Presented byPresented by

Sherif Mohamed Abd ElsamadSherif Mohamed Abd Elsamad

Definition of VTEDefinition of VTE

VTE is a term that includes both deep vein VTE is a term that includes both deep vein

thrombosis (DVT) and pulmonary embolism thrombosis (DVT) and pulmonary embolism

(PE). They share common risk factors, patho-(PE). They share common risk factors, patho-

physiologies and management.physiologies and management.

Risk factors for VTERisk factors for VTEThree main factors contribute to the development of Three main factors contribute to the development of

VTE:VTE:Stasis: Stasis: mainly caused by heart failure, prolonged mainly caused by heart failure, prolonged

immobilityimmobilityEndothelial injury: Endothelial injury: mainly caused by either direct mainly caused by either direct

trauma (severed vein) or local irritation (by trauma (severed vein) or local irritation (by chemotherapy, past DVT, phlebitis)chemotherapy, past DVT, phlebitis)

Hypercoagulability:Hypercoagulability: inherited (AT III deficiency, inherited (AT III deficiency, protein C or S deficiency) or acquired (malignancy, protein C or S deficiency) or acquired (malignancy, pregnancy, AT III deficiency, protein C or S pregnancy, AT III deficiency, protein C or S deficiency as in nephritic syndrome, disseminated deficiency as in nephritic syndrome, disseminated intra-vascular coagulopathy (DIC) and liver failure.intra-vascular coagulopathy (DIC) and liver failure.

These represent the Virchow triadThese represent the Virchow triad

Risk factors for VTE (cont’d)Risk factors for VTE (cont’d)ImmobilizationImmobilizationSurgery within the last 3 Surgery within the last 3

monthsmonthsStrokeStrokeHistory of venous History of venous

thromboembolismthromboembolismMalignancyMalignancyPreexisting respiratory Preexisting respiratory

diseasediseaseChronic Heart DiseaseChronic Heart DiseaseAge >60Age >60Surgery requiring Surgery requiring

>30mins of anesthesia>30mins of anesthesiaBehçet’s diseaseBehçet’s disease

Recent travel (past Recent travel (past 2weeks, >4 hours)2weeks, >4 hours)

Varicose veinsVaricose veinsSuperficial vein Superficial vein

thrombosisthrombosisCentral venous Central venous

catheter/port/pacemakercatheter/port/pacemakerAdditional risk factors Additional risk factors in women:in women:

Obesity BMI ≥ 29Obesity BMI ≥ 29Heavy smoking Heavy smoking

(>25cigs/day)(>25cigs/day)HypertensionHypertensionPregnancyPregnancyOCP’sOCP’s

Well’s risk score for VTEWell’s risk score for VTE

VariablesVariables PointsPoints

Clinical Signs and Symptoms of DVT?Clinical Signs and Symptoms of DVT?

(Calf tenderness, swelling >3cm, erythema, (Calf tenderness, swelling >3cm, erythema, pitting edema affected leg only)pitting edema affected leg only)

+3+3

PE is the 1PE is the 1ryry Diagnosis, or equally likely Diagnosis, or equally likely +3+3

Heart Rate > 100Heart Rate > 100 +1.5+1.5

Immobilization at least 3 days, or Surgery in Immobilization at least 3 days, or Surgery in the Previous 4 weeksthe Previous 4 weeks +1.5+1.5

Previous, objectively diagnosed PE or DVT?Previous, objectively diagnosed PE or DVT? +1.5+1.5

HemoptysisHemoptysis +1+1

Malignancy with Rx within 6 mo, or palliative?Malignancy with Rx within 6 mo, or palliative? +1+1

Well’s risk score for VTE Well’s risk score for VTE (cont’d)(cont’d)

ScoreScore RiskRisk

>6>6 HighHigh

2 to 62 to 6 ModerateModerate

<2<2 LowLow

PathogenesisPathogenesis

The thrombus usually originates in the soleal The thrombus usually originates in the soleal venous sinuses or valvular sinuses (the calf vein is venous sinuses or valvular sinuses (the calf vein is the usual site). the usual site).

It may also originate in the iliac or femoral vein It may also originate in the iliac or femoral vein (pelvic veins).(pelvic veins).

Other sites also include the renal veins, upper Other sites also include the renal veins, upper limb veins, the right side of the heart and in-situ limb veins, the right side of the heart and in-situ thrombosis in the pulmonary circulation.thrombosis in the pulmonary circulation.

Symptoms & signsSymptoms & signs

Symptoms of DVT:Dull pain, heaviness, oedema and warm limb Dull pain, heaviness, oedema and warm limb With extensive DVTWith extensive DVT: massive oedema, cyanosis, : massive oedema, cyanosis,

dilated superficial collateral veins and low grade dilated superficial collateral veins and low grade fever.fever.

With ilio-femoral DVTWith ilio-femoral DVT::Phlegmasia cerulea dolens (cyanosed limb due to Phlegmasia cerulea dolens (cyanosed limb due to

obstructed vein)obstructed vein)Phlegmasia alba dolens (pale, pulseless cold limb Phlegmasia alba dolens (pale, pulseless cold limb

due to concurrent arterial spasm)due to concurrent arterial spasm)The last two entities are limb-threatening conditions The last two entities are limb-threatening conditions

and considered vascular emergencies.and considered vascular emergencies.

Symptoms & signs (cont’d)Symptoms & signs (cont’d)Symptoms of PE:Symptoms of PE:Dyspnea: Acute onset of exertional dyspnea, Dyspnea: Acute onset of exertional dyspnea,

usually not associated with orthopneausually not associated with orthopneaPalpitation: Usually rapid and regular but may be Palpitation: Usually rapid and regular but may be

irregular if atrial fibrillation (AF) or multi-focal atrial irregular if atrial fibrillation (AF) or multi-focal atrial tachycardia (MAT) developtachycardia (MAT) develop

Pleuritic chest painPleuritic chest painCough: Dry, irritant in natureCough: Dry, irritant in natureHemoptysis: either blood-tinged or blood-streaked Hemoptysis: either blood-tinged or blood-streaked

sputum or fresh bloodsputum or fresh blood

Symptoms & signs (cont’d)Symptoms & signs (cont’d)

Signs of DVT:Signs of DVT:Increased girth of the affected limb Increased girth of the affected limb Hotness, cyanosis and oedema (non-pitting): Hotness, cyanosis and oedema (non-pitting):

usually unilateralusually unilateralHoman’s sign (tenderness during passive Homan’s sign (tenderness during passive

dorsiflexion of foot): it is contraindicated because dorsiflexion of foot): it is contraindicated because of it’s role in thrombus detachment and thus of it’s role in thrombus detachment and thus emobilization emobilization

Moses sign (tenderness on touching the calf Moses sign (tenderness on touching the calf muscle)muscle)

Symptoms & signs (cont’d)Symptoms & signs (cont’d)

Signs of PE:Signs of PE:TachypneaTachypneaTachycardiaTachycardiaRight-sided SRight-sided S44 gallop gallop

Accentuated pulmonic component of SAccentuated pulmonic component of S22 (A (A22))Fever: Temperature < 39°CFever: Temperature < 39°CMassive PE: Hemodynamic instability SBP Massive PE: Hemodynamic instability SBP

<90mmHg or ≥ 40mmHg drop in baseline SBP, <90mmHg or ≥ 40mmHg drop in baseline SBP, elevated jugular venous pressure, right-sided Selevated jugular venous pressure, right-sided S33, , and para-sternal lift. and para-sternal lift.

InvestigationsInvestigationsLab:Lab:CBC: For abnormalities in Hb%, WBC’s or plateletsCBC: For abnormalities in Hb%, WBC’s or plateletsBleeding and coagulation profile: May show Bleeding and coagulation profile: May show

prolongation of PT and aPTT (consumption)prolongation of PT and aPTT (consumption)D-dimer: Unspecific but excellent negative D-dimer: Unspecific but excellent negative

predictive valuepredictive valueTroponin: High in moderate to large PETroponin: High in moderate to large PEArterial blood gases (ABG): May show hypoxemia, Arterial blood gases (ABG): May show hypoxemia,

hypocapnea, respiratory alkalosis or respiratory hypocapnea, respiratory alkalosis or respiratory failure in cases of massive PEfailure in cases of massive PE

Investigations (Cont’d)Investigations (Cont’d)

ECG:ECG:Sinus tachycardia (most common presentation)Sinus tachycardia (most common presentation)Non-specific ST-T changesNon-specific ST-T changesRight atrial abnormalityRight atrial abnormalityRight ventricular strain and hypertrophyRight ventricular strain and hypertrophyRight axis deviationRight axis deviationRight bundle branch block (RBBB)Right bundle branch block (RBBB)AF or MATAF or MATSSIIQQIIIIIITTIIIIII: Deep S-waves in lead I with pathological : Deep S-waves in lead I with pathological

Q-waves and inverted T-waves in lead III Q-waves and inverted T-waves in lead III

Investigations (Cont’d)Investigations (Cont’d)ImagingImagingChest X-ray: Chest X-ray: Normal, atelectasis and/or pulmonary Normal, atelectasis and/or pulmonary

parenchymal abnormality, pleural effusion or parenchymal abnormality, pleural effusion or cardiomegaly. A wedge-shaped, pleural-based cardiomegaly. A wedge-shaped, pleural-based opacity (Hampton’s hump) or central oligemia opacity (Hampton’s hump) or central oligemia (Westermark’s sign)(Westermark’s sign)

Duplex U/S:Duplex U/S: Sensitivity and specificity >95%, Sensitivity and specificity >95%, Include both B-mode and Doppler studies. Able Include both B-mode and Doppler studies. Able to detect other pathology like Baker’s cyst. Highly to detect other pathology like Baker’s cyst. Highly operator-dependant.operator-dependant.

Ventilation/perfusion (V/Q) scan: Rarely used. Ventilation/perfusion (V/Q) scan: Rarely used. Results are low, intermediate or high probabilityResults are low, intermediate or high probability

Investigations (Cont’d)Investigations (Cont’d)Imaging (cont’d)Imaging (cont’d)Multi-slice CT (MSCT) pulmonary angiography: Multi-slice CT (MSCT) pulmonary angiography:

Increased availability and use nowadays. Useful in Increased availability and use nowadays. Useful in triple rule-out of patients with chest pain. triple rule-out of patients with chest pain.

Echocardiography: May show right ventricular Echocardiography: May show right ventricular enlargement, right atrial enlargement or tricuspid enlargement, right atrial enlargement or tricuspid regurgitation. Regional right ventricular wall-regurgitation. Regional right ventricular wall-motion abnormality sparing the RV apex motion abnormality sparing the RV apex (McConnell’s sign) or RV/RVOT thrombus may (McConnell’s sign) or RV/RVOT thrombus may rarely be seen.rarely be seen.

Other rarely used: Phlebography, magnetic Other rarely used: Phlebography, magnetic resonance venography and invasive pulmonary resonance venography and invasive pulmonary angiography.angiography.

Hypercoagulability work-upHypercoagulability work-upNo consensus on who to testNo consensus on who to testIncreased likelihood if:Increased likelihood if:

Age <50 years without immediate identifiable Age <50 years without immediate identifiable risk factors (idiopathic or unprovoked)risk factors (idiopathic or unprovoked)

Family historyFamily historyRecurrent clotsRecurrent clotsIf clot is in an unusual site (portal, hepatic, If clot is in an unusual site (portal, hepatic,

mesenteric, cerebral)mesenteric, cerebral)Unprovoked upper extremity clot (no catheter, Unprovoked upper extremity clot (no catheter,

no surgeries)no surgeries)Patients with warfarin-induced skin necrosis Patients with warfarin-induced skin necrosis

(they may have protein C deficiency)(they may have protein C deficiency)

Hypercoagulability work-up Hypercoagulability work-up (cont’d)(cont’d)

Protein C or S deficiencyProtein C or S deficiencyFactor V leiden deficiencyFactor V leiden deficiencyAnti-thrombin III deficiencyAnti-thrombin III deficiencyProthrombin gene mutationProthrombin gene mutationAntiphospholipid antibodyAntiphospholipid antibodyHigh HomocysteineHigh Homocysteine

The most common cause of congenital hyper-The most common cause of congenital hyper-coagulability is protein C resistance due to factor coagulability is protein C resistance due to factor V Leiden mutationV Leiden mutation

Differential diagnosisDifferential diagnosis

Unilateral limb involvement: Muscular strain, Unilateral limb involvement: Muscular strain, tendon rupture, cellulitis, lymphodema or tendon rupture, cellulitis, lymphodema or retroperitoneal fibrosis pressing over the vein.retroperitoneal fibrosis pressing over the vein.

Bilateral limb involvement: Liver, heart or renal Bilateral limb involvement: Liver, heart or renal failure or IVC obstructionfailure or IVC obstruction

PE: Other causes of acute chest pain mainly acute PE: Other causes of acute chest pain mainly acute coronary syndromes, aortic dissection and diffuse coronary syndromes, aortic dissection and diffuse oesophageal spasmoesophageal spasm

Complications of VTEComplications of VTE

Recurrent VTERecurrent VTEVaricose veinsVaricose veinsChronic venous insufficiency (CVI)Chronic venous insufficiency (CVI)Post-phlebitic syndrome (pain, edema, ulceration Post-phlebitic syndrome (pain, edema, ulceration

and pigmentation)and pigmentation)Chronic pulmonary hypertension and vascular cor-Chronic pulmonary hypertension and vascular cor-

pulmonalepulmonaleDeath due to massive or sub-massive PEDeath due to massive or sub-massive PE

Management of VTEManagement of VTE

ProphylaxisProphylaxisMechanicalMechanical

PharmacologicalPharmacologicalIVC filter (2IVC filter (2ryry))

TreatmentTreatmentAnti-coagulationAnti-coagulation

ThrombolysisThrombolysisEmbolectomyEmbolectomy

Prophylaxis of VTEProphylaxis of VTE

Mechanical:Mechanical:Leg elevationLeg elevationGraded compression stockingGraded compression stockingEarly ambulationEarly ambulationPneumatic compression bootPneumatic compression boot

Prophylaxis of VTE (cont’d)Prophylaxis of VTE (cont’d)

PharmacologicalPharmacologicalUn-fractionated heparin (UFH): given every 8 Un-fractionated heparin (UFH): given every 8

hours SChours SCLow-molecular weight heparin: Enoxaparin 30-Low-molecular weight heparin: Enoxaparin 30-

40mg SC every 24 hours40mg SC every 24 hoursFondaparinux: 2.5mg SC every 24 hoursFondaparinux: 2.5mg SC every 24 hoursDesirudin: A recombinant direct thrombin Desirudin: A recombinant direct thrombin

inhibitor. Dose: 15mg SC every 12 hoursinhibitor. Dose: 15mg SC every 12 hoursRivaroxaban: A novel oral anti-Xa agent. Dose: Rivaroxaban: A novel oral anti-Xa agent. Dose:

10mg every 24 hours10mg every 24 hours

Prophylaxis of VTE (cont’d)Prophylaxis of VTE (cont’d)

Inferior vena cava (IVC) filterInferior vena cava (IVC) filterConsidered as secondary prophylaxis or Considered as secondary prophylaxis or

secondary prevention against PE but not DVT.secondary prevention against PE but not DVT.IVC filter is indicated in patients with high risk of IVC filter is indicated in patients with high risk of

recurrence when other methods are contra-recurrence when other methods are contra-indicated (Class IIb, LOE B).indicated (Class IIb, LOE B).

The routine use of IVC filters is not recommended The routine use of IVC filters is not recommended (Class III, LOE B). (Class III, LOE B).

Treatment of VTETreatment of VTE

Anti-coagulationAnti-coagulationUFH: Given as a bolus 5000 Units IV followed by UFH: Given as a bolus 5000 Units IV followed by

continuous IV infusion at a rate of 1000 Units/h. continuous IV infusion at a rate of 1000 Units/h. The dose is adjusted to keep the aPTT 1.5-2.5 The dose is adjusted to keep the aPTT 1.5-2.5 times normal which should be evaluated every 6h. times normal which should be evaluated every 6h.

LMWH: Enoxaparin is used in a dose of 1mg/Kg LMWH: Enoxaparin is used in a dose of 1mg/Kg every 12h. every 12h.

Fondaparinux: The dose is adjusted to the body Fondaparinux: The dose is adjusted to the body weight given SC every 24h (<50Kg- 5mg, 50-weight given SC every 24h (<50Kg- 5mg, 50-100Kg- 7.5mg, >100Kg- 10mg)100Kg- 7.5mg, >100Kg- 10mg)

Treatment of VTE (cont’d)Treatment of VTE (cont’d)Anticoagulation (cont’d)Anticoagulation (cont’d)

Warfarin: Started as early as possible to achieve a Warfarin: Started as early as possible to achieve a target INR of 2-3. Duration of treatment depends target INR of 2-3. Duration of treatment depends on several factors. on several factors.

Event Duration

First Time event of reversible cause (surgery/trauma)

At least 3 months

First episode of idiopathic VTE At least 6 months

Recurrent idiopathic VTE or continuing risk factor

At least 12 months

Symptomatic isolated calf-vein thrombosis

6 to 12 weeks

Treatment of VTE (cont’d)Treatment of VTE (cont’d)

ThrombolysisThrombolysis

Thrombolytic therapy is indicated in the following:Thrombolytic therapy is indicated in the following:Persistent arterial hypotensionPersistent arterial hypotensionCardiogenic shockCardiogenic shockRight ventricular dysfunctionRight ventricular dysfunctionLarge perfusion defects on V/Q scanLarge perfusion defects on V/Q scanSevere hypoxemiaSevere hypoxemia

Intermediate-risk patients may also be considered Intermediate-risk patients may also be considered candidates for thrombolytic therapy.candidates for thrombolytic therapy.

Treatment of VTE (cont’d)Treatment of VTE (cont’d)ThrombolysisThrombolysis

Approved thrombolytic regimens for PEApproved thrombolytic regimens for PE

AgentAgent DoseDose

StreptokinaseStreptokinase

250,000 IU as loading dose over 30 250,000 IU as loading dose over 30 min, followed by 100,000 IU/h min, followed by 100,000 IU/h

over 12 to 24 hover 12 to 24 h

1,500,000 IU over 2 h1,500,000 IU over 2 h

UrokinaseUrokinase

4,400 IU/Kg as a loading dose over 10 4,400 IU/Kg as a loading dose over 10 min, followed by 4,400 IU/Kg/h min, followed by 4,400 IU/Kg/h

over 12-24 hover 12-24 h

3 million IU over 2 h 3 million IU over 2 h

Reteplase (rtPA)Reteplase (rtPA) 100mg over 2 h100mg over 2 h

0.6mg/Kg over 15 min (max. 50mg)0.6mg/Kg over 15 min (max. 50mg)

Treatment of VTE (cont’d)Treatment of VTE (cont’d)EmbolectomyEmbolectomyEither surgical or catheter-basedEither surgical or catheter-basedSurgical pulmonary embolectomy is indicated in Surgical pulmonary embolectomy is indicated in

patients in whom thrombolysis is absolutely patients in whom thrombolysis is absolutely contra-indicated or has failed (Class I, LOE C)contra-indicated or has failed (Class I, LOE C)

Catheter embolectomy or fragmentation of Catheter embolectomy or fragmentation of proximal pulmonary arterial clots may be proximal pulmonary arterial clots may be considered as an alternative to surgical treatment considered as an alternative to surgical treatment in high-risk patients when thrombolysis is in high-risk patients when thrombolysis is absolutely contra-indicated or has failed (Class IIb, absolutely contra-indicated or has failed (Class IIb, LOE C)LOE C)