Tromboza Ghid ACCP GUIDELINES

8/10/2019 Tromboza Ghid ACCP GUIDELINES

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CHEST Supplement

www.chestpubs.org CHEST / 141 / 2 / FEBRUARY, 2012 SUPPLEMENT 7S

ANTITHROMBOTIC THERAPY AND PREVENTION OF THROMBOSIS, 9TH ED: ACCP GUIDELINES

T he eighth iteration of the American College ofChest Physicians Antithrombotic Guidelines pre-sented, in a paper version, a narrative evidence sum-mary and rationale for the recommendations, a smallnumber of evidence proles summarizing bodies of

evidence, and some articles with quite extensivesummary tables of primary studies. In total, thisrepresented 600 recommendations summarized in968 pages of text. Many readers responded that theresult was too voluminous for their liking or prac-tical use.

Cognizant of this feedback, we worked hard tominimize the length of the text for the ninth iterationof the guidelines Antithrombotic Therapy and Pre- vention of Thrombosis, 9th ed: American College ofChest Physicians Evidence-Based Clinical PracticeGuidelines (AT9) without sacricing key content. Anumber of topic editors found our shortening editsdraconian, but we were determined to produce theleanest product possible.

There were, however, a number of obstacles. In what we believe is a key advance in AT9, we con-ducted a systematic review of what is known aboutpatients values and preferences regarding antithrom-botic therapy and included the results as an articlein AT9. In another forward step, we recognized theproblems with asymptomatic thrombosis as a surro-gate outcome, and devised strategies to estimatereductions in symptomatic DVT and pulmonaryembolism with antithrombotic prophylaxis. We felt itimportant to explain this innovation to users of AT9,and this meant another article.

We included, for the rst time, an article on diag-nosis addressing patients with symptoms and signssuggesting DVT. We increased the range of interven-tions we have covered, resulting in additional recom-mendations. Finally, we produced many summaryof ndings tables, which offer extremely succinct andinformative presentations of best estimates of effectand the condence associated with those estimates.

If published in the same fashion as the Antithrom-botic and Thrombolytic Therapy, 8th ed: American

Abbreviations: ACS5 acute coronary syndrome; AF5 atrialbrillation; AIS5 arterial ischemic stroke; APLA5 antiphospolipidantibodies; ASA5 acetylsalicylic acid; AT95 AntithromboticTherapy and Prevention of Thrombosis, 9th ed: AmericanCollege of Chest Physicians Evidence-Based Clinical PracticeGuidelines; BMS5 bare-metal stent; CABG5 coronary arterybypass graft; CAD5 coronary artery disease; CDT5 catheter-directed thrombosis; CHADS2 5 congestive heart failure, hyperten-sion, age 75 years, diabetes mellitus, prior stroke or transientischemic attack; CSVT5 cerebral sinovenous thrombosis; CTPH5 chronic thromboembolic pulmonary hypertension; CUS5 com-pression ultrasound; CVAD5 central venous access device;DES 5 drug-eluting stent; GCS5 graduated compression stockings;HFS 5 hip fracture surgery; HIT 5 heparin-induced thrombocy-topenia; HITT 5 heparin-induced thrombocytopenia complicatedby thrombosis; IA5 intraarterial; ICH 5 intracerebral hemor-rhage; IE 5 infective endocarditis; INR5 international normalizedratio; IPC 5 intermittent pneumatic compression; IPCD 5 inter-mittent pneumatic compression device; IVC5 inferior vena cava;LDUH 5 low-dose unfractionated heparin; LMWH5 low-molecular- weight heparin; LV5 left ventricular; MBTS5 modied Blalock-Taussig shunt; MR5 magnetic resonance; PAD5 peripheral arterydisease; PCI5 percutaneous coronary inter vention; PE 5 pul-monary embolism; PFO5 patent foramen ovale; PMBV5 percuta-neous mitral balloon valvotomy; PTS5 postthrombotic syndrome;PVT5 prosthetic valve thrombosis; r-tPA5 recombinant tissue plas-minogen activator; RVT5 renal vein thrombosis; SC5 subcuta-

neous; TEE 5 transesophageal echocardiography; THA5 totalhip arthroplasty; TIA5 transient ischemic attack; TKA5 total kneearthroplasty; UAC5 umbilical arterial catheter; UEDVT5 upper-extremity DVT; UFH5 unfractionated heparin; US5 ultrasound;UVC5 umbilical venous catheter; VAD5 ventricular assist device; VKA5 vitamin K antagonist

Executive Summary

Antithrombotic Therapy and Prevention of Thrombosis,9th ed: American College of Chest PhysiciansEvidence-Based Clinical Practice Guidelines

Gordon H. Guyatt , MD, FCCP ; Elie A. Akl , MD, PhD, MPH ; Mark Crowther , MD ;David D. Gutterman , MD, FCCP ; Holger J. Sch nemann , MD, PhD, FCCP ; for the AmericanCollege of Chest Physicians Antithrombotic Therapy and Prevention of Thrombosis Panel*

CHEST 2012; 141(2)(Suppl):7S47S

wnloaded From: http://journal.publications.chestnet.org/ on 01/08/2014


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8S Executive Summary

tables) and some tables summarizing the methodsand results, and the risk of bias, associated with theindividual studies that contributed to the evidenceproles and summary of ndings tables.

The world of medical information is rapidly becom-ing a world of electronic storage and presentationof primary studies, recommendations, and a wide variety of other information of interest to health care

practitioners. Although our abbreviated paper copypresentation represents a necessary response to achallenging situation, it is also a harbinger of theincreasingly electronic world of medical informationinto which future editions of guidelines are destinedto move.

Summary of Recommendations

Note on Shaded Text: Throughout this guideline,shading is used within the summary of recommenda-tions sections to indicate recommendations that arenewly added or have been changed since the publica-tion of Antithrombotic and Thrombolytic Therapy:American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Rec-ommendations that remain unchanged are not shaded.

Evidence-Based Management ofAnticoagulant Therapy

For further details, see Holbrook et al.1

2.1 Loading Dose for Initiation of Vitamin K Antagonist(VKA) Therapy 2.1. For patients sufciently healthy to betreated as outpatients, we suggest initiating VKAtherapy with warfarin 10 mg daily for the rst2 days followed by dosing based on internationalnormalized ratio (INR) measurements rather thanstarting with the estimated maintenance dose(Grade 2C).

2.2 Initial Dose Selection and PharmacogeneticTesting

2.2. For patients initiating VKA therapy, werecommend against the routine use of pharma-cogenetic testing for guiding doses of VKA (Grade 1B).

2.3 Initiation Overlap for Heparin and VKA 2.3. For patients with acute VTE, we suggestthat VKA therapy be started on day 1 or 2of low-molecular-weight heparin (LMWH) orlow-dose unfractionated heparin (UFH) therapyrather than waiting for several days to start(Grade 2C).

College of Chest Physicians Antithrombotic Guide-lines, this would have resulted in a document with . 850 pages of paper text, an unacceptablelength. Given this and with the advice of the journal, we decided to adopt a highly focused print versionthat includes only this executive summary and thefollowing articles:

An introduction describing the major innovationsin AT9

A methods article explaining how we devel-oped the guidelines (a potential model for otherguideline groups interested in optimal rigor)

Recommendations and grading from each arti-cle embedded in the table of contents of eacharticle

Those seeking the rationale for the recommenda-tions, including the supporting evidence, shouldaccess the online version of the guideline (http:// http://chestjournal.chestpubs.org/content/141/2_suppl)that includes a narrative summaries and support-ing summary of ndings tables. The numbering indi-cated beside the recommendations in this summaryis aligned with the sections and tables found in thefull articles. Those interested in a deeper under-standing of the evidence can turn to online datasupplements for each of the articles that include rec-ommendations. There, they will nd evidence pro-les (expanded versions of the summary of ndings

Revision accepted August 31, 2011. Afliations: From the Department of Clinical Epidemiologyand Biostatistics (Drs Guyatt, Akl, and Schnemann) and Depart-ment of Medicine (Drs Guyatt, Crowther, and Schnemann),McMaster University Faculty of Health Sciences, Hamilton,ON, Canada; Departments of Medicine and Family Medicine(Dr Akl), State University of New York, Buffalo, NY; CardiovascularResearch Center (Dr Gutterman), Medical College of Wisconsin,Milwaukee, WI.* For complete panel list, see: http://chestjournal.chestpubs.org/ content/141/2_suppl/2SFunding/Support : The Antithrombotic Therapy and Preventionof Thrombosis, 9th ed: American College of Chest PhysiciansEvidence-Based Clinical Practice Guidelines received support fromthe National Heart, Lung, and Blood Institute [R13 HL104758]and Bayer Schering Pharma AG. Support in the form of educa-

tional grants were also provided by Bristol-Myers Squibb; Pzer,Inc; Canyon Pharmaceuticals; and sano-aventis US.Disclaimer: American College of Chest Physician guidelines areintended for general information only, are not medical advice,and do not replace professional medical care and physician advice, which always should be sought for any medical condition. Thecomplete disclaimer for this guideline can be accessed at http:// chestjournal.chestpubs.org/content/141/2_suppl/1SCorrespondence to: Gordon H. Guyatt, MD, FCCP, Departmentof Clinical Epidemiology and Biostatistics, McMaster University,Hamilton, ON, L8N 3Z5, Canada; e-mail: [email protected] 2012 American College of Chest Physicians. Reproductionof this article is prohibited without written permission from theAmerican College of Chest Physicians (http://www.chestpubs.org/ site/misc/reprints.xhtml).DOI: 10.1378/chest.1412S3



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3.8 VKA Drug Interactions to Avoid

3.8. For patients taking VKAs, we suggest avoid-ing concomitant treatment with nonsteroidalantiinammatory drugs, including cyclooxyge-nase-2-selective nonsteroidal antiinammatorydrugs, and certain antibiotics (see Table 8 in mainarticle 1) (Grade 2C).

For patients taking VKAs, we suggest avoidingconcomitant treatment with antiplatelet agentsexcept in situations where benet is known or ishighly likely to be greater than harm frombleeding, such as patients with mechanical valves,patients with acute coronary syndrome, or patients

with recent coronary stents or bypass surgery(Grade 2C).

4.1 Optimal Therapeutic INR Range

4.1. For patients treated with VKAs, we recom-

mend a therapeutic INR range of 2.0 to 3.0 (tar-get INR of 2.5) rather than a lower (INR , 2) orhigher (INR 3.0-5.0) range (Grade 1B).

4.2 Therapeutic Range for High-Risk Groups

4.2. For patients with antiphospholipid syn drome with previous arterial or venous thromboembolism, we suggest VKA therapy titrated to a moderate-intensity INR range (INR 2.0-3.0) rather thanhigher intensity (INR 3.0-4.5) (Grade 2B).

5.0 Discontinuation of Therapy

5.0. For patients eligible to discontinue treat-ment with VKA, we suggest abrupt discontinua-tion rather than gradual tapering of the dose todiscontinuation (Grade 2C).

6.1 Unfractionated Heparin (UFH) Dose Adjustment by Weight

6.1. For patients starting IV UFH, we suggestthat the initial bolus and the initial rate of thecontinuous infusion be weight adjusted (bolus80 units/kg followed by 18 units/kg per h for VTE;bolus 70 units/kg followed by 15 units/kg per hfor cardiac or stroke patients) or use of a xeddose (bolus 5,000 units followed by 1,000 units/h)rather than alternative regimens (Grade 2C).

6.2 Dose Management of Subcutaneous (SC) UFH

6.2. For outpatients with VTE treated with SCUFH, we suggest weight-adjusted dosing (rstdose 333 units/kg, then 250 units/kg) with-out monitoring rather than xed or weight-adjusted dosing with monitoring (Grade 2C).

3.1 Monitoring Frequency for VKAs

3.1. For patients taking VKA therapy with con-sistently stable INRs, we suggest an INR testingfrequency of up to 12 weeks rather than every4 weeks (Grade 2B).

3.2 Management of the Single Out-of-Range INR

3.2. For patients taking VKAs with previouslystable therapeutic INRs who present with asingle out-of-range INR of 0.5 below or abovetherapeutic, we suggest continuing the currentdose and testing the INR within 1 to 2 weeks(Grade 2C).

3.3 Bridging for Low INRs

3.3. For patients with stable therapeutic INRspresenting with a single subtherapeutic INRvalue, we suggest against routinely adminis-tering bridging with heparin (Grade 2C).

3.4 Vitamin K Supplementation

3.4. For patients taking VKAs, we suggestagainst routine use of vitamin K supplementa-tion (Grade 2C).

3.5 Anticoagulation Management Services for VKAs

3.5. (Best Practices Statement) We suggest thathealth-care providers who manage oral antico-agulation therapy should do so in a systematicand coordinated fashion, incorporating patient

education, systematic INR testing, tracking,follow-up, and good patient communication ofresults and dosing decisions.

3.6 Patient Self-Testing and Self-Management

3.6. For patients treated with VKAs who aremotivated and can demonstrate competencyin self-management strategies, including theself-testing equipment, we suggest patient self-management rather than usual outpatient INRmonitoring (Grade 2B). For all other patients,

we suggest monitoring that includes the safe-

guards in our best practice statement 3.5. 3.7 Dosing Decision Support

3.7. For dosing decisions during maintenance VKA therapy, we suggest using validated deci-sion support tools (paper nomograms or com-puterized dosing programs) rather than nodecision support (Grade 2C).

Remarks: Inexperienced prescribers may be morelikely to improve prescribing with use of decision sup-port tools than experienced prescribers.



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knee GCS providing 15 to 30 mm Hg of pressureat the ankle during travel (Grade 2C). For allother long-distance travelers, we suggest againstthe use of GCS (Grade 2C).

6.1.3. For long-distance travelers, we suggestagainst the use of aspirin or anticoagulants toprevent VTE (Grade 2C).

7.0 Persons With Asymptomatic Thrombophilia

7.1. In persons with asymptomatic thrombo-philia (ie, without a previous history of VTE),

we recommend against the long-term daily useof mechanical or pharmacologic thrombopro-phylaxis to prevent VTE (Grade 1C).

Prevention of VTE in NonorthopedicSurgical Patients

For further details, see Gould et al.3

3.6 Patients Undergoing General, GI, Urological,Gynecologic, Bariatric, Vascular, Plastic, or Recon- structive Surgery

3.6.1. For general and abdominal-pelvic sur-gery patients at very low risk for VTE ( , 0.5%;Rogers score, , 7; Caprini score, 0), we recom-mend that no specic pharmacologic (Grade 1B)or mechanical (Grade 2C) prophylaxis be usedother than early ambulation.

3.6.2. For general and abdominal-pelvic sur-gery patients at low risk for VTE ( 1.5%; Rog-ers score, 7-10; Caprini score, 1-2), we suggestmechanical prophylaxis, preferably with inter-mittent pneumatic compression (IPC), over noprophylaxis (Grade 2C).

3.6.3. For general and abdominal-pelvic sur-gery patients at moderate risk for VTE ( 3.0%;Rogers score, . 10; Caprini score, 3-4) who arenot at high risk for major bleeding complica-tions, we suggest LMWH (Grade 2B), LDUH (Grade 2B), or mechanical prophylaxis, prefer-ably with IPC (Grade 2C), over no prophylaxis.

Remarks:Three of the seven authors favored a strong(Grade 1B) recommendation in favor of LMWH orLDUH over no prophylaxis in this group.

3.6.4. For general and abdominal-pelvic sur-gery patients at moderate risk for VTE (3.0%;Rogers score, . 10; Caprini score, 3-4) who areat high risk for major bleeding complicationsor those in whom the consequences of bleed-ing are thought to be particularly severe, we

bleeding risk decreases, rather than no mechan-ical thromboprophylaxis. When bleeding riskdecreases, we suggest that pharmacologic throm-boprophylaxis be substituted for mechanicalthromboprophylaxis (Grade 2C).

4.0 Patients With Cancer in the Outpatient Setting

4.2.1. In outpatients with cancer who have noadditional risk factors for VTE, we suggestagainst routine prophylaxis with LMWH orLDUH (Grade 2B) and recommend againstthe prophylactic use of VKAs (Grade 1B).

Remarks: Additional risk factors for venous throm-bosis in cancer outpatients include previous venousthrombosis, immobilization, hormonal therapy, angio-genesis inhibitors, thalidomide, and lenalidomide.

4.2.2. In outpatients with solid tumors who haveadditional risk factors for VTE and who are at

low risk of bleeding, we suggest prophylactic-dose LMWH or LDUH over no prophylaxis(Grade 2B).

Remarks: Additional risk factors for venous thrombo-sis in cancer outpatients include previous venousthrombosis, immobilization, hormonal therapy, angio-genesis inhibitors, thalidomide, and lenalidomide.

4.4. In outpatients with cancer and indwellingcentral venous catheters, we suggest againstroutine prophylaxis with LMWH or LDUH(Grade 2B) and suggest against the prophylacticuse of VKAs (Grade 2C).

5.0 Chronically Immobilized Patients

5.1. In chronically immobilized persons residingat home or at a nursing home, we suggest againstthe routine use of thromboprophylaxis (Grade 2C).

6.0 Persons Traveling Long-Distance

6.1.1. For long-distance travelers at increasedrisk of VTE (including previous VTE, recentsurgery or trauma, active malignancy, preg-

nancy, estrogen use, advanced age, limitedmobility, severe obesity, or known thrombo-philic disorder), we suggest frequent ambula-tion, calf muscle exercise, or sitting in an aisleseat if feasible (Grade 2C).

6.1.2. For long-distance travelers at increasedrisk of VTE (including previous VTE, recentsurgery or trauma, active malignancy, pregnancy,estrogen use, advanced age, limited mobility,severe obesity, or known thrombophilic disor-der), we suggest use of properly tted, below-



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gest use of mechanical prophylaxis, preferably with optimally applied IPC, over either no pro-phylaxis (Grade 2C) or pharmacologic prophy-laxis (Grade 2C).

4.4.2. For cardiac surgery patients whose hos-pital course is prolonged by one or more non-hemorrhagic surgical complications, we suggest

adding pharmacologic prophylaxis with LDUHor LMWH to mechanical prophylaxis (Grade 2C).

5.0 Patients Undergoing Thoracic Surgery

5.4.1. For thoracic surgery patients at mod-erate risk for VTE who are not at high risk forperioperative bleeding, we suggest LDUH (Grade 2B), LMWH (Grade 2B), or mechanicalprophylaxis with optimally applied IPC (Grade 2C)over no prophylaxis.

Remarks:Three of the seven authors favored a strong

(Grade 1B) recommendation in favor of LMWH orLDUH over no prophylaxis in this group.

5.4.2. For thoracic surgery patients at high riskfor VTE who are not at high risk for periopera-tive bleeding, we suggest LDUH (Grade 1B) orLMWH (Grade 1B) over no prophylaxis. In addi-tion, we suggest that mechanical prophylaxis

with elastic stockings or IPC should be added topharmacologic prophylaxis (Grade 2C).

5.4.3. For thoracic surgery patients who are athigh risk for major bleeding, we suggest use ofmechanical prophylaxis, preferably with opti-mally applied IPC, over no prophylaxis until therisk of bleeding diminishes and pharmacologicprophylaxis may be initiated (Grade 2C).

6.0 Patients Undergoing Craniotomy

6.4.1. For craniotomy patients, we suggest thatmechanical prophylaxis, preferably with IPC,be used over no prophylaxis (Grade 2C) or phar-macologic prophylaxis (Grade 2C).

6.4.2. For craniotomy patients at very high riskfor VTE (eg, those undergoing craniotomy formalignant disease), we suggest adding pharma-cologic prophylaxis to mechanical prophylaxisonce adequate hemostasis is established and therisk of bleeding decreases (Grade 2C).

7.0 Patients Undergoing Spinal Surgery

7.4.1. For patients undergoing spinal surgery, we suggest mechanical prophylaxis, prefer-ably with IPC, over no prophylaxis (Grade 2C), unfractionated heparin (Grade 2C), or LMWH (Grade 2C).

suggest mechanical prophylaxis, preferably withIPC, over no prophylaxis (Grade 2C).

3.6.5. For general and abdominal-pelvic sur-gery patients at high risk for VTE ( 6.0%;Caprini score, 5) who are not at high risk formajor bleeding complications, we recommendpharmacologic prophylaxis with LMWH (Grade

1B) or LDUH (Grade 1B) over no prophylaxis. We suggest that mechanical prophylaxis withelastic stockings or IPC should be added to phar-macologic prophylaxis (Grade 2C).

3.6.6. For high-VTE-risk patients undergoingabdominal or pelvic surgery for cancer who arenot otherwise at high risk for major bleedingcomplications, we recommend extended-durationpharmacologic prophylaxis (4 weeks) with LMWHover limited-duration prophylaxis (Grade 1B).

Remarks: Patients who place a high value on mini-

mizing out-of-pocket health-care costs might preferlimited-duration over extended-duration prophylaxisin settings where the cost of extended-duration pro-phylaxis is borne by the patient.

3.6.7. For high-VTE-risk general and abdominal-pelvic surgery patients who are at high risk formajor bleeding complications or those in whom theconsequences of bleeding are thought to beparticularly severe, we suggest use of mechan-ical prophylaxis, preferably with IPC, over noprophylaxis until the risk of bleeding diminishesand pharmacologic prophylaxis may be initiated (Grade 2C). 3.6.8. For general and abdominal-pelvic sur-gery patients at high risk for VTE (6%; Capriniscore, 5) in whom both LMWH and unfrac-tionated heparin are contraindicated or unavail-able and who are not at high risk for majorbleeding complications, we suggest low-doseaspirin (Grade 2C), fondaparinux (Grade 2C), ormechanical prophylaxis, preferably with IPC (Grade 2C), over no prophylaxis.

3.6.9. For general and abdominal-pelvic sur-gery patients, we suggest that an inferior venacava (IVC) lter should not be used for primary

VTE prevention (Grade 2C).

3.6.10. For general and abdominal-pelvic surgerypatients, we suggest that periodic surveillance

with venous compression ultrasound shouldnot be performed (Grade 2C).

4.0 Patients Undergoing Cardiac Surgery

4.4.1. For cardiac surgery patients with anuncomplicated postoperative course, we sug-



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igatran, rivaroxaban, low-dose unfractionatedheparin (LDUH), adjusted-dose VKA, aspirin (all Grade 1B), or an intermittent pneumatic com-pression device (IPCD) (Grade 1C).

Remarks: We recommend the use of only portable,battery-powered IPCDs capable of recording andreporting proper wear time on a daily basis for inpa-

tients and outpatients. Efforts should be made toachieve 18 h of daily compliance. One panel memberbelieved strongly that aspirin alone should not beincluded as an option.

2.1.2. In patients undergoing HFS, we recom-mend use of one of the following rather than noantithrombotic prophylaxis for a minimum of10 to 14 days: LMWH, fondaparinux, LDUH,adjusted-dose VKA, aspirin (all Grade 1B), or anIPCD (Grade 1C).

Remarks: We recommend the use of only portable,battery-powered IPCDs capable of recording andreporting proper wear time on a daily basis for inpa-tients and outpatients. Efforts should be made toachieve 18 h of daily compliance. One panel memberbelieved strongly that aspirin alone should not beincluded as an option.

2.2. For patients undergoing major orthopedicsurgery (THA, TKA, HFS) and receiving LMWHas thromboprophylaxis, we recommend startingeither 12 h or more preoperatively or 12 h or morepostoperatively rather than within 4 h or less pre-operatively or 4 h or less postoperatively (Grade 1B).

2.3.1. In patients undergoing THA or TKA,irrespective of the concomitant use of an IPCDor length of treatment, we suggest the useof LMWH in preference to the other agents

we have recommended as alternatives: fonda-parinux, apixaban, dabigatran, rivaroxaban,LDUH (all Grade 2B), adjusted-dose VKA, oraspirin (all Grade 2C).

Remarks: If started preoperatively, we suggest admin-istering LMWH 12 h before surgery. Patients who place a high value on avoiding the inconvenienceof daily injections with LMWH and a low value onthe limitations of alternative agents are likely tochoose an alternative agent. Limitations of alter-native agents include the possibility of increasedbleeding (which may occur with fondaparinux, rivar-oxaban, and VKA), possible decreased efcacy (LDUH, VKA, aspirin, and IPCD alone), and lack of long-termsafety data (apixaban, dabigatran, and rivaroxaban).Furthermore, patients who place a high value onavoiding bleeding complications and a low value on

7.4.2. For patients undergoing spinal surgery athigh risk for VTE (including those with malig-nant disease or those undergoing surgery witha combined anterior-posterior approach), wesuggest adding pharmacologic prophylaxis tomechanical prophylaxis once adequate hemo-stasis is established and the risk of bleedingdecreases (Grade 2C).

8.0 Patients With Major Trauma: Traumatic BrainInjury, Acute Spinal Injury, and Traumatic SpineInjury

8.4.1. For major trauma patients, we suggestuse of LDUH (Grade 2C), LMWH (Grade 2C), ormechanical prophylaxis, preferably with IPC (Grade 2C), over no prophylaxis.

8.4.2. For major trauma patients at high risk for VTE (including those with acute spinal cordinjury, traumatic brain injury, and spinal sur-

gery for trauma), we suggest adding mechan-ical prophylaxis to pharmacologic prophylaxis (Grade 2C) when not contraindicated by lower-extremity injury.

8.4.3. For major trauma patients in whomLMWH and LDUH are contraindicated, we sug-gest mechanical prophylaxis, preferably withIPC, over no prophylaxis (Grade 2C) when notcontraindicated by lower-extremity injury. Wesuggest adding pharmacologic prophylaxis witheither LMWH or LDUH when the risk of

bleeding diminishes or the contraindication toheparin resolves (Grade 2C).

8.4.4. For major trauma patients, we suggestthat an IVC lter should not be used for pri-mary VTE prevention (Grade 2C).

8.4.5. For major trauma patients, we suggest thatperiodic surveillance with venous compressionultrasound should not be performed (Grade 2C).

Prevention of VTE in Orthopedic

Surgery Patients

For further details, see Falck-Ytter et al.4

2.0 Patients Undergoing Major Orthopedic Surgery:Total Hip Arthroplasty (THA), Total Knee Arthroplasty(TKA), Hip Fracture Surgery (HFS)

2.1.1. In patients undergoing THA or TKA, werecommend use of one of the following for aminimum of 10 to 14 days rather than no anti-thrombotic prophylaxis: low-molecular-weightheparin (LMWH), fondaparinux, apixaban, dab-



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nience of IPCD and a low value on avoiding a smallabsolute increase in bleeding with pharmacologicagents when only one bleeding risk factor is present(in particular the continued use of antiplatelet agents)are likely to choose pharmacologic thromboprophy-laxis over IPCD.

2.7. In patients undergoing major orthopedicsurgery and who decline or are uncooperative

with injections or an IPCD, we recommendusing apixaban or dabigatran (alterna tivelyrivaroxaban or adjusted-dose VKA if apixa-ban or dabigatran are unavailable) rather thanalternative forms of prophylaxis (all Grade 1B).

2.8. In patients undergoing major orthopedicsurgery, we suggest against using IVC lterplacement for primary prevention over no throm-boprophylaxis in patients with an increasedbleeding risk or contraindications to both phar-macologic and mechanical thromboprophylaxis (Grade 2C). 2.9. For asymptomatic patients following majororthopedic surgery, we recommend againstDoppler (or duplex) ultrasound screening beforehospital discharge (Grade 1B).

3.0 Patients With Isolated Lower-Leg Injuries Distal to the Knee 3.0. We suggest no prophylaxis rather thanpharmacologic thromboprophylaxis in patients

with isolated lower-leg injuries requiring leg

immobilization (Grade 2C). 4.0 Patients Undergoing Knee Arthroscopy

4.0. For patients undergoing knee arthroscopy without a history of prior VTE, we suggest nothromboprophylaxis rather than prophylaxis (Grade 2B).

Perioperative Management ofAntithrombotic Therapy

For further details, see Douketis et al.5

2.1 Interruption of VKAs Before Surgery

2.1. In patients who require temporary inter-ruption of a VKA before surgery, we recom-mend stopping VKAs approximately 5 daysbefore surgery instead of stopping VKAs ashorter time before surgery (Grade 1C).

2.2 Resumption of VKAs After Surgery

2.2. In patients who require temporary interrup-tion of a VKA before surgery, we recommend

its inconvenience are likely to choose an IPCD overthe drug options.

2.3.2. In patients undergoing HFS, irrespectiveof the concomitant use of an IPCD or length oftreatment, we suggest the use of LMWH in pref-erence to the other agents we have recommendedas alternatives: fondaparinux, LDUH (Grade 2B),

adjusted-dose VKA, or aspirin (all Grade 2C). Remarks: For patients in whom surgery is likely tobe delayed, we suggest that LMWH be initiatedduring the time between hospital admission and sur-gery but suggest administering LMWH at least 12 hbefore surgery. Patients who place a high value onavoiding the inconvenience of daily injections withLMWH and a low value on the limitations of alterna-tive agents are likely to choose an alternative agent.Limitations of alternative agents include the possi-bility of increased bleeding (which may occur withfondaparinux) or possible decreased efcacy (LDUH, VKA, aspirin, and IPCD alone). Furthermore, patients who place a high value on avoiding bleeding compli-cations and a low value on its inconvenience are likelyto choose an IPCD over the drug options.

2.4. For patients undergoing major orthopedicsurgery, we suggest extending thromboprophy-laxis in the outpatient period for up to 35 daysfrom the day of surgery rather than for only 10to 14 days (Grade 2B).

2.5. In patients undergoing major orthopedic

surgery, we suggest using dual prophylaxis withan antithrombotic agent and an IPCD duringthe hospital stay (Grade 2C).

Remarks: We recommend the use of only portable,battery-powered IPCDs capable of recording andreporting proper wear time on a daily basis for inpa-tients and outpatients. Efforts should be made toachieve 18 h of daily compliance. Patients who placea high value on avoiding the undesirable consequencesassociated with prophylaxis with both a pharmacologicagent and an IPCD are likely to decline use of dual

prophylaxis.2.6. In patients undergoing major orthopedicsurgery and increased risk of bleeding, wesuggest using an IPCD or no prophylaxis ratherthan pharmacologic treatment (Grade 2C).

Remarks: We recommend the use of only portable,battery-powered IPCDs capable of recording andreporting proper wear time on a daily basis for inpa-tients and outpatients. Efforts should be made toachieve 18 h of daily compliance. Patients who placea high value on avoiding the discomfort and inconve-



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time of the procedure instead of stopping ASA7 to 10 days before the procedure (Grade 2C).

3.5. In patients at moderate to high risk forcardiovascular events who are receiving ASAtherapy and require noncardiac surgery, wesuggest continuing ASA around the time of sur-gery instead of stopping ASA 7 to 10 days before

surgery (Grade 2C). In patients at low risk forcardiovascular events who are receiving ASAtherapy, we suggest stopping ASA 7 to 10 daysbefore surgery instead of continuation of ASA(Grade 2C).

3.6 Patients Undergoing Coronary Artery BypassGraft Surgery

3.6. In patients who are receiving ASA andrequire coronary artery bypass graft (CABG)surgery, we suggest continuing ASA around thetime of surgery instead of stopping ASA 7 to

10 days before surgery (Grade 2C). In patients who are receiving dual antiplatelet drug therapyand require CABG surgery, we suggest con-tinuing ASA around the time of surgery andstopping clopidogrel/prasugrel 5 days beforesurgery instead of continuing dual antiplatelettherapy around the time of surgery (Grade 2C).

3.7 Surgical Patients With Coronary Stents

3.7. In patients with a coronary stent who arereceiving dual antiplatelet therapy and requiresurgery, we recommend deferring surgery for

at least 6 weeks after placement of a bare-metalstent and for at least 6 months after placementof a drug-eluting stent instead of undertakingsurgery within these time periods (Grade 1C). Inpatients who require surgery within 6 weeksof placement of a bare-metal stent or within6 months of placement of a drug-eluting stent,

we suggest continuing dual antiplatelet therapyaround the time of surgery instead of stoppingdual antiplatelet therapy 7 to 10 days beforesurgery (Grade 2C).

Remarks: Patients who are more concerned aboutavoiding the unknown, but potentially large increasein bleeding risk associated with the perioperativecontinuation of dual antiplatelet therapy than avoid-ing the risk for coronary stent thrombosis are unlikelyto choose continuation of dual antiplatelet therapy.

4.2 Perioperative Use of IV UFH

4.2. In patients who are receiving bridging anti-coagulation with therapeutic-dose IV UFH, wesuggest stopping UFH 4 to 6 h before surgery

instead of closer to surgery (Grade 2C).

resuming VKAs approximately 12 to 24 h aftersurgery (evening of or next morning) and whenthere is adequate hemostasis instead of laterresumption of VKAs (Grade 2C).

2.4 Bridging Anticoagulation During Interruption ofVKA Therapy

2.4. In patients with a mechanical heart valve,atrial brillation, or VTE at high risk for throm-boembolism, we suggest bridging anticoagula-tion instead of no bridging during interruptionof VKA therapy (Grade 2C).

Remarks: Patients who place a higher value on avoid-ing perioperative bleeding than on avoiding peri-operative thromboembolism are likely to declineheparin bridging.

In patients with a mechanical heart valve, atrialbrillation, or VTE at low risk for thrombo-embolism, we suggest no bridging instead of bridging anticoagulation during interruptionof VKA therapy (Grade 2C).

In patients with a mechanical heart valve, atrial bril-lation, or VTE at moderate risk for thromboembo-lism, the bridging or no-bridging approach chosen is,as in the higher- and lower-risk patients, based on anassessment of individual patient- and surgery-relatedfactors.

2.5 Perioperative Management of VKA-Treated

Patients Who Require Minor Procedures 2.5. In patients who require a minor dental pro-cedure, we suggest continuing VKAs with coad-ministration of an oral prohemostatic agent orstopping VKAs 2 to 3 days before the procedure

instead of alternative strategies (Grade 2C). Inpatients who require minor dermatologic pro-cedures and are receiving VKA therapy, we sug-gest continuing VKAs around the time of theprocedure and optimizing local hemostasis

instead of other strategies (Grade 2C). In patients who require cataract surgery and are receiving VKA therapy, we suggest continuing VKAsaround the time of the surgery instead of otherstrategies (Grade 2C).

3.4 Patients Undergoing a Minor Dental, Dermatologic,or Ophthalmologic Procedure

3.4. In patients who are receiving acetylsali-cylic acid (ASA) for the secondary preventionof cardiovascular disease and are having minordental or dermatologic procedures or cataractsurgery, we suggest continuing ASA around the



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DVT is not present. Initial testing with US would bepreferred if the patient has a comorbid condition associ-ated with elevated D-dimer levels and is likely to havea positive D-dimer result, even if DVT is absent. Inpatients with suspected rst lower extremity DVT in whom US is impractical (eg, when leg casting orexcessive SC tissue or uid prevent adequate assess-ment of compressibility) or nondiagnostic, we sug-

gest CT scan venography or magnetic resonance(MR) venography, or MR direct thrombus imagingcould be used as an alternative to venography.

If the D-dimer is negative, we recommend nofurther testing over further investigation with(i) proximal CUS, (ii) whole-leg US, or (iii) venog-raphy (Grade 1B for all comparisons). If the prox-imal CUS is negative, we recommend no furthertesting compared with (i) repeat proximal CUSafter 1 week, (ii) whole-leg US, or (iii) venog-raphy (Grade 1B for all comparisons).

If the D-dimer is positive, we suggest furthertesting with CUS of the proximal veins ratherthan (i) whole-leg US (Grade 2C) or (ii) venog-raphy (Grade 1B). If CUS of the proximal veins ispositive, we suggest treating for DVT and per-forming no further testing over performingconrmatory venography (Grade 2C).

Remarks: In circumstances when high-quality venog-raphy is available, patients who are not averse to thediscomfort of venography, are less concerned aboutthe complications of venography, and place a high value on avoiding treatment of false-positive resultsare likely to choose conrmatory venography if nd-ings for DVT are less certain (eg, a short segment of venous noncompressibility).

3.3. In patients with a moderate pretest proba-bility of rst lower extremity DVT, we recom-mend one of the following initial tests: (i) a highlysensitive D-dimer or (ii) proximal CUS, or (iii)

whole-leg US rather than (i) no testing (Grade 1Bfor all comparisons)or (ii) venography (Grade 1B forall comparisons). We suggest initial use of a highlysensitive D-dimer rather than US (Grade 2C).

Remarks: The choice between a highly sensitiveD-dimer test or US as the initial test will depend onlocal availability, access to testing, costs of testing,and the probability of obtaining a negative D-dimerresult if DVT is not present. Initial testing with USmay be preferred if the patient has a comorbid condi-tion associated with elevated D-dimer levels and islikely to have a positive D-dimer result even if DVTis absent. Whole-leg US may be preferred in patientsunable to return for serial testing and those with

4.3 Preoperative Interruption of Therapeutic-DoseBridging LMWH

4.3. In patients who are receiving bridging anti-coagulation with therapeutic-dose SC LMWH,

we suggest administering the last preoperativedose of LMWH approximately 24 h before sur-gery instead of 12 h before surgery (Grade 2C).

4.4 Postoperative Resumption of Therapeutic-DoseBridging LMWH

4.4. In patients who are receiving bridging anti-coagulation with therapeutic-dose SC LMWHand are undergoing high-bleeding-risk surgery,

we suggest resuming therapeutic-dose LMWH48 to 72 h after surgery instead of resumingLMWH within 24 h after surgery (Grade 2C).

Diagnosis of DVT

For further details, see Bates et al.6

3.0 Diagnosis of Suspected First Lower ExtremityDVT

3.1. In patients with a suspected rst lowerextremity DVT, we suggest that the choice ofdiagnostic tests process should be guided by theclinical assessment of pretest probability ratherthan by performing the same diagnostic tests inall patients (Grade 2B).

Remarks: In considering this recommendation, vepanelists voted for a strong recommendation and four voted for a weak recommendation (one declinedto vote and two did not participate). Accordingto predetermined criteria, this resulted in weakrecommendation.

3.2. In patients with a low pretest probabilityof rst lower extremity DVT, we recommendone of the following initial tests: (i) a moder-ately sensitive D-dimer, (ii) a highly sensitiveD-dimer, or (iii) compression ultrasound (CUS)of the proximal veins rather than (i) no diagnos-tic testing (Grade 1B for all comparisons), (ii) venog-raphy (Grade 1B for all comparisons), or (iii)

whole-leg ultrasound (US) (Grade 2B for all com-parisons). We suggest initial use of a moderatelysensitive (Grade 2C) or highly sensitive (Grade2B) D-dimer rather than proximal CUS.

Remarks: The choice between a moderately sensitiveD-dimer test, a highly sensitive D-dimer test, or prox-imal CUS as the initial test will depend on local avail-ability, access to testing, costs of testing, and theprobability of obtaining a negative D-dimer result if



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3.4. In patients with a high pretest probabilityof rst lower extremity DVT, we recommendeither (i) proximal CUS or (ii) whole-leg US overno testing (Grade 1B for all comparisons)or venog-raphy (Grade 1B for all comparisons).

Remarks: Whole-leg US may be preferred to prox-imal CUS in patients unable to return for serial test-

ing and those with severe symptoms consistent withcalf DVT. In patients with extensive unexplainedleg swelling, if there is no DVT on proximal CUS or whole-leg US and d-dimer testing has not beenperformed or is positive, the iliac veins should beimaged to exclude isolated iliac DVT. In patients withsuspected rst lower extremity DVT in whom US isimpractical (eg, when leg casting or excessive SCtissue or uid prevent adequate assessment of com-pressibility) or nondiagnostic, we suggest CT scan venography, MR venography, or MR direct thrombusimaging could be used as an alternative to venography.

If proximal CUS or whole-leg US is positive forDVT, we recommend treatment rather thanconrmatory venography (Grade 1B).

In patients with a negative proximal CUS, werecommend additional testing with a highlysensitive D-dimer or whole-leg US or repeatproximal CUS in 1 week over no furthertesting (Grade 1B for all comparisons)or venog-raphy (Grade 2B for all comparisons). We rec-ommend that patients with a single negative

proximal CUS and positive D-dimer undergo whole-leg US or repeat proximal CUS in 1 weekover no further testing (Grade 1B) or venography (Grade 2B). In patients with negative serial prox-imal CUS, a negative single proximal CUS andnegative highly sensitive D-dimer, or a negative

whole-leg US, we recommend no further testingover venography or additional US (Grade 1B fornegative serial proximal CUS and for negative singleproximal CUS and highly sensitive D-dimer; Grade2B for negative whole-leg US).

We recommend that in patients with high pre-test probability, moderately or highly sensitiveD-dimer assays should not be used as stand-alone tests to rule out DVT (Grade 1B).

3.5. If risk stratication is not performed inpatients with suspected rst lower extremityDVT, we recommend one of the followinginitial tests: (i) proximal CUS or (ii) whole-leg US rather than (i) no testing (Grade 1B),(ii) venography (Grade 1B), or D-dimer testing (Grade 2B).

severe symptoms consistent with calf DVT. In patients with suspected rst lower extremity DVT in whomUS is impractical (eg, when leg casting or excessiveSC tissue or uid prevent adequate assessment ofcompressibility) or nondiagnostic, we suggest CT scan venography, MR venography, or MR direct thrombusimaging could be used as an alternative to venography.

If the highly sensitive D-dimer is negative, werecommend no further testing over furtherinvestigation with (i) proximal CUS, (ii) whole-leg US, or (iii) venography (Grade 1B for allcomparisons). If the highly sensitive D-dimeris positive, we recommend proximal CUS or

whole-leg US rather than no testing (Grade 1Bfor all comparisons)or venography (Grade 1B forall comparisons).

If proximal CUS is chosen as the initial test andis negative, we recommend (i) repeat proximalCUS in 1 week or (ii) testing with a moderate orhighly sensitive D-dimer assay over no furthertesting (Grade 1C) or venography (Grade 2B). Inpatients with a negative proximal CUS but apositive D-dimer, we recommend repeat prox-imal CUS in 1 week over no further testing (Grade 1B) or venography (Grade 2B).

In patients with (i) negative serial proximal CUSor (ii) a negative single proximal CUS and nega-tive moderate or highly sensitive D-dimer, werecommend no further testing rather than fur-ther testing with (i) whole-leg US or (ii) venog-raphy (Grade 1B for all comparisons).

If whole-leg US is negative, we recommendno further testing over (i) repeat US in one

week, (ii) D-dimer testing, or (iii) venography (Grade 1B for all comparisons). If proximal CUSis positive, we recommend treating for DVTrather than conrmatory venography (Grade 1B).If isolated distal DVT is detected on whole-leg US, we suggest serial testing to rule outproximal extension over treatment (Grade 2C).

Remarks: Patients with abnormal isolated distal USndings on whole-leg US who place a high value onavoiding the inconvenience of repeat testing and alow value on avoiding treatment of false-positiveresults are likely to choose treatment over repeat US.Patients with severe symptoms and risk factors forextension as outlined in Perioperative Managementof Antithrombotic Therapy. Antithrombotic Therapyand Prevention of Thrombosis, 9th ed: AmericanCollege of Chest Physicians Evidence-Based ClinicalPractice Guidelines are more likely to benet fromtreatment over repeat US.



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4.1 Venography in Patients With Suspected Recur-rent DVT

4.1. In patients suspected of having recurrentlower extremity DVT, we recommend initialevaluation with proximal CUS or a highly sensi-tive D-dimer over venography, CT venography,or MRI (all Grade 1B).

Remarks: Initial D-dimer testing with a high-sensitivityassay is preferable if prior US is not available forcomparison.

If the highly sensitive D-dimer is positive, werecommend proximal CUS over venography, CTvenography, or MRI (Grade 1B for all comparisons).

In patients with suspected recurrent lowerextremity DVT in whom initial proximal CUS isnegative (normal or residual diameter increaseof , 2 mm), we suggest at least one further

proximal CUS (day 7 1) or testing with a mod-erately or highly sensitive D-dimer (followed byrepeat CUS [day 7 1] if positive) rather thanno further testing or venography (Grade 2B).

Remarks: In patients with an abnormal proximal CUSat presentation that does not meet the criteria for thediagnosis of recurrence, an additional proximal CUSon day 2 1 in addition to that on (day 7 1) may bepreferred. Patients who place a high value on anaccurate diagnosis and a low value on avoiding theinconvenience and potential side effects of a venog-raphy are likely to choose venography over misseddiagnosis (in the case of residual diameter increaseof , 2 mm).

We recommend that patients with suspectedrecurrent lower extremity DVT and a negativehighly sensitive D-dimer or negative proximalCUS and negative moderately or highly sensi-tive D-dimer or negative serial proximal CUSundergo no further testing for suspected recur-rent DVT rather than venography (Grade 1B).

If CUS of the proximal veins is positive, we rec-

ommend treating for DVT and performing nofurther testing over performing conrmatoryvenography (Grade 1B for the nding of a new non-compressible segment in the common femoral orpopliteal vein, Grade 2B for a 4-mm increase in venous diameter during compression compared withthat in the same venous segment on a previous result).

Remarks: Patients with US abnormalities at pre-sentation that do not include a new noncompressiblesegment who place a high value on an accurate diag-nosis and a low value on avoiding the inconvenience

Remarks: Whole-leg US may be preferred to prox-imal CUS in patients unable to return for serialtesting and those with severe symptoms consistent with calf DVT or risk factors for extension of distalDVT. In patients with suspected rst lower extremityDVT in whom US is impractical (eg, when leg cast-ing or excessive SC tissue or uid prevent adequateassessment of compressibility) or nondiagnostic, we

suggest that CT scan venography, MR venography,or MR direct thrombus imaging could be used as analternative to venography.

We recommend that patients with a negativeproximal CUS undergo testing with a mod-erate- or high-sensitivity D-dimer, whole-legUS, or repeat proximal CUS in 1 week overno further testing (Grade 1B) or venography (Grade 2B). In patients with a negative prox-imal CUS, we suggest D-dimer rather thanroutine serial CUS (Grade 2B) or whole-leg US

(Grade 2C). We recommend that patients witha single negative proximal CUS and positiveD-dimer undergo further testing with repeatproximal CUS in 1 week or whole-leg USrather than no further testing (Grade 1B forboth comparisons).

We recommend that in patients with (i) nega-tive serial proximal CUS, (ii) a negative D-dimerfollowing a negative initial proximal CUS, or (iii)negative whole-leg US, no further testing beperformed rather than venography (Grade 1B).

If proximal US is positive for DVT, we recom-mend treatment rather than conrmatory venog-raphy (Grade 1B). If isolated distal DVT isdetected on whole-leg US, we suggest serialtesting to rule out proximal extension over treat-ment (Grade 2C).

Remarks: Patients with abnormal isolated distal USndings on whole-leg US who place a high value onavoiding the inconvenience of repeat testing anda low value on avoiding treatment of false-positive

results are likely to choose treatment over repeat US.Patients with severe symptoms and risk factors forextension as outlined in Perioperative Managementof Antithrombotic Therapy. Antithrombotic Therapyand Prevention of Thrombosis, 9th ed: AmericanCollege of Chest Physicians Evidence-Based ClinicalPractice Guidelines are more likely to benet fromtreatment over repeat US.

3.6. In patients with suspected first lowerextremity DVT, we recommend against the rou-tine use of CT venography or MRI (Grade 1C).



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D-dimer done at the time of presentation (Grade2B) over no further testing for DVT. We recom-mend that patients with an initial negativeproximal CUS and a subsequent negative sensi-tive D-dimer or negative serial proximal CUSundergo no further testing for DVT (Grade 1B)and that patients with positive D-dimer have anadditional follow-up proximal CUS (day 3 and

day 7) rather than venography (Grade 1B) or whole-leg US (Grade 2C).

5.3 Pretest Probability in Pregnancy-Related DVT

5.3. In pregnant patients with symptoms sug-gestive of isolated iliac vein thrombosis (swellingof the entire leg, with or without ank, buttock,or back pain) and no evidence of DVT on stan-dard proximal CUS, we suggest further testing

with either Doppler US of the iliac vein (Grade2C), venography (Grade 2C), or direct MRI (Grade 2C), rather than standard serial CUS ofthe proximal deep veins.

6.1 Ultrasonography in Patients With Upper-Extremity DVT (UEDVT)

6.1. In patients suspected of having UEDVT, wesuggest initial evaluation with combined modalityUS (compression with either Doppler or colorDoppler) over other initial tests, including highlysensitive D-dimer or venography (Grade 2C).

6.2 Clinical Pretest Probability Assessment in PatientsWith UEDVT

6.2. In patients with suspected UEDVT in whominitial US is negative for thrombosis despite ahigh clinical suspicion of DVT, we suggest fur-ther testing with a moderate or highly sensitiveD-dimer, serial US, or venographic-based imaging(traditional, CT scan, or MRI), rather than nofurther testing (Grade 2C).

In patients with suspected UEDVT and an ini-tial negative combined-modality US and sub-sequent negative moderate or highly sensitive

D-dimer or CT or MRI, we recommend no fur-ther testing, rather than conrmatory venog-raphy (Grade 1C). We suggest that patients withan initial combined negative modality US andpositive D-dimer or those with less than com-plete evaluation by US undergo venographyrather than no further testing, unless there isan alternative explanation for their symptoms (Grade 2B), in which case testing to evaluate forthe presence an alternative diagnosis should beperformed. We suggest that patients with a pos-itive D-dimer or those with less than complete

and potential side effects of a venography are likelyto choose venography over treatment (in the caseof 4-mm increase in venous diameter).

4.2 Compression Ultrasonography in Patients WithSuspected Recurrent DVT

4.2. In patients with suspected recurrent lowerextremity DVT and abnormal but nondiagnosticUS results (eg, an increase in residual venousdiameter of , 4 but 2 mm), we recommendfurther testing with venography, if available (Grade 1B); serial proximal CUS (Grade 2B) ortesting with a moderately or highly sensitiveD-dimer with serial proximal CUS as above ifthe test is positive (Grade 2B), as opposed toother testing strategies or treatment.

4.3 Pretest Probability Assessment in Patients WithSuspected Recurrent DVT

4.3. In patients with suspected recurrent ipsilat-eral DVT and an abnormal US without a priorresult for comparison, we recommend furthertesting with venography, if available (Grade 1B)or a highly sensitive D-dimer (Grade 2B) overserial proximal CUS. In patients with suspectedrecurrent ipsilateral DVT and an abnormal US

without prior result for comparison and a nega-tive highly sensitive D-dimer, we suggest nofurther testing over venography (Grade 2C). Inpatients with suspected recurrent ipsilateralDVT and an abnormal US without prior resultfor comparison and a positive highly sensitiveD-dimer, we suggest venography if available overempirical treatment of recurrence (Grade 2C).

Remarks: Patients who place a high value on avoid-ing the inconvenience and potential side effects ofa venography are likely to choose treatment over venography.

5.1 Venography in Pregnancy-Related DVT

5.1. In pregnant patients suspected of havinglower extremity DVT, we recommend initialevaluation with proximal CUS over other initialtests, including a whole-leg US (Grade 2C), mod-erately sensitive D-dimer (Grade 2C), highlysensitive D-dimer (Grade 1B), or venography (Grade 1B).

5.2 Compression Ultrasonography in Pregnancy-Related DVT

5.2. In pregnant patients with suspected DVT in whom initial proximal CUS is negative, we sug-gest further testing with either serial proximalCUS (day 3 and day 7) (Grade 1B) or a sensitive



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2.13.1. In patients with acute DVT of the leg, werecommend against the use of an IVC lter inaddition to anticoagulants (Grade 1B).

2.13.2. In patients with acute proximal DVT of theleg and contraindication to anticoagulation, werecommend the use of an IVC lter (Grade 1B).

2.13.3. In patients with acute proximal DVT ofthe leg and an IVC lter inserted as an alterna-tive to anticoagulation, we suggest a conven-tional course of anticoagulant therapy if theirrisk of bleeding resolves (Grade 2B).

Remarks: We do not consider that a permanentIVC lter, of itself, is an indication for extendedanticoagulation.

2.14 Early Ambulation of Patients With Acute DVT

2.14. In patients with acute DVT of the leg, wesuggest early ambulation over initial bed rest (Grade 2C).

Remarks: If edema and pain are severe, ambulationmay need to be deferred. As per section 4.1, we suggestthe use of compression therapy in these patients.

3.0 Long-term Anticoagulation in Patients With AcuteDVT of the Leg

3.0. In patients with acute VTE who are treated with anticoagulant therapy, we recommend long-term therapy (see section 3.1 for recommendedduration of therapy) over stopping anticoagu-lant therapy after about 1 week of initial therapy (Grade 1B).

3.1 Duration of Long-term Anticoagulant Therapy

3.1.1. In patients with a proximal DVT of the legprovoked by surgery, we recommend treatment

with anticoagulation for 3 months over (i) treat-ment of a shorter period (Grade 1B), (ii) treat-ment of a longer time-limited period (eg, 6 or12 months) (Grade 1B), or (iii) extended therapy (Grade 1B regardless of bleeding risk).

3.1.2. In patients with a proximal DVT of the legprovoked by a nonsurgical transient risk factor,

we recommend treatment with anticoagulationfor 3 months over (i) treatment of a shorterperiod (Grade 1B), (ii) treatment of a longer time-limited period (eg, 6 or 12 months) (Grade 1B),and (iii) extended therapy if there is a highbleeding risk (Grade 1B). We suggest treatment

with anticoagulation for 3 months over extendedtherapy if there is a low or moderate bleedingrisk (Grade 2B).

2.7 At-Home vs In-Hospital Initial Treatment of PatientsWith DVT 2.7. In patients with acute DVT of the leg and

whose home circumstances are adequate, werecommend initial treatment at home overtreatment in hospital (Grade 1B).

Remarks: The recommendation is conditional on the

adequacy of home circumstances: well-maintainedliving conditions, strong support from family or friends,phone access, and ability to quickly return to the hos-pital if there is deterioration. It is also conditional onthe patient feeling well enough to be treated at home(eg, does not have severe leg symptoms or comorbidity).

2.9 Catheter-Directed Thrombolysis for Patients With Acute DVT

2.9. In patients with acute proximal DVT of theleg, we suggest anticoagulant therapy alone overcatheter-directed thrombolysis (CDT) (Grade 2C).

Remarks: Patients who are most likely to benet fromCDT (see text), who attach a high value to preven-tion of postthrombotic syndrome (PTS), and a lower value to the initial complexity, cost, and risk ofbleeding with CDT, are likely to choose CDT overanticoagulation alone.

2.10 Systemic Thrombolytic Therapy for Patients With Acute DVT

2.10. In patients with acute proximal DVT ofthe leg, we suggest anticoagulant therapy alone

over systemic thrombolysis (Grade 2C). Remarks: Patients who are most likely to benet fromsystemic thrombolytic therapy (see text), who donot have access to CDT, and who attach a high valueto prevention of PTS, and a lower value to the initialcomplexity, cost, and risk of bleeding with systemicthrombolytic therapy, are likely to choose systemicthrombolytic therapy over anticoagulation alone.

2.11 Operative Venous Thrombectomy for Acute DVT

2.11. In patients with acute proximal DVT of theleg, we suggest anticoagulant therapy alone overoperative venous thrombectomy (Grade 2C). 2.12 Anticoagulation in Patients Who Have Had AnyMethod of Thrombus Removal Performed

2.12. In patients with acute DVT of the leg whoundergo thrombosis removal, we recommendthe same intensity and duration of anticoagu-lant therapy as in comparable patients who donot undergo thrombosis removal (Grade 1B).

2.13 Vena Cava Filters for the Initial Treatment ofPatients With DVT



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5.2.2. In patients with an intermediate clinicalsuspicion of acute PE, we suggest treatment

with parenteral anticoagulants compared withno treatment if the results of diagnostic testsare expected to be delayed for more than 4 h (Grade 2C).

5.2.3. In patients with a low clinical suspicion of

acute PE, we suggest not treating with paren-teral anticoagulants while awaiting the resultsof diagnostic tests, provided test results areexpected within 24 h (Grade 2C).

5.3 Timing of Initiation of VKA and AssociatedDuration of Parenteral Anticoagulant Therapy

5.3. In patients with acute PE, we recommendearly initiation of VKA (eg, same day as paren-teral therapy is started) over delayed initiation,and continuation of parenteral anticoagulationfor a minimum of 5 days and until the INR is 2.0

or above for at least 24 h (Grade 1B). 5.4 Choice of Initial Parenteral Anticoagulant Regimen in Patients With PE

5.4.1. In patients with acute PE, we suggestLMWH or fondaparinux over IV UFH (Grade 2Cfor LMWH; Grade 2B for fondaparinux)and overSC UFH (Grade 2B for LMWH; Grade 2C forfondaparinux).

Remarks: Local considerations such as cost, availability,and familiarity of use dictate the choice betweenfondaparinux and LMWH. LMWH and fondaparinuxare retained in patients with renal impairment, whereas this is not a concern with UFH. In patients with PE where there is concern about the adequacyof SC absorption or in patients in whom thrombolytictherapy is being considered or planned, initial treat-ment with IV UFH is preferred to use of SC therapies.

5.4.2. In patients with acute PE treated withLMWH, we suggest once- over twice-daily admin-istration (Grade 2C).

Remarks: This recommendation only applies when

the approved once-daily regimen uses the samedaily dose as the twice-daily regimen (ie, the once-daily injection contains double the dose of eachtwice-daily injection). It also places value on avoidingan extra injection per day.

5.5 Early vs Standard Discharge of Patients With Acute PE

5.5. In patients with low-risk PE and whosehome circumstances are adequate, we suggestearly discharge over standard discharge (eg,after rst 5 days of treatment) (Grade 2B).

same anticoagulant chosen for the rst 3 months (Grade 2C).

3.5 Treatment of Patients With Asymptomatic DVTof the Leg

3.5. In patients who are incidentally found to haveasymptomatic DVT of the leg, we suggest the sameinitial and long-term anticoagulation as for compa-rable patients with symptomatic DVT (Grade 2B).

4.1 Compression Stockings and Bandages to PreventPTS

4.1. In patients with acute symptomatic DVT ofthe leg, we suggest the use of compression stock-ings (Grade 2B).

Remarks: Compression stockings should be worn for2 years, and we suggest beyond that if patients havedeveloped PTS and nd the stockings helpful.Patients who place a low value on preventing PTS ora high value on avoiding the inconvenience and dis-comfort of stockings are likely to decline stockings.

4.2 Physical Treatment of Patients With PTS

4.2.1. In patients with PTS of the leg, we sug-gest a trial of compression stockings (Grade 2C).

4.2.2. In patients with severe PTS of the leg thatis not adequately relieved by compression stock-ings, we suggest a trial of an intermittent com-pression device (Grade 2B).

4.3 Pharmacologic Treatment of Patients With PTS 4.3. In patients with PTS of the leg, we suggest thatvenoactive medications (eg, rutosides, debrot-ide, and hidrosmin) not be used (Grade 2C).

Remarks: Patients who value the possibility of responseover the risk of side effects may choose to undertake atherapeutic trial.

5.1 Initial Anticoagulation for Patients With AcutePulmonary Embolism (PE)

5.1. In patients with acute PE, we recommendinitial treatment with parenteral anticoagula-tion (LMWH, fondaparinux, IV UFH, or SCUFH) over no such initial treatment (Grade 1B).

5.2 Parenteral Anticoagulation Prior to Receipt of theResults of Diagnostic Work-up for PE

5.2.1. In patients with a high clinical suspicionof acute PE, we suggest treatment with paren-teral anticoagulants compared with no treat-ment while awaiting the results of diagnostictests (Grade 2C).



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5.9. Vena Cava Filters for the Initial Treatment ofPatients With PE

5.9.1. In patients with acute PE who are treated with anticoagulants, we recommend against theuse of an IVC lter (Grade 1B).

5.9.2. In patients with acute PE and contraindi-cation to anticoagulation, we recommend theuse of an IVC lter (Grade 1B). 5.9.3. In patients with acute PE and an IVClter inserted as an alternative to anticoagu-lation, we suggest a conventional course ofanticoagulant therapy if their risk of bleedingresolves (Grade 2B).

Remarks: We do not consider that a permanentIVC lter, of itself, is an indication for extendedanticoagulation.

6.0 Long-term Treatment of Patients With PE

6.1. In patients with PE provoked by surgery, we recommend treatment with anticoagulationfor 3 months over (i) treatment of a shorterperiod (Grade 1B), (ii) treatment of a longer time-limited period (eg, 6 or 12 months) (Grade 1B),or (iii) extended therapy (Grade 1B regardless ofbleeding risk).

6.2. In patients with PE provoked by a non-surgical transient risk factor, we recommendtreatment with anticoagulation for 3 months

over (i) treatment of a shorter period (Grade 1B),(ii) treatment of a longer time-limited period(eg, 6 or 12 months) (Grade 1B), and (iii) extendedtherapy if there is a high bleeding risk (Grade1B). We suggest treatment with anticoagulationfor 3 months over extended therapy if there is alow or moderate bleeding risk (Grade 2B).

6.3. In patients with an unprovoked PE, we rec-ommend treatment with anticoagulation for atleast 3 months over treatment of a shorter dura-tion (Grade 1B). After 3 months of treatment,patients with unprovoked PE should be evaluatedfor the risk-benet ratio of extended therapy.

6.3.1. In patients with a rst VTE that is anunprovoked PE and who have a low or mod-erate bleeding risk, we suggest extended anti-coagulant therapy over 3 months of therapy (Grade 2B).

6.3.2. In patients with a rst VTE that is anunprovoked PE and who have a high bleedingrisk, we recommend 3 months of anticoagulanttherapy over extended therapy (Grade 1B).

Remarks: Patients who prefer the security of the hos-pital to the convenience and comfort of home arelikely to choose hospitalization over home treatment.

5.6 Systemic Thrombolytic Therapy for Patients WithPE

5.6.1.1. In patients with acute PE associated with hypotension (eg, systolic BP , 90 mm Hg) who do not have a high bleeding risk, we sug-gest systemically administered thrombolytictherapy over no such therapy (Grade 2C).

5.6.1.2. In most patients with acute PE not asso-ciated with hypotension, we recommend againstsystemically administered thrombolytic therapy (Grade 1C).

5.6.1.3. In selected patients with acute PE notassociated with hypotension and with a low bleed-ing risk whose initial clinical presentation, orclinical course after starting anticoagulant ther-apy, suggests a high risk of developing hypoten-sion, we suggest administration of throm bolytictherapy (Grade 2C).

5.6.2.1. In patients with acute PE, when a throm-bolytic agent is used, we suggest short infusiontimes (eg, a 2-h infusion) over prolonged infu-sion times (eg, a 24-h infusion) (Grade 2C).

5.6.2.2. In patients with acute PE when a throm-bolytic agent is used, we suggest administrationthrough a peripheral vein over a pulmonaryartery catheter (Grade 2C).

5.7 Catheter-Based Thrombus Removal for the InitialTreatment of Patients With PE

5.7. In patients with acute PE associated withhypotension and who have (i) contraindicationsto thrombolysis, (ii) failed thrombolysis, or (iii)shock that is likely to cause death before systemicthrombolysis can take effect (eg, within hours), ifappro priate expertise and resources are avail-able, we suggest catheter-assisted thrombusremoval over no such intervention (Grade 2C).

5.8 Surgical Embolectomy for the Initial Treatmentof Patients With PE

5.8. In patients with acute PE associated withhypotension, we suggest surgical pulmonaryembolectomy over no such intervention if theyhave (i) contraindications to thrombolysis, (ii)failed thrombolysis or catheter-assisted embo-lectomy, or (iii) shock that is likely to causedeath before thrombolysis can take effect (eg,

within hours), provided surgical expertise andresources are available (Grade 2C).



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6.8. In patients with PE who receive extendedtherapy, we suggest treatment with the sameanticoagulant chosen for the rst 3 months (Grade 2C).

6.9. In patients who are incidentally found tohave asymptomatic PE, we suggest the sameinitial and long-term anticoagulation as for

comparable patients with symptomatic PE (Grade 2B).

7.1 Pulmonary Thromboendarterectomy, AnticoagulantTherapy, and Vena Cava Filter for the Treatment ofChronic Thromboembolic Pulmonary Hypertension(CTPH)

7.1.1. In patients with CTPH, we recommendextended anticoagulation over stopping therapy (Grade 1B).

7.1.2. In selected patients with CTPH, such as

those with central disease under the care ofan experienced thromboendarterectomy team, we suggest pulmonary thromboendarterectomyover no pulmonary thromboendarterectomy (Grade 2C).

8.1 Treatment of Patients With Supercial VeinThrombosis

8.1.1. In patients with supercial vein thrombo-sis of the lower limb of at least 5 cm in length,

we suggest the use of a prophylactic dose offondaparinux or LMWH for 45 days over noanticoagulation (Grade 2B).

Remarks: Patients who place a high value on avoidingthe inconvenience or cost of anticoagulation and alow value on avoiding infrequent symptomatic VTEare likely to decline anticoagulation.

8.1.2. In patients with supercial vein throm-bosis who are treated with anticoagulation, wesuggest fondaparinux 2.5 mg daily over a pro-phylactic dose of LMWH (Grade 2C).

9.1 Acute Anticoagulation for Patients With UEDVT

9.1.1. In patients with UEDVT that involvesthe axillary or more proximal veins, we recom-mend acute treatment with parenteral anti-coagulation (LMWH, fondaparinux, IV UFH,or SC UFH) over no such acute treatment (Grade 1B).

9.1.2. In patients with acute UEDVT thatinvolves the axillary or more proximal veins, wesuggest LMWH or fondaparinux over IV UFH (Grade 2C) and over SC UFH (Grade 2B).

6.3.3. In patients with a second unprovoked VTE, we recommend extended anticoagulanttherapy over 3 months of therapy in those whohave a low bleeding risk (Grade 1B), and we sug-gest extended anticoagulant therapy in those

with a moderate bleeding risk (Grade 2B).

6.3.4. In patients with a second unprovoked

VTE who have a high bleeding risk, we suggest3 months of therapy over extended therapy (Grade 2B).

6.4. In patients with PE and active cancer, ifthere is a low or moderate bleeding risk, werecommend extended anticoagulant therapyover 3 months of therapy (Grade 1B), and if thereis a high bleeding risk, we suggest extended anti-coagulant therapy (Grade 2B).

Remarks: In all patients who receive extended anti-

coagulant therapy, the continuing use of treatmentshould be reassessed at periodic intervals (eg, annually).

6.5. In patients with PE who are treated with VKA, we recommend a therapeutic INR rangeof 2.0 to 3.0 (target INR of 2.5) over a lower(INR , 2) or higher (INR 3.0-5.0) range for alltreatment durations (Grade 1B).

6.6. In patients with PE and no cancer, we sug-gest VKA therapy over LMWH for long-termtherapy (Grade 2C). For patients with PE and nocancer who are not treated with VKA therapy,

we suggest LMWH over dabigatran or rivaroxa-ban for long-term therapy (Grade 2C).

6.7. In patients with PE and cancer, we suggestLMWH over VKA therapy (Grade 2B). In patients

with PE and cancer who are not treated withLMWH, we suggest VKA over dabigatran orrivaroxaban for long-term therapy (Grade 2C).

Remarks (6.6-6.7 ): Choice of treatment in patients with and without cancer is sensitive to the individualpatients tolerance for daily injections, need for labo-ratory monitoring, and treatment costs. Treatment of VTE with dabigatran or rivaroxaban, in addition tobeing less burdensome to patients, may prove to beassociated with better clinical outcomes than VKAand LMWH therapy. When these guidelines werebeing prepared (October 2011), postmarketing studiesof safety were not available. Given the paucity of cur-rently available data and that new data are rapidlyemerging, we give a weak recommendation in favorof VKA and LMWH therapy over dabigatran andrivaroxaban, and we have not made any recommen-dation in favor of one of the new agents over the other.



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9.4 Prevention of PTS of the Arm

9.4. In patients with acute symptomatic UEDVT, we suggest against the use of compressionsleeves or venoactive medications (Grade 2C).

9.5 Treatment of Patients With PTS of the Arm

9.5.1. In patients who have PTS of the arm, we

suggest a trial of compression bandages orsleeves to reduce symptoms (Grade 2C).

9.5.2. In patients with PTS of the arm, we sug-gest against treatment with venoactive medica-tions (Grade 2C).

10.0 Patients With Splanchnic Vein Thrombosis

10.1. In patients with symptomatic splanchnicvein thrombosis (portal, mesenteric, and/orsplenic vein thromboses), we recommend anti-coagulation over no anticoagulation (Grade 1B).

10.2. In patients with incidentally detectedsplanchnic vein thrombosis (portal, mesen-teric, and/or splenic vein thromboses), we sug-gest no anticoagulation over anticoagulation (Grade 2C).

11.0 Patients With Hepatic Vein Thrombosis

11.1. In patients with symptomatic hepatic veinthrombosis, we suggest anticoagulation over noanticoagulation (Grade 2C).

11.2. In patients with incidentally detectedhepatic vein thrombosis, we suggest no antico-agulation over anticoagulation (Grade 2C).

Treatment and Prevention ofHeparin-Induced Thrombocytopenia

For further details, see Linkins et al.8

2.1 Platelet Count Monitoring Combined With the4Ts Score for Patients Receiving Heparin/LMWH

2.1.1. For patients receiving heparin in whomclinicians consider the risk of heparin-inducedthrombocytopenia (HIT) to be . 1%, we suggestthat platelet count monitoring be performedevery 2 or 3 days from day 4 to day 14 (or untilheparin is stopped, whichever occurs rst) (Grade 2C).

2.1.2. For patients receiving heparin in whomclinicians consider the risk of HIT to be , 1%,

we suggest that platelet counts not be moni-tored (Grade 2C).

9.2 Thrombolytic Therapy for the Initial Treatmentof Patients With UEDVT

9.2.1. In patients with acute UEDVT thatinvolves the axillary or more proximal veins, wesuggest anticoagulant therapy alone over throm-bolysis (Grade 2C).

Remarks: Patients who (i) are most likely to benetfrom thrombolysis (see text); (ii) have access to CDT;(iii) attach a high value to prevention of PTS; and (iv)attach a lower value to the initial complexity, cost,and risk of bleeding with thrombolytic therapy arelikely to choose thrombolytic therapy over anticoagu-lation alone.

9.2.2. In patients with UEDVT who undergothrombolysis, we recommend the same inten-sity and duration of anticoagulant therapy as insimilar patients who do not undergo thromboly-sis (Grade 1B).

9.3 Long-term Anticoagulation for Patients WithUEDVT

9.3.1. In most patients with UEDVT that is asso-ciated with a central venous catheter, we sug-gest that the catheter not be removed if it isfunctional and there is an ongoing need for thecatheter (Grade 2C).

9.3.2. In patients with UEDVT that involvesthe axillary or more proximal veins, we suggesta minimum duration of anticoagulation of3 months over a shorter period (Grade 2B).

Remarks: This recommendation also applies if theUEDVT was associated with a central venous cath-eter that was removed shortly after diagnosis.

9.3.3. In patients who have UEDVT that is asso-ciated with a central venous catheter that isremoved, we recommend 3 months of antico-agulation over a longer duration of therapy inpatients with no cancer (Grade 1B), and we sug-gest this in patients with cancer (Grade 2C).

9.3.4. In patients who have UEDVT that is asso-ciated with a central venous catheter that is notremoved, we recommend that anticoagulationis continued as long as the central venous cath-eter remains over stopping after 3 months oftreatment in patients with cancer (Grade 1C),and we suggest this in patients with no cancer (Grade 2C).

9.3.5. In patients who have UEDVT that is notassociated with a central venous catheter or withcancer, we recommend 3 months of anticoagula-tion over a longer duration of therapy (Grade 1B).



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and until the INR is within the target range overshorter periods of overlap and that the INR berechecked after the anticoagulant effect of thenonheparin anticoagulant has resolved (Grade 1C).

4.1 Discontinuation of Heparin or Initiation of VKAs vs Treatment With Nonheparin Anticoagulants

4.1. In patients with isolated HIT (HIT withoutthrombosis), we recommend the use of lepirudinor argatroban or danaparoid over the further useof heparin or LMWH or initiation/continuationof a VKA (Grade 1C).

4.2 Choice of Nonheparin Anticoagulants in PatientsWith Isolated HIT

4.2. In patients with isolated HIT (HIT withoutthrombosis) who have normal renal function,

we suggest the use of argatroban or lepirudinor danaparoid over other nonheparin anticoag-ulants (Grade 2C).

Remarks: Other factors such as drug availability, cost,and ability to monitor the anticoagulant effect mayinuence the choice of agent. The dosing consider-ations are the same as for patients with HITT (seesection 3.2). For a recommendation on choice ofnonheparin anticoagulants in the setting of renalinsufciency, see Recommendation 3.2.2.

5.1 Patients Who Require Urgent Cardiac Surgery

5.1.1. In patients with acute HIT (thrombocyto-penic, HIT antibody positive) or subacute HIT(platelets recovered but still HIT antibody pos-itive) who require urgent cardiac surgery, wesuggest the use of bivalirudin over other non-heparin anticoagulants and over heparin plusantiplatelet agents (Grade 2C).

5.1.2. In patients with acute HIT who requirenonurgent cardiac surgery, we recommenddelaying the surgery (if possible) until HIT hasresolved and HIT antibodies are negative (seesection 6.1) (Grade 2C).

Remarks: Other factors not covered by our analysis,such as drug availability, cost, and ability to monitorthe anticoagulant effect may inuence the choice ofagent. For recommendations for patients with a pasthistory of HIT (. 3 months previous) who requirecardiac surgery, see section 6.1.

5.2 Patients Who Require Urgent PercutaneousCoronary Interventions

5.2. In patients with acute HIT or subacute HIT who require percutaneous coronary interven-tions, we suggest the use of bivalirudin (Grade 2B)

3.1 Discontinuation of Heparin or Initiation of VKAs vs Treatment With Nonheparin Anticoagulants

3.1. In patients with HIT complicated by thrombosis(HITT), we recommend the use of nonheparinanticoagulants, in particular lepirudin, arga-troban, and danaparoid, over the further use ofheparin or LMWH or initiation/continuation ofa VKA (Grade 1C).

3.2 Choice of Nonheparin Anticoagulants in PatientsWith HITT

3.2.1. In patients with HITT who have normalrenal function, we suggest the use of argatrobanor lepirudin or danaparoid over other nonhepa-rin anticoagulants (Grade 2C).

Remarks: Other factors not covered by our analysis,such as drug availability, cost, and ability to monitor theanticoagulant effect, may inuence the choice of agent.

3.2.2. In patients with HITT and renal insuf-ciency, we suggest the use of argatroban overother nonheparin anticoagulants (Grade 2C).

3.3 Platelet Transfusions

3.3 In patients with HIT and severe thrombocy-topenia, we suggest giving platelet transfusionsonly if bleeding or during the performanceof an invasive procedure with a high risk ofbleeding (Grade 2C).

3.4 Starting VKAs Before Platelet Recovery

3.4.1. In patients with strongly suspected orconrmed HIT, we recommend against starting

VKA until platelets have substantially recovered(ie, usually to at least 150 3 109 /L) over starting

VKA at a lower platelet count and that the VKAbe initially given in low doses (maximum, 5 mgof warfarin or 6 mg phenprocoumon) over usinghigher doses (Grade 1C).

3.4.2. We further suggest that if a VKA has alreadybeen started when a patient is diagnosed with

HIT, vitamin K should be administered (Grade 2C). Remarks: We place a high value on the preventionof venous limb gangrene and a low value on the costof the additional days of the parental nonheparinanticoagulant.

3.5 Discontinuation of Thrombin Inhibitor After aMinimum of 5 Days of Overlap With VKAs

3.5. In patients with conrmed HIT, we recom-mend that that the VKA be overlapped with a non-heparin anticoagulant for a minimum of 5 days



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absent who require cardiac catheterization orpercutaneous coronary interventions, the rec-ommended treatment is the same as 5.2.

6.3 Patients Who Require Prophylaxis or Treatmentof Thrombosis

6.3. In patients with a past history of HIT whohave acute thrombosis (not related to HIT) andnormal renal function, we suggest the use offondaparinux at full therapeutic doses untiltransition to a VKA can be achieved (Grade 2C).

Antithrombotic Therapy forAtrial Fibrillation

For further details, see You et al.9

2.1 Patients With Nonrheumatic Atrial Fibrillation(AF)

2.1.8. For patients with AF, including those withparoxysmal AF, who are at low risk of stroke(eg, CHADS 2 [congestive heart failure, hyper-tension, age 75 years, diabetes mellitus, priorstroke or transient ischemic attack] score 5 0),

we suggest no therapy rather than antithrom-botic therapy (Grade 2B). For patients who dochoose antithrombotic therapy, we suggest aspi-rin (75 mg to 325 mg once daily) rather thanoral anticoagulation (Grade 2B) or combinationtherapy with aspirin and clopidogrel (Grade 2B).

Remarks : Patients who place an exceptionally high value on stroke reduction and a low value on avoidingbleeding and the burden associated with antithrom-botic therapy are likely to choose antithrombotictherapy rather than no antithrombotic therapy. Otherfactors that may inuence the choices above are aconsideration of patient-specic bleeding risk andthe presence of additional risk factors for stroke,including age 65 to 74 years and female gender, whichhave been more consistently validated, and vasculardisease, which has been less well validated (see sec-

tion 2.1.12). The presence of multiple non-CHADS2 risk factors for stroke may favor oral anticoagulationtherapy.

2.1.9. For patients with AF, including those withparoxysmal AF, who are at intermediate risk ofstroke (eg, CHADS 2 score 5 1), we recommendoral anticoagulation rather than no therapy(Grade 1B). We suggest oral anticoagulationrather than aspirin (75 mg to 325 mg oncedaily) (Grade 2B) or combination therapy withaspirin and clopidogrel (Grade 2B). For patients

or argatroban (Grade 2C) over other nonheparinanticoagulants.

Remarks: Other factors, such as drug availability,cost, and ability to monitor the anticoagulant effect,may inuence the choice of agent.

5.3 Patients Who Require Renal Replacement Therapy

5.3.1. In patients with acute or subacute HIT who require renal replacement therapy, wesuggest the use of argatroban or danaparoidover other nonheparin anticoagulants (Grade 2C).

Remarks: We acknowledge that the cost of argatrobanmay be prohibitive at some clinical centers. We fur-ther suggest that if the prothrombotic state of HITappears to have resolved (as seen by normalization ofthe platelet count), saline ushes during dialysis wouldbe a reasonable option. This suggestion is based onthe presumed pathogenesis of thrombosis in this

condition and not on the results of clinical trials. 5.3.2. In patients with a past history of HIT whorequire ongoing renal replacement therapyor catheter locking, we suggest the use ofregional citrate over the use of heparin orLMWH (Grade 2C).

5.4 Pregnant Patients

5.4. In pregnant patients with acute or subacuteHIT, we suggest danaparoid over other non-heparin anticoagulants (Grade 2C). We suggest

the use of lepirudin or fondaparinux only ifdanaparoid is not available (Grade 2C).

Remarks: Other factors, such as drug availability,cost, and ability to monitor the anticoagulant effect,may inuence the choice of agent.

6.1 Patients With a History of HIT Who RequireCardiac Surgery

6.1.1. In patients with a history of HIT in whomheparin antibodies have been shown to beabsent who require cardiac surgery, we suggest

the use of heparin (short-term use only) overnonheparin anticoagulants (Grade 2C).

6.1.2. In patients with a history of HIT in whomheparin antibodies are still present who requirecardiac surgery, we suggest the use of nonhepa-rin anticoagulants (see 5.1.1) over heparin orLMWH (Grade 2C).

6.2 Patients Who Require PCI

6.2. In patients with a history of HIT in whomheparin antibodies have been shown to be



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Grade 1B). For patients with AF and mitral ste-nosis who are unsuitable for or choose not totake adjusted-dose VKA therapy (for reasonsother than concerns about major bleeding), werecommend combination therapy with aspirinand clopidogrel rather than aspirin (75 mg to325 mg once daily) alone (Grade 1B).

3.1 Patients With AF and Stable Coronary ArteryDisease

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