Upper ExtremityUpper ExtremityDeep Vein ThrombosisDeep Vein Thrombosis
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DefinitionDefinition
Originally described in late 19th century by Originally described in late 19th century by Paget and von Schroetter.Paget and von Schroetter.
Thrombosis in any of the following veins:Thrombosis in any of the following veins: Ulnar/Radial/InterosseousUlnar/Radial/Interosseous BrachialBrachial AxillaryAxillary SubclavianSubclavian Jugular/Brachiocephalic/SVCJugular/Brachiocephalic/SVC
Basilic and cephalic are considered superficialBasilic and cephalic are considered superficial
Dark Blue: Deep vein
Blue: Superficial vein
IncidenceIncidence
Prior to 1970, accounted for < 2% DVTsPrior to 1970, accounted for < 2% DVTs May now account for 4-8%, higher in May now account for 4-8%, higher in
critical care areas (up to 33% in some critical care areas (up to 33% in some studies).studies).
Male≈FemaleMale≈Female Idiopathic UE DVT tend to be in younger Idiopathic UE DVT tend to be in younger
patients.patients.
EtiologyEtiology
Virchow’s Triad:Virchow’s Triad: Venous trauma (Endothelial wall)Venous trauma (Endothelial wall) Venous stasis (external compression) Venous stasis (external compression) HypercoagulabilityHypercoagulability
Dark Blue: Deep vein
Blue: Superficial vein
Red: “Choke” points
Risk FactorsRisk Factors
Trauma/SurgeryTrauma/Surgery Malignancy/XRTMalignancy/XRT Inherited Hypercoagulable statesInherited Hypercoagulable states Anatomical deformities/Malformations (e.g. Anatomical deformities/Malformations (e.g.
Cervical ribs)Cervical ribs) Hyperviscosity (Sickle cell/Polycythemia)Hyperviscosity (Sickle cell/Polycythemia) Athletes (with repetitive motions of arms)/”Effort Athletes (with repetitive motions of arms)/”Effort
thrombosis”/Paget-von-Schroetter syndromethrombosis”/Paget-von-Schroetter syndrome Thoracic Outlet SyndromeThoracic Outlet Syndrome Previous DVT/VTEPrevious DVT/VTE
Risk FactorsRisk Factors
Venous catherizationVenous catherization Oral contraceptives/Hormone Replacement TherapyOral contraceptives/Hormone Replacement Therapy TobaccoTobacco ObesityObesity CHFCHF Nephrotic syndrome/PNHNephrotic syndrome/PNH LymphedemaLymphedema HyperhomocysteinemiaHyperhomocysteinemia ThrombophlebitisThrombophlebitis
SymptomsSymptoms
Arm/Neck/Facial swellingArm/Neck/Facial swelling Arm/Neck/Facial painArm/Neck/Facial pain ErythemaErythema Bluish discolorationBluish discoloration Collateral Venous distention (including Collateral Venous distention (including
chest veins)chest veins) FeverFever
DiagnosisDiagnosis
D-Dimer: High sensitivity/Low specificity. D-Dimer: High sensitivity/Low specificity. Measures degradation product of cross-linked Measures degradation product of cross-linked fibrinfibrin
Doppler Ultrasound: High sensitivity and Doppler Ultrasound: High sensitivity and specificity, though operator dependent.specificity, though operator dependent.
Venography: Gold standard. Requires contrastVenography: Gold standard. Requires contrast MRI: Relatively low sensitivity/High specificity. MRI: Relatively low sensitivity/High specificity.
Limited due to time constraints/costLimited due to time constraints/cost
ComplicationsComplications
Pulmonary EmbolismPulmonary Embolism Historically, 1% PE were attributed to UE Historically, 1% PE were attributed to UE
DVTs.DVTs. More likely 5-10%.More likely 5-10%. More centrally located the thrombosis, the More centrally located the thrombosis, the
higher the risk of PE (Subclavian > higher the risk of PE (Subclavian > Brachial)Brachial)
Complications - PEComplications - PE
QuickTime™ and aTIFF (Uncompressed) decompressor
are needed to see this picture.
ComplicationsComplications
Recurrent DVT/PE:Recurrent DVT/PE: Risk increases on a yearly basisRisk increases on a yearly basis
2% in 1st year2% in 1st year 4% in 3rd year4% in 3rd year 7% in 5th year7% in 5th year
Risk is further increased in malignancyRisk is further increased in malignancy
ComplicationsComplications
Post-thrombotic syndrome: 15-25% of Post-thrombotic syndrome: 15-25% of patients with UE DVT may develop PTS.patients with UE DVT may develop PTS.
Characterized by persistent/severe pain Characterized by persistent/severe pain and persistent edema.and persistent edema.
Can often be debilitating adversely Can often be debilitating adversely affecting quality of life.affecting quality of life.
TreatmentTreatment
American College of Chest Physicians:American College of Chest Physicians: Recommends the UE DVT be treated the Recommends the UE DVT be treated the
same as LE DVT.same as LE DVT. Treatment was shown to decrease the Treatment was shown to decrease the
recurrence of DVT/PE in two prospective recurrence of DVT/PE in two prospective cohort studies.cohort studies.
QuickTime™ and aTIFF (Uncompressed) decompressor
are needed to see this picture.
TreatmentTreatment
Heparin (Unfractionated): Activates Heparin (Unfractionated): Activates antithrombin III, which inactivates thrombin. antithrombin III, which inactivates thrombin. Also inhibits factor Xa and factor IXa.Also inhibits factor Xa and factor IXa.
Requires monitoring of the aPTT (1.5X Requires monitoring of the aPTT (1.5X baseline PTT) due to heparin-binding baseline PTT) due to heparin-binding proteins (which tend to increase during proteins (which tend to increase during illness).illness).
Half-life: 60 min when given IV.Half-life: 60 min when given IV. Can be reversed with protamine sulfate.Can be reversed with protamine sulfate.
TreatmentTreatment
Low-molecular weight heparin (LMWH)Low-molecular weight heparin (LMWH) Less affected by heparin-binding proteinsLess affected by heparin-binding proteins More active against antithrombin IIIMore active against antithrombin III Lower rate of HIT.Lower rate of HIT. Reversal with protamine sulfate is limitedReversal with protamine sulfate is limited
TreatmentTreatment
Fondaparinux (Arixtra): Binds to Fondaparinux (Arixtra): Binds to antithrombin, which inhibits factor Xa.antithrombin, which inhibits factor Xa.
No action against thrombinNo action against thrombin Not metabolized, renally excreted.Not metabolized, renally excreted. Half-life 15 hrs Half-life 15 hrs
TreatmentTreatment
Direct thrombin inhibitors:Direct thrombin inhibitors: Lepirudin, renally excreted.Lepirudin, renally excreted. ArgatrobanArgatroban Can inhibit clot-bound thrombinCan inhibit clot-bound thrombin Not affected by circulating inhibitors of Not affected by circulating inhibitors of
heparin (released by platelets)heparin (released by platelets) Does not cause HIT.Does not cause HIT.
TreatmentTreatment
Vitamin K antagonists:Vitamin K antagonists: Warfarin (Coumadin): Inhibits Vitamin K epoxide Warfarin (Coumadin): Inhibits Vitamin K epoxide
reductase, which recycles oxidized Vit K. Initially reductase, which recycles oxidized Vit K. Initially developed as a rodenticide (rat poison).developed as a rodenticide (rat poison).
Acenocoumarol: Outside US, shorter half life Acenocoumarol: Outside US, shorter half life than warfarin.than warfarin.
Phenprocoumon: Outside US, longer half life Phenprocoumon: Outside US, longer half life than warfarin.than warfarin.
INR goal 2-3INR goal 2-3
FutureFuture
Ximelagatran: PO Direct thrombin Ximelagatran: PO Direct thrombin inhibitor.inhibitor.
Denied approval by FDA in 2004Denied approval by FDA in 2004 Pulled from market in 2006Pulled from market in 2006 Found to have caused severe liver Found to have caused severe liver
damage and heart attacks.damage and heart attacks.
FutureFuture
Rivaroxaban: PO Factor Xa inhibitorRivaroxaban: PO Factor Xa inhibitor Compared to LMWH in orthopedic surgery Compared to LMWH in orthopedic surgery
patients in several trials.patients in several trials. Reduced LE DVT/nonfatal PE/death with no Reduced LE DVT/nonfatal PE/death with no
significant difference in major bleeding.significant difference in major bleeding. Approved in Europe and Canada for DVT Approved in Europe and Canada for DVT
prophylaxis in orthopedic surgery patients.prophylaxis in orthopedic surgery patients. May potentially be used in HIT?May potentially be used in HIT?
FutureFuture
Dabigatran: PO direct thrombin inhibitor.Dabigatran: PO direct thrombin inhibitor. RECOVER trial: End point recurrent VTE/fatal RECOVER trial: End point recurrent VTE/fatal
PE:PE: 2.4% dabigatran vs 2.1% warfarin2.4% dabigatran vs 2.1% warfarin Hazard ratio 1.1, dabigatran not inferiorHazard ratio 1.1, dabigatran not inferior 1.6% major bleeding dabigatran vs 1.9% warfarin, not 1.6% major bleeding dabigatran vs 1.9% warfarin, not
significantsignificant Significant reduction in all bleeding with dabigatran of Significant reduction in all bleeding with dabigatran of
29%29% Approved for DVT prophylaxis in orthopedic Approved for DVT prophylaxis in orthopedic
surgery patients in Europe and Canada.surgery patients in Europe and Canada.
Treatment DurationTreatment Duration
First DVT: Provoked: 3-6 monthsFirst DVT: Provoked: 3-6 months Unprovoked: 6-12 monthsUnprovoked: 6-12 months DVT with cancer/antiphospholipid DVT with cancer/antiphospholipid
syndrome: Life-long therapysyndrome: Life-long therapy Second DVT: Life-long therapySecond DVT: Life-long therapy
TreatmentTreatment Catheter-directed thrombolysis: Infuses a thrombolytic Catheter-directed thrombolysis: Infuses a thrombolytic
agent (usually tPA) between two inflated balloons via a agent (usually tPA) between two inflated balloons via a catheter.catheter.
Early restoration of venous patency/improved venous Early restoration of venous patency/improved venous return/Decreases pain/discomfort.return/Decreases pain/discomfort.
No change in rates of recurrent DVT/PE/bleeding/PTS.No change in rates of recurrent DVT/PE/bleeding/PTS. Contraindications include hemorrhage/recent Contraindications include hemorrhage/recent
neurosurgeryneurosurgery ACCP recommends against routine use (Grade 1C). ACCP recommends against routine use (Grade 1C).
With severe symptoms of recent onset with low risk of With severe symptoms of recent onset with low risk of bleeding, may be used (Grade 2C)bleeding, may be used (Grade 2C)
TreatmentTreatment
SVC FilterSVC Filter Rates of PE 2.4% and PTS 0% in one study Rates of PE 2.4% and PTS 0% in one study
(n=41).(n=41). Another study showed no episodes of PE Another study showed no episodes of PE
(n=72).(n=72). ACCP recommends against routine use (Grade ACCP recommends against routine use (Grade
1C). If anticoagulation contraindicated and DVT 1C). If anticoagulation contraindicated and DVT progression occurs, then SVC may be placed progression occurs, then SVC may be placed (Grade 2C).(Grade 2C).
TreatmentTreatment
Graded Compression sleeves/Elastic Graded Compression sleeves/Elastic bandagesbandages
Useful in relieving symptoms of persistent Useful in relieving symptoms of persistent pain/swelling such as in PTS.pain/swelling such as in PTS.
ACCP: Routine use not recommended ACCP: Routine use not recommended (Grade 2C), except in patients with (Grade 2C), except in patients with persistent pain (Grade 2C)persistent pain (Grade 2C)
TreatmentTreatment
Graded Compression sleeves/Elastic Graded Compression sleeves/Elastic bandagesbandages
Useful in relieving symptoms of persistent Useful in relieving symptoms of persistent pain/swelling such as in PTS.pain/swelling such as in PTS.
ACCP: Routine use not recommended ACCP: Routine use not recommended (Grade 2C), except in patients with (Grade 2C), except in patients with persistent pain (Grade 2C)persistent pain (Grade 2C)
TreatmentTreatment
In a retrospective study of 189 Surgical In a retrospective study of 189 Surgical ICU patients, 33% had UE DVTs,ICU patients, 33% had UE DVTs, Central catheters (45%) was the highest risk Central catheters (45%) was the highest risk
factor identifiedfactor identified 6% had PE, all nonfatal, all with IJ clots6% had PE, all nonfatal, all with IJ clots 60% were anticoagulated60% were anticoagulated No difference in LOS/survival to 30 days, and No difference in LOS/survival to 30 days, and
1 year mortality1 year mortality
TreatmentTreatment
RIETE Registry:RIETE Registry: 512 of 11564 DVTs were UE DVT (4.4%)512 of 11564 DVTs were UE DVT (4.4%) 9% had PE (vs 29% for LE DVT)9% had PE (vs 29% for LE DVT) 3 month outcomes of major bleeding/fatal 3 month outcomes of major bleeding/fatal
bleeding/recurrent DVT/recurrent PE were bleeding/recurrent DVT/recurrent PE were similar between UE and LE DVTssimilar between UE and LE DVTs
Slightly higher mortality rate for UE DVTsSlightly higher mortality rate for UE DVTs Cancer patients had increased rates in Cancer patients had increased rates in
recurrent DVT/PE/major bleeding.recurrent DVT/PE/major bleeding. 56% of patients had received anticoagulation.56% of patients had received anticoagulation.
ConclusionsConclusions
Most studies are retrospective or cohort Most studies are retrospective or cohort studies with small numbers of patients.studies with small numbers of patients.
ACCP recommends to treat UE DVTs ACCP recommends to treat UE DVTs same as LE DVTssame as LE DVTs
Use heparin/LMWH, until INR therapeutic Use heparin/LMWH, until INR therapeutic with coumadin (INR goal 2-3)with coumadin (INR goal 2-3)
Thrombolysis/Thrombectomy/SVC Filter Thrombolysis/Thrombectomy/SVC Filter not routinely indicated.not routinely indicated.
Future PO meds may replace warfarinFuture PO meds may replace warfarin
ReferencesReferences Chest 2008; 133; 454S-545S.Chest 2008; 133; 454S-545S. ChestChest January 2008 vol. 133 no. 1 143-148January 2008 vol. 133 no. 1 143-148 Dabigatran versus Warfarin in the Treatment ofDabigatran versus Warfarin in the Treatment of Acute Venous Thromboembolism. Acute Venous Thromboembolism.
NEJM 361: 2342-2352. Dec 10, 2009.NEJM 361: 2342-2352. Dec 10, 2009. Hingorani A, Ascher E, Lorenson E, et al. Upper extremity deep venous 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 thrombosis and its impact on morbidity and mortality rates in a hospital-based population J Vasc Surg 1997;26:853–60.population J Vasc Surg 1997;26:853–60.
Hingorani A, Ascher E, Markevich N, et al. Risk factors for mortality in Hingorani A, Ascher E, Markevich N, et al. Risk factors for mortality in patients with upper extremity and internal jugular deep venous patients with upper extremity and internal jugular deep venous thrombosis J Vasc Surg 2005;41:476–8.thrombosis J Vasc Surg 2005;41:476–8.
Paget J., London: Longmans, Green & Co; 1875. Clinical lectures and essays.Paget J., London: Longmans, Green & Co; 1875. Clinical lectures and essays. Prandoni P, Polistena P, Bernardi E, et al. Upper-extremity deep vein thrombosis: Prandoni P, Polistena P, Bernardi E, et al. Upper-extremity deep vein thrombosis:
risk factors, diagnosis and complications Arch Intern Med 1997;157:57–62.risk factors, diagnosis and complications Arch Intern Med 1997;157:57–62. Vascular. 2008;16(2):73-79.Vascular. 2008;16(2):73-79. von Schroetter L. Nothnagel Handbuch der Pathologie und Therapie Holder 1884von Schroetter L. Nothnagel Handbuch der Pathologie und Therapie Holder 1884
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