Deep Venous Thrombosis (DVT) in Trauma: a Literature Review

Low Molecular Weight Heparin - Reviews and Meta-Analyses

First Author	Year	Reference Title	Class	Conclusions
Hirsh J	1994	Low molecular weight heparin: Laboratory properties and clinical evaluation: A review. Eur J Surg Suppl 571:9-22	III	Review of biologic properties of LMWH compared to unfractionated heparin (UH). LMWHs have superior bioavailability, however, UH produces more bleeding compared to LMWHs. LMWHs are superior to placebo in general and orthopedic surgery, and medical patients for prevention of thrombosis. LMWHs tend to be superior to UH for prevention of DVT in general and orthopedic surgery, spinal cord injury, and stroke patients.
Samama MM	1994	Mechanisms for the antithrombotic activity in man of low molecular weight heparins. Haemostasis 24:105-117	III	Review of the differences of antithrombotic action between UH and LMWH. LMWHs work primarily by a combination of anti-Xa and anti-IIa activities. LMWHs have important antithrombotic action in vivo.
Fareed J	1988	Comparative study on the in vitro and in vivo activities of seven low-molecular-weight heparins. Haemostasis 18 (Suppl 3):3-15	III	Summary of in vivo and in vitro differences among 7 LMWHs. Antithrombotic actions varied between 7 agents. There were significant differences between bleeding profiles in both intravenous and subcutaneous routes. Individual composition of each LMWH determines its in vivo behavior which may account for the different safety/efficacy ratios observed in clinical trials.
Nurmohamed MT	1992	Low-molecular-weight heparin vs. standard heparin in general and orthopaedic surgery: A meta-analysis. Lancet 340:152-6	III	Meta-analysis (1984-1991) of LMWHs compared with standard heparin (SH) for postop prophylaxis in general surgery (17 studies, 6878 patients) and orthopedic surgery (6 studies, 1294 patients). LMWH reduced DVT & PE in general and orthopedic surgery patients. There was increased risk of bleeding in general surgery patients. Analysis did not show the expected major improvement in thrombosis prevention comparing LMWH to SH.
Leizorovicz A	1992	Low molecular weight heparin in prevention of perioperative thrombosis. BMJ 305:913-20	III	Analysis of 52 randomized trials; 29 general surgery (14,567 patients), 23 orthopedic surgery (3976 patients) in which LMWH was compared with placebo (9 studies), UH (39 studies) and dextran (4 studies). LMWHs were more efficacious for prophylactic treatment of DVT than placebo (p<0.001), dextran (p<0.001), and UH (p=0.02), with no significant difference in incidence of major hemorrhage. LMWH seemed to have higher benefit:risk ratio than UH.
Clagett GP	1995	Prevention of venous thromboembolism. Chest 108:321S-334S	III	Review of VTE prophylaxis with Consensus Panelís recommendations and tabular summary of DVT prophylaxis in orthopedic and general surgery patients. LMWH pooling-analysis included 16 studies, 2571 patients with DVT incidence of 15 and risk reduction of 71% vs 61% with low-dose oral anti-coagulants. There was no advantage of LMWH with hip surgery. 5 studies showed lower total DVT rate in LMWH patients compared to warfarin with similar bleeding risks in total knee replacement patients. LMWH or SCD should be the prophylaxis of choice in total knee replacement, whereas either LMWH or warfarin appear adequate and similar after total hip replacement.

Low Molecular Weight Heparin - Reviews and Meta-Analyses

First Author	Year	Reference Title	Class	Conclusions
Imperiale TF	1994	A meta-analysis of methods to prevent venous thromboembolism following total hip replacement. JAMA 271:1780-5	III	Analysis of human studies (1966-1993) using warfarin, dextran, heparin, LMWH, compression stockings but not aspirin for prophylaxis in total hip replacement. All were effective in reducing DVT (p<0.05) and the risk of proximal venous DVT (p<0.05). Only LMWH and stockings reduced PE risk. LMWH and compression stockings had the greatest relative efficacy in preventing VTE following total hip replacement. LMWH may be more effective though at a small risk of clinically important bleeding.
Colwell CW Jr	1995	Efficacy and safety of enoxaparin to prevent deep vein thrombosis after hip arthroplasty. Clin Orthop 319:215-22	III	Summary of 4 clinical studies from the US and Canada comparing efficacy and safety of enoxaparin (30 mg bid or 40 mg qd) with low dose UH and placebo. 30 mg bid was favored because it would theoretically provide higher and more sustained blood levels which might be critical to prevent thrombus propagation during the early postoperative period. Enoxaparin offers the advantages of postop administration thereby reducing risk of excessive intraop and early postop bleeding, and the convenience of a fixed-dose regimen without need for any dosage adjustment based on coagulation test results or patient body weight.
Orthopedics: Hip Surgery
Menzin J	1994	Prevention of deep-vein thrombosis following total hip replacement surgery with enoxaparin versus unfractionated heparin: A pharmacoeconomic evaluation. Ann Pharmacother 28:271-5	I	Pharmacoeconomic evaluation of enoxaparin 30 mg q12 hr, enoxaparin 40 mg qd, and UH 5000 units q8 for prophylaxis in total hip replacement patients. There were less DVTs in the 30 mg bid group compared to UH (4.7% vs 11.6%). The 40 mg qd group had a DVT rate of 14.9% with less bleeding (1.5%) vs the UH group (6.2%) or 30 mg bid group. There was a decreased length of stay in both enoxaparin groups compared to UH group (9.5 vs 9.9 vs 11.3 days) and a trend toward fewer hospital readmissions in both enoxaparin groups. Compared with UH, enoxaparin use following total hip replacement may decrease the risk of DVT and length of hospital stay.
Spiro TE	1994	Efficacy and safety of enoxaparin to prevent deep venous thrombosis after hip replacement surgery. Ann Intern Med 121:81-9	I	Comparison of enoxaparin 10 mg once daily (n=161), 40 mg enoxaparin once daily (n=199), and 30 mg q12 hr (n=208) in double-blind, random-ized multicenter trial of total hip replacements. 10 mg enoxaparin once daily was discontinued due to increased DVT incidence. DVT rates were 25% - 10 mg group, 14% - 40 mg once daily group, and 11% - 30 mg bid. There was more major bleeding in both 40 mg q day (4%) and the 30 mg bid groups (5%). Risk:benefit ratio supports use of enoxaparin as a therapeutic agent to prevent DVT in a dose of 40 mg once daily or 30 mg q12 hr in total hip replacement patients.

Low Molecular Weight Heparin - Orthopedics: Hip Surgery

First Author	Year	Reference Title	Class	Conclusions
Bergqvist D	1996	Low-molecular-weight heparin (enoxaparin) as prophylaxis against venous thromboembolism after total hip replacement. N Engl J Med 335:696-700	I	Study showed that enoxaparin continued for 1 month postop was more effective in preventing DVT compared to enoxaparin in hospital only. Patients received 40 mg enoxaparin/day in hospital after hip replacement, and at discharge, 1 group continued with 40 mg enoxaparin/day for 1 month and another received placebo. DVT rate - 39% in placebo group, 18% in enoxaparin group (p<0.001). Proximal DVT - 24% in placebo vs 7% in enoxaparin groups (p<0.001).
Levine MN	1991	Prevention of deep vein thrombosis after elective hip surgery: A randomized trial comparing low molecular weight heparin with standard unfractionated heparin. Ann Intern Med 114:545-51	I	Double-blind randomized controlled trial comparing 30 mg enoxaparin bid (n=333) to standard heparin (SH) 7500 units bid (n=332). DVT rates were 17% - LMWH group and 19% - SH group. There was less major and minor bleeding in LMWH group vs SH group (p=0.035). Enoxaparin was significantly less hemorrhagic than SH. The difference in DVT rate, though not statistically significant, favored LMWH in these patients.
Planes A	1986	Enoxaparine low molecular weight heparin: Its use in the prevention of deep venous thrombosis following total hip replacement. Haemostasis 16:152-8	I	Dose-ranging study for enoxaparin 60 mg q day (n=50), 30 mg bid (n=28), 40 mg q day (n=50), and 20 mg bid (n=100). DVT rate was 6%-8% in all groups. Transfusion requirement was increased between doses 40-60 mg (p=0.06). Increasing dosage of 40-60 mg significantly increased bleeding tendency without increasing protection.
Planes A	1987	Prevention of deep vein thrombosis after total hip replacement by enoxaparine: Once daily injection of 40 mg versus two daily injections of 20 mg. [Abstract] Thrombosis and Haemostasis 58:117	I	Multicenter trial of 2 dosing enoxaparin regimens: Group A - enoxaparin 20 mg 12 hr preop, then 20 mg evening postop and 20 mg q12 hr. Group B - 40 mg 12 hr preop and 40 mg q day. DVT rate: 1/57-Group A, 6/57- Group B, p=0.11. There was no difference in transfusion requirement or hematoma formation in either group. They concluded that a regimen of 40 mg enoxaparin daily with 1st dose preop is a reasonable regimen compared to unfractionated heparin.
Planes A	1988	Prevention of postoperative venous thrombosis: A randomized trial comparing unfractionated heparin with low molecular weight heparin in patients undergoing total hip replacement. Thrombosis and Hemostasis 60:407-10	I	Multicenter trial comparing enoxaparin 40 mg daily (1st dose 12 hr preop) to UH 5000 units (q 8 hr, 1st dose 2 hr preop) for 14 days or until hospital discharge. DVT was detected in 12.5% of enoxaparin group and 25% in UH group, p=0.03. Postop transfusion requirements were significantly higher in UH group. There were no deaths. 5 patients had PE symptoms, 2 in enoxaparin group and 3 in UH group. When 40 mg of enoxaparin is used, a delay of 12 hr is necessary preop for when this was shortened, a dramatic increase in operative bleeding was seen.

Low Molecular Weight Heparin - Orthopedics: Hip Surgery

First Author	Year	Reference Title	Class	Conclusions
Turpie AGG	1986	A randomized controlled trial of a low-molecular-weight heparin (enoxaparin) to prevent deep-vein thrombosis in patients undergoing elective hip surgery. N Engl J Med 315:925-9	I	50 patients received enoxaparin (30 mg bid) SQ begun 12-24 hours after surgery, and 50 received placebo. DVT rate: 42% in placebo and 12% in enoxaparin group, p=0.0007. 4% bleeding incidence in each group.
Barsotti J	1990	Comparative double-blind study of two dosage regimens of low-molecular weight heparin in elderly patients with a fracture of the neck of the femur. J Orthop Trauma 4:371-5	I	Randomized double-blind study comparing efficacy and safety of enoxaparin. Group A - 20 mg bid and Group B - 40 mg q day in 103 elderly patients with femur neck fracture. Distal and proximal thrombosis were 18.3% in Group A and 10.4% in Group B. No major hemorrhagic complications in either group. Enoxaparin (40 mg daily) is effective for DVT prevention in elderly patients.
Jørgensen PS	1992	The thromboprophylactic effect of a low-molecular-weight heparin (Fragmin) in hip fracture surgery: A placebo-controlled study. Clin Orthop 278:95-100	I	Prospective randomized double-blind trial comparing dalteparin [5000 units SQ 2 hr preop, 12 hr postop, then daily for 6 days (n=30)] to placebo (n=38). DVT rate: 30% dalteparin group, 58% in placebo. Transfusion requirement was higher in LMWH group. Recommend altered dose regimens on admission combined with other prophylaxis.
Tørholm C	1991	Thromboprophylaxis by low-molecular-weight heparin in elective hip surgery: A placebo controlled study. J Bone Joint Surg 73-B:434-8	I	Double-blind randomized trial comparing dalteparin [2500 units 2 hr preop, 2500 units postop, and 5000 units for the next 6 days (n=58)] to placebo (n=54). DVT rates were lower in dalteparin group (16%) vs placebo group (35%), p<0.02. There was no difference in perioperative bleeding or transfusion between groups.
Eriksson BI	1988	Thrombosis prophylaxis with low molecular weight heparin in total hip replacement. Br J Surg 75:1053-7	I	Randomized prospective trial comparing dalteparin (2500 anti-factor Xa units) for 7 days (1st dose 2 hrs preop) vs dextran 70 (500 mL 2X day of surgery, single infusion 500 mL on 1st and 3rd postop day). DVT rate: 22/49 patients dextran, and 10/49 patients LMWH group, (p<0.01). 2 non-fatal PEs in each group. Periop/postop blood loss and transfusion requirements were lower in dalteparin group.
Monreal M	1989	A prospective double-blind trial of a low molecular weight heparin once daily compared with conventional low-dose heparin three times daily to prevent pulmonary embolism and venous thrombosis in patients with hip fractures. J Trauma 29:873-5	II	Randomized prospective double-blind trial comparing dalteparin [2500 U 2 hr preop, 5000 U SQ every day for 9 days (n=46)] vs UH (5000 U SQ 2 hr postop, then tid for 9 days). DVT rate:14/46 LMWH vs 6/44 UH, p=0.041. PE rate: 6/46 LMWH vs 0/44, p=0.016. Therapeutic scheme for this LMWH was not adequate to prevent DVT in this high risk patient group. A letter in J Trauma by Eriksson pointed out the flaws of this study.

Low Molecular Weight Heparin - Orthopedics: Hip Surgery

First Author	Year	Reference Title	Class	Conclusions
Eriksson BI	1991	Prevention of deep-vein thrombosis and pulmonary embolism after total hip replacement: Comparison of low-molecular-weight heparin and unfractionated heparin. J Bone Joint Surg 73A:484-93	I	Prospective, randomized double-blind study of dalteparin [5000 units 12 hr preop, then 5000 units daily x 10 (n=63)] vs standard heparin (SH) [5000 units 2 hr preop, then 5000 units tid x 10 (n=59)]. Total DVT rate:19/63 dalteparin vs 25/59 SH group (p=0.189). Proximal DVT: 6/63 dalteparin vs 18/59 SH group (p=0.01). There was less postop bleeding and transfusion requirements in dalteparin group (p=0.01). LMWH was superior to SH in preventing femoral thrombosis and PE. PE rates: 8/63 dalteparin group vs 19/59 SH group (p=0.016).
Oertli D	1992	Prevention of deep vein thrombosis in patients with hip fractures: Low molecular weight heparin versus dextran. World J Surg 16:980-5	II	Randomized, open trial comparing Sandoparin [3600 units preop once daily, then 10 days postop (n=113)] vs dextran 70 [500 mL intraop, then 8 and 24 hr postop, ± dose at day 5 (n=103)]. DVT rate:16 Sandoparin group vs 31 dextran group (p<0.005). 2 PEs in each group, 1 fatal in each. There was no difference in hematoma formation, estimated blood loss, or transfusions between groups. LMWH was safe, well-tolerated, and provided better thromboprophylaxis than dextran 70.
Planes A	1996	Risk of deep-venous thrombosis after hospital discharge in patients having undergone total hip replacement: Double-blind randomised comparison of enoxaparin versus placebo. Lancet 348:224-8	I	179 consecutive total hip replacement patients without DVT at discharge received enoxaparin [40 mg qd (n=90)] or placebo (n=89) for 21 days. DVT rate post-discharge: 6.7% enoxaparin vs 19.1% placebo group, p=0.018. DVT was detected in 1 enoxaparin patient (1.1%) and in 10 placebo patients (11.2%, p=0.006). In total hip replacement surgery patients who did not have venogram-proven DVT at hospital discharge and did not receive antithrombotic prophylaxis post-discharge, the risk of late occurring DVT remains high at least until day 35. Continued prophylaxis with enoxaparin is effective and safe in reducing this risk.
Warwick D	1995	Perioperative low-molecular-weight heparin. Is it effective and safe? J Bone Joint Surgery 77-B:715-9	I	Patients were randomized to enoxaparin (12 hr preop, then 12 & 36 hr postop) or placebo to determine if short course of periop prophy was effective. DVT rate:15.4% enoxaparin vs 32.1% placebo, p=0.01. Proximal DVT rates were equivalent. No difference in hemorrhagic side effects or wound discharge but there was more bruising in the enoxaparin group.
Planes A	1991	Efficacy and safety of a perioperative enoxaparin regimen in total hip replacement under various anesthesias. Am J Surg 161:525-31	I	Fourth study to examine safety of enoxaparin (40 mg 12 hr postop, then once daily) in spinal anesthesia total hip replacement patients. Group 1= no preop dose; Group 2=20 mg enoxaparin 1 hr post-lumbar puncture at start of surgery; Group 3=general anesthesia + 20 mg 12 hr preop, then standard protocol postop. No difference in intraop blood loss, transfusions or wound hematomas, but higher incidence of distal DVT in Group 1 vs Group 3. No difference regarding total DVT. Recommend 20 mg 1 hr post- placement of spinal anesthesia, then 40 mg 12 hr postop & 40 mg per day. They caution about LMWH use with an epidural catheter.

Low Molecular Weight Heparin - Orthopedics: Total Knee Arthroplasty

First Author	Year	Reference Title	Class	Conclusions
Leclerc JR	1992	Prevention of deep vein thrombosis after major knee surgery - a randomized, double-blind trial comparing a low molecular weight heparin fragment (enoxaparin) to placebo. Thrombosis and Haemostasis 67:417-23	I	Compared enoxaparin 30 mg q12 hr started day after total knee arthroplasty (TKA) or tibial osteotomy (n=66) to placebo (n=65). DVT rate by venography: 65% in placebo vs 19% in enoxaprin, risk reduction=71% (p<0.0001). Proximal vein thrombosis:19% placebo vs 0% enoxaparin, risk reduction=100% (p<0.001). Bleeding complica-tions: 8% placebo vs 6% enoxaparin (p=0.71). Enoxaparin fixed-dose regimen started postop is effective & safe to reduce DVT after TKA.
Faunø P	1994	Prophylaxis for the prevention of venous thromboembolism after total knee arthroplasty. J Bone Joint Surg 76A:1814-8	I	Trial compared enoxaparin 40 mg night before surgery and daily until discharge (n=92) vs SH 5000 units night before surgery and tid until discharge (n=93). DVT rate:21/92 enoxaparin vs 23/93 SH group. No bleeding difference between groups. Enoxaparin is safe, efficient prophylaxis against VTE after TKA.
Colwell CW Jr	1995	Efficacy and safety of enoxaparin versus unfractionated heparin for prevention of venous thrombosis after elective knee arthroplasty. Clin Orthop 321:19-27	I	Multicenter trial of enoxaparin 30 mg q12 hr (n=228) vs UH 5000 units q8 hr (n=225). DVT rate: 24.6% enoxaparin vs 34.2% UH (p=0.02). 1 fatal PE in UH group, no PE in enoxaparin group. Major hemorrhage= 1.3% in each group. Enoxaparin was more effective and as safe as UH for prophylaxis of VTE complications in elective TKA.
Spiro TE	1994	Enoxaparin a low molecular weight heparin and warfarin for the prevention of venous thromboembolic disease after elective knee replacement surgery. Blood 84 (10 Suppl 1):26a [Abstract]	I	Randomized parallel group, open label clinical trial comparing safety and efficacy of enoxaparin 30 mg q12 hr (n=173) vs warfarin [INR of 2.0 to 3.0 (n=176)] to prevent DVT after TKA. DVT rate:25.4% enoxaparin vs 45% low dose warfarin group. Enoxaparin group had 33.5% bleeding vs 23.3% in warfarin group (p=0.04). Major hemorrhage was not different. 1 non-fatal PE in warfarin group, no PE in enoxaparin group. Enoxaparin administered postop (30 mg q12 hr) was more effective than warfarin for VTE prevention in TKA patients.
Leclerc JR	1996	Prevention of venous thromboembolism after knee arthroplasty.:A randomized, double-blind trial comparing enoxaparin with warfarin Ann Intern Med 124:619-26	I	Compared enoxaparin 30 mg bid (n=206) to warfarin [INR of 2 to 3 (n=211)] in TKA patients. DVT rate:37% enoxaparin vs 52% warfarin, p<0.05. Proximal DVT rates and bleeding incidence were similar. between groups. 0

Low Molecular Weight Heparin - Orthopedics: Total Knee Arthroplasty

First Author	Year	Reference Title	Class	Conclusions
Levine MN	1996	Ardeparin (low-molecular-weight heparin) vs graduated compression stockings for the prevention of venous thromboembolism. A randomized trial in patients undergoing knee surgery. Arch Intern Med 156:851-6	I	Double-blind, randomized trial of LMWH [ardeparin-50 anti-Xa IU/kg (n=122)] and graduated compression stockings vs graduated compression stockings alone (n=124) X 14 days or until discharge in major knee surgery patients. Proximal DVT rate: 2 in ardeparin vs 16 in placebo group; 1 PE in each group. Overall VTE risk: 29.9% ardeparin group and 58.7% placebo group, relative risk reduction= 49% (p<0.01). Major bleeding rate:2.5% ardeparin vs 2.4% placebo group. Ardeparin, postop 2X daily is effective and safe for prevention of VTE in major knee surgery patients. Graduated compression stockings are prophylactic in general surgery but they have little effect in knee surgery.
Heit J	1995	Efficacy and safety of ardeparin compared to warfarin for prevention of venous thromboembolism following total knee replacement: A double-blind dose ranging. [Abstract] Thrombosis and Haemostasis 73:978	I	Double-blind study compared ardeparin 50 units/kg bid (n=231) to warfarin [INR of 2 to 3 (n=222)] using operated leg venogram as endpoint. Less total DVT in ardeparin group (27%) vs warfarin (38%), p<0.05. Proximal DVT rates were the same and bleeding complication rates were similar.
Orthopedics: Hip & Knee Surgery
Hamulyak K	1995	Subcutaneous low-molecular weight heparin or oral anticoagulants for the prevention of deep-vein thrombosis in elective hip and knee replacement? Fraxiparine Oral Anticoagulant Study Group. Thrombosis and Haemostasis 74:1428-31	I	SQ LMWH (nadroparine) 60 anti-Xa IU once daily was compared to oral anticoagulant (acenocoumarol) target INR 2 to 3, both started preop and continued for 10 days in 672 consecutive patients scheduled for elective hip or knee replacement surgery. Outcomes were judged by independent committee members unaware of treatment allocation. All patients wore bilateral graduated compression stockings. DVT rate:20% oral anticoagulants vs 17% nadroparine (p=0.45), absolute difference in DVT incidence of 2.9% in favor of nadroparine. Bleeding rate:2.3% oral anticoagulant vs 1.5% nadroparine (p=0.62), absolute difference of 0.8% in favor of nadroparine. Once daily fixed dose of SQ nadroparin is at least as efficacious and safe as daily adjusted oral anticoagulation for prophylaxis against DVT.
Hull RC	1993	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 329:1370-6	I	Randomized double-blind prospective study comparing Logiparin 75 units/kg/day (n=332) vs warfarin [INR of 2 to 3 (n=340)]. Total DVT was 21% in Logiparin group vs 23% in warfarin group. Bleeding rates were 4% in each group, indicating no advantage over warfarin and LMWH in total hip replacement.

Low Molecular Weight Heparin - Orthopedics: Hip and Knee Surgery

First Author	Year	Reference Title	Class	Conclusions
RD Heparin Arthroplasty Group	1994	RD heparin compared with warfarin for prevention of venous thromboembolic disease following total hip or knee arthroplasty J Bone Joint Surg 76-A:1174-85	I	Compared RD heparin 90 units/kg/day (n=149) to warfarin [PT ratio of 1.2 to 1.5 (n=147)] in TKA patients. DVT rate: 28% RD heparin vs 41% warfarin. 7 proximal DVT in RD heparin group vs 15 in warfarin group (not statistically significant).
General Surgery
Ockelford PA	1989	A double-blind randomized placebo controlled trial of thromboprophylaxis in major elective general surgery using once daily injections of a low molecular weight heparin fragment (Fragmin). Thrombosis and Haemostasis 62:1046-9	I	Double-blind randomized study proving efficacy of dalteparin, 2500 anti-factor Xa units once daily to prevent DVT compared to placebo. DVT rate:15.9% placebo vs 4.2% dalteparin group, p=0.008. 2500 anti-factor Xa units of dalteparin only once daily is effective thromboprophylaxis in patients undergoing major elective abdominal surgery.
Caen JP	1988	A randomized double-blind study between a low molecular weight heparin Kabi 2165 and standard heparin in the prevention of deep vein thrombosis in general surgery: A French multicenter trial. Thrombosis and Haemostasis 59:216-20		Multicenter double-blind randomized trial comparing LMWH Kabi 2165 (dalteparin), 2500 anti-Xa units vs standard heparin (SH), 5000 units bid on intention to treat basis (1 dose preop or 7 days postop with 30-day follow-up) in 385 patients scheduled for major surgery. There was no difference in DVT rate (3.1% Kabi vs 3.7% SH) or bleeding complications
Bergqvist D	1990	Thromboprophylactic effect of low molecular weight heparin started in the evening before elective general abdominal surgery: a comparison with low-dose heparin Seminars in Thrombosis and Hemostasis 16 Suppl:19-24	I	Scandinavian, multicenter prospective randomized double-blind trial comparing dalteparin (1st dose night before surgery) to UH (1st dose morning of surgery) in elective general abdominal surgical patients. Treatment was continued for 5-8 days. DVT was reduced in patients with correct prophylaxis with dalteparin from 9.2% to 5.0%, (p=0.02). In patients with malignancy, reduction was from 11.2% to 6.4% (p=0.06). Minor nonsignificant bleeding was more frequent in dalteparin (6.7%) vs UH group (2.7%, p=0.01). Mortality rates were the same. Dalteparin administered the night before surgery, then every evening postop is an acceptable alternative to prevent postop DVT in elective abdominal surgery patients.
Kakkar VV	1993	Low molecular weight versus standard heparin for prevention of thromboembolism after major abdominal surgery. Lancet 341:259-65	I	Multicenter (19 hospitals in the Midlands and southeast England) double-blind randomized trial comparing dalteparin (2500 units) once daily vs SH (5000 units bid) in major elective abdominal surgery patients from. Similar efficacy of drugs, although study fell short of providing any significant information on therapeutic window between bleeding risk and efficacy because of absence of objective endpoints.

Low Molecular Weight Heparin - General Surgery

First Author	Year	Reference Title	Class	Conclusions
Bergqvist D	1995	Low molecular weight heparin started before surgery as prophylaxis against deep vein thrombosis: 2500 versus 5000 XaI units in 2070 patients Br J Surg 82:496-501	I	Compared efficacy and safety of 2500 vs 5000 anti-factor Xa IU dalteparin in patients undergoing elective general surgery for malignant and benign abdominal disease. DVT rate was lower in patients given 5000 IU, 6.8% vs 13.1%, p<0.01. Patients with malignant disease who received 5000 IU had lower DVT rates (8.5% vs 14.9%, p<0.001). Dalteparin (5000 IU) started night before surgery has good thromboprophylaxis with small bleeding risk in high risk general surgery patients. Patients with malignant disease had no increased bleeding risk. Overall frequency of fatal PE with dalteparin is extremely low even in this high risk group of patients.
Samama M	1988	Low molecular weight heparin compared with unfractionated heparin in prevention of postoperative thrombosis. Br J Surg 75:128-31	I	3 consecutive open randomized trials (892 patients) compared varying dose regimens of enoxaparin (20, 40, or 60 mg once daily) with SH 5000 units tid. Heparins were given preop, then 7 days postop. VTE rates were not different among groups. Enoxaparin (20 mg/day) is safe and effective to prevent postop VTE.
Nurmohamed MT	1995	A comparative trial of a low molecular weight heparin (enoxaparin) versus standard heparin for the prophylaxis of postoperative deep vein thrombosis in general surgery. Am J Surg 169:567-71		Patients were randomized to receive either 20 mg LMWH daily (n=718) versus 5000 units SH tid (n=709), both started preop. DVT rate: 8.1% enoxaparin vs 6.3% SQ heparin (p>0.05). Enoxaparin appeared as effective and safe as SH.
Wiig JN	1995	Prophylaxis of venographically diagnosed deep vein thrombosis in gastrointestinal surgery. Multicenter trials 20 mg and 40 mg enoxaparin versus dextran. Eur J Surg 161:663-8	I	2-part study. Part 1: randomized double-blind trial compared 20 mg enoxaparin 2 hr preop, then daily X 10 days or until patient was fully mobilized, to a placebo infusion (0.9% sodium chloride), compared to dextran 70, 500 mL at the start and evening of surgery, then 1st, 3rd, and 5th postop days and placebo injections. DVT rates:33% in enoxaparin and 31% in dextran 70 groups. Enoxaparin was increased for Part 2 due to high DVT rate. DVT rate:12% in enoxaparin vs 38% dextran 70 group from Part 1. Enoxaparin 20 mg and dextran 70 are effective prophylaxis for medium risk patients. Enoxaparin 40 mg is required for high risk patients.
The European Fraxiparin Study (EFS) Group	1988	Comparison of a low molecular weight heparin and unfractionated heparin for the prevention of deep vein thrombosis in patients undergoing abdominal surgery. Br J Surg 75:1058-63	I	Prospective randomized multicenter trial compared Fraxiparin [7500 units 2 hr preop, 8 hr postop, then daily X 7 days (n=960)] to UH [5000 units 2 hr preop, 8 hr postop, and q 8 hr X 7 days (n=936)]. DVT rate: 2.8% fraxiparin group vs 4.5% UH group, p=0.034. They concluded that fraxiparin is more effective than low dose SQ heparin prophylaxis used in abdominal surgery. All patients had compression stockings.

Low Molecular Weight Heparin - General Surgery

First Author	Year	Reference Title	Class	Conclusions
Koppenhagen K	1992	Low molecular weight heparin and prevention of postoperative thrombosis in abdominal surgery. Thrombosis and Haemostasis 67:627-30	III	Prospective randomized double-blind multicenter trial of elective abdominal surgery patients (n=653) who received either 3000 anti-Xa units of LMWH (Mono-Embolex NM, Sandoz) 1X day or 5000 units SH tid. Treatment was 2 hrs preop, then 7 days postop. DVT rates were the same. There were 3 PE in SH group. Blood loss, wound hema-toma, and transfusion requirements were similar.
Gallus A	1993	Orgaran (Org 10172) or heparin for preventing venous thrombosis after elective surgery for malignant disease? A double-blind, randomised, multicentre comparison. Thrombosis and Haemostasis 70:562-7	I	Double-blind randomized multicenter trial in elective surgery patients (n=513) for intraabdominal or intrathoracic malignancy compared efficacy and safety of Orgaran (a mixture of LMW heparinoids using 750 anti-factor Xa units) given SQ bid with 5000 units SH bid. DVT rate: 10.4% Orgaran and 14.9% SH. No difference in bleeding complications between the two groups.
Bergqvist D	1996	Thromboprophylaxis with a low molecular weight heparin (Tinzaparin) in emergency abdominal surgery. A double-blind multicenter trial. Vasa 25:156-60	I	Prospective randomized double-blind study comparing tenzaparin vs placebo in 80 patients undergoing emergency abdominal surgery. Although the labeled fibrinogen used was taken from the market, the authors thought it was important to report their results. DVT was reduced with prophylaxis from 22% to 8%, risk reduction of 65% (not significant). It was concluded that patients undergoing emergency abdominal surgery seem to benefit from prophylaxis.
Bounameaux H	1993	Unexpectedly high rate of phlebographic deep venous thrombosis following elective general abdominal surgery among patients given prophylaxis with low-molecular-weight heparin. Arch Surg 128:326-8	I	194 elective abdominal surgery patients randomized to receive dalteparin (2500 units) or nadroparin (3075 IU) once daily. DVT was significantly higher in dalteparin group (32% vs 16%). 47% of patients had malignancy, suggesting that these LMWH dosages may not be sufficient to protect these higher risk patients. DVT rate was unacceptably high in both groups which points out the need for using a higher dose in this patient population.

Low Molecular Weight Heparin - Trauma

First Author	Year	Reference Title	Class	Conclusions
Green D	1990	Prevention of thromboembolism after spinal cord injury using low-molecular-weight heparin. Ann Intern Med 113:571-4	I	Compared Logiparin 3500 units daily for 8 weeks (n=20) vs SH 5000 units tid q8 hr for 8 weeks (n=21) in spinal cord injury patients. DVT and bleeding rates were 0/20 in Logiparin group and 7/21 in SH group. LMWH is safe and effective for VTE prevention in selected patients with spinal cord injury & complete motor paralysis, and is superior to SH.
Geerts WH	1996	A comparison of low-dose heparin with low-molecular-weight heparin as prophylaxis against venous thromboembolism after major trauma. N Engl J Med 335:701-7	I	Landmark study of trauma patients with ISS„9 who could receive anti-coagulants. 173 had low-dose heparin and 171 had enoxaparin 30 mg bid. DVT rate:31% enoxaparin vs 44% heparin group (p=0.014). Proximal DVT rate lowered 15% to 6%, (p=0.012) in enoxaparin group compared to heparin group. 5 bleeding cases in enoxaparin group and 1 in heparin group (p=0.12). LMWH was more effective than low-dose heparin to prevent VTE after major trauma.
Knudson MM	1996	Use of low molecular weight heparin in preventing thromboembolism in trauma patients. J Trauma 41:446-59	II	Prospective trial in trauma patients with AIS„3, major head injury, spine, pelvic or lower extremity fractures, acute venous injury or age>50 years assigned to heparin vs no heparin, depending on injury. Heparin patients were randomized to receive LMWH (enoxaparin 30 mg bid) or mechanical compression with SCDs or AVIs. Enoxaparin was safe and effective for preventing DVT in high risk trauma patients. When heparin is contraindicated, mechanical compression is warranted.
Greenfield LJ	1997	Posttrauma thromboembolism prophylaxis J Trauma 42:100-3	II (pilot study)	Small pilot study of 53 patients compared enoxaparin vs SH vs SCDs in high risk trauma patients with ISS>9 and in patients considered to be at high risk for DVT. Overall DVT rate was 43%. Enoxaparin group had half the DVTs of either SH or SCD groups, though not statistically significant due to sample size.

Low Molecular Weight Heparin - Cost-Effectiveness

First Author	Year	Reference Title	Class	Conclusions
Menzin J	1995	Cost-effectiveness of enoxaparin vs low-dose warfarin in the prevention of deep-vein thrombosis after total hip replacement surgery. Arch Intern Med 155:757-64	III	Decision-analysis model compared 2 DVT prophylaxis strategies to no prophylaxis in a hypothetical cohort of 10,000 patients undergoing total hip replacement surgery. Data were primarily from published literature. They concluded that, although enoxaparin was more costly than low-dose warfarin, its cost-effectiveness in total hip replacement compared favorably with that of other generally accepted medical interventions.
OíBrien BJ	1994	Cost-effectiveness of enoxaparin versus warfarin prophylaxis against deep-vein thrombosis after total hip replacement. Can Med Assoc J 150:1083-90	III	Compared efficacy and cost-effectiveness of enoxaparin (4 trials/567 patients) vs low-dose warfarin (6 trials/630 patients) for prevention of DVT after total hip replacement. Pooled DVT rate: 13.6% enoxaparin vs 20.6% warfarin. Total cost per patient of enoxaparin exceeded that of warfarin by about $121. The estimated incremental cost-effectiveness of enoxaparin was judged to be $29,120 per life-year gained. Based on current Canadian cost-effectiveness guidelines, results suggest this is moderate to strong evidence to adopt enoxaparin prophylaxis against DVT after total hip replacement.
Anderson DR	1993	Efficacy and cost of low-molecular-weight heparin compared with standard heparin for the prevention of deep vein thrombosis after total hip arthroplasty Ann Intern Med 119:1105-12	III	Retrospective meta-analysis of 447 total hip arthoplasty patients from 6 recently completely randomized controlled studies. LMWH was significantly more effective than standard heparin (SH) at preventing DVT after total hip arthroplasty. No significant differences were found in rates of distal DVT or total major or minor bleeding between groups. Based on price ratio of 2.6:1 between LMWH and SH, LMWH would save the health care system about $50,000 for 1000 patients treated. This entire analysis is based on price of LMWH that was set in France, and the use of LMWH in North America would result in overall savings and cost, dependent on the price ratio between the two drugs.