Description of the condition
Trauma is one of the leading causes of death and disability in young people (Evans 2003). Worldwide, about five million people die as a result of trauma every year (WHO 2008). For patients who reach hospital within one hour of trauma (called the 'golden hour'), blood loss and traumatic brain injury are the main causes of death (Sauaia 1995). For patients who survive beyond the first day, multiple organ failure, central nervous system (CNS) injury and venous thromboembolism (VTE) are the principal causes of death (Acosta 1998).
Trauma patients are at known risk of entering into a hypercoagulable state (intrinsic alterations in the nature of the blood itself). Mechanisms of hypercoagulability in the trauma setting include stasis, vessel wall dysfunction and alterations in clotting mechanisms (Virchow's triad). Injured patients are often immobilized after high-energy trauma. Being in a static position causes a reduction in venous blood returns and a decrease in the supply of oxygen and nutrients to endothelial cells. In addition, endothelial damage caused by direct trauma to the vessels causes the exposition of tissue factor bearing cells. This initiates a procoagulant factor that amplifies the coagulant response. These tissue factor bearing cells move to the cell surface of the platelets, which produces a propagation of the signal through the accumulation of thrombin, activated cofactors and more platelets, inducing thrombosis (Hoffman 2001).
On the other hand, trauma patients experience a reduction of fibrinolytic pathways that seems to result from increased plasminogen activator inhibitor (PAI) 1. PAI 1 inhibits tissue plasminogen activator (tPA) and thus decreases the production of plasmin (Rogers 1995; Kelsey 2000). Coagulation abnormalities and the reduced ability to use the muscular pump of the calf in the injured patient can produce deep venous thrombosis (DVT) in the inferior and superior extremities (Spaniolas 2008). When the thrombus extends to the proximal segments, there is an increased risk of clot migration to the lungs and a fatal outcome (Geerts 2008).
Trauma patients are at high risk for DVT, with an incidence of 11.8% to 65% (Sevitt 1961; Geerts 1994; Velmahos 2000). The incidence varies according to the method used to measure the DVT and the location of the thrombosis. Incidence of thrombosis in the thigh (proximal DVT) is estimated at 18% (Geerts 1994). The incidence of pulmonary embolism (PE) is estimated between 1.5% and 20% (Shackford 1988; O'Malley 1990; Velmahos 2000). Many risk factors for DVT and PE in trauma patients have been identified such as spinal cord injury, lower extremity and pelvic fractures, need for surgical procedures, increasing age, femoral venous line insertion or surgical repair of venous injuries, prolonged immobility, long duration of hospital stay, severity of the trauma, and mechanism of injury (Geerts 1994; Knudson 1994; Frezza 1996; Velmahos 2000; Cipolle 2002; Rogers 2002; Meissner 2003).
Description of the intervention
Thromboprophylaxis describes any intervention used to prevent the development of VTE, and can be categorized into mechanical and pharmacological interventions.
External mechanical devices such as graded compression devices or intermittent pneumatic compression (IPC) have been shown to be effective in preventing DVT, but they cannot be used in patients with lower extremity trauma (Fisher 1995; Elliott 1999; Velmahos 2000). Internal mechanical devices are used to prevent the migration of thrombus from DVT to the lungs, thus preventing PE. One such device is the inferior vena cava filter (IVCF) which may be particularly useful in trauma patients because of the risk of ongoing bleeding at injured sites (McMurty 1999).
Pharmacological thromboprophylaxis was first described in the 1940s by Bauer 1944, and since then a number of interventions have been proposed. The anticoagulant effect of unfractionated heparin (UH) is initiated by the activation of antithrombin III (ATIII). The ATIII/heparin complex inactivates the thrombin factor IIa, and factors Xa, IXa, XIa and XIIa. However, UH is associated with a number of adverse events, such as thrombocytopenia. More recently, alternatives such as low molecular weight heparin (LMWH), a derivative of UH, have been proposed. LMWH acts in the same way as UH, but its low molecular weight fragments reduce the binding to other cells and proteins (and it also has a major affinity to factor Xa) (Hirsh 2004). These drugs have potential as effective prophylactic interventions for trauma, although there is concern due to the associated increased risk of bleeding (Geerts 1996; Haentjens 1996; Knudson 1996; Cohn 1999). Other methods of thromboprophylaxis, such as anticoagulants (warfarin) or antiplatelets (aspirin), seem less practical for use in critically ill patients, because of their delayed action and oral presentation. Pentassacharides (a new class of synthetic selective factor Xa inhibitor, with parenteral presentation which does not bind to platelets, other cells or proteins) have been studied as prophylaxis in surgical orthopedic patients and have been shown to be as effective as UH and LMWH (Nijkeuter 2004).
How the intervention might work
Due to prolonged rest and coagulation abnormalities, trauma patients are at increased risk of thrombus formation. Thromboprohylaxis, either mechanical or pharmacological, may decrease the mortality and morbidity in trauma patients who survive beyond the first day in hospital, by decreasing the risk of DVT and PE in this population. A previous Cochrane review focusing on high-risk patients indicated that combined methods (pharmacologic and mechanical interventions) decreased the incidence of DVT (Kakkos 2008). However, this systematic review did not examine the effects in the subgroup of trauma patients.
Why it is important to do this review
Trauma patients are at an increased risk of VTE, and thromboprophylaxis has the potential to be effective in this population. However, trauma patients are at an increased risk of bleeding, which is one of the adverse events associated with pharmacological interventions. For some trauma patients with injured extremities, the use of mechanical interventions (e.g. external mechanical compression) is not feasible. A previous systematic review (Velmahos 2000) did not find evidence of effectiveness for either pharmacological or mechanical interventions. However, this systematic review was conducted 10 years ago and most of the included studies were of poor quality. Since then new trials have been conducted. Although current guidelines (Rogers 2002; Geerts 2008) recommend the use of thromboprophylaxis in trauma patients, there has not been a comprehensive and updated systematic review since the one published by Velmahos et al. Furthermore, there are still uncertainties about the relative benefit of interventions for different subgroups of trauma patients. Therefore it is necessary to conduct a systematic review to establish whether the effect of different thromboprophylaxis interventions varies according to the type of trauma, location of the trauma, severity of trauma and type of management (surgical or medical management).
To assess the effects of thromboprophylaxis in trauma patients on mortality and incidence of DVT and PE.
To compare the effects of different thromboprophylaxis interventions and their effects according to the type of trauma.
Criteria for considering studies for this review
Types of studies
Randomized controlled clinical trials.
Types of participants
People of any age with major trauma defined by one or more of the following criteria;
- physiological: penetrating or blunt trauma with more than two organs and unstable vital signs,
- anatomical: patients with an Injury Severity Score (ISS) higher than 9,
- mechanism: patients who are involved in a 'high energy' event with a risk for severe injury despite stable or normal vital signs.
We excluded trials that only recruited outpatients, trials than recruited patients with hip fractures only, or patients with only acute spinal injuries.
Types of interventions
We included trials investigating any of the following interventions;
- Unfractionated heparin (UH),
- Low weight molecular heparin (LWMH),
- Mechanical methods: graded compression stocking, and sequential compression devices,
- Oral anticoagulants (e.g. warfarin),
- Antiplatelet drugs (e.g. aspirin),
- Pulmonary embolism prophylaxis (e.g. inferior vena cava filter (IVCF)).
We compared the effects of any intervention with placebo, and any two interventions (e.g. LMWH versus UH) or combination of interventions (UH plus mechanical methods versus UH).
Types of outcome measures
The primary outcome was mortality.
The secondary outcomes were the incidence of DVT, PE and adverse events, such as:
- bleeding (major and minor);
- whether the adverse event (bleeding of the injured site, intracranial bleeding, gastrointestinal bleeding, epistaxis, etc.) required transfusion or any procedure to control it;
- and other adverse events as defined by the trial authors.
Search methods for identification of studies
We did not restrict searches by date, language or publication status.
We searched the following electronic databases:
- Cochrane Injuries Group’s Specialised Register (searched April 30 2009);
- Cochrane Central Register of Controlled Trials 2009, issue 2 (The Cochrane Library);
- MEDLINE (Ovid) 1950 to April (week 3) 2009;
- EMBASE (Ovid) 1980 to (week 17) April 2009;
- PubMed [http://www.ncbi.nlm.nih.gov/sites/entrez] (searched 29 April 2009);
- ISI Web of Science: Science Citation Index Expanded (SCI-EXPANDED) (1970 to April 2009);
- ISI Web of Science: Conference Proceedings Citation Index-Science (CPCI-S) (1990 to April 2009).
Search strategies are listed in full in Appendix 1.
Searching other resources
We searched the bibliographies of all included studies and other relevant papers for further potentially eligible trials. We searched the Internet using the Google (www.google.com) search engine with selected terms from the strategy to identify any further unpublished or grey literature.
Data collection and analysis
The Injuries Group Trials Search Co-ordinator ran the electronic database searches, collated the search results, removed duplicates then sent the remaining records to the authors for screening
Selection of studies
Four authors, in pairs (LB and CM, EF and RC), independently examined titles, abstracts, and keywords of citations from electronic databases for eligibility. We obtained the full texts of all potentially relevant records and two authors (EF and CM) independently assessed whether each met the pre-defined inclusion criteria. We resolved any disagreement through discussion with a third author (PP).
Data extraction and management
Four authors, in pairs (LB and CM, EF and RC) extracted data independently, using a standardized data extraction form. LB entered the extracted information into Review Manager (RevMan 2008) for analysis. We extracted data on the following:
- General Information: title, authors, source of publication, country, published or not, language and year of publication.
- Trial characteristics: study design and information that meets the Cochrane Collaboration's tool for assessing risk of bias.
- Participants: sample size, inclusion criteria, exclusion criteria, location of trauma (brain, chest, abdomen, pelvis, extremity, polytrauma), severity of trauma (ISS, RTS, or according to the scale used by the trialists), type of injury (blunt or penetrating), and type of surgical procedure (non-operative or surgical management).
- Intervention: type and dose of thromboprophylaxis used, type and dose of control or placebo used.
- Outcomes: incidence of mortality, incidence of DVT (symptomatic or asymptomatic) and diagnostic test used, incidence of PE and diagnostic test used. Incidence of adverse events as follows: any bleeding, major bleeding defined as use of transfusion or any procedure to control bleeding (bleeding from the injured site, gastrointestinal bleeding, brain bleeding, epistaxis, etc.) and minor bleeding. Other outcomes recorded by the authors.
- Results: number of patients in each group, missing patients.
- Subgroup characteristics: number of patients by localization of trauma, by severity, by type (blunt or penetrating), by type of management (surgical or non-surgical).
- Other information: funding source.
Assessment of risk of bias in included studies
Four authors in pairs (LB and CM, EF and RC) assessed the risk of bias of each included trial using the Cochrane Collaboration's tool for assessing risk of bias presented in Higgins 2008. We assessed the following domains: sequence generation; allocation concealment; blinding; incomplete outcome data; and selective outcome reporting. We completed risk of bias tables for each trial, incorporating a description of the trial's performance against each domain and our overall judgment of the risk of bias for each entry as follows: 'Yes' for low risk of bias; 'No' for high risk of bias, or 'Unclear'. We resolved disagreements by consulting a third author (PP).
Measures of treatment effect
For dichotomous data we calculated risk ratios (RR) and 95% confidence intervals (CIs). We also calculated number needed to treat (NNT) and number needed to harm (NNH).
For continuous data we calculated the mean difference (MD) and 95% CIs when the same scale was used in a similar manner across studies. If results for continuous outcomes were reported using different scales or different versions of the same scale, we calculated the standardised mean difference (SMD) and 95% CIs.
Dealing with missing data
We did not contact the trial authors for missing information.
Assessment of heterogeneity
We examined trial characteristics in terms of participants, interventions and outcomes for evidence of clinical heterogeneity. We examined statistical heterogeneity by both the I
Assessment of reporting biases
We planned to investigate the presence of reporting (publication) bias using funnel plots, however there were too few included trials contributing data to each outcome to enable meaningful analysis.
We judged that the trials were sufficiently homogenous, both clinically and statistically, to pool the outcome data. Dichotomous data were pooled using the Mantel-Haenszel fixed-effect method and continuous data were pooled using the fixed-effect inverse-variance method.
Because different effects were expected according to the intervention, we performed data synthesis separately for each type (e.g. UH, LWMH or mechanical devices).
Subgroup analysis and investigation of heterogeneity
There were insufficient data to perform the following planned subgroup analyses:
- type of trauma (blunt, penetrating);
- location of the trauma (brain, chest, abdominal, pelvis, extremity or polytrauma);
- severity of trauma defined with ISS or other similar scores;
- management (surgical or medical management);
- diagnostic method.
We performed a sensitivity analysis to investigate whether the results were robust. We examined the effect of excluding certain studies according to their risk of bias. We reported the data synthesis for all the included studies and repeated the calculations after excluding studies judged as having a high risk of bias for allocation concealment. We also examined the effect of using a different effect measure (odds ratio) for the dichotomous outcomes.
Description of studies
Results of the search
The combined search strategy identified 2858 citations, of which 38 were judged to be potentially eligible based on title or abstract, or both, and the full texts were obtained. After a full text review, 16 trials were judged to be eligible and were included in the review, one was reported as an abstract.
We included 3005 people of any age who had major trauma. 1898 people had blunt trauma and 225 people had penetrating trauma. Four trials did not report the injury mechanism (Fuchs 2005; Ginzburg 2003; Knudson 1996; Yanar 2007). Most of the studies reported the ISS. The average of the ISS reported by the trials varies between 13 and 30. Five studies did not report the ISS value. Six studies reported a specific management. 816 with operative treatment and 173 with non operative treatment.
The Knudson 1994 All groups study was divided in four groups: Knudson 1994 All groups, Knudson 1994 group I (UH vs SCD vs Placebo), Knudson 1994 group II (UH vs Placebo) and Knudson 1994 group III (SCD vs Placebo).
Five trials compared pharmacological with mechanical methods, of which three compared LMWH with Intermittent Pneumatic Compression (IPC) devices (Ginzburg 2003; Kurtoglu 2004; Yanar 2007) and two compared UH with Sequential Compression Devices (SCD) (Knudson 1992; Knudson 1994 group I).
Four trials compared a combination of pharmacological and mechanical interventions. One trial allocated patients to three groups to compare IPC, IPC plus LMWH and LMWH alone (Yanar 2007). The other three trials compared pharmacological plus mechanical methods with pharmacological prophylactics (Fuchs 2005; Stannard 2006; Yanar 2007).
All 16 trials used doppler ultrasound (Duplex) to diagnose DVT. The diagnosis was confirmed with venography in three trials (Geerts 1996; Fuchs 2005; Fisher 1995), and by Duplex and MRI venography in one trial (Stannard 2001).
Sixteen trials presented data on pulmonary embolism. PE was diagnosed clinically in two trials (Anglen 1998; Fuchs 2005); by a V/Q scan and pulmonary angiography in five trials (Knudson 1992; Knudson 1994 All groups; Knudson 1996; Geerts 1996; Cohn 1999); by CT scan angiography on clinically suspected cases in two trials (Kurtoglu 2004; Yanar 2007); by clinical suspicion and autopsy in one trial (Elliot 1999); by angiography and autopsy in two trials (Fisher 1995; Dennis 1993); by used ventilation/perfusion scan (V/Q scan), angiography and CT scan angiography in one trial (Ginzburg 2003); and by MRI angiography in one trial (Stannard 2006). The method used in the remaining two trials was not described (Velmahos 2005; Stannard 2001).
Further details of the individual trials are presented in the Characteristics of included studies table.
Of the trials excluded from our review three were not randomised (Greenfiel 1997; Holzheimer 2004; Reilmann 1986), two included only outpatients or elective surgery patients (Haas 2003; Wolf 1992), one involved hip fracture surgery patients (Breyer 1986) and one did not measure any outcomes of interest to this review (Murakami 2003).
Details are presented in the Characteristics of excluded studies.
Risk of bias in included studies
Eleven of the 16 studies had a low risk in the sequence generation of the treatment groups, three of them had high risk of bias and two were unclear.
In half of the studies included the allocation concealment was unclear, four of the 16 had low risk in the allocation and the other four studies had high risk of bias.
Blinding was well conducted in seven of the 16 studies, in five there was a high risk of bias and in four the data were insufficient to establish the quality of blinding.
Incomplete outcome data
Six studies performed an intention to treat analysis, in nine there was a high risk bias because outcome data were analysed in an incomplete fashion, and just one of them did not allow us to establish the risk.
We were unable to obtain the protocols for any of the trials, therefore the reporting bias was unclear for all 16 trials.
Effects of interventions
All the collected material allowed us to perform 7 comparisons, we made four comparisons as a sensitivity analysis. As established in the protocol we compared any method of prophylaxis versus no prophylaxis, between prophylaxis methods and combinations of them. The most important are highlighted in this text section. The detailed analysis can be seen in the Data and analyses section.
Prophylaxis versus no prophylaxis
Four trials involving 997 people compared the effect of any type (mechanical and/or pharmacological) of prophylaxis versus no prophylaxis. Prophylaxis reduced the risk of DVT in trauma patients (RR 0.52; 95% CI 0.32 to 0.84). There was no evidence of statistical heterogeneity between trials (I
Three trials reported the effect on bleeding, no events were observed in any trial.
Mechanical prophylaxis versus no prophylaxis
Six trials involving 811 people compared the effect of mechanical prophylaxis with no prophylaxis.
Mechanical prophylaxis reduced the risk of DVT (RR 0.55; 95% CI 0.34 to 0.90). There was no evidence of statistical heterogeneity between trials (I
Four trials (507 patients) reported the effect on bleeding, no events were observed in any trial.
Pharmacological prophylaxis versus mechanical prophylaxis
Six trials involving 1033 people compared pharmacological prophylaxis with mechanical prophylaxis.
Pharmacological prophylaxis was more effective than mechanical methods at reducing the risk of DVT (RR 0.48; 95% CI 0.25 to 0.95). There was no evidence of heterogeneity between trials (I
Five of the trials (953 patients) reported bleeding outcome data. Pharmacological prophylaxis increased the risk of bleeding (RR 2.04; 95% CI 1.08 to 3.86) compared to mechanical methods. There was no evidence of heterogeneity (I
Low Molecular Weight Heparin versus Unfractionated Heparin
Two trials involving 331 patients compared low molecular weight heparin (LMWH) with unfractionated heparin (UH). LMWH appeared to reduce the risk of DVT compared to UH (RR 0.68; 95% CI 0.50 to 0.94). There was no evidence for heterogeneity between trials (I
There was no statistically significant difference in the risk of PE between the two groups (RR 3.16; 95% CI 0.13 to 76.91) and there were no deaths reported in either trial.
There was no statistically significant difference in the risk of bleeding between LMWH and UH (RR 1.63; 95% CI 0.63 to 4.22).
Mechanical plus pharmacological prophylaxis versus Pharmacological prophylaxis
Three trials involving 507 patients compared mechanical prophylaxis plus pharmacological prophylaxis with pharmacological prophylaxis alone. Patients who received both mechanical and pharmacological prophylaxis had a lower risk of DVT (RR 0.34; 95% CI 0.19 to 0.60). However, there was evidence for statistical heterogeneity between trials (I
There was no evidence for a difference in effect on the risk of PE (RR 0.32; 95% CI 0.05 to 2.01) or death (RR 0.50; 95% CI 0.05 to 5.30).
One trial assessed the effect on bleeding and found no difference in the risk of bleeding between the two groups (RR 0.99; 95% CI 0.56 to 1.78).
One study compared mechanical plus pharmacological prophylaxis versus mechanical prophylaxis (Yanar 2007) and did not find difference. Also three trials compared thigh-calf versus calf-foot methods (Anglen 1998; Elliot 1999; Stannard 2001) did not find either statistical difference.
The sensitivity analysis included only the studies that were considered at low risk of bias for allocation concealment. We made four comparisons of the results, which showed a statistically significant difference.
The comparisons of prophylaxis vs no prophylaxis and mechanical methods vs no prophylaxis, could include only one study (Fisher 1995). It showed a tendency to be superior for prophylaxis, but without reaching a statistically significant difference (RR 0.35; 95% CI 0.11 to 1.10).
When we compare LMWH vs UH, we could include just one study (Geerts 1996) which showed strong evidence that LMWH was superior for prevention of DVT (RR 0.57; 95% CI 0.34 to 0.94).
When we compare mechanical with pharmacological prophylaxis we also could include just one study (Ginzburg 2003) but did not show any significant difference (RR 0.17; 95% CI 0.02 to 1.41).
Summary of main results
This systematic review gathers all the available evidence from all randomised controlled trials which compare the use of pharmacological and mechanical thromboprophylaxis in patients with severe trauma. We excluded trials that only recruited outpatients, patients presenting only with hip fractures, acute spinal injuries and low energy trauma.
Among trauma patients who did not receive any prophylaxis we found that deep venous thrombosis (DVT) incidence was 8.72% (37/424) diagnosed by Dupplex. The incidence of pulmonary embolism (PE) was 3.3% (14/424) for PE diagnosed by VQ scan or angiography or autopsy (Dennis 1993; Fisher 1995; Knudson 1994 All groups; Velmahos 2005).
We did not find evidence that thromboprophylaxis reduces the primary outcome mortality or the secondary outcome PE for any of the comparisons assessed.
However, we found some evidence of effective interventions for the prevention of the secondary outcome DVT. Prophylaxis was more effective than no prophylaxis, pharmacological prophylaxis than mechanical prophylaxis, and LMWH than UH. However, these results were based on a few small trials with relatively few events and poor methodology quality. We also found some evidence that patients who received pharmacological thromboprophylaxis have a higher risk of minor bleeding compared to patients who received mechanical therapy. At the moment there is no RCT published for major trauma with dabigatran or rivaroxiban.
Although the strength of the evidence found in this review was not strong our findings are similar to previous reviews conducted in different but related conditions (Surgical non traumatized, cancer, hip fractures) (Wille-Jørgensen 2008; Bani-Hani 2011; Handoll 2008). The present review strengthens the clinical practice guidelines recommendations from Eastern Association for the Surgery of Trauma (Rogers 2002) and American College of Chest Physicians (Kahn 2012; Geerts 2008), providing further evidence for thromboprophylaxis in patients with severe trauma.
Overall completeness and applicability of evidence
We did not find enough studies to allow any comparison between pharmacological prophylaxis against placebo. There are also not enough studies which evaluate specific pharmacological interventions (UW or LMWH) vs specific mechanical therapies (SCD or AVI).
Quality of the evidence
The quality of evidence was low as only one of the four studies included for the main comparison (prophylaxis versus no prophylaxis) had low risk of selection bias as judged by the allocation concealment process. Also the external validity could be threatened because of sponsorship by mechanical devices manufacturers (Velmahos 2005).
Potential biases in the review process
Potential biases in the review process are mainly defined by an impossibility to analyse a study due to an abstract inclusion in the meta-analysis (Yanar 2007). We tried to minimize selection bias by working, collecting and analysing all studies in pairs (LB-CM and EF-RC). All differences where resolved by consensus and also through the input of PP.
Agreements and disagreements with other studies or reviews
Previous meta-analyses (Velmahos 2000) have shown no evidence that low-dose unfractionated heparin, mechanical prophylaxis, or low-molecular weight heparin are more effective than no prophylaxis or among each other. In addition, unlike ours, this systematic review included observational studies which provide less reliable evidence of effectiveness for medical interventions.
A recent systematic review (Smith 2011) with severe skeletal trauma as its main inclusion criteria suggested that low molecular weight heparin (LMWH) may be superior to low dose heparin (LDH), and that LMWH should be used in addition to mechanical prophylaxis measures in patients following major skeletal trauma for the prevention of thromboembolic events, this findings do not differ from ours. The analysed studies were included in this meta-analysis, the difference between these systematic reviews were that they just include major skeletal trauma.
Bleeding was not analysed as an outcome in previous meta-analysis and not all of the trials considered bleeding as an outcome.
Implications for practice
Although the strength of the evidence included in this review was not high, taking into account existing information from other related conditions such as surgery, we believe that the use thromboprophylaxis for preventing DVT in severe trauma patients is recommended.
Implications for research
Adequately powered trials should be conducted to compare different thromboprophylaxis strategies. Also we would recommend that future RCTs should have a more uniform and defined method of diagnosing both DVT and PE so as to measure the true effect thromboprophylaxis.
In addition to mortality, DVT and PE, future trials should assess the following outcomes which have important clinical implications:
1. Adverse events of pharmacological prophylaxis such as bleeding.
2. Post-discharge consequences of DVT in postraumatic patients including postphlebitic syndrome, chronic DVT or chronic PE.
We thank Karen Blackhall for designing and performing the bibliographic database searches.
Data and analyses
- Top of page
- Authors' conclusions
- Data and analyses
- Contributions of authors
- Declarations of interest
- Differences between protocol and review
- Index terms
Appendix 1. Search strategy
Cochrane Injuries Group Specialised Register (searched April 30 2009)
1. (wound* or trauma* or injur* or fracture* or burn* or stab* or shot* or shoot* or lacerat* or accident*)
2. (thrombus* or thrombotic* or thrombolic* or thromboemboli* or thrombos* or thromboph*) or ((deep* and (vein* or ven*) and (thromb* or embol*)) or ((pulmonary or lung*) and (thromb* or embol*)) or (DVT or PE or VTE)
3. 1 and 2
4. Thromboprophylaxis or prophylactic* or prophylaxis or Heparin* or Anticoagulant* or Warfarin or Coumadin* or apo-warfarin or gen-warfarin or warfant or Coumadin or aldocumar or tedicumar or Antiplatelet* or anticoagulant* or Aspirin* or "acetylsalicylic acid" or acylpyrin or aloxiprimum or colfarit or dispril or easprin or ecotrin or endosprin or magnecyl or micristin or polopirin or polopiryna or solprin or solupsan or zorprin or acetysal or Pentassacharide* or fondaparinux or Heparin* or "vena cava filter" or "umbrella filter" anti-platelet*
5. 3 and 4
MEDLINE (Ovid) 1950 to April (Week 3) 2009
1. exp "Wounds and Injuries"/
2. (wound* or trauma* or injur* or fracture* or burn* or stab* or shot* or shoot* or lacerat* or accident*).mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer name]
3. 1 or 2
4. exp Venous Thromboembolism/
5. exp Venous Thrombosis/
6. exp Pulmonary embolism/
7. exp Thrombophlebitis/
8. (thrombus* or thrombotic* or thrombolic* or thromboemboli* or thrombos* or thromboph*).ab,ti.
9. (deep* adj3 (vein* or ven*) adj5 (thromb* or embol*)).ab,ti.
10. ((pulmonary or lung*) adj3 (thromb* or embol*)).ab,ti.
11. (DVT or PE or VTE).ab,ti.
12. 4 or 5 or 6 or 7 or 8 or 9 or 10 or 11
13. (thromboprophylaxis or prophylactic* or prophylaxis).ab,ti.
14. exp Heparin/
15. exp Heparin, Low-Molecular-Weight/
16. exp Heparinoids/
17. exp Stockings, Compression/
18. exp Intermittent Pneumatic Compression Devices/
19. exp Stockings, Compression/
20. exp Anticoagulants/
21. exp Warfarin/
22. exp Platelet Aggregation Inhibitors/
23. exp Aspirin/
25. ((compression or impulse or pneumatic or elastic*) adj3 (device* or stocking* or hose* or dressing* or bandage*)).ab,ti.
26. (Anticoagulant* or Warfarin or Coumadin* or apo-warfarin or gen-warfarin or warfant or Coumadin or aldocumar or tedicumar).ab,ti.
27. (Antiplatelet* or (platelet* adj3 aggregation adj3 inhibit*) or ((blood or platelet*) adj3 (antagonist* or antiaggrega*))).ab,ti.
28. (Aspirin* or acetylsalicylic acid or acylpyrin or aloxiprimum or colfarit or dispril or easprin or ecotrin or endosprin or magnecyl or micristin or polopirin or polopiryna or solprin or solupsan or zorprin or acetysal).ab,ti.
29. exp Vena Cava Filters/
30. ((vena adj3 cava adj3 filter*) or (umbrella adj3 filter*)).ab,ti.
31. (Pentassacharide* or fondaparinux).ab,ti.
34. randomized controlled trial.pt.
35. controlled clinical trial.pt.
37. clinical trials as topic.sh.
40. 33 or 34 or 35 or 36 or 37 or 38 or 39
41. (animals not (humans and animals)).sh.
42. 40 not 41
43. 3 and 12 and 32 and 42
EMBASE (Ovid) 1980 to 2009 (Week 17)
2.(wound* or trauma* or injur* or fracture* or burn* or stab* or shot* or shoot* or lacerat* or accident*).mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer name]
3.1 or 2
4.exp Vein Thrombosis/
5.exp Lung Embolism/
6.exp venous thromboembolism/
7.exp deep vein thrombosis/
9.(thrombus* or thrombotic* or thrombolic* or thromboemboli* or thrombos* or thromboph*).ab,ti.
10.(deep* adj3 (vein* or ven*) adj5 (thromb* or embol*)).ab,ti.
11.(deep* adj3 (vein* or ven*) adj5 (thromb* or embol*)).ab,ti.
12.((pulmonary or lung*) adj3 (thromb* or embol*)).ab,ti.
13.(DVT or PE or VTE).ab,ti.
15.(thromboprophylaxis or prophylactic* or prophylaxis).ab,ti.
17.exp Low Molecular Weight Heparin/
19.exp compression garment/
20.exp Compression Bandage/
21.exp intermittent pneumatic compression device/
22.exp Vena Cava Filter/
23.exp Anticoagulant Agent/
24.exp Coumarin Anticoagulant/
25.exp Antithrombocytic Agent/
26.exp Acetylsalicylic Acid/
28.(Anticoagulant* or Warfarin or Coumadin* or apo-warfarin or gen-warfarin or warfant or Coumadin or aldocumar or tedicumar).ab,ti.
29.(Antiplatelet* or (platelet* adj3 aggregation adj3 inhibit*) or ((blood or platelet*) adj3 (antagonist* or antiaggrega*))).ab,ti.
30.(Aspirin* or acetylsalicylic acid or acylpyrin or aloxiprimum or colfarit or dispril or easprin or ecotrin or endosprin or magnecyl or micristin or polopirin or polopiryna or solprin or solupsan or zorprin or acetysal).ab,ti.
31.((vena adj3 cava adj3 filter*) or (umbrella adj3 filter*)).ab,ti.
32.(Pentassacharide* or fondaparinux).ab,ti.
33.((compression or impulse or pneumatic or elastic*) adj3 (device* or stocking* or hose* or dressing* or bandage*)).ab,ti.
35.exp Randomized Controlled Trial/
36.exp controlled clinical trial/
42.35 or 36 or 37 or 38 or 39 or 40 or 41
43.exp animal/ not (exp human/ and exp animal/)
44.42 not 43
45.34 and 3 and 44 and 14
CENTRAL (The Cochrane Library 2009, Issue 2)
#1 MeSH descriptor Venous Thromboembolism explode all trees
#2 MeSH descriptor Venous Thrombosis explode all trees
#3 MeSH descriptor Pulmonary Embolism explode all trees
#4 MeSH descriptor Thrombophlebitis explode all trees
#5 (thrombus* or thrombotic* or thrombolic* or thromboemboli* or thrombos* or thromboph*)
#6 ((deep*) near3 (vein* or ven*)) near5 (thromb* or embol*)
#7 (pulmonary or lung*) near3 (thromb* or embol*)
#8 DVT or PE or VTE
#9 (#1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8)
#10 thromboprophylaxis or prophylactic* or prophylaxis
#11 MeSH descriptor Heparin explode all trees
#12 MeSH descriptor Heparin, Low-Molecular-Weight explode all trees
#13 MeSH descriptor Heparinoids explode all trees
#14 MeSH descriptor Stockings, Compression explode all trees
#15 MeSH descriptor Intermittent Pneumatic Compression Devices explode all trees
#16 MeSH descriptor Stockings, Compression explode all trees
#17 MeSH descriptor Anticoagulants explode all trees
#18 MeSH descriptor Warfarin explode all trees
#19 MeSH descriptor Platelet Aggregation Inhibitors explode all trees
#20 MeSH descriptor Aspirin explode all trees
#22 ((compression or impulse or pneumatic or elastic*) near3 (device* or stocking* or hose* or dressing* or bandage*))
#23 (Anticoagulant* or Warfarin or Coumadin* or apo-warfarin or gen-warfarin or warfant or Coumadin or aldocumar or tedicumar)
#24 Antiplatelet* or (platelet* near3 aggregation near3 inhibit*)
#25 (blood or platelet*) near3 (antagonist* or antiaggrega*)
#26 Aspirin* or acetylsalicylic acid or acylpyrin or aloxiprimum or colfarit or dispril or easprin or ecotrin or endosprin or magnecyl or micristin or polopirin or polopiryna or solprin or solupsan or zorprin or acetysal
#27 MeSH descriptor Vena Cava Filters explode all trees
#28 (vena near3 cava near3 filter*) or (umbrella near3 filter*)
#29 Pentassacharide* or fondaparinux
#30 (#10 OR #11 OR #12 OR #13 OR #14 OR #15 OR #16 OR #17 OR #18 OR #19 OR #20 OR #21 OR #22 OR #23 OR #24 OR #25 OR #26 OR #27 OR #28 OR #29)
#31 (#9 AND #30)
#32 MeSH descriptor Wounds and Injuries explode all trees
#33 wound* or trauma* or injur* or fracture* or burn* or stab* or shot* or shoot* or lacerat* or accident*
#34 (#32 OR #33)
#35 (#31 AND #34)
ISI Web of Science: Science Citation Index Expanded (SCI-EXPANDED) (1970 to April 2009),
ISI Web of Science: Conference Proceedings Citation Index-Science (CPCI-S) (1990 to April 2009)
#1 Topic=(wound* or trauma* or injur* or fracture* or burn* or stab* or shot* or shoot* or lacerat* or accident*)
#2 Topic=(thrombus* or thrombotic* or thrombolic* or thromboemboli* or thrombos* or thromboph*) OR Topic=(deep* same (vein* or ven*) same (thromb* or embol*)) OR Topic=((pulmonary or lung*) same (thromb* or embol*)) OR Topic=(DVT or PE or VTE)
#3 #1 and #2
#4 Topic=(thromboprophylaxis or prophylactic* or prophylaxis or Heparin* or Anticoagulant* or Warfarin or Coumadin* or apo-warfarin or gen-warfarin or warfant or Coumadin or aldocumar or tedicumar or Antiplatelet* or Aspirin* or acetylsalicylic acid or acylpyrin or aloxiprimum or colfarit or dispril or easprin or ecotrin or endosprin or magnecyl or micristin or polopirin or polopiryna or solprin or solupsan or zorprin or acetysal or Pentassacharide* or fondaparinux)
#5 Topic=(platelet* same aggregation same inhibit*) OR Topic=((blood or platelet*) same (antagonist* or antiaggrega*)) OR Topic=((compression or impulse or pneumatic or elastic*) same (device* or stocking* or hose* or dressing* or bandage*)) OR Topic=(vena same cava same filter*) OR Topic=(umbrella same filter*)
#6 #4 or #5
#7 #3 and #6
#8 Topic=(((singl* OR doubl* OR trebl* OR tripl*) SAME (blind* OR mask*))) OR Topic=(randomised OR randomized OR randomly OR random order OR random sequence OR random allocation OR randomly allocated OR at random OR randomized controlled trial) OR Topic=(controlled clinical trial OR controlled trial OR clinical trial OR placebo) AND Topic=(human*)
#9 #7 and #8
PubMed [http://www.ncbi.nlm.nih.gov/sites/entrez] (searched 29 April 2009: limited to: added to PubMed in the Last 180 days)
#1 wound* OR trauma OR traumatic OR traumas OR traumatolog* OR injur* OR fracture* OR burn* OR stab OR stabbing* OR stabbed OR stabwound* OR stabs OR shot* OR shoot* OR lacerat* OR accident*
#2 thrombus* OR thrombotic* OR thrombolic* OR thromboemboli* OR thrombos* OR thromboph*
#3 DVT OR PE OR VTE
#4 deep* AND (vein* OR venous) AND (thrombos OR thromboe* OR emboli*)
#5 #2 OR #3 OR #4
#6 (hromboprophylaxis OR prophylactic* OR prophylaxis OR Heparin* OR Anticoagulant* OR Warfarin OR Coumadin* OR apo-warfarin OR gen-warfarin OR warfant OR Coumadin OR aldocumar OR tedicumar OR Antiplatelet* OR Aspirin* OR acetylsalicylic acid OR acylpyrin OR aloxiprimum OR colfarit OR dispril OR easprin OR ecotrin OR endosprin OR magnecyl OR micristin OR polopirin OR polopiryna OR solprin OR solupsan OR zorprin OR acetysal OR Pentassacharide* OR fondaparinux
#7 platelet* AND aggregation AND inhibitor*
#8 (blood or platelet*) AND (antagonist* or antiaggrega*)
#9 (compression OR impulse OR pneumatic OR elastic*) AND (device* OR stocking* OR hose* OR dressing* OR bandage*)
#10 (vena AND cava AND filter*) OR (umbrella AND filter*)
#11 #6 OR #7 OR #8 OR #9 OR #10
#12 #1 AND #5 AND #11
#13 ((randomized controlled trial[pt] OR controlled clinical trial[pt]) OR (randomized OR randomised OR randomly OR placebo[tiab]) OR (trial[ti]) OR ("Clinical Trials as Topic"[MeSH Major Topic])) NOT (("Animals"[Mesh]) NOT ("Humans"[Mesh] AND "Animals"[Mesh]))
#14 #12 AND #13
Contributions of authors
All authors contributed to this manuscript.
Declarations of interest
Differences between protocol and review
On the advice of the Cochrane Injuries Group's editors we have specified mortality as the primary outcome of the review. DVT and PE are listed as secondary outcomes.
Medical Subject Headings (MeSH)
Anticoagulants [therapeutic use]; Compression Bandages; Heparin, Low-Molecular-Weight [therapeutic use]; Pulmonary Embolism [etiology; *prevention & control]; Randomized Controlled Trials as Topic; Venous Thromboembolism [etiology; prevention & control]; Venous Thrombosis [etiology; *prevention & control]; Wounds and Injuries [blood; *complications]
MeSH check words
* Indicates the major publication for the study