participating in the 2 trials, 870 matching pairs of evaluable venograms and CCUS videos were obtained. Observed prevalences of any DVT, including muscle vein thrombosis, were 19.1% with venography and 13.0% with CCUS. Sensitivity for detecting any DVT using CCUS was 27.4% (proximal: 13.0%; distal: 25.9%) and specificity for detecting any DVT was 95.8% (proximal: 99.2%; distal: 96.2%). Although false positives did not severely impair specificity, the small number of true positives detected by CCUS resulted in low sensitivity, particularly for proximal DVT.

Based on these external validation figures, the study authors conclude that centrally adjudicated CCUS is not a viable technique to replace venography for the screening of DVT following major orthopedic surgery in confirmatory trials of new antithrombotic agents.

Reference  
Schellong SM, Beyer J, Halbritter K, et al. VENUS – a study to validate centrally adjudicated venous ultrasound against venography after major orthopaedic surgery. Blood. 2005;106(11). Abstract 281.

Evidence suggests that upper-extremity DVT has become more common over the past few decades, although the prevalence has not been established. The purpose of this study was to compare the occurrence rate, risk-factor profile, management strategies, and hospital outcomes in patients with upper-extremity versus lower-extremity DVT in a cohort of all Worcester, Massachusetts, residents diagnosed with VTE in 1999, 2001, and 2003.

Medical records of residents from the Worcester statistical metropolitan area (2000 census: 478,000) diagnosed with ICD-9 codes consistent with possible DVT and/or PE at all 11 Worcester hospitals during the years 1999, 2001, and 2003 were reviewed by trained data abstractors. Validation of each case of VTE was based on prespecified criteria.

A total of 483 cases were validated as acute DVT events. For the purposes of this analysis, 4 patients with both upper- and lower-extremity DVT were excluded. Upper-extremity DVT was diagnosed in 69 (15%) patients versus 414 (85.8%) cases of lower-extremity DVT. Compared with patients with lower-extremity DVT, patients with upper-extremity DVT were younger, more likely to be Hispanic, more likely to have renal disease, and more likely to have had a recent central venous catheter, infection, surgery, intensive care unit stay, or chemotherapy. They were less likely to have had a prior DVT or to have developed their current DVT as an outpatient. Although less likely to be treated with heparin, LMWH, or warfarin, patients with upper-extremity DVT were more likely to suffer major bleeding complications. Recurrence rates of VTE during hospitalization were very low in both groups.

Based on results from the analysis to date, the authors conclude that patients with upper-extremity DVT comprise a small but clinically important portion of all patients with DVT in the community setting. Their risk profiles differ from patients with lower-extremity DVT, suggesting the need for tailored strategies for DVT prophylaxis and treatment.

Reference  
Spencer FA, Goldberg RJ, Lessard D, Emery C, Bains A, Anderson FA. Upper extremity deep vein thrombosis – incidence, risk factors, and management: the Worcester Venous Thromboembolism Study. Blood. 2005;106(11). Abstract 584.