Deep vein thrombosis (DVT) and

pulmonary embolism (PE)

Major Dr. Md Aminul Haque

MD (Cardiology)

Classified Cardiologist

CMH, Dhaka

Introduction

• Deep vein thrombosis (DVT) and pulmonaryembolism (PE), collectively referred to as venousthromboembolism (VTE), constitute a major globalburden of disease.

• It is associated with significant morbidity andmortality, but potentially treatable condition.

Incidence

• About 10 million cases occurring every year, therebyrepresenting the 3rd leading vascular disease afterAMI and stroke , but a under diagnosed condition.

• Incidence is steadily increasing because ofpopulation ageing, a higher prevalence ofcomorbidities, such as obesity, heart failure andcancer.

Incidence

• Incidence is higher in black people, but lower inAsian people.

• Risk does not differ by sex, although it seems to be2 times higher in men than in women, when VTErelated to pregnancy and Oestrogen therapy arenot considered.

Etiology

• 1/3 to 1/2 of VTE episodes do not have anidentifiable provoking factor and are thereforeclassified as unprovoked.

• Hypercoagulability , stasis or vascular wall damageor dysfunction.

• About 20% of all VTE are cancer related, whereassurgery and immobilization both account for 15% ofcases.

Virchow’s triad

• Hypercoagulability

• Stasis

• Vascular wall damage

or dysfunction

Risk factors for VTE

PresentationsDVT-

Swelling or pitting oedema,

redness,

tenderness and

presence of collateral superficial veins.

Homan’s sign: Tenderness during passive dorsiflexion of foot. It is contraindicated due to risk of thrombus detachment and thus embolization.

Moses sign: Tenderness on touching the calf muscle.Pratt’s sign: Squeezing of posterior calf elicits pain.

Presentations

PE-

sudden onset of dyspnoea or deterioration of existing dyspnoea,

chest pain,

syncope or dizziness due to hypotension or shock,

haemoptysis,

tachycardia or

tachypnoea.

Deferential diagnosis

DVT:

• Cellulitis

• Ruptured Baker cyst

• Calf muscle tear

• Lymphangitis

• Lypmhedema

• Varicose veins

• Superficial thrombophlibitis

PE:

• AMI

• Pericardial tamponade

• Aortic dissection.

Wells DVT score

Clinical decision rules for PE

D-Dimer• High sensivity and negative predictive value.

• Low specificity.

• May be elevated in trauma, recent surgery,haemorrhage, cancer and sepsis.

• Clinical decision rules ( Wells DVT score and RevisedGeneva scores) with negative D-Dimer rules out VTE.

• All patients with a positive D-dimer assay requires adiagnostic imaging study.

• For patients older than 50 years age adjusted D-Dimerthreshold, defined as-

Patients age x 10 micrograms/L.

Compression ultrasonography ( CUS )• CUS replaced contrast venography as the

preferred method for the diagnosis of DVT.

• Whole leg CUS- Groin to the calf

• Limited (2 point) CUS- Only the popliteal andfemoral vein.

Compression ultrasonography ( CUS )

• Whole leg and limited CUS are consideredequivalent in terms of safety since largemanagement studies show both approaches toyield false negative results below 1 %.

• The diagnosis of pelvic or IVC DVT is challengingwith CUS and so CT/MRV considered.

CT Scan

ECG• The “classic”S1Q3T3 pattern present only in

approximately 10% of PE cases.

• RBBB

• P-pulmonale

• Right axis deviation.

CXR

Pulmonary infarct in right lower lobe

Imaging for PECT pulmonary angiography

( CTPA ) ventilation-perfusion lung scintigraphy(VQ Scan)

TTE

• CT pulmonary angiography ( CTPA ) has replacedventilation-perfusion lung scintigraphy (VQ Scan).

• VQ Scan has a role when CTPA is contraindicatedbecause of severe renal insufficiency or allergy tocontrast medium and can be considered inpregnant women and young women to reduceradiation exposure to the breast.

• In haemodynamically unstable patients withsuspected PE who require a rapid diagnosis andcannot undergo CTPA, bedside TTE can be used todisclose signs of RV dysfunction, which couldjustify emergency repurfusion.

ManagementAnticoagulant therapy is the mainstay for the treatment of VTE.

3 phases-• Acute phase- first 5-10 days.

• Maintenance phase ( 3- 6 months )- 3 months anticoagulation isenough for patients with VTE secondary to a transient riskfactor, such as major surgery, since the annual risk of recurrenceafter stopping treatment is only 1%.By contrast, the 6 month risk of recurrence in patients withcancer is around 8% despite treatment, which strongly supportscontinuing anticoagulation as long as the cancer is active.

• Extended phase ( beyond 6 months)- In patients withunprovoked VTE, the risk of recurrence after stopping treatmentis 10% at 1 yr and 30% at 5 yr.

Anticoagulant

• Heparin ( UFH / LMWH )

• Parenteral Factor Xa inhibitor ( Fondaparinux )

• Oral factor Xa inhibitors ( Rivaroxaban, apixaban and edoxaban )

• Direct oral thrombin inhibitor ( Dabigatran )

• Vitamin K antagonist ( Warfarin )

Anticoagulant for VTERoute of

administrationRenal

clearanceHalf life Initial

treatmentMaintenance

treatmentExtended treatment

UFH I/V 30% 1.5h Target APTT 1.5 times of

normal

LMWH S/C 80 % 3-4h

Fondaparinux S/C 100% 17-21h

Warfarin 0ral negligible 36h Target INR 2-3 and Heparin for at least 5

days

Target INR 2-3 Target INR 2-3

Rivaroxaban oral 30% 7-11h 15mg bd3weeks

20 mg od 20 mg od

Dabigatran oral 80% 14-17h Heparin for at least 5 days

150mg bd 150mg bd

Apixaban oral 25% 8-12h 10mg bd 5mg bd 2.5mg bd

Anticoagulant• LMWH are preferred over UFH because of both

superior efficacy and safety. UFH needs doseadjustment based on APTT, whereas weightadjusted LMWH can be given in fixed doseswithout monitoring.

• However, UFH should be used in patientsundergoing thrombolysis because of its shorerhalf-life, ease of monitoring and the possibility ofimmediately reverse the anticoagulant effect withprotamine.

• UFH also preferred in severe renal impairment

( CCR < 30 ml/min).

Anticoagulant• In patients with suspected or confirmed HIT,

heparin should be stopped immediately andanticoagulation continued with other parenteralanticoagulant ( Fondaparinux ).

• At least 5 days overlap with Warfarin needed forHeparin/Fondaparinux . Discontinue when INR>2.0. Maintain INR between 2.0-3.0.

Anticoagulant• Over the past decade, direct oral thrombin

inhibitor ( Dabigatran ) and factor Xa inhibitors

( Rivaroxaban, apixaban and edoxaban ) overcomemany disadvantages of Warfarin.

• Direct oral anticoagulants have a rapid onset ofaction with peak levels reached within 2-4 hrsand a half life of about 12 hrs, which is muchshorter than Warfarin.

• They have little interaction with othermedications and food and can be given on fixeddoses without routine monitoring, hence greatlysimplifying treatment.

Anticoagulant• However concurrent use of strong P-glycoprotein

inhibitors or potent cytochrome P450 3A4 inhibitorsor inducers ( eg. certain protease inhibitors,antimycotics ant antiepilepics ) should be avoidedwith direct oral anticoagulants.

• Renal clearance for direct oral anticoagulants rangesfrom 27% to 80%, whereas warfarin minimallycleared by the kidneys.

• Dabigatran and edoxaban require a 5 day lead-inwith LMWH, whereas rivaroxaban and apixaban havebeen evaluated in a single-drug approach withoutheparin, although a higher dose during the first 3weeks and 7 days respectively.

Anticoagulant• 6 large phase III trials showed non-inferiority of

direct oral anticoagulants compared with Warfarin inrespect to recurrent VTE and a lower risk of clinicallyrelevant bleeding.

• A subsequent metaanalysis confirmed these findingsand reported that direct oral anticoagulants areassociated with a significant overall 39% relativereduction in the risk of major bleeding, includinghigh risk patients ( PE, aged >75 yrs, bodyweight>100 kg, moderate renal insufficiency with CCR 30-50ml/min).

• Given the similar efficacy, superior safety profile andease of use compared to Warfarin, direct oralanticoagulants should be first-line drug for VTE.

Anticoagulant• Pregnant women with VTE require treatment with

LMWH, because Warfarin and direct oralanticoagulants cross the placental barrier andcause fetal harm.

• However Warfarin can be safely used inbreastfeeding women, but direct oralanticoagulants are contraindicated in thesewomen.

• When recurrent VTE develops in patients takingWarfarin or direct oral anticoagulants, switch toLMWH.

• If recurrence happen during treatment withLMWH , a dose increase of 25% is recommended.

Thrombolysis• Thrombolysis in PE did not lower mortality and

was associated with a significant 9% absoluteincrease in major bleeding including a 2% higherabsolute risk of haemorrhagic stroke.

• Thrombolysis should be limited to PE associatedwith haemodynamic instability.

• In selected patients with ileofemoral DVTendovascular techniques ( catheter-directedthrombolysis ) can be considered. It reduce theoverall incidence of post-thrombotic syndromeafter 24 months.

IVC filters• IVC filters are indicated in patients who have

absolute contraindications to anticoagulation, suchas those with active bleeding or with objectivelyconfirmed recurrent PE despite adequateanticoagulant treatment.

• Retrievable filters preferred over permanent filters.

Graduated elastic compression stockings

Graduated elastic compression stockings lower therisk of post-thrombotic syndrome.

Prognosis• About 20% of patients with PE die before diagnosis and

shortly thereafter.

• About 30% of all patients with VTE have a recurrencewithin 10 years.

• Post-thrombotic syndrome develop in 20-50% ofpatients with DVT.

• Chronic thromboembolic pulmonary hypertensioncomplicates 0.1-4.0% of PE.

Take Home Message

• The diagnostic work-up of suspected DVT or PE includesthe sequential application of a clinical decision rule and D-dimer testing.

• Imaging and anticoagulation can be safely withheld inpatients who are unlikely to have VTE and have a normalD-dimer.

• All other patients should undergo CUS in case of suspectedDVT and CT in case of suspected PE.

• Direct oral anticoagulants are first-line treatment optionsfor VTE because they are associated with a lower risk ofbleeding than Warfarin and are easier to use.

Take Home Message

• Use of thrombolysis should be limited to PEassociated with haemodynamic instability.

• Anticoagulant treatment should be continued forat least 3 months to prevent early recurrences.

• When VTE is unprovoked or secondary topersistent risk factors, extended treatmentbeyond this period should be considered whenthe risk of recurrence outweighs the risk of majorbleeding.