Upper ExtremityDeep Vein Thrombosis4/6/10

DefinitionOriginally described in late 19th century by Paget and von Schroetter.Thrombosis in any of the following veins:Ulnar/Radial/InterosseousBrachialAxillarySubclavianJugular/Brachiocephalic/SVCBasilic and cephalic are considered superficial

Dark Blue: Deep veinBlue: Superficial vein

IncidencePrior to 1970, accounted for < 2% DVTsMay now account for 4-8%, higher in critical care areas (up to 33% in some studies).MaleFemaleIdiopathic UE DVT tend to be in younger patients.

EtiologyVirchows Triad:Venous trauma (Endothelial wall)Venous stasis (external compression) Hypercoagulability

Dark Blue: Deep veinBlue: Superficial veinRed: Choke points

Risk FactorsTrauma/SurgeryMalignancy/XRTInherited Hypercoagulable statesAnatomical deformities/Malformations (e.g. Cervical ribs)Hyperviscosity (Sickle cell/Polycythemia)Athletes (with repetitive motions of arms)/Effort thrombosis/Paget-von-Schroetter syndromeThoracic Outlet SyndromePrevious DVT/VTE

Risk FactorsVenous catherizationOral contraceptives/Hormone Replacement TherapyTobaccoObesityCHFNephrotic syndrome/PNHLymphedemaHyperhomocysteinemiaThrombophlebitis

SymptomsArm/Neck/Facial swellingArm/Neck/Facial painErythemaBluish discolorationCollateral Venous distention (including chest veins)Fever

DiagnosisD-Dimer: High sensitivity/Low specificity. Measures degradation product of cross-linked fibrinDoppler Ultrasound: High sensitivity and specificity, though operator dependent.Venography: Gold standard. Requires contrastMRI: Relatively low sensitivity/High specificity. Limited due to time constraints/cost

ComplicationsPulmonary EmbolismHistorically, 1% PE were attributed to UE DVTs.More likely 5-10%.More centrally located the thrombosis, the higher the risk of PE (Subclavian > Brachial)

Complications - PE

ComplicationsRecurrent DVT/PE:Risk increases on a yearly basis2% in 1st year4% in 3rd year7% in 5th yearRisk is further increased in malignancy

ComplicationsPost-thrombotic syndrome: 15-25% of patients with UE DVT may develop PTS.Characterized by persistent/severe pain and persistent edema.Can often be debilitating adversely affecting quality of life.

TreatmentAmerican College of Chest Physicians:Recommends the UE DVT be treated the same as LE DVT.Treatment was shown to decrease the recurrence of DVT/PE in two prospective cohort studies.

TreatmentHeparin (Unfractionated): Activates antithrombin III, which inactivates thrombin. Also inhibits factor Xa and factor IXa.Requires monitoring of the aPTT (1.5X baseline PTT) due to heparin-binding proteins (which tend to increase during illness).Half-life: 60 min when given IV.Can be reversed with protamine sulfate.

TreatmentLow-molecular weight heparin (LMWH)Less affected by heparin-binding proteinsMore active against antithrombin IIILower rate of HIT.Reversal with protamine sulfate is limited

TreatmentFondaparinux (Arixtra): Binds to antithrombin, which inhibits factor Xa.No action against thrombinNot metabolized, renally excreted.Half-life 15 hrs

TreatmentDirect thrombin inhibitors:Lepirudin, renally excreted.ArgatrobanCan inhibit clot-bound thrombinNot affected by circulating inhibitors of heparin (released by platelets)Does not cause HIT.

TreatmentVitamin K antagonists:Warfarin (Coumadin): Inhibits Vitamin K epoxide reductase, which recycles oxidized Vit K. Initially developed as a rodenticide (rat poison).Acenocoumarol: Outside US, shorter half life than warfarin.Phenprocoumon: Outside US, longer half life than warfarin.INR goal 2-3

FutureXimelagatran: PO Direct thrombin inhibitor.Denied approval by FDA in 2004Pulled from market in 2006Found to have caused severe liver damage and heart attacks.

FutureRivaroxaban: PO Factor Xa inhibitorCompared to LMWH in orthopedic surgery patients in several trials.Reduced LE DVT/nonfatal PE/death with no significant difference in major bleeding.Approved in Europe and Canada for DVT prophylaxis in orthopedic surgery patients.May potentially be used in HIT?

FutureDabigatran: PO direct thrombin inhibitor.RECOVER trial: End point recurrent VTE/fatal PE:2.4% dabigatran vs 2.1% warfarinHazard ratio 1.1, dabigatran not inferior1.6% major bleeding dabigatran vs 1.9% warfarin, not significantSignificant reduction in all bleeding with dabigatran of 29%Approved for DVT prophylaxis in orthopedic surgery patients in Europe and Canada.

Treatment DurationFirst DVT: Provoked: 3-6 monthsUnprovoked: 6-12 monthsDVT with cancer/antiphospholipid syndrome: Life-long therapySecond DVT: Life-long therapy

TreatmentCatheter-directed thrombolysis: Infuses a thrombolytic agent (usually tPA) between two inflated balloons via a catheter.Early restoration of venous patency/improved venous return/Decreases pain/discomfort.No change in rates of recurrent DVT/PE/bleeding/PTS.Contraindications include hemorrhage/recent neurosurgeryACCP recommends against routine use (Grade 1C). With severe symptoms of recent onset with low risk of bleeding, may be used (Grade 2C)

TreatmentSVC FilterRates of PE 2.4% and PTS 0% in one study (n=41).Another study showed no episodes of PE (n=72).ACCP recommends against routine use (Grade 1C). If anticoagulation contraindicated and DVT progression occurs, then SVC may be placed (Grade 2C).

TreatmentGraded Compression sleeves/Elastic bandagesUseful in relieving symptoms of persistent pain/swelling such as in PTS.ACCP: Routine use not recommended (Grade 2C), except in patients with persistent pain (Grade 2C)

TreatmentGraded Compression sleeves/Elastic bandagesUseful in relieving symptoms of persistent pain/swelling such as in PTS.ACCP: Routine use not recommended (Grade 2C), except in patients with persistent pain (Grade 2C)

TreatmentIn a retrospective study of 189 Surgical ICU patients, 33% had UE DVTs,Central catheters (45%) was the highest risk factor identified6% had PE, all nonfatal, all with IJ clots60% were anticoagulatedNo difference in LOS/survival to 30 days, and 1 year mortality

TreatmentRIETE Registry:512 of 11564 DVTs were UE DVT (4.4%)9% had PE (vs 29% for LE DVT)3 month outcomes of major bleeding/fatal bleeding/recurrent DVT/recurrent PE were similar between UE and LE DVTsSlightly higher mortality rate for UE DVTsCancer patients had increased rates in recurrent DVT/PE/major bleeding.56% of patients had received anticoagulation.

ConclusionsMost studies are retrospective or cohort studies with small numbers of patients.ACCP recommends to treat UE DVTs same as LE DVTsUse heparin/LMWH, until INR therapeutic with coumadin (INR goal 2-3)Thrombolysis/Thrombectomy/SVC Filter not routinely indicated.Future PO meds may replace warfarin

ReferencesChest 2008; 133; 454S-545S.Chest January 2008 vol. 133 no. 1 143-148Dabigatran versus Warfarin in the Treatment of Acute Venous Thromboembolism. NEJM 361: 2342-2352. Dec 10, 2009.Hingorani A, Ascher E, Lorenson E, et al. Upper extremity deep venous thrombosis and its impact on morbidity and mortality rates in a hospital-based population J Vasc Surg 1997;26:85360.Hingorani A, Ascher E, Markevich N, et al. Risk factors for mortality in patients with upper extremity and internal jugular deep venous thrombosis J Vasc Surg 2005;41:4768.Paget J., London: Longmans, Green & Co; 1875. Clinical lectures and essays.Prandoni P, Polistena P, Bernardi E, et al. Upper-extremity deep vein thrombosis: risk factors, diagnosis and complications Arch Intern Med 1997;157:5762.Vascular.2008;16(2):73-79.von Schroetter L. Nothnagel Handbuch der Pathologie und Therapie Holder 1884