Low-Molecular-Weight Heparinoid Orgaran Is More Effective Than Aspirin in the Prevention of Venous Thromboembolism After Surgery for Hip Fracture

Gent, Michael; Hirsh, Jack; Ginsberg, JS; Powers, P.; Levine, Mark; Geerts, William; Jay, RichardM; Leclerc, Jacques; Neemeh, Jean; Turpie, Alexander G. G.

doi:10.1161/01.cir.93.1.80

Cited by 97 publications

(56 citation statements)

References 17 publications

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“…47 Our findings, consistent with these in vivo thrombosis models, provide a mechanistic basis for the effectiveness of ␤3-blocking strategies in preventing platelet-rich arterial thrombi 48 versus anticoagulants to prevent fibrin-rich venous thrombi. 49,50 Our findings show a crucial role for TF activity in fibrin network formation, structure, and stability. Compared with unstimulated HUVECs, TNF␣-stimulated HUVECs expressed significantly higher TF activity, but similar lipid and thrombomodulin expression.…”

Section: Discussionmentioning

confidence: 64%

Contributions of extravascular and intravascular cells to fibrin network formation, structure, and stability

Campbell

Overmyer

Selzman

et al. 2009

Blood

132

159

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Fibrin is essential for hemostasis; however, abnormal fibrin formation is hypothesized to increase thrombotic risk. We previously showed that in situ thrombin generation on a cell's surface modulates the 3-dimensional structure and stability of the fibrin network. Currently, we compared the abilities of extravascular and intravascular cells to support fibrin formation, structure, and stability. Extravascular cells (fibroblasts, smooth muscle) supported formation of dense fibrin networks that resisted fibrinolysis, whereas unstimulated intravascular (endothelial) cells produced coarse networks that were susceptible to fibrinolysis. All 3 cell types produced a fibrin structural gradient, with a denser network near, versus distal to, the cell surface. Although fibrin structure depended on cellular procoagulant activity, it did not reflect interactions between integrins and fibrin. These findings contrasted with those on platelets, which influenced fibrin structure via interactions between ␤3 integrins and fibrin. Inflammatory cytokines that induced prothrombotic activity on endothelial cells caused the production of abnormally dense fibrin networks that resisted fibrinolysis. Blocking tissue factor activity significantly reduced the density and stability of fibrin networks produced by cytokine-stimulated endothelial cells. Together, these findings indicate fibrin structure and stability reflect the procoagulant phenotype of the endogenous cells, and suggest abnormal fibrin structure is a novel link between inflammation and thrombosis. (Blood. 2009;114:4886-4896)

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Section: Discussionmentioning

confidence: 64%

Contributions of extravascular and intravascular cells to fibrin network formation, structure, and stability

Campbell

Overmyer

Selzman

et al. 2009

Blood

132

159

View full text Add to dashboard Cite

show abstract

“…[23][24][25][26][27][28][29][30] The trials included a combined total of 1408 subjects, and took place in 4 different countries, including the United States, 24,26,[28][29][30] Spain, 23 Sweden, 27 and Canada. 25 Enrolled patients had a mean age of 76 years (range, 74-77 years) among hip fracture surgery studies and 66 years (range, 59-69 years) among elective knee/hip arthroplasty studies. Pneumatic compression devices were used in addition to pharmacologic prevention in 2 studies.…”

Section: Results Of Searchmentioning

confidence: 99%

Aspirin versus anticoagulation for prevention of venous thromboembolism major lower extremity orthopedic surgery: A systematic review and meta-analysis

et al. 2014

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BACKGROUND Hip fracture surgery and lower extremity arthroplasty are associated with increased risk of both venous thromboembolism and bleeding. The best pharmacologic strategy for reducing these opposing risks is uncertain. PURPOSE To compare venous thromboembolism (VTE) and bleeding rates in adult patients receiving aspirin versus anticoagulants after major lower extremity orthopedic surgery. DATA SOURCES Medline, Cumulative Index to Nursing and Allied Health Literature, and the Cochrane Library through June 2013; reference lists, ClinicalTrials.gov, and scientific meeting abstracts. STUDY SELECTION Randomized trials comparing aspirin to anticoagulants for prevention of VTE following major lower extremity orthopedic surgery. DATA EXTRACTION Two reviewers independently extracted data on rates of VTE, bleeding, and mortality. DATA SYNTHESIS Of 298 studies screened, 8 trials including 1408 participants met inclusion criteria; all trials screened participants for deep venous thrombosis (DVT). Overall rates of DVT did not differ statistically between aspirin and anticoagulants (relative risk [RR]: 1.15 [95% confidence interval {CI}: 0.68–1.96]). Subgrouped by type of surgery, there was a nonsignificant trend favoring anticoagulation following hip fracture repair but not knee or hip arthroplasty (hip fracture RR: 1.60 [95% CI: 0.80–3.20], 2 trials; arthroplasty RR: 1.00 [95% CI: 0.49–2.05], 5 trials). The risk of bleeding was lower with aspirin than anticoagulants following hip fracture repair (RR: 0.32 [95% CI: 0.13–0.77], 2 trials), with a nonsignificant trend favoring aspirin after arthroplasty (RR: 0.63 [95% CI: 0.33–1.21], 5 trials). Rates of pulmonary embolism were too low to provide reliable estimates. CONCLUSION Compared with anticoagulation, aspirin may be associated with higher risk of DVT following hip fracture repair, although bleeding rates were substantially lower. Aspirin was similarly effective after lower extremity arthroplasty and may be associated with lower bleeding risk. Journal of Hospital Medicine 2014;9:579–585. © 2014 Society of Hospital Medicine

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“…In the second study, 251 patients undergoing surgery for hip fracture were randomly allocated to either 100 mg ASA twice daily or 750 U of danaparoid sodium twice daily for 14 d (Gent et al, 1996). Patients, care-givers and event adjudicators were all blinded to treatment assignment.…”

Section: Evidence From Randomized Trialsmentioning

confidence: 99%

Does acetyl salicylic acid (ASA) have a role in the prevention of venous thromboembolism?

et al. 2009

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SummaryGuidelines differ on whether acetyl salicylic acid (ASA, aspirin) should be used for prophylaxis in patients at high-risk of venous thromboembolism (VTE), principally because of differences in perceptions of its efficacy. ASA is an attractive therapeutic option because it is inexpensive, easy to administer and does not require monitoring. We critically reappraised the evidence from randomized controlled trials for the efficacy of ASA in VTE prevention. ASA is clearly efficacious in preventing VTE compared to placebo or no treatment, but appears to be less efficacious than the low molecular weight heparins in small trials. There is little data for ASA in comparison with unfractionated heparin and warfarin. A large randomized controlled trial is required to clarify the role of ASA compared to contemporary anticoagulant strategies for the prevention of VTE.

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Low-Molecular-Weight Heparinoid Orgaran Is More Effective Than Aspirin in the Prevention of Venous Thromboembolism After Surgery for Hip Fracture

Abstract: This study demonstrates that Orgaran is significantly more efficacious than aspirin in preventing postoperative venous thromboembolism in patients undergoing surgery for fractured hips, with no evidence of any increase in hemorrhagic complications.

Cited by 97 publications

References 17 publications

Contributions of extravascular and intravascular cells to fibrin network formation, structure, and stability

Contributions of extravascular and intravascular cells to fibrin network formation, structure, and stability

Aspirin versus anticoagulation for prevention of venous thromboembolism major lower extremity orthopedic surgery: A systematic review and meta-analysis

Does acetyl salicylic acid (ASA) have a role in the prevention of venous thromboembolism?

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