DEEP VENOUS THROMBOSIS

Definition Definition

formation of a blood clot in one of the formation of a blood clot in one of the deep veins of the body, usually in the legdeep veins of the body, usually in the leg

AnatomyAnatomy

Etiology and risk factorsEtiology and risk factors3 main factors contribute in development of DVT3 main factors contribute in development of DVT

StasisStasis

Endothelial injuryEndothelial injury

HypercoagulabilityHypercoagulability

Venous stasis Venous stasis

prolonged bed rest (4 days or more) prolonged bed rest (4 days or more)

a cast on the leg a cast on the leg

limb paralysis from stroke or spinal cord limb paralysis from stroke or spinal cord injury injury

extended travel in a vehicle extended travel in a vehicle

heart failureheart failure

HypercoagulabilityHypercoagulability

Surgery and trauma - responsible for up to 40% Surgery and trauma - responsible for up to 40% of all thromboembolic disease of all thromboembolic disease

Malignancy Malignancy

Increased estrogen (due to a fall in protein ‘S) Increased estrogen (due to a fall in protein ‘S) Increased estrogen occurs during Increased estrogen occurs during all stages of pregnancyall stages of pregnancy the first three months postpartum, the first three months postpartum, after elective abortion, andafter elective abortion, and during treatment with oral contraceptive pills during treatment with oral contraceptive pills

Inherited disorders of coagulation Inherited disorders of coagulation

deficiencies of protein ‘S’,deficiencies of protein ‘S’, protein ‘C’ andprotein ‘C’ and antithrombin III. antithrombin III.

Acquired disorders of Acquired disorders of coagulation coagulation

nephrotic syndromenephrotic syndrome results in urinary results in urinary loss of antithrombin III, this diagnosis loss of antithrombin III, this diagnosis should be considered in children should be considered in children presenting with thromboembolic disease presenting with thromboembolic disease

Antiphospholipid antibodies Antiphospholipid antibodies accelerate accelerate coagulation and include the lupus coagulation and include the lupus anticoagulant and anticardiolipin anticoagulant and anticardiolipin antibodies.antibodies.

Inflammatory processesInflammatory processes, such as, such as

• systemic lupus erythematosus (SLE),systemic lupus erythematosus (SLE),

• sickle cell disease, and sickle cell disease, and

•inflammatory bowel disease (IBD), inflammatory bowel disease (IBD),

also predispose to thrombosis, presumably due also predispose to thrombosis, presumably due to hypercoagulability to hypercoagulability

Symptoms:Symptoms:

Dull pain, heaviness, oedema and warm limb Dull pain, heaviness, oedema and warm limb With extensive DVTWith extensive DVT:-massive oedema, cyanosis, dilated :-massive oedema, cyanosis, dilated superficial collateral veins and low grade fever.superficial collateral veins and low grade fever.With ilio-femoral DVTWith ilio-femoral DVT:-:-Phlegmasia cerulea dolens Phlegmasia cerulea dolens (cyanosed limb due to (cyanosed limb due to obstructed vein)obstructed vein)Phlegmasia alba dolens Phlegmasia alba dolens (pale, pulseless cold limb due (pale, pulseless cold limb due to concurrent arterial spasm)to concurrent arterial spasm)

AND THESE TWO UPPER CASES ARE LIMB AND THESE TWO UPPER CASES ARE LIMB THREATENING CONDITION!!THREATENING CONDITION!!

Phlegmasia cerulea dolensPhlegmasia cerulea dolens Venous gangreneVenous gangrene

SignsSignsHOMAN'S sign (tenderness HOMAN'S sign (tenderness during passive dorsiflexion of during passive dorsiflexion of foot). And it was foot). And it was contraindicated because of it’s contraindicated because of it’s role in thrombus deattachment role in thrombus deattachment and thus emobilization and thus emobilization

Hotness, cyanosis, oedema Hotness, cyanosis, oedema (non-pitting)(non-pitting)

Diagnostic Studies Diagnostic Studies

- Clinical examination alone is able to confirm only - Clinical examination alone is able to confirm only 20-30% of cases of DVT20-30% of cases of DVT

- Blood Tests - Blood Tests

the D-dimer - have predictive value for DVTthe D-dimer - have predictive value for DVT

INR - useful for guiding the management of INR - useful for guiding the management of patients with known DVT who are on warfarin patients with known DVT who are on warfarin (Coumadin) (Coumadin)

D-dimerD-dimer

D-dimer is a specific degradation product of D-dimer is a specific degradation product of cross-linked fibrin. Because concurrent cross-linked fibrin. Because concurrent production and breakdown of clot characterize production and breakdown of clot characterize thrombosis, patients with thromboembolic thrombosis, patients with thromboembolic disease have elevated levels of D-dimer disease have elevated levels of D-dimer three major approaches for measuring D-dimer three major approaches for measuring D-dimer ELISA ELISA latex agglutination latex agglutination blood agglutination test - SimpliRED blood agglutination test - SimpliRED

False-positive D-dimers False-positive D-dimers occur in patients occur in patients with:with: recent (within 10 days) surgery or trauma,recent (within 10 days) surgery or trauma, recent myocardial infarction or stroke,recent myocardial infarction or stroke, acute infection,acute infection, disseminated intravascular coagulation,disseminated intravascular coagulation, pregnancy or recent delivery, pregnancy or recent delivery, active collagen vascular diseaseactive collagen vascular disease metastatic cancer metastatic cancer

Imaging Studies Imaging Studies

InvasiveInvasivevenography, venography, radiolabeled fibrinogen radiolabeled fibrinogen

NoninvasiveNoninvasive ultrasound, ultrasound, plethysmography, plethysmography, MRI techniques MRI techniques

Imaging studies:Imaging studies:

*The *The standard toolstandard tool for diagnosis is for diagnosis is phlebographyphlebography using fluoroscope. The use of using fluoroscope. The use of this study limited by is complications which this study limited by is complications which are allergy, nephropathy and phlebitis.are allergy, nephropathy and phlebitis.

*Duplex ultrasound:*Duplex ultrasound:

Test of choiceTest of choice

Sensitivity and specificity >95%Sensitivity and specificity >95%

Able to detect other pathology like BAKER Able to detect other pathology like BAKER cyst.cyst.

VenographyVenography

"gold standard” "gold standard” modality for the diagnosis modality for the diagnosis of DVT of DVT

AdvantagesAdvantages venography is also useful if the patient has venography is also useful if the patient has a high clinical probability of thrombosis and a high clinical probability of thrombosis and a negative ultrasound, a negative ultrasound, it is also valuable in symptomatic patients it is also valuable in symptomatic patients with a history of prior thrombosis in whom with a history of prior thrombosis in whom the ultrasound is non-diagnostic. the ultrasound is non-diagnostic.

Venogram Venogram shows DVTshows DVT

Ultrasonography Ultrasonography

color-flow Duplex scanning is the imaging color-flow Duplex scanning is the imaging test of choice for patients with suspected DVT test of choice for patients with suspected DVT inexpensive,inexpensive, noninvasive, noninvasive, widely available widely available

Ultrasound can also distinguish other causes Ultrasound can also distinguish other causes of leg swelling, such as tumor, popliteal cyst, of leg swelling, such as tumor, popliteal cyst, abscess, aneurysm, or hematoma.     abscess, aneurysm, or hematoma.     

clinical limitations clinical limitations

reader dependent reader dependent

Duplex scans are less likely to detect Duplex scans are less likely to detect non-non-occluding thrombioccluding thrombi. .

During the second half of During the second half of pregnancypregnancy, , ultrasound becomes less specific, because ultrasound becomes less specific, because the gravid uterus compresses the inferior the gravid uterus compresses the inferior vena cava, thereby changing Doppler flow vena cava, thereby changing Doppler flow in the lower extremities in the lower extremities

The finding are:The finding are:

Acute DVT: Acute DVT: • Absence of spontaneous flow.Absence of spontaneous flow.

• Loss of flow variation with respiration.Loss of flow variation with respiration.• Failure to increase the flow after distal augmentation.Failure to increase the flow after distal augmentation.

• Not visible thrombi (anechoic thrombi).Not visible thrombi (anechoic thrombi).

Chronic DVT:Chronic DVT: Not well established Not well established Narrow veinNarrow vein Patent collateralPatent collateral Visible thrombiVisible thrombi

Color duplex scan of DVTColor duplex scan of DVT

The only disadvantage of duplex study is The only disadvantage of duplex study is that, it is highly operator dependant!!!that, it is highly operator dependant!!!

Magnetic Resonance Imaging Magnetic Resonance Imaging

It detects leg, pelvis, and pulmonary It detects leg, pelvis, and pulmonary thrombi and is 97% sensitive and 95% thrombi and is 97% sensitive and 95% specific for DVT.specific for DVT.

It distinguishes a mature from an It distinguishes a mature from an immature clot.immature clot.

MRI is safe in all stages of pregnancy. MRI is safe in all stages of pregnancy.

Differential diagnoses:Differential diagnoses:

Unilateral limb involvementUnilateral limb involvement: muscular : muscular strain, tendon rupture, cellulites, strain, tendon rupture, cellulites, lymphodema or retroperitoneal fibrosis lymphodema or retroperitoneal fibrosis pressing over the vein.pressing over the vein.

Bilateral limb involvementBilateral limb involvement: liver, heart or : liver, heart or renal failure or IVC obstruction.renal failure or IVC obstruction.

Complication of DVTComplication of DVT

Recurrent DVTRecurrent DVT

Varicose veinVaricose vein

Chronic venous insufficiencyChronic venous insufficiency

Post phlebitic syndrome (pain, oedema Post phlebitic syndrome (pain, oedema and ulceration)and ulceration)

PEPE

Patient with suspect symptomatic Acute lower extremity DVT

Venous duplex scan negative Low clinical probability observe

High clinical probability

Repeat scan /Venography

negativepositive

Evaluate coagulogram /thrombophilia/ malignancy

Anticoagulant therapycontraindication

yes IVC filter

No

pregnancy LMWH

OPD LMWH

hospitalisation UFH+ warfarin

Compression treatment

ManagementManagement

The aim of management is:The aim of management is:

Prophylaxis against DVTProphylaxis against DVT

Treatment of ongoing DVTTreatment of ongoing DVT

Methods of Prophylaxis:Methods of Prophylaxis:

1) 1) MechanicalMechanical

Leg elevationLeg elevation

Graded compression stockingGraded compression stocking

Early ambulationEarly ambulation

Pneumatic compression booPneumatic compression boo..

2) Pharmacological agents:2) Pharmacological agents:

AspirinAspirin (anti platelet factor) not recommended (anti platelet factor) not recommended currently.currently.

Dextran solution Dextran solution (40 and70) branched (40 and70) branched polysaccharide. Decrease platelets polysaccharide. Decrease platelets adhesiveness and aggregation.adhesiveness and aggregation.

Disadvantages:Disadvantages: Increase rate of bleedingIncrease rate of bleeding Pulmonary edema (due to overload)Pulmonary edema (due to overload) Allergic reaction in 1%Allergic reaction in 1%Recommended dose is15-20 cc/h IV infusion Recommended dose is15-20 cc/h IV infusion

before surgery.before surgery.

Warfarine (coumadine):-Warfarine (coumadine):-

Decrease incidence of DVT by 66% and PE by Decrease incidence of DVT by 66% and PE by 80%.80%.

Disadvantages:Disadvantages: Sever hemorrhageSever hemorrhage Must be started 2-3 days preoperative.Must be started 2-3 days preoperative. Require careful monitoring for PT.Require careful monitoring for PT.

Warfarine nomographWarfarine nomograph

HeparinHeparin

Unfractionated heparin:Unfractionated heparin:Inhibits AT III and potentiate disintegration of thrombi Inhibits AT III and potentiate disintegration of thrombi that form while it administeredthat form while it administeredLow dose regimen is 5000 IU twice daily SQ two Low dose regimen is 5000 IU twice daily SQ two hours pre-operatively then q12hours post operative hours pre-operatively then q12hours post operative till the patient is completely ambulating.till the patient is completely ambulating.For morbidly obese patient: - micro-heparin drip at For morbidly obese patient: - micro-heparin drip at 1u/kg/hour 1u/kg/hour Disadvantages:Disadvantages:

Risk of bleedingRisk of bleeding Thrombocytopenia (rare)Thrombocytopenia (rare)

Contraindicated in patient with actively bleeding Contraindicated in patient with actively bleeding peptic ulcer, uncontrolled HTN, bleeding disorder or peptic ulcer, uncontrolled HTN, bleeding disorder or recent use of ASArecent use of ASA

Heparin-dihydroergotamine (DHE) combination:Heparin-dihydroergotamine (DHE) combination:

Cause vasoconstriction of capacitance veins Cause vasoconstriction of capacitance veins and thus increase the venous return.and thus increase the venous return.

Particular effectiveness in orthopedic cases.Particular effectiveness in orthopedic cases.

Contraindicated in case of hypotension, IHD Contraindicated in case of hypotension, IHD and peripheral arterial occlusive diseases.and peripheral arterial occlusive diseases.

Low molecular weight (enoxaparin):Low molecular weight (enoxaparin):

Lesser effect on thrombin and platelets Lesser effect on thrombin and platelets aggregation.aggregation.

Longer life time so the dose will be once daily.Longer life time so the dose will be once daily.

More expensive than unfractionated heparinMore expensive than unfractionated heparin..

Heparin nomographHeparin nomograph

Fibrinogen-depleting compoundFibrinogen-depleting compound

New class of anticoagulants but not well New class of anticoagulants but not well known.known.

Prophylactic IVC filter placement.Prophylactic IVC filter placement.

Also known as Greenfield filter.Also known as Greenfield filter.

Used in high risk patient when other Used in high risk patient when other methods are contraindicated.methods are contraindicated.

Effective in preventing PE not DVT.Effective in preventing PE not DVT.

An approach to ProphylaxisAn approach to Prophylaxis

1.1. determine patient at riskdetermine patient at risk Low risk (<40 years old, ambulating, Low risk (<40 years old, ambulating, minor surgery)minor surgery) Moderate risk (>40 years old, Moderate risk (>40 years old, abdominal, pelvic or thoracic surgery)abdominal, pelvic or thoracic surgery) High risk (>60years old, prior DVT or PE High risk (>60years old, prior DVT or PE malignancy, orthopedic surgery malignancy, orthopedic surgery hypercoagulability state).hypercoagulability state).

2. 2. prohylaxis of choiceprohylaxis of choice

Encourage all patients to ambulate as soon as Encourage all patients to ambulate as soon as possiblepossible

Low risk patient don't need prophylaxis.Low risk patient don't need prophylaxis.

Moderate risk pneumatic compression boot or Moderate risk pneumatic compression boot or low dose heparin prophylaxis.low dose heparin prophylaxis.

High risk combination of pneumatic High risk combination of pneumatic compression boot and low dose heparin compression boot and low dose heparin prophylaxis or Dextran.prophylaxis or Dextran.

Coumadine or IVCfilter are considered.Coumadine or IVCfilter are considered.

Ophthalmology or neurosurgery patient are Ophthalmology or neurosurgery patient are NOT candidates for prophylaxis.NOT candidates for prophylaxis.

Treatment of DVTTreatment of DVT

A: - anticoagulationA: - anticoagulation

HeparinHeparin bolus 100-150 u/kg IV stat then bolus 100-150 u/kg IV stat then followed by constant infusion of 1000 u/hour followed by constant infusion of 1000 u/hour with checking aPTT q 4-6hours and keeping with checking aPTT q 4-6hours and keeping the ratio 50-70sec.the ratio 50-70sec.

Coumadine (Warfarine) Coumadine (Warfarine) usually started at day usually started at day 3-5 after initial heparin is given and continue 3-5 after initial heparin is given and continue for 3-6 months . PT should be 17-20sec. and for 3-6 months . PT should be 17-20sec. and INR 2.0-2.5.INR 2.0-2.5.

Duration of anticoagulation in patients with Duration of anticoagulation in patients with deep vein thrombosis deep vein thrombosis

Transient cause and no other risk factors: 3 months Transient cause and no other risk factors: 3 months

Idiopathic: 3-6 months Idiopathic: 3-6 months

Ongoing risk for example, malignancy: 6 -Ongoing risk for example, malignancy: 6 -12 months 12 months

Recurrent pulmonary embolism or deep vein Recurrent pulmonary embolism or deep vein thrombosis: 6-12 months thrombosis: 6-12 months

Patients with high risk of recurrent thrombosis Patients with high risk of recurrent thrombosis exceeding risk of anticoagulation: indefinite exceeding risk of anticoagulation: indefinite duration (subject to review)duration (subject to review)

B:-thrombolytic treatmentB:-thrombolytic treatment( alteplase, ( alteplase, streptokinase, urokinase)streptokinase, urokinase)

Promote rapid thrombus lysis. Used in cases of Promote rapid thrombus lysis. Used in cases of sever PE . They have more bleeding sever PE . They have more bleeding complication.complication. C:-venal cava interruption (IVC filter)C:-venal cava interruption (IVC filter)

Prevent further embolism of thrombiPrevent further embolism of thrombi D:- venous thrombectomyD:- venous thrombectomy

May be necessary in venous gangrene and May be necessary in venous gangrene and septic thrombosis. septic thrombosis.

Thrombolytic therapy for DVTThrombolytic therapy for DVT

AdvantagesAdvantages include include

prompt resolution of symptoms, prompt resolution of symptoms,

prevention of pulmonary embolism, prevention of pulmonary embolism,

restoration of normal venous circulation, restoration of normal venous circulation,

preservation of venous valvular function, preservation of venous valvular function,

and prevention of postphlebitic syndrome. and prevention of postphlebitic syndrome.

Thrombolytic therapy Thrombolytic therapy does not preventdoes not prevent

clot propagation,clot propagation,

rethrombosis, orrethrombosis, or

subsequent embolization.subsequent embolization.

Heparin therapy and oral anticoagulantHeparin therapy and oral anticoagulant

therapy always must follow a course oftherapy always must follow a course of

thrombolysis. thrombolysis.

Thrombolytic therapy Thrombolytic therapy is also not effective once is also not effective once the thrombus is adherent and begins to the thrombus is adherent and begins to organizeorganize

The hemorrhagic complications of thrombolytic The hemorrhagic complications of thrombolytic therapy are formidable (about 3 times higher), therapy are formidable (about 3 times higher), including the small but potentially fatal risk of including the small but potentially fatal risk of intracerebral hemorrhage.intracerebral hemorrhage.

Catheter directed-thrombolysisCatheter directed-thrombolysis

Consider in: Acute< 10 days iliofemoral Consider in: Acute< 10 days iliofemoral DVT.DVT.

Long-term benefit in preventing Long-term benefit in preventing post-phlebitic syndrome is unknown. post-phlebitic syndrome is unknown.

Filters for DVT Filters for DVT

Indications for insertion of an inferiorIndications for insertion of an inferior

vena cava filtervena cava filter : :

Pulmonary embolism with contraindication Pulmonary embolism with contraindication to anticoagulation to anticoagulation

Recurrent pulmonary embolism despite Recurrent pulmonary embolism despite adequate anticoagulation adequate anticoagulation

Filters for DVTFilters for DVT

Controversial indications:Controversial indications:Deep vein thrombosis with Deep vein thrombosis with contraindication to anticoagulation contraindication to anticoagulation Deep vein thrombosis in patients with pre-Deep vein thrombosis in patients with pre-existing pulmonary hypertension existing pulmonary hypertension Free floating thrombus in proximal vein Free floating thrombus in proximal vein Failure of existing filter device Failure of existing filter device Post pulmonary embolectomyPost pulmonary embolectomy

Filters for DVTFilters for DVT

Inferior vena cava filters reduce the rate of Inferior vena cava filters reduce the rate of pulmonary embolism but have no effect on pulmonary embolism but have no effect on the other complications of deep vein the other complications of deep vein thrombosis. thrombosis.

Surgery for DVT Surgery for DVT

Indications:Indications:

when anticoagulant therapy is ineffectivewhen anticoagulant therapy is ineffective

unsafe, unsafe,

contraindicated. contraindicated.

The major surgical procedures for DVT areThe major surgical procedures for DVT are

clot removal and partial interruption of theclot removal and partial interruption of the

inferior vena cava to prevent pulmonaryinferior vena cava to prevent pulmonary

embolism. embolism.

These pulmonary emboli removed at autopsy look like These pulmonary emboli removed at autopsy look like casts of the deep veins of the leg where they casts of the deep veins of the leg where they originated. originated.

This patient underwent a thrombectomy. The thrombus has This patient underwent a thrombectomy. The thrombus has been laid over the approximate location in the leg veins where been laid over the approximate location in the leg veins where

it developed.it developed.

Prognosis: Prognosis:

All patients with proximal vein DVT are at long-All patients with proximal vein DVT are at long-term risk of developing chronic venous term risk of developing chronic venous insufficiency.insufficiency.

About 20% of untreated proximal (above the calf) About 20% of untreated proximal (above the calf) DVTs progress to pulmonary emboli, and 10-20% DVTs progress to pulmonary emboli, and 10-20% of these are fatal. With aggressive anticoagulant of these are fatal. With aggressive anticoagulant therapy, the mortality is decreased 5- to 10-fold.therapy, the mortality is decreased 5- to 10-fold.

DVT confined to the calf virtually never causes DVT confined to the calf virtually never causes clinically significant emboli and thus does not clinically significant emboli and thus does not require anticoagulationrequire anticoagulation