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Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_3751_Библиотеки_им_академика_М_И_Перельмана

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improve symptoms if the burden of disease is distal. This procedure has been described in detail elsewhere.
75,82,87,89
Briefly, after median sternotomy, cardiopulmonary bypass (CPB) is established to
prevent collateral bleeding and ensure a clear surgical field. Profound hypothermia to 18-20°C is induced.AnincisionismadeintotherightPAandtheendarterectomyplaneisestablished88;iftoodeep, perforationmay occur and if tooshallow, PHwill not resolve. This plane can be followed downto involved branches as necessary. Organized fibrous tissue is then removed. Given that the maximum coolingperiodis20minutesandPEAisusuallybilateral,therightsideisusuallydonefirst,thepatientis reperfused,CPBisre-established,andthenleftPEAisperformed.88Anticoagulationisusuallystarted4- 8hafterPEAwithIVunfractionatedheparin.Warfarincanberestartedatdays8-14.88Theroleofother director“novel”anticoagulantsisnotestablishedinthispopulation.
b.BalloonPulmonaryAngioplasty
TheroleofBPAinCTEPHisnotyetdefined,giventhelimitedoutcomesdata.
87,90
In selectpatients, it
improveshemodynamicsand6MWD.ThereisnoconsensusyetonanoptimalBPApopulation,butthis proceduremaybeconsideredinpatientswhoareinoperable,havedistaldisease,havepost-PEAPH,or fail medical therapy.87Giventhat BPAis minimallyinvasive, itmayalso have apalliative role. It is contraindicatedinpatientswithcontrastallergiesorsevererenaldysfunction. InBPA,internaljugularveinaccessisobtained.Theprocedurehasbeendescribedindetailelsewhere.
91
Briefly, asheathisinsertedanda smallerintroducer sheathis advanced through itintothemainPA.
87
Heparin is given and selective pulmonary angiography is done. Intravascular ultrasound is used to determinevesseldiameterforthecorrectballoonsize.Aguidewireisintroduceduntilitcrossestheclot, andthenaballooncatheterisusedtocompressthethrombusanddilatethevessel.Generally,oneBPA session can only target a few vessels, so multiple treatments may be needed. In early BPA studies, reperfusionpulmonaryedemawasnotuncommon;however,ratesofthiscomplicationhavedecreasedas techniqueimproves.
c.MedicalTherapy
Medical therapy may be indicated in post-BPA/PEA CTEPH and nonintervenable candidates.
85,90
Riociguatisapprovedfor both populations.87Ofnote, all inoperable patientsshould receive asecond opinionatanexpertCTEPHcenter,asdefinitionsofsurgicalcandidacymaydifferbetweenfacilitiesand surgeons.
IV.Conclusions
PVD encompasses a spectrum of conditions with effects ranging from mild to severe. Significant improvements indiagnosis and therapy have been made, andpatients benefit froma multidisciplinary approach. As research in this field continues, it is likely that therapeutic strategies will continue to rapidlyevolve.
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C H A P T E R  2 2
DeepVeinThrombosis
RobertR.AttaranMD,FACC,FASE,FSCAI,RPVI
I.VenousThromboembolism
II.VenousThromboembolismandRiskofSubsequentRecurrentVenousThromboembolism
III.PharmacologicalTreatment
A.Anticoagulation
B.AmericanCollegeofChestPhysicianGuidelines
C.Catheter-DirectedTherapy
IV.SuperficialVenousThrombosisoftheLegs
A.Presentation
B.EtiologicFactors
C.ClinicalDiagnosis
D.Treatment
V.IsolatedBelow-the-KneeDeepVeinThrombosis
A.HistoryandManagement
B.RisksofRecurrence
C.Recommendations
VI.IndicationsforHypercoagulableWorkup
VII.ChronicDeepVeinThrombosis
A.Effects
B.TreatmentandManagement
VIII.ImagingofVenousThromboembolism
A.Ultrasound
B.MagneticResonance
IX.VenousThromboembolismandRiskofSubsequentArterialThrombosis
A.AssociatedDisorders
B.TrialsandStudies
X.ThePotentialRoleofStatinsinVenousDisease
A.JupiterTrial
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B.StatinTherapy
C.PlateletRecruitment
D.OralAnticoagulation
XI.Summary
KeyPoints
■Venousthromboembolismisacommonandsometimesdevastatingcondition.
■Insomecases,mechanicalthrombusremovalcanbebeneficial.
■TherateofrecurrentDVTishigh.
■OptimaldurationofanticoagulationforDVTiscontroversial.
■Treatmentofpost-thromboticsyndromeshouldideallyaddressbothvenousobstructionand
reflux.
I.VenousThromboembolism
Venous thromboembolism (VTE) (deep vein thrombosis [DVT] and pulmonary embolism [PE]) is a common cause of mortality, morbidity, and loss of quality of life, particularly due to postthrombotic syndrome(PTS).Thisisachronicconditionofthelegthatcanresultinpain,swelling,discoloration,and evenulceration,whichoccursinatleast30%afterDVT.1Rarelylimblosscanoccurthroughphlegmasia ceruleandolens.Thereare over250,000casesofVTEper annumin the UnitedStatesalone.2 Venous thrombosisisinitiatedbyacombinationofvesselinjury,inflammation,hypercoagulability,andstasis.A firstoccurrenceofVTEdramaticallyincreasestheriskofasubsequentone.
II.VenousThromboembolismandRiskofSubsequent RecurrentVenousThromboembolism
In a prospective cohort study, 355 patients with a first episode of DVT were followed for 8 years. Recurrent VTE occurred at17.5% after 2years and 24.6%after5years.PTSwas reportedin22.8% after2yearsand28%after5years.3Thesameinvestigatorsinalargerprospectivecohortstudyof1626 patients withVTE reporteda recurrence of 11% at 1year, 19.6%at3 years, and 29.1%at5 years.
4
Anticoagulationiseffectiveatloweringrecurrencesbutcarriesanincreasedriskofbleeding.
5
III.PharmacologicalTreatment
A.Anticoagulation
Parenteralanticoagulationwith a heparinoidfollowedbyoralanticoagulation hasbeenthe mainstayof treatment for acute DVT. Anticoagulants help prevent thrombus propagation and embolization. Both vitamin K antagonists (VKAs) and non–vitamin K oral anticoagulants which are the novel oral anticoagulants (NOACs) have been used. An advantage of NOACs is the steady anticoagulation they provide(withouttheneedforroutinemonitoring).Theymayalsoresultinlessintracranialbleedingthan VKAs,althoughpossiblymoregastrointestinalbleedsasshowninsomestudies.
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B.AmericanCollegeofChestPhysicianGuidelines
TherequireddurationforanticoagulanttherapyinDVThasbeenacontentiousissuewithsignificant variabilityinpracticepattern.Somepatientsaremaintainedonanticoagulationforyears.The2016 American College of Chest Physician Guidelines8 made the following recommendations for anticoagulationinDVT:
■In patients with proximal DVT or PE, 3monthsofanticoagulant therapy are recommended
(Grade1B).NOACsarepreferredoverVKAs.
■In proximal DVT or PE provoked by surgery or a transient risk factor, 3 months of
anticoagulanttherapyarerecommended(Grade1B).
■In proximal DVT of the leg or PE and cancer (“cancer-associated thrombosis”), low-
molecular-weightheparinisrecommendedoveroralanticoagulants.Anticoagulationshouldbe extendedbeyond3monthsinthosewithoutahighbleedrisk(Grade1B).
■In unprovoked first proximal DVT or PE with low-moderate bleed risk, extended
anticoagulanttherapybeyond3monthsissuggested(Grade2B).
In a second unprovoked proximal DVT or PE, extended anticoagulant therapy beyond 3 months is recommendedwithlowbleedrisk(Grade1B)andmoderatebleedrisk(Grade2B).
Whileanticoagulantspreventthrombuspropagation,thrombolyticsdirectlyeliminatethrombus.One of the troublesome sequelae of DVT is PTS. DVT can acutely lead to elevated limb venous pressures and diminishedvenous outflow leading to inflammation,fibrosis, andvalvular damage. ThisisparticularlyaconcerniftheDVTinvolvesthevenousoutflowatthecommonfemoralveinor evenmoreproximallevel(iliacveinorIVC).Thrombolysiscanrelievetheobstructionmorerapidly thanmereanticoagulation.ACochranereviewofrandomizedtrialscomparingthrombolysisagainst anticoagulationidentified17trials(n=1103).ThrombolysisreducedratesofPTSbyathirdandleg ulcerationapproximatelyahalf,butthereweremoreinstancesofbleeding(RR2.23;95%CI1.41-
3.52,P=.0006).Therewasnodifferenceinmortality.
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C.Catheter-DirectedTherapy
SystemicthrombolysisforDVTcarriesasignificantbleedriskandhaslargelybeensupersededby catheter-directedtherapy(CDT).WithCDT,lowerdosesofthrombolyticsarerequiredandareoften administeredoveralongerperiod.Inadditiontotheavailabilityofsimpleperfusioncatheters,some availabledeviceshaveamechanicalcomponentthatcanhelpdisruptthethrombus.
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Twoofthedevices currently usedformechanicalthrombectomyin the UnitedStatesare AngioJet (Boston Scientific, Marlborough,MA)andEKOS (BTG,West Conshohocken,PA). AngioJet is a pharmacomechanicalthrombectomycatheter.12Multiplehigh-velocitysalinejetsthroughorificesat the tip create a low-pressure zone using the Venturi-Bernoulli effect, resulting indissociation of thrombus which is concurrently removed by suction. The power pulse function allows for local infusion of a thrombolytic agent (eg, 12-25 mg tissue plasminogen activator), while the suction function is stoppedtopreventremoval of the lytic.
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With the AngioJet catheter tip positioned
withinthethrombus,powerpulselyticinfusioncanberunforapproximately90minutesbeforethe thrombectomymodeisreactivatedandthetipmanipulatedupanddowntoretrievethrombus.14The largercaliberAngioJetZelanteDVTcatheter(8F)iscapableofremovingthrombusmorequickly.
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1.Trials
The EKOS device is an ultrasound-assisted lysis perfusion catheter. In vitro studies have demonstratedimproveddispersionoftissueplasminogenactivatorintothrombus,whenassistedby ultrasound.15 The EKOS catheter is advanced into the venous thrombus and activated, infusing thrombolytics.Thedeviceistypicallyrunforupto24hoursbeforeremoval.
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TherearetworandomizedcontrolledtrialscomparingCDTwithanticoagulationinDVTthatmerit discussion. In the TORPEDO trial 91 patients with proximal DVT received CDT in addition to anticoagulation, versus92 patientswhoreceivedanticoagulation only. TheCDTdevices included Trellis (Covidien, Plymouth, MN) and AngioJet (Boston Scientific, Marlborough, MA). Approximately3rdofCDTpatientsalsounderwentvenousballoonangioplastyand3rdunderwent venousstenting.TheCDTgroupdemonstratedsignificantlylowerratesofrecurrentVTEandPTSat 6 and 30 months.11 CaVenT was a Norwegianmulticenter trial that enrolled patients with acute iliofemoral DVT.IntheCDT group(n =101), a catheter perfused intravenous alteplase, andthe control group(n = 108) received anticoagulationonly. With CDT, iliofemoral vein patency was significantlyhigherat65.9%versus47.4%inthecontrolgroup(P=.012).CDTledtoanabsolute riskreductionof14.4%(NNT=7)inPTSbyVillaltascore,at24months.17Five-yearfollow-up dataofCaVenTcontinuetofavorCDToveranticoagulationonly.
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Sponsored by the National Institute of Health, the ATTRACT trial has evaluated pharmacomechanicalCDTinproximalDVT,enrolling692patients.Theprimaryendpointisrateof PTSonfollow-up.Enrollmenthasbeencompleted,andthestudyiscurrentlyinthefollow-upphase.
a. While there is some consensus thatCDTshould especiallybe considered for treating acute
DVTscausingvenousoutflowobstruction(thoseinvolvingthecommonfemoral,iliacveinsor
IVC),morerobustdataareneeded.TheATTRACTtrialmayhelpshedmorelightonthisissue. Sahaetal19havesuggestedthefive-component“BLAST”mnemonicwhenassessingcandidatesfor CDT. BLAST stands for Bleeding risk, Lifeexpectancy, AnatomyofDVT,Severity of DVT,and Timing.Lysis is less desirable inthrombi that are older than14 days, although some trials have includedpatientswithin21days.
a. Webelievethatiliacstentingforvenousoutflowobstructionshouldbeperformedinadditionto
CDTforDVT,asitmayenhancesubsequentvenouspatencyrates.
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IV.SuperficialVenousThrombosisoftheLegs
A.Presentation
Frequently, “superficial venous thrombosis” is also referred to as “superficial thrombophlebitis,” signifyinginflammationofsuperficialveinswiththrombosis.Itappearstobemorecommoninolderage, particularly inwomen.21 Patients typicallypresent withtender, erythematous legs along theregionof affectedveins.Itcansometimesbemistakenforcellulitis,althoughinfectionisfrequentlynotpresent.The affectedveinsmayfeelfirmtopalpation.Overtime,pigmentationcandevelop.
B.EtiologicFactors
Associated or etiologic factors include varicose veins, immobility, hypercoagulable states, surgery, intravenousaccess,pregnancy,malignancy, and estrogentherapy.22Karathanos23 followed 97patients with superficial thrombosis and varicose veins for a mean period of 55 months. Thirteen had a recurrence.Therewerehigherratesofprothrombingene(G20210A)mutationanddyslipidemiainthose
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withrecurrence.
C.ClinicalDiagnosis
Although superficial thrombosis is a clinical diagnosis, it may coincide with DVT.24 It is therefore reasonabletoconsidervenousdupleximagingtogaugeitsextentandtoruleoutdeepveininvolvement.
D.Treatment
Superficialvenousthrombosishasbeentreatedinanumberofwaysincludingtopicalororalnonsteroidal anti-inflammatorydrugs(NSAIDs),aspirin,anticoagulants,andcompression.25Thereissomeevidence tosupporttheroleofNSAIDsaswellassomeanticoagulantsinreducingrecurrence,thrombusextension, orDVT.A2013Cochranereviewnotedapaucityofrandomizedcontrolleddatafortreatmentmodalities insuperficialvenousthrombosis.Prophylacticdosefondaparinuxfor6weeksappearedtoshowbenefit byreducingthrombusextension.26Itisourpracticetoablatevenousinsufficiencyandvaricoseveinsin patients with a history of superficial venous thrombosis, particularly if more than one episode has occurred.
V.IsolatedBelow-the-KneeDeepVeinThrombosis
A.HistoryandManagement
Theinfrapoplitealdeepveinsincludethepairedperoneal,anteriortibial,andposteriortibialveins, as well the gastrocnemius and soleal veins. Significant anatomic variability can exist. Isolated below-the-knee DVT, also referred toas isolated distal deep veinthrombosis (IDDVT), denotes thrombosis in any of the deep veins without involvement of the popliteal vein. Thrombotic involvementofthepoplitealvein(orabove)isreferredtoasproximalDVT. ThenaturalhistoryofIDDVTisnotclear,andtherefore,itsmanagementiscontroversial.Between 23%and59%ofindividualsdiagnosedwithDVTalsohaveIDDVT.27Fewstudieshaveevaluated the natural historyof IDDVT without anticoagulation.TheCALTHRO study followed 59 patients withIDDVT.No anticoagulationwasadministered. Afteroneweek,proximal thrombus extension occurredin3.1%.
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B.RisksofRecurrence
IDDVTmaycarrya lowerriskofrecurrencecompared with proximalDVT.29However, chronic sequelaesuchasPTScanoccur.
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Ameta-analysisof(≥1monththerapy)anticoagulationtrialsforIDDVTsuggestedreducedratesof thrombuspropagationandPE(odds ratio,0.12;95% confidenceinterval,0.02-0.77;P =.03) and thrombuspropagation(oddsratio,0.29;95%confidenceinterval,0.14-0.62;P=.04).31However, the studies were small (126 patients treatedwith anticoagulationversus 328 controls), and many werejudgedtobeofpoorquality.
C.Recommendations
The International ConsensusStatement on Prevention andTreatment ofVenous Thromboembolism
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recommends3monthsoforalanticoagulantsforpatientswithsymptomaticIDDVT.
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The 2016 American College of Chest Physicians Guidelines8 have identified a number of risk factorsforIDDVTextensionincludingD-dimerelevation,thrombuslongerthan5cmorinmultiple sites,lackofreversibleprovokingfactor,activecancer,historyofVTE,inpatientstatus,andtibialor peronealveininvolvement.Inpatients withoutseveresymptoms orriskfactorsforextension,they recommendserial imagingofthe deep veinsover anticoagulation (Grade 2C). Anticoagulationis recommendedifthepatienthasseveresymptoms. Below-knee compression stockings should be worn and may have therapeutic benefit beyond reductionofedemaanddiscomfort.
28
VI.IndicationsforHypercoagulableWorkup
The evaluation and management of DVT in patients with thrombophilia is beyond the scope of this chapter.TheAmericanSociety ofHematology provides anumber ofguidelinesas partofitsChoosing Wiselycampaigntominimize unnecessaryanticoagulation and testing.33In evaluatingany patient with DVT,weseekthefollowinginformation:whethertheeventwasprovokedorunprovoked,pastmedical history,historyofmiscarriages,familyhistory,andmedications.Thefollowinginitiallaboratorytestsare obtained:completebloodcount,peripheral bloodsmear,erythrocytesedimentationrate andC-reactive protein,coagulationpanel,basicmetabolicpanel,andurinalysiswithmicroscopy.Wetypicallytestfora hereditarythrombophiliaifoneormoreofthefollowingcriteriaapply:thepatientisyoung(age<45y), hasa positivefamilyhistoryforVTE(age<45y),hasrecurrentVTE,and/orhasunprovokedVTE.
34
However, screening all individuals with unprovoked VTE and their subsequent management are controversial.
35
Owing topaucity ofdata and the inherent challenges of study implementation, it is difficult todefine whichpopulationsshouldremainonanticoagulationindefinitely.Basedonthecurrentstateofknowledge,
36–39
itis probablyreasonable to offer indefiniteanticoagulation inthefollowing scenarios: 2or more
episodes of unprovoked VTE, unprovoked VTE and antithrombin deficiency, unprovoked massive PE, unprovoked cerebral or mesenteric vein thrombosis, and unprovoked VTE and two hereditary thrombophilias.
VII.ChronicDeepVeinThrombosis
A.Effects
Chronic disease of the deep veins can lead toPTS. Its harmful effects can be from a combinationof obstruction, reflux, or both.40 The reflux may also involve superficial veins. The severity of PTS is greatestamongthosewithiliofemoralDVT,recurrentDVT,andolderage.
1,41,42
After a DVT the thrombus may resolve leaving minimal scarring. In many cases, however, the thrombusbecomesmoreorganizedandfibrosisoccurswithinthevein,makingthelumennarrower or occluded. Hardened cribriform synechiae formed from endothelialized strands of residual thrombuscanremain.
43,44
Collateralformationmayoccur.Stenosisorobstructioninaproximalvein
resultsinvenousstasisandhypertensionmoredistally.Exerciseandtheuseofthecalfmusclepump are unable to lower venous pressures and ambulatory venous hypertension ensues.43 Valvular dysfunctionandvenousdilatationcanfollowcontributingtoinflammationandedemaintheaffected limb.
45
Approximately75%ofiliacveinsarethoughttodevelopobstructionafteraDVT.
40,46
Overthepast
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