trombocitopenia

Interventions for preventing venous thromboembolism in

adults undergoing knee arthroscopy (Review)

Ramos J, Perrotta C, Badariotti G, Berenstein G

This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library2011, Issue 3

http://www.thecochranelibrary.com

Interventions for preventing venous thromboembolism in adults undergoing knee arthroscopy (Review)

Copyright 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

T A B L E O F C O N T E N T S

1HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

1ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

2PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

2BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

3OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

3METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

4RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

5DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

6AUTHORS CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

6ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

7REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

8CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

13DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Analysis 1.1. Comparison 1 Prophylactic treatment (all LMWH) versus no treatment, Outcome 1 Participants with

thrombotic events (both clinical and through diagnostic procedure). . . . . . . . . . . . . . . . 13

Analysis 1.2. Comparison 1 Prophylactic treatment (all LMWH) versus no treatment, Outcome 2 Participants with clinical

thrombotic events. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14

Analysis 1.3. Comparison 1 Prophylactic treatment (all LMWH) versus no treatment, Outcome 3 Participants with adverse

events. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

15APPENDICES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

16FEEDBACK . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

16WHATS NEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

17HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

17CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

17DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

17SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

18INDEX TERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

iInterventions for preventing venous thromboembolism in adults undergoing knee arthroscopy (Review)


[Intervention Review]

Interventions for preventing venous thromboembolism inadults undergoing knee arthroscopy

Jorge Ramos1, Carla Perrotta2, Gustavo Badariotti3 , Graciela Berenstein4

1Department of Orthopedics, Hospital Britnico de Buenos Aires, Buenos Aires, Argentina. 2Woodview House, UCD School of Public

Health and Population Sciences, Dublin, Ireland. 3Internal Medicine, Sanatorio Mater Dei, Buenos Aires, Argentina. 4Epidemiology

Department, Hospital Nacional Dr Alejandro Posadas, Buenos Aires, Argentina

Contact address: Jorge Ramos, Department of Orthopedics, Hospital Britnico de Buenos Aires, Dorrego 1471, Victoria, Buenos Aires,

CP 1644, Argentina. [email protected].

Editorial group: Cochrane Peripheral Vascular Diseases Group.

Publication status and date: Edited (no change to conclusions), published in Issue 3, 2011.

Review content assessed as up-to-date: 13 December 2006.

Citation: Ramos J, Perrotta C, Badariotti G, Berenstein G. Interventions for preventing venous thromboembolism in

adults undergoing knee arthroscopy. Cochrane Database of Systematic Reviews 2008, Issue 4. Art. No.: CD005259. DOI:10.1002/14651858.CD005259.pub3.


A B S T R A C T

Background

Knee arthroscopy is a frequent surgical procedure. Arthroscopy procedures are considered minimally invasive. However, some patients

will need extended surgical time, suffer injury and immobilization thus increasing the risk for thromboembolic events. Incidence of

deep venous thrombosis (DVT) in patients undergoing knee arthroscopy is reported to be from 0.6% to 17.9% depending on the

diagnostic method used. Different approaches are available for thromboprophylaxis (mechanical or pharmacological).

Objectives

To assess the effectiveness and safety of thromboprophylaxis to reduce the incidence of DVT in patients undergoing knee arthroscopy.

Search methods

We searched the Cochrane Peripheral Vascular Diseases Group Specialized Register (last searched October 2006) the CENTRAL (last

searched Issue 4, 2006), MEDLINE (1966 to 2006), EMBASE (1980 to 2006), and Lilacs (1988 to 2006). We contacted specialists

known to be involved in phlebology and interested in post thrombotic syndrome for details of unpublished and ongoing trials.

Selection criteria

Randomized clinical trials (RCTs) and controlled clinical trials (CCTs), whether blinded or not (i.e. double blinded, single blinded or

unblinded) of all type of interventions, whether mechanical or pharmacological, single or in combination, used to prevent DVT in

males and females over 18 years old undergoing knee arthroscopy. There was no restriction on language.

Data collection and analysis

Two authors independently assessed trial quality and extracted data. Study authors were contacted for additional information.

1Interventions for preventing venous thromboembolism in adults undergoing knee arthroscopy (Review)


Main results

Four trials involving 527 predominantly male participants were included. The main weakness of the studies was the lack of correct

stratification of the arthroscopic intervention.

The relative risk (RR) of thrombotic events was 0.16 (95% confidence interval (CI); 0.05 to 0.52) comparing any type of lowmolecular

weight heparin (LMWH) versus placebo. All thrombotic events but one (pulmonary embolism in the LMWH group) were distal

venous thrombosis. Adverse events were most common in the intervention group than in the control group, RR 2.04 (95% CI 1.21

to 3.44). There were 66 episodes of adverse events. The number needed to harm was 20 for any adverse events.

Authors conclusions

This meta-analysis suggests that LMWH reduces the incidence of distal DVT diagnosed by sonogram. The clinical benefit of this is

uncertain. No strong evidence was found to conclude thromboprophylaxis is effective to prevent thromboembolic events and safe, in

people with unknown risk factors for thrombosis, undergoing knee arthroscopy.

P L A I N L A N G U A G E S U M M A R Y

Interventions for preventing venous thromboembolism in adults undergoing knee arthroscopy

Knee arthroscopy is a common, minimally invasive surgical procedure used both for diagnosis and treatment of knee conditions. It is

increasingly carried out in day surgery using various types of anaesthesia. Some people are at increased risk of developing deep vein

thrombosis (DVT) because of factors including a previous history, immobilization, smoking, obesity, varicose veins and increasing

age. Different approaches are available for preventing DVT (thromboprophylaxis), both mechanically and with drug medication. The

characteristic symptoms of DVT are limb pain and swelling (edema) but often there are no obvious signs or symptoms. DVT at or above

knee level (proximal) is associated with an increased risk of pulmonary embolism (which can be fatal) but isolated calf DVT (distal)

rarely causes symptoms and is asymptomatic. Arthroscopy patients are often young and soon become mobile again. The incidence of

DVT is reported to be from 0.6% when diagnosed clinically to 17.9% using the most sensitive imaging techniques (venography).

This review reports that low molecular weight heparin reduces the incidence of distal DVT diagnosed but the clinical benefits of this

are uncertain. The review authors identified four completed studies from three countries that randomly assigned a total of 527 adults

to low molecular weight heparin (LMWH) or no intervention or placebo. The mean age of participants ranged from 31 to 44 years

and nearly three quarters were male. The relative risk (RR) of thrombotic events was 0.16 (range 0.05 to 0.52). The number needed to

treat to prevent one thrombotic event was 17. All the blood clots were distal and were mainly diagnosed by sonogram. Adverse events

were most common in the intervention group. The most common complication was minor bleeding with a RR of 2.23 (range 0.99

to 4.99). The number needed to harm was 20. No completed studies were found that looked at mechanical devices such as graduated

elastic stockings or intermittent pneumatic compression, for patients immobilized in bed.

B A C K G R O U N D

Deep venous thrombosis (DVT) occurs when a blood clot devel-

ops within the venous system, typically in the lower limbs. The

characteristic symptoms of DVT are limb pain and edema but

often there will be no obvious signs or symptoms (asymptomatic

DVT). The risk of developing DVT depends on multiple factors

including a previous history of DVT, immobilization, smoking,

obesity, varicose veins, increasing age, trauma, any hypercoagula-

ble state (increased tendency for the blood to clot), and surgery.

Deep vein thrombosis increases the risk of pulmonary embolism

(PE) which can be fatal in 20% to 50% of cases, depending on the

population. After an episode of PE, 5% of patients have chronic

thromboembolic pulmonary hypertension (Hollerwerger 2000;

Kearon 2003).

Classically, DVT has been classified as proximal (thrombosis at or

above the popliteal vein) and distal, occurring below that level. The

distinction is important as while proximal DVT has been clearly

shown to increase the risk of pulmonary embolism (50% of people

with symptomatic proximal DVT will have PE in lung scans), the



clinical relevance of distal DVT is controversial in the literature.

The consensus is that isolated calf DVT is rarely symptomatic

(Kearon 2003). However, when DVT is both symptomatic and

untreated, 25%of cases may extend to the proximal veins (Kearon

2003 ) and thus increase the incidence of post thrombotic syn-

drome in the affected leg, characterized by chronic persistent pain,

swelling, and other signs in the affected limb, increased risk of

recurrent venous thromboembolism, and venous ulcers (5% to

10%) (Kahn 2002), or result in PE.

Diagnosis of DVT may be difficult in the absence of symptoms

and consequently it is often under diagnosed (50 % of DVT cases

are asymptomatic) (Delis 2001). Venography (phlebography) is

the gold standard diagnostic method for DVT, but it is difficult

to justify its use as a screening method in a low-risk population,

due to its invasive character. Sonography (ultrasound) is used as a

diagnostic method, with the variation in accuracy dependent on

the technique used. Higher sensitivity is achieved using duplex

(71%) and higher specificity (98%) using compression ultrasound

alone (Goodacre 2005).

Orthopedic surgery increases the risk of DVT. Knee arthroscopy

is a frequently performed surgical procedure in orthopedics, tra-

ditionally carried out on a young population, but the indication

for this procedure is now extending to older patients. Increasingly

arthroscopy is performed on an outpatient day-case basis with

early active/passive mobilization in the rehabilitation programs.

Arthroscopically-assisted surgery may be used for the treatment of

a variety of pathologies with different technical requirements for

example, washout, meniscectomy (removal of fibrocartilage from

the knee joint), anterior/posterior cruciate ligament reconstruc-

tion, lateral release, chondroplasty (repair of cartilage), articular

debridement (fibrosis, dead or infectedmaterial removal), synovial

resection, and tibial plateau fractures. Some of these procedures

may be considered minimally-invasive procedures; other proce-

dures require the use of a tourniquet, extended surgical time, and

can cause more soft tissue and bone damage. General anesthesia,

subarachnoid blockade, femoral blockade, intraarticular or com-

bined anesthesia, may be performed, each carrying independent

risks for DVT. The incidence of DVT in patients who undergo

venographically-screened, knee arthroscopy, is reported to be as

high as 17.9% (Demers 1998). Other studies report the incidence

of clinically diagnosed DVT as 0.6 % (Dahl 2000). If ultrasound

is used, the incidence is between 4.1% and 15.6% if ultrasound

is used (Michot 2002).

Surgeons generally agree that thromboprophylaxis should be used

in moderate and high risk patients who undergo surgery. Gradu-

ated elastic stockings and intermittent pneumatic compression are

mechanical devices used to prevent DVT, the latter often used in

patients immobilized in bed. There are different opinions about

whether or not prophylaxis should be used in knee arthroscopy,

partly reflecting different perceptions of the underlying risk of

DVT.

O B J E C T I V E S

To assess the effectiveness and safety of interventions, mechanical

or pharmacological, or in combination, for thromboprophylaxis

in adult patients undergoing knee arthroscopy.

M E T H O D S

Criteria for considering studies for this review

Types of studies

Randomized clinical trials (RCTs) and controlled clinical tri-

als (CCTs), whether blinded or not (i.e. double blinded, single

blinded or unblinded).

Types of participants

People over 18 years old undergoing knee arthroscopy. Trials of

arthroscopic-assisted osteosynthesis of tibial plateau fractures were

excluded.

Types of interventions

All type of interventions, whether mechanical or pharmacological,

single or in combination, used to prevent DVT in patients under-

going all types of knee arthroscopic interventions except arthro-

scopic-assisted osteosynthesis of tibial plateau fractures.

Types of outcome measures

Primary outcomes

Proximal and distal DVT events clinically, venographically

or sonographically diagnosed.

Pulmonary embolism diagnosed by V/Q lung scan, spiral

computed tomography (CT), or pulmonary angiography.

Death related to embolic events.

Secondary outcomes

Reported side/adverse effects.

Death.

Major bleeding (overt and requiring transfusion of red

blood cells or surgical interventions, and which may lead to

permanent disability).

Minor bleeding (did not meet the above major criteria for

intervention for example, hematoma, hemarthrosis,

thrombocytopenia (reduction of circulating platelets) of 50% of the initial count).



Search methods for identification of studies

Electronic searches

The Cochrane Peripheral Vascular Diseases (PVD) Group

searched their SpecializedRegister (last searched25October 2006)

and the Cochrane Central Register of Controlled Trials (CEN-

TRAL) inThe Cochrane Library (last searched Issue 4, 2006) for allpublications describing (or which might describe) RCTs or CCTs

of mechanical or pharmacological interventions used to prevent

DVT in patients undergoing knee arthroscopy.

The PVD Groups Specialized Register contains citations of tri-

als identified through electronic searches of MEDLINE (1966

to date); EMBASE (1980 to date); CINAHL (1982 to date);

and through handsearching journals and conference proceedings.

The full list of journals that have been handsearched, as well

as the search strategies used to search databases are described

in the editorial information about the Cochrane PVD Group

in The Cochrane Library http://www.mrw.interscience.wiley.com/cochrane/clabout/articles/PVD/frame.html.

For details of the search strategy used to search CENTRAL see(Appendix 1).

We also searched the following electronic databases according to

the methods described in the Cochrane Handbook for Systematic

Reviews of Interventions (Higgins 2005):

(1)MEDLINE from1966 toOctober 2006 using the search terms

thrombotic [in all fields] AND arthro* [in all fields] AND pro-

phy* [in all fields] OR preven* [in all fields], AND Hepar*[in all

fields] combined with the MEDLINE search strategies for ran-

domized controlled trials suggested by the Cochrane Collabora-

tion Handbook;

(2) EMBASE from 1980 to October 2006;

(3) Lilacs from 1988 to October 2006.

Searching other resources

In addition,we searched the reference lists of identified studies, and

articles and abstracts of international meetings of Orthopedics,

Hematology andThrombosis journals from the year 1998 to2004.

We contacted specialists known to be involved in phlebology and

interested in post thrombotic syndrome for details of unpublished

and ongoing trials. There were no restrictions on language.

Data collection and analysis

Study Selection

Two authors (J Ramos and G Badariotti) independently screened

the initial results of all the databases and references lists to identify

citations which seemed relevant to our review. Once identified, we

checked the citations and abstracts and, if the inclusion criteria

were met, we obtained the full text articles. Both authors decided

independently on trial inclusion using a standard form. The third

author (C Perrota) resolved any disagreements.

Quality assessment

J Ramos and G Badariotti evaluated each trial. The assessment of

quality included:

(1) The quality of allocation concealment categories:

Category A: adequate concealment

Category B: uncertain, indication of adequate

Category C: inadequate concealment

(2) Blinding: we evaluated if investigators, participants, outcome

assessor and data analysts were blinded to the treatment status. For

each one we commented yes, no, or not stated.

(3) Intention-to-treat analysis: we specified if the analysis was done

on an intention-to-treat basis (specifically reported by the authors,

or confirmed after reading the paper), or if the analysis was done

without intention-to-treat analysis, or if it was unclear in the arti-

cle.

(4) Completeness of follow up: we checked the number of partic-

ipants with data against the number of participants randomized,

expressed as a percentage overall, and in each intervention group.

Data extraction

J Ramos and G Badariotti independently extracted data. C Perrota

resolved any disagreements.When necessary, we sought additional

information from authors of relevant articles.

Data analysis

C Perrota entered the independently extracted data into RevMan.

We analyzed dichotomous outcomes as relative risks and recorded

their 95% confidence intervals. We combined the results using a

random-effects model to assess overall treatment effects. We used

a test of heterogeneity (chi-square) to assess potential differences

between trials. We explored the results from different methods

of outcome assessment, specifically the clinical diagnosis of DVT

compared with other methods. We planned other sensitivity anal-

yses if there was significant heterogeneity. First we excluded indi-

vidual studies one at time to assess whether any individual study

excessively influenced the analyses and then we excluded lower

quality studies without allocation concealment from the analyses

of primary outcomes.

R E S U L T S



Description of studies

See:Characteristics of included studies; Characteristics of excluded

studies; Characteristics of ongoing studies.

We identified six potentially eligible trials, of which four met the

review inclusion criteria (Canata 2003; Michot 2002; Roth 1995;

Wirth 2001). We excluded one trial (Marlovits 2004) that tested

the effects of extending the duration of LMWH prophylaxis (seeCharacteristics of excluded studies table). The remaining trial by

Camporese et al (KANT Study) which compares two regimens of

Nadroparin with elastic stocking for seven days is described in the

Characteristics of ongoing studies table.We contacted the author

(last contact on December 2005) who confirmed that enrollment

was complete. Future updates of this review will discuss the results

of this trial.

Details of the four included trials are given in the Characteris-

tics of included studies table. Three trials (Michot 2002; Roth

1995; Wirth 2001) were published as full reports; Canata 2003

is only available as an abstract for a conference poster. The four

trials were single centre studies conducted in three countries (Italy,

Switzerland, and two in Germany). All four included trials com-

pared different regimens of thromboprophylaxis versus no inter-

vention (control group). Overall, 527 predominantly male (aver-

age 70%) adults (trial mean ages where given, range from 31 to

44 years) were randomized between the two groups in the four

trials. The type of knee arthroscopy intervention performed varied

across studies: ACL reconstruction was done by the same surgeon

in Canata 2003; and ambulatory meniscus arthroscopy surgery

in Roth 1995. Michot 2002 included both diagnostic procedures

and a variety of therapeutic interventions, with ACL reconstruc-

tion. Over half of the participants in Wirth 2001 had a partial

meniscectomy; none of the rest had a ligamentous reconstruction.

History of previous DVT was an exclusion criterion and potential

risk factors were taken into account in both the Wirth 2001 and

Michot 2002 studies as well as use of tourniquet and type of

anesthesia. These topics were not as well established in Roth 1995

and Canata 2003.

The outcomes assessed were clinical suspicion of venous thrombo-

sis or PE as the only outcome in one study (Canata 2003), clinical

suspicion of venous thrombosis or PE andDVT evaluated through

compression sonography were assessed in the other three (Michot

2002; Roth 1995; Wirth 2001).

All studies evaluated minor and major bleedings or other relevant

adverse events.

Risk of bias in included studies

Two studies had acceptable quality standards (Michot 2002;Wirth

2001). Both studies randomized participants although themethod

of allocationwas not reported. Blindingwas intended inboth stud-

ies however Wirth 2001 did not report how blinding was secured

in those who performed the sonograms. Inclusion and exclusion

criteria were clear as well as the analysis undertaken. Wirth 2001

excluded four patients in the control group from the intention-to-

treat analysis (not having had tourniquet or general anesthesia or

both) and reported to do so trying to gain homogeneity. Loss of

follow up was 8% in the intervention group (5/65) and 2% in the

control group (1/64) (Michot 2002) and 7% of patients withdraw

their informed consent in Wirth 2001.

Canata 2003 andRoth 1995were the poorest quality trials. In both

studies allocation methods and how randomization was achieved

were not described. Inclusion and exclusion criteria were not de-

scribed and intention-to-treat analysis was not done. Adverse event

definitions are not clear.

Effects of interventions

The relative risk (RR) of thrombotic events (all sites, diagnosed

both clinically and by ultrasound) was 0.16 (95% Confidence In-

terval (CI) 0.05 to 0.52). This RR was obtained through pool-

ing data from the four studies with an overall 527 participants

(Canata 2003; Michot 2002; Roth 1995; Wirth 2001) evaluating

any LMWHversus no treatment before or after the procedure. In

these four studies all but one thrombotic events were distal DVT

(one event of pulmonary embolism inMichot 2002). Canata 2003

did not report any thrombotic events therefore its RR was not

estimable and has no effect on the calculated pooled RR.

Considering all the studies, there were three distal DVT in the

LMWH and one PE compared to 20 DVT in those who received

no treatment. We did a sensitivity analysis including only higher

quality studies and the RR did not change (RR 0.14; 95%CI 0.03

to 0.61) (Michot 2002;Wirth 2001). The number needed to treat

to prevent one thrombotic event was 17.

We intended to extract data only in those episodes of DVT that

were first noticed through clinical diagnosis. Only Wirth 2001

reported this outcome clearly and three patients out of 239 had

clinical symptoms of DVT (all in the control group) and the cal-

culated RR was 0.15 (95% CI 0.01 to 2.85 P < 0.21).

Therewas only one episode of PE (in the treatment group) (Michot

2002).

Adverse events were most common in the intervention group than

in the control group with a RR 2.04 (95%CI 1.21 to 3.44). There

were 66 episodes of any adverse events, including allergies, one

patient with transient low levels of platelets, minor gastrointestinal

bleeding, two episodes of hemarthrosis in the intervened knee.

The most common complication was minor bleeding with a RR

of 2.23 (95% CI 1.99 to 4.99). The number needed to harm was

20.

We did not find heterogeneity in any of the comparisons made.

D I S C U S S I O N



The RR of distal DVT (combining both clinically and sonogram-

diagnosed DVT) comparing LMWH with no intervention for

knee arthroscopy was 0.16 (95% CI 0.05 to 0.52) and the RR of

any adverse events because of the intervention was RR 2.04 (95%

CI 1.21 to 3.44). The RR for clinically relevant thrombosis was

not statistically significant. All the thromboses were distal and the

majority were diagnosed by sonogram. There was no difference

between groups in relation to those DVT that were clinically rel-

evant.

The incidence of DVT during arthroscopy varies from 3.1% to

17.9% in a meta-analysis by Ilahi et al (Ilahi 2005). However, the

question we are looking for an answer to is: what is the clinical

relevance of distal thrombosis diagnosed through sonogram? The

literature is not conclusive in this area. The incidence of PE in

distal asymptomatic DVT varies between 1.6% and 21% (Haas

1992; Kazmers 1999) and it is probably related to the patient risk

factors and type of thrombosis (Kearon 2003).

When performing arthroscopy, we are picturing a usually healthy

individual who will undergo a minor intervention. As in any other

medical intervention, the risk should outweigh the benefit. We

should weigh the risk of having a distal thrombosis with its un-

predictable and quite low incidence outcomes against the mi-

nor complications caused by LMWH administration (although

some may argue that having a minor gastrointestinal bleeding or

hemarthrosis should not be called minor in these patients since

both will require intervention). It is difficult with only four studies

(and with only two good quality studies) to draw a conclusion. An

additional factor that should be taken into account is the cost of

treatment.

According to the results of a meta-analysis (Goodacre 2005), com-

pression ultrasound seems to be appropriate as a screening method

in this low risk population where high specificity is required to

avoid false positive results.

The number needed to treat to benefit (NNTB) (17) relates to

asymptomatic DVT, and the number needed to harm (NNTH)

(20) is about a clinical event. Assuming a ratio of asymptomatic

distal DVT to clinically apparentDVTof 1:10 to 1:20, theNNTB

to prevent a clinical event would range from 170 to 340, with 8.5

to 17 times as frequent as harm occurring.

We conclude that the physician needs to discuss these benefits and

possible complications with the patient until new studies are per-

formed. It is essential that future studies stratify patients according

to their risk factors, and also stratify arthroscopic procedures.

Since knee arthroscopy is a widely-used method and each center

may have its own guidelines on procedures, it would be helpful

to set up surveillance methods in each center to detect either ad-

verse events or thrombotic events, with and without the use of

LMWH. Future epidemiological studies as well as clinical trials

will be needed to assess the natural history of non-clinical distal

DVT in these patients.

Studies should be carried out to evaluate the efficacy of mechanical

methods in knee arthroscopy for the prevention of thrombotic

events.

A U T H O R S C O N C L U S I O N S

Implications for practice

The meta-analysis showed a reduction in the number of distal

thrombosis diagnosed through sonogram.

Although this review suggests that some benefit may be obtained

from prophylaxis, we considered only two studies to be of ade-

quate methodological quality with small sample size, and poorly

defined or stratified in their arthroscopic intervention. No studies

on mechanical devices alone were found, other than the ongoing

combined protocol (Camporese 2003a).

No strong evidence was found to conclude thromboprophylaxis is

effective in preventing thromboembolic events in people under-

going knee arthroscopy with unknown risk factors for DVT.

Implications for research

Arthroscopic surgery includes different types of interventions with

different operation times, techniques, injury, recovery time, and

return to activity.

Future studies need to stratify patients according to their risk fac-

tors, and type of arthroscopic procedure. Surveillance studies will

be important to assess the detection of both adverse events and

thrombotic events, with and without the use of LMWH.

A C K N OW L E D G E M E N T S

The authors would like to thank the contribution made to the

Plain Language Summary by Dr Janet Wale of the Consumer

Network.



R E F E R E N C E S

References to studies included in this review

Canata 2003 {published data only}

Canata GL, Chiey A. Prevention of venous

thromboembolism after ACL reconstruction: a prospective,

randomized study. ISAKOS (International Society of

Arthroscopy, Knee Surgery and Orthopaedic Sports

Medicine). 2003; Vol. Poster 712003.

Michot 2002 {published data only}

Michot M, Conen D, Holtz D, Erni D, Zumstein MD,

Ruflin GB, et al.Prevention of deep-vein thrombosis in

ambulatory arthroscopic knee surgery: A randomized

trial of prophylaxis with low-molecular weight heparin.

Arthroscopy 2002;18(3):25763.

Roth 1995 {published data only}

Roth P. Prophylaxis of deepvein thrombosis in

outpatients undergoing arthroscopic meniscus operation

[Thromboembolieprophylaxe bei ambulant durchgefrten

arthroskopischen Meniskusoperationen]. Orthopdische

Praxis 1995;5:3458.

Wirth 2001 {published data only}

Wirth T, Schneider B, Misselwitz F, Lomb M, Tyl H,

Egbring R, et al.Prevention of venous thromboembolism

after knee arthroscopy with low-molecular weight heparin

(Reviparin): Results of a randomized controlled trial.

Arthroscopy 2001;17(4):3939.

References to studies excluded from this review

Marlovits 2004 {published data only}

Marlovits S, Striessnig G, Schuster R, Stocker R, Luxl

M, Trattnig R, et al.A prospective, randomized, placebo-

controlled study of extended-duration post-discharge

thromboprophylaxis with enoxaparin following arthroscopic

reconstruction of the anterior cruciate ligament. Blood

2004;104(11 Part 1):Abstract 1764.

References to ongoing studies

KANT Study {published data only}

Camporese G, Bernardi E, NTita K, Verlato F, Salmistraro

G, Cordova R, et al.Different thromboprophylaxis

approaches in patients undergoing knee arthroscopy

(KANT Study): A prospective randomized study. Journal

of Thrombosis & Haemostasis. 3 2005; Vol. 3, issue 1:

Abstract number: P1618.

Camporese G, Bernardi E, Prandoni P, Noventa F, Verlato

F, Simioni P, et al.Low-molecular-weight heparin versus

compression stockings for thromboprophylaxis after knee

arthroscopy: a randomized trial. Annals of Internal Medicine

2008;149(2):7382.

Camporese G, NTita K, Rossi F, Bernardi E, Verlato

F, Salmistraro G, et al.Different thromboprophylaxis

approaches in patients undergoing knee arthroscopy

(KANT study): interim report of prospective randomized

study. Journal of Thrombosis & Haemostasis. 1 2003; Vol.

1, issue Suppl 1:Abstract P1888.

Additional references

Dahl 2000

Dahl OE, Gudmunsen TE, Haukeland L. Late occurring

clinical deep vein thrombosis in joint-operated patients.

Acta Orthopaedica Scandinavaca 2000;71(1):4750.

Delis 2001

Delis KT, Hunt N, Strachan RK, Nicolaides AN. Incidence,

natural history and risk factors of deep vein thrombosis in

elective knee arthroscopy. Thrombosis & Haemostasis 2001;

86(3):81721.

Demers 1998

Demers C, Marcoux S, Ginsberg JS, Laroche F, Cloutier R,

Poulin J. Incidence of venographically proved deep vein

thrombosis after knee arthroscopy. Archives of Internal

Medicine 1998;158(1):4750.

Goodacre 2005

Steve Goodacre, Fiona Sampson, Steve Thomas, Edwin van

Beek, Alex Sutton. Systematic review and meta-analysis of

the diagnostic accuracy of ultrasonography for deep vein

thrombosis. BMC Medical Imaging 2005;5:6.

Haas 1992

Hass SB, Tribus CB, Insall JN, Becker MW, Windsor RE.

The significance of calf thrombi after total knee arthroplasty.

Journal of Bone & Joint Surgery - British Volume 1992;74(6):

799802.

Higgins 2005

Higgins JPT, Green S, editors. Cochrane Handbook for

Systematic Reviews of Interventions 4.2.5 [updated May

2005]. The Cochrane Library [database on CDROM]. The

Cochrane Collaboration, Chichester, UK: John Wiley &

Sons Ltd; 2005, issue 3.

Hollerwerger 2000

Hollerweger A, Macheiner P, Rettenbacher T, Gritzmann

N. Sonographic diagnosis of thrombosis of the calf muscle

veins and the risk of pulmonary embolism. Ultraschall in

der Medizin 2000;21(2):6672.

Ilahi 2005

Ilahi O, Reddy J, Ahmad I. Deep venous thrombosis after

knee arthroscopy: a meta-analysis. Artrhoscopy 2005;21(6):

72730.

Kahn 2002

Kahn SR, Ginsberg JS. The post-thrombotic syndrome:

current knowledge, controversies, and directions for future

research. Blood Reviews 2002;16(3):15565.

Kazmers 1999

Kazmers A, Groehn H, Meeker C. Acute calf vein

thrombosis: outcomes and implications. American Surgeon

1999;65(12):11247.

Kearon 2003

Kearon C. Natural history of venous thromboembolism.

Circulation 2003;107(23 Suppl 1):12230.



Indicates the major publication for the study

C H A R A C T E R I S T I C S O F S T U D I E S

Characteristics of included studies [ordered by study ID]

Canata 2003

Methods Study design: prospective, randomized controlled trial.

Method of randomization: not stated.

Concealment of allocation: not stated.

Intention to treat: no.

Participants Country: Italy.

Setting: hospital.

Number: 36; 18 in each group.

Age: (mean) treatment group 29.6 years (range 22 to 59); control group 32.5 years (range 16 to 59)

Sex: treatment group 12 males, 6 females; control group 13 males, 5 females

Inclusion criteria: symptomatic ACL-deficient knees.

Exclusion criteria: none stated.

Interventions Treatment: LMWH (enoxaparin sodium) sc daily (no dose specified)

Control: no intervention.

Duration: 6 days.

Outcomes Compression color-coded sonography in case of clinically-suspected venous thrombosis; major (no cases)

and minor bleeding (2 in the intervention group and 3 in the control); range of motion

Notes Surgery : ACL reconstruction performed by the same surgeon using a single technique and the same

rehabilitation protocol

Risk of bias

Item Authors judgement Description

Allocation concealment? Unclear B - Unclear

Michot 2002

Methods Study design: prospective, single-blind, randomized controlled trial


Concealment of allocation: sealed envelope.

Losses to follow up: treatment group 5; control group 1.

Intention to treat: yes.

Participants Country: Switzerland.

Setting: hospital outpatient department.

Number: 130; treatment group 66; control group 64.



Michot 2002 (Continued)

Age: (mean) treatment group 42.0 years (SD 14.7); control group 46.5 years (SD 13.2)


Inclusion criteria: patients requiring diagnostic or therapeutic arthoscopic knee surgery as outpatients;

aged 18 to 80 years

Exclusion criteria: inability or unwillingness to give written informed consent; past medical history of

DVT or PE, known deficiency of AT III, Protein C or Protein S; ongoing anti-thrombotic therapy, history

of GI bleeding in the previous 2 weeks; hypersensitivity to heparin; history of CVA in the previous 6

months; or severe renal or hepatic failure

All patients underwent bilateral compression ultrasonography of the legs the day before the operation.

Preoperative ultrasonography was inconclusive in 5 patients and revealed DVT in 2 patients

Included patients with independent risk factors for deep thrombosis

Interventions Treatment: First dose of LMWH sc (2,500 IU anti-FXa deltaparin; Low Liquemin, Roche, Basel, Switzer-

land) 60 to 120 minutes before starting the procedure

Six hours after the end of the operation, a second, weight-adapted dose (2,500 IU if weight < 70 kg, 5,

000 if > 70 kg) was administered, and daily up to 30 days postoperatively

Control: no treatment.

Duration: 30 days.

Outcomes Patients were seen on days 12 and 31 post operation for systematic questioning for symptoms of DVT and

PE, or bleeding complications and bilateral compression ultrasonography (US). If US was not conclusive,

venography was performed

Lower limb DVT was diagnosed in 10 patients in the control group (15.6%) and 1 in the intervention

group (1.5%)

All DVTs occurred in the operated leg.

Notes Sample size was calculated at 400 patients was calculated to be the sample size but the trial was stopped

at 130 because it was decided that witholding LMWH was unethical. A wide variety of procedures was

carried out

Risk of bias



Roth 1995

Methods Study design: prospective, randomized controlled trial.



Exclusions post randomization: 22 due to non-compliance.

Intention to treat: no

Participants Country: Germany.

Setting: hospital outpatient department.

Number: 122, (n = 61 in each group) (144 randomized, 22 excluded)

Age: Included patients more than 60 years old.

Sex: not stated.



Roth 1995 (Continued)

Inclusion criteria: patients undergoing ambulatory arthroscopic meniscus intervention, sinovectomy,

chondroplasty, loose-bodies resection

Included patients with independent risk factors for thrombosis

Interventions Treatment: 0.3 ml sc fraxiparine 2 hours before the operation and self administered daily (except the first

two doses) for 4 days after surgery


Duration: 4 days.

Outcomes Lower limb DVT and PE; bleeding; hematomas; allergic reactions were clinically evaluated 6 to 8 weeks

after surgery

DVT (6, one in the intervention group) were diagnosed, and venographically confirmed, all in the operated

limb. Venography indication was established after clinical assessment or ultrasonography. No PE was

detected (gammagraphy). No full weight bearing was allowed up to the 5th day

Five hematomas were found in the intervention group, and one in the control

Notes Originally they were 144 patients but 22 were excluded due to non-compliance

Risk of bias



Wirth 2001

Methods Study design: prospective, randomized, controlled, blinded-outcome assessment trial



Exclusions pre-randomization: 23.

Withdrawals: 17 (withdrew informed consent).

Intention to treat: yes.

Participants Country: Germany.

Setting: hospital.

Number: 239, treatment group 117; control group 122; 222 completed the trial, 111 in each group

Age: year SD, treatment group 37.6 13.0; control group 38.5 11.6


Inclusion criteria: elective knee arthroscopy.

Exclusion criteria: pregnant; < 18 years; history of DVT; or contraindication to contrast venography or

trial medication

Patients also screened for additional risk factors (obesity, nicotine abuse, oral contraceptives and family

history of thrombosis). If 3 or more present, patients were excluded

Interventions Treatment: once daily injection of reviparin (1,750 anti Xa IU equivalent to 0.25 ml, sc) (Clivarin; Knoll

Deutchland GmbH, Ludwingshafen, Germany)


Duration: 7 to 10 days.



Wirth 2001 (Continued)

Outcomes Primary: DVT diagnosed by compression color-coded ultrasonography and clinically symptomatic pul-

monary embolism at days 7 to 10, or earlier in case of clinical symptoms

6 of 239 (2.5%), 5 (4.1%) in the control group, and 1 (0.85%) in the intervention group, had ultrasound

criteria for distal DVT. Four patients had minor bleeding complications (one in the control and three in

the intervention group)

4 patients (not having had tourniquet and/or general anesthesia) were excluded to achieve homogenity

Notes Population size was calculated to be 196 patients in each group to detect a significant difference with an

alpha of 0.05 and a power of 0.80,

262 patients were eligible, 23 met exclusion criteria.

An interim analysis was planned after completion of 50% or 15 thromboembolic events, whichever

occured first

Risk of bias



ACL: anterior cruciate ligament

AT III: antithrombin III

CVA: cerebrovascular accident

DVT: deep vein thrombosis

GI: gastrointestinal

LMWH: low molecular weight heparin

PE: pulmonary embolism

sc: subcutaneous

Characteristics of excluded studies [ordered by study ID]

Study Reason for exclusion

Marlovits 2004 Evaluate the efficacy of an extended treatment with LMWH. Patients were randomly assigned to receive LMWH

until days 3 to 8 or until 20 days after surgery

As the goal of this trial was to assess the efficacy of an extended prophylaxis treatment, there is no comparison

with no treatment

LMWH: low molecular weight heparin



Characteristics of ongoing studies [ordered by study ID]

KANT Study

Trial name or title KANT Study (Knee Arthroscopy Nadroparin Thromboprophylaxis)

Methods Assessor-blinded, randomized controlled trial.

Participants Consecutive patients undergoing knee arthroscopy for menisci lesions or for ACL or cartilage reconstruction

were eligible for inclusion

Interventions Full length graduated compression stockings for 7 days (group A); or Nadroparin 0.4 ml sc once daily for 7

days (group B); or Nadroparin 0.4 ml sc once daily for 14 days (group C)

Outcomes Thromboembolic events.

Starting date Not available

Contact information

Notes Enrollment is complete (a total of 2043 consecutive patients were considered, 282 were excluded and the

remaining 1761 patients wre assigned to treatment). Definitive results will be reported in 2008

ACL: anteior cruciate ligament

sc: subcutaneous



D A T A A N D A N A L Y S E S

Comparison 1. Prophylactic treatment (all LMWH) versus no treatment

Outcome or subgroup titleNo. of

studies

No. of

participants Statistical method Effect size

1 Participants with thrombotic

events (both clinical and

through diagnostic procedure)

4 527 Risk Ratio (M-H, Random, 95% CI) 0.16 [0.05, 0.52]

2 Participants with clinical

thrombotic events

4 529 Risk Ratio (M-H, Random, 95% CI) 0.42 [0.06, 3.14]

3 Participants with adverse events 4 Risk Ratio (M-H, Random, 95% CI) Subtotals only

3.1 All adverse events 4 527 Risk Ratio (M-H, Random, 95% CI) 1.92 [0.97, 3.80]

3.2 Minor bleedings 4 527 Risk Ratio (M-H, Random, 95% CI) 2.23 [0.99, 4.99]

Analysis 1.1. Comparison 1 Prophylactic treatment (all LMWH) versus no treatment, Outcome 1

Participants with thrombotic events (both clinical and through diagnostic procedure).

Review: Interventions for preventing venous thromboembolism in adults undergoing knee arthroscopy

Comparison: 1 Prophylactic treatment (all LMWH) versus no treatment

Outcome: 1 Participants with thrombotic events (both clinical and through diagnostic procedure)

Study or subgroup Treatment Control Risk Ratio Risk Ratio

n/N n/N

M-H,Random,95%

CI

M-H,Random,95%

CI

Canata 2003 0/18 0/18 0.0 [ 0.0, 0.0 ]

Michot 2002 1/66 10/64 0.10 [ 0.01, 0.74 ]

Roth 1995 1/61 5/61 0.20 [ 0.02, 1.66 ]

Wirth 2001 1/117 5/122 0.21 [ 0.02, 1.76 ]

Total (95% CI) 262 265 0.16 [ 0.05, 0.52 ]

Total events: 3 (Treatment), 20 (Control)

Heterogeneity: Tau2 = 0.0; Chi2 = 0.34, df = 2 (P = 0.84); I2 =0.0%

Test for overall effect: Z = 3.01 (P = 0.0026)

0.01 0.1 1 10 100

Favours treatment Favours control




Participants with clinical thrombotic events.



Outcome: 2 Participants with clinical thrombotic events

Study or subgroup Treatment Control Risk Ratio Risk Ratio

n/N n/N

M-H,Random,95%

CI

M-H,Random,95%

CI

Canata 2003 0/18 0/18 0.0 [ 0.0, 0.0 ]

Michot 2002 0/66 0/64 0.0 [ 0.0, 0.0 ]

Roth 1995 1/61 1/63 1.03 [ 0.07, 16.15 ]

Wirth 2001 0/117 3/122 0.15 [ 0.01, 2.85 ]

Total (95% CI) 262 267 0.42 [ 0.06, 3.14 ]




0.001 0.01 0.1 1 10 100 1000





Participants with adverse events.



Outcome: 3 Participants with adverse events

Study or subgroup Treatment Control Risk Ratio Weight Risk Ratio

n/N n/N

M-H,Random,95%

CI

M-H,Random,95%

CI

1 All adverse events

Canata 2003 3/18 2/18 16.8 % 1.50 [ 0.28, 7.93 ]

Michot 2002 8/66 4/64 35.2 % 1.94 [ 0.61, 6.12 ]

Roth 1995 7/61 1/61 10.9 % 7.00 [ 0.89, 55.20 ]

Wirth 2001 7/117 5/122 37.1 % 1.46 [ 0.48, 4.47 ]

Subtotal (95% CI) 262 265 100.0 % 1.92 [ 0.97, 3.80 ]




2 Minor bleedings

Canata 2003 3/18 2/18 23.4 % 1.50 [ 0.28, 7.93 ]

Michot 2002 8/66 4/64 49.2 % 1.94 [ 0.61, 6.12 ]

Roth 1995 5/61 1/61 14.5 % 5.00 [ 0.60, 41.55 ]

Wirth 2001 3/117 1/122 12.9 % 3.13 [ 0.33, 29.65 ]

Subtotal (95% CI) 262 265 100.0 % 2.23 [ 0.99, 4.99 ]




0.01 0.1 1 10 100




A P P E N D I C E S

Appendix 1. CENTRAL search strategy

#1 MeSH descriptor Arthroscopy explode all trees

#2 arthroscop*

#3 knee near arthroscop*

#4 meniscectom*

#5 (#1 OR #2 OR #3 OR #4)

#6 MeSH descriptor Venous Thrombosis explode all trees

#7 MeSH descriptor Venous Thromboembolism explode all trees

#8 veno* or vein near thrombo*

#9 DVT

#10 MeSH descriptor Pulmonary Embolism, this term only

#11 pulmonary embol* or PE

#12 (#6 OR #7 OR #8 OR #9 OR #10 OR #11)

#13 (#5 AND #12)

F E E D B A C K

Anticoagulant feedback, 14 February 2011

Summary

Feedback received on this review, and other reviews and protocols on anticoagulants, is available on the Cochrane Editorial Unit website

at http://www.editorial-unit.cochrane.org/anticoagulants-feedback.



WH A T S N E W

Last assessed as up-to-date: 13 December 2006.

Date Event Description

14 February 2011 Amended Link to anticoagulant feedback added

H I S T O R Y

Protocol first published: Issue 2, 2005

Review first published: Issue 2, 2007

Date Event Description

5 August 2008 New citation required but conclusions have not changed Amendment to correct spelling error in title and labelling

of one of the graphs. Additional reference for ongoing

study (KANT Study) added

31 July 2008 Amended Converted to new review format.

C O N T R I B U T I O N S O F A U T H O R S

Jorge Ramos identified and selected potential trials, evaluated trial quality, and extracted data.

Gustavo Badariotti identified and selected potential trials, evaluated trial quality, and extracted data.

Carla Perrotta extracted data from selected trials, analyzed the results, and revised the text of the review.

Graciela Berestein contributed to the text of the review.

D E C L A R A T I O N S O F I N T E R E S T

None known.



S O U R C E S O F S U P P O R T

Internal sources

No sources of support supplied

External sources

Chief Scientist Office, Scottish Government Health Directorates, The Scottish Government, UK.

National Academy of Medicine, Centre for Epidemiologic Research, Cochrane Center, Argentina.

I N D E X T E R M S

Medical Subject Headings (MeSH)

Anticoagulants [therapeutic use]; Arthroscopy [adverse effects]; Heparin, Low-Molecular-Weight [therapeutic use]; Knee Joint

[surgery]; Randomized Controlled Trials as Topic; Stockings, Compression; Venous Thrombosis [prevention & control]

MeSH check words

Adult; Humans



trombocitopenia

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