VTE
DEEP VEIN THROMBOSIS
PULMONARY EMBOLISM
Wong Cai Hui
Supervisor: Dr Pradeep
Case
■ 45 years old male
■ Left leg swelling x30 days
■ right sided abdominal pain x20 days
■ SOB x4 days
■ History of admission to hospital, swelling and pain subsided following treatment
■ Abdominal pain- dull aching, more on right hypochondrium, no aggravating/relieving factor
■ SOB x4days
■ +orthopnea
■ + vomiting once
Otherwise
No fever/headache
No chest pain/palpitations
No cough
No trauma
No altered bladder/bowel habits
No altered sensorium
Past Medical History
Arthritis-NSAIDS, no HPT, no DM, no BA
Past Medications History
Started on warfarin 15 days ago
Family History
No similar illness
Social History
not smoking/alcoholic
Menstrual History
Regular 30days cycle
H/O 3 spontaneous abortions, 2 live children
Contact History
No contact with tuberculosis patient
General examination
Alert conscious oriented
Afebrile
Dyspnoeic, tachypnoeic
Pallor
Malar rash
Raised JVP
No icterus/cyanosis/clubbing
No lymphadenopathy
Bilateral pitting pedal edema
Generalised left lower limb swelling
Vital Signs
BP: 110/60mmHg
PR: 76/min
RR: 24/min
T: 36.8
CVS: DRNM, muffled
Lungs: dullness at left lower zone
PA: soft, non tender, hepatomegaly, bowel sounds are heard
Left LL
Swollen, tender, dusky appearance, peripheral pulses are felt
Investigations
WBC 4000
PLT 80,000
MCV 83
MCH 25.3
MCHC 30.5
HB 9.4
ESR 36
PT 38
APTT 38
INR 2.2
Renal Profile
Ur 43
K4
Na 138
Creat 1.1
Liver Function Test
TB 5.4
DB 4.3
AST 87.1
ALT 242
TP 6.8
Alb 3.1
HBSag –
Anti Hbc –
HIV –
UFEME
Nitrites –
Leukocytes 8-10hpf
RBC 2-3hpf
Glucose –
Albumin –
Ph 6.5
SP gravity 1.025
Urine C&S: no growth
ANA+
Lupus anticoagulant+
ACL antibody –
ECHO
Pericardial effusion+
Normal LV systolic function
Mild diastolic dysfunction
Mild hypokinesia of IVS and LV apex
No evidence of tamponade
Normal chamber dimension
USG Abdomen
Minimal free fluid in Morrison pouch
Hepatomegaly
Minimal ascites
Doppler Study
Left popliteal vein thrombosis extending into superficial femoral vein
Diagnosis
DVT left lower limb probably due to hypercoagulable state (anti phospholipid antibody
syndrome secondary to SLE) with pericardial effusion, pleural effusion, ascites due to
polyserositis
Definition
■ Formation of blood clot in one of the deep vein, usually in the leg
Deep vein system
EPIDEMIOLOGY
■ third most common cardiovascular disease after myocardial
infarction and stroke
■ overall rates are 100 per 100,000 population per year
■ 70% are hospital acquired
In Asia, VTE is increasing due to
■ Aging population
■ Higher rates of major complex surgeries
■ Higher rates of caesarean deliveries
■ Rise in Obesity
■ Rise in Cancer
■ Low rates for thromboprophylaxis
PATHOGENESIS
■ major pathophysiologic determinants
NATURAL HISTORY OF VTE
■ Begins at lower extremities venous, starting at calf, progressing proximally to popliteal,
femoral, or illiac
■ In pregnancy it begins in the proximal and pelvic veins
■ Risk of VTE is highest following major orthopedic surgery where vessel damage and
immobility
■ Risk of symptomatic VTE is highest within 2 weeks of surgery and remains elevated for
a further 2 to 3 months
■ Risk of fatal PE is highest within 1 week of surgery
■ Following treatment, the resolution of DVT is slower than for PE with complete
resolution being more common with PE than in DVT, where recanalisation is commoner
■ Risk of mortality is higher with recurrent PE than recurrent DVT
Risk Factors
■ Active cancer
■ Obesity (BMI >30 kg/m2)
■ Use of oestrogen containing oral contraceptive pill
■ Use of Hormone Replacement Therapy
■ Previous VTE
■ Family h/o VTE
■ One or more significant medical comorbidities:
1/Heart disease
2/ Metabolic, endocrine or respiratory pathologies
3/ Acute infectious disease
4/ Inflammatory conditions
5/ Sickle cell disease
6/ Thalassaemia
7/ Varicose veins with phlebitis
Risk factors for VTE recurrence
■ Unprovoked (idiopathic) than in provoked (recent surgery)
■ Active cancer
■ Antiphospholipid syndrome
■ Previous VTE
■ Male gender
■ Proximal versus distal DVT
■ Post thrombotic syndrome
RISK ASSESSMENT FOR VTE
DVT Signs and symptoms
■ Calf pain/tenderness
■ Swelling with pitting edema
■ Swelling below knee in distal DVT and up to groin in proximal DVT
■ Increased skin temperature
■ Superficial vein dilatation
■ Cyanosis (severe obstruction)
■ Homan sign: pain in posterior calf/knee with forced dorsiflexion of foot
■ Moses sign: squeeze calf
PE Signs and symptoms
■ SOB
■ cough
■ Pleuritic chest pain
■ Hypotension
■ Raised JVP
■ Tachycardic
■ ABG: low PaO2 and low O2 saturation
■ CXR: normal/atelectasis/wedge shape lesion and pruning of pulmonary vessels
■ ECG: tachycardic, S1 Q3 T3, right strain pattern including RBBB and RV hypertrophy
■ ECHO: right side strain, blood clot in RA, RV, RVOT and pulmonary artery (severe)
Massive bilateral pulmonary embolus
■ Sinus tachycardia
■ RBBB
■ T-wave inversions in the right precordial leads (V1-3) as well as lead III
Massive bilateral pulmonary embolus
■RBBB
■Extreme right axis deviation (+180 degrees)
■S1 Q3 T3
■T-wave inversions in V1-4 and lead III
■Clockwise rotation with persistent S wave in V6
Massive pulmonary embolus
■ Sinus tachycardia.
■ Simultaneous T-wave inversions in the anterior (V1-4) and inferior leads (II, III, aVF).
■ Non-specific ST changes – slight ST elevation in III and aVF.
bilateral PEs confirmed on CTPA.
■ Sinus tachycardia.
■ Terminal T-wave inversion in V1-3 (this morphology is commonly seen in PE). There is also T-wave inversion in lead III.
■ Right axis deviation.
■ T-wave inversions in V1-4 (extending to V5).
■ Clockwise rotation with persistent S wave in V6.
■ Note: This patient had confirmed pulmonary hypertension on echocardiography with dilation of the RA and
RV
■ Sinus tachycardia.
■ RBBB.
■ Simultaneous T-wave inversions in precordial leads V1-3 plus inferior leads III and
aVF.
Saddle embolus confirmed on CTPA
■ Sinus tachycardia.
■ Right axis deviation.
■ Marked interventricular conduction delay – most likely RBBB given the RSR’ pattern in V1
■ Persistent S waves in V6.
Complications of VTE
■ Post thrombotic syndrome
-occurs more frequently following pregnancy associated VTE
-because proximal iliofemoral veins usually involved
■ Chronic thromboembolic pulmonary hypertension
VTE PROPHYLAXIS
■ Mechanical Prophylaxis
■ Pharmacological Prophylaxis
■ Low Molecular Weight Heparins
■ Fondaparinux
■ Unfractionated Heparin
■ Vitamin K Antagonist
■ Oral Direct Thrombin Inhibitors
■ Oral Direct Factor Xa Antagonists/Inhibitors
Mechanical Prophylaxis
■ Graded Elastic Compression Stockings (GECS)
■ Intermittent Pneumatic Compression (IPC) of the calf or calf and thigh
-relative contraindications : 1. severe leg ischemia/ peripheral artery disease
2. acute superficial and deep vein thrombosis
3. congestive heart failure
■ Venous Foot Pump (VFP)
■ applicable pre and intraoperatively, should be continued postoperatively until the patient
is fully ambulating
■ Advantage: 1/ effective when used in combination with early ambulation
2/ no significant adverse effects (bleeding)
■ Disadvantage: less efficacious than pharmacologic methods when used as a standalone
modality
Low Molecular Weight Heparins
■ preventing thrombosis without increasing the risk of bleeding
■ less likely to produce 1/haematomas at injection site
2/heparininducedthrombocytopenia/ thrombosis (HITT)
3/osteoporosis
Fondaparinux (Pentasaccharide
Sodium)
■ selectively binds to antithrombin, inducing a conformational change that increases antifactor
Xa without inhibiting thrombin
■ long elimination half life of 17 to 21 hours allows OD dosing
■ eliminated unchanged in urine (prolonged in patients aged >75 years and in those weight
<50kg)
■ effective in preventing VTE in knee and hip replacement surgeries, hip fracture surgeries,
abdominal surgeries and acute medically ill patients
■ alternative to LMWH
■ prophylactic dose is 2.5 mg given no earlier than 6 to 8 hours after surgery
Unfractionated Heparin
■ Requires complex labor intensive administration, monitoring and dose adjustment
■ Disadvantage: Major bleeding events, risk of HITT
■ Subcutaneous low dose UFH administered in a dose of 5000 IU every 12 hours
Vitamin K Antagonist - warfarin
■ Preoperatively (risk of major bleeding event), at the time of surgery or at the early postoperative period
(may not prevent small venous thrombi formation during or soon after surgery because anticoagulation
effect is not achieved until the third or fourth postoperative day).
■ If started at a low dose before surgery, it may reduce the risk of bleeding compared to full
anticoagulation at the time of surgery
■ Advantage: oral administration and low cost
■ Disadvantages: 1/delayed onset on action
2/narrow therapeutic range
3/drug drug interaction
■ 4/daily monitoring of the INR (the recommended therapeutic range is
■ 2.0 to 2.5 in orthopaedic surgery).
Oral Direct Thrombin Inhibitors
■ Dabigatran etexilate: alternative to LMWH and fondaprinux for the prevention of VTE
following THR and TKR surgeries
■ 110 mg given 1 to 4 hours postoperatively and continued with a dose of 220 mg daily
for 10 days after knee replacement and for 35 days after hip replacement.
■ moderate renal impairment and age >75 years, reduced dose of 75 mg starting dose and
150 mg continuing dose once daily is recommended
Oral Direct Factor Xa
Antagonists/Inhibitors
Rivaroxaban
■ rapid onset of action by reaching peak concentration at 3hours
■ metabolized via CYP3A4 and eliminated by both the renal and fecal/ biliary routes
■ elimination half life between 5 to 9 hours.
■ single dose of rivaroxaban produces pharmacologic effects that persist for 24 hours, making it
suitable for once daily administration.
■ predictable pharmacokinetics, does not require monitoring
■ superior to enoxaparin in VTE prevention studies during hip and knee replacement surgeries with
similar bleeding rates
■ 10 mg orally once daily with or without food
■ initial dose should be taken at least 6 to 10 hours after surgery once haemostasis has been established.
Apixaban
■ bioavailability of 50 to 85% after oral intake reaches peak concentration at 3 hours
■ excretes predominantly via the biliary tract
■ superior to enoxaparin in reducing VTE following hip and knee replacement surgeries with
no difference in the bleeding rates.
■ 2.5 mg orally twice daily.
■ initial dose should be taken 12 to 24 hours after surgery
■ safe to be used in renal impairment
Low molecular weight heparin
■ decreased mortality, lower recurrence of VTE and decreased incidence of major
bleeding when compared with unfractionated heparin
■ does not require monitoring
■ continued for at least 5 days or until the INR is above 2 for at least 24 hours, whichever
is longer
Fondaparinux
■ indirect inhibitor of activated factor X
■ does not inhibit thrombin and has no effect on platelets
■ given subcutaneously
■ Eliminated unchanged in the kidneys
■ continued for at least 5 days or until the INR is above 2 for at least 24 hours, whichever
is longer
Rivaroxaban
■ highly selective, direct factor Xa inhibitor
■ orally active with a rapid onset of action
■ 15 mg twice a day as the loading dose for 3 weeks followed by 20 mg daily.
Switching heparin to rivaroxaban
■ started 0 to 2 hours before the time of the next scheduled administration of LMWH or
■ at the time of discontinuation of continuous intravenous unfractionated heparin
Switching rivaroxaban to heparin
■ first dose of LMWH at the time the next rivaroxaban dose would be taken or 12 hours
after the last dose of rivaroxaban
Switching VKAs to rivaroxaban
■ Stop VKA and allow INR to fall.
■ Rivaroxaban can be given as soon as INR <= 2.5
Switching rivaroxaban to VKA
■ potential for inadequate anticoagulation
■ VKA should be given concurrently until INR>=2
■ For the first few days of conversion period, standard initial dosing of VKA should be
used followed by VKA dosing guided by INR testing.
■ While patients are on both rivaroxaban and VKA, the INR should not be tested earlier
than 24 hours after the previous dose but prior to the next dose of rivaroxaban.
■ Once rivaroxaban is discontinued, INR testing may be done reliably at least 24 hours
after the last dose
Intravenous unfractionated heparin
■ given as an infusion with frequent APTT monitoring
■ may take more than 12 hours to achieve therapeutic level.
■ All patients receiving UFH should have a platelet count performed at baseline but do
not necessitate platelet count monitoring unless postoperative.
■ duration of initial IV UFH therapy in patients with VTE is between 5 to 7 days
MAINTENANCE TREATMENT OF VTE
■ Following initial heparinisation or fondaparinux in patients with VTE, maintenance of
anticoagulation with oral anticoagulants is recommended.
■ Following discharge, those on warfarin should be followed up within a week with a
repeat INR.
■ If the INR remains within therapeutic range, the same dose is maintained and the next
followup will be 2 weeks later.
■ If the INR still remains within therapeutic range, then monthly follow up with INR is
advised.
■ More frequent visits are required if therapeutic INR is not achieved
■ Patients on rivaroxaban do not need initial heparinisation or laboratory monitoring.
■ Patients are seen within 1 to 2 weeks of treatment to monitor response and to assess
drug tolerability. Thereafter monthly followup is advised
Duration of anticoagulation
■ aim of anticoagulant therapy is to prevent extension of the thrombus and recurrence of
the disease
■ should be continued until the reduction of recurrent VTE no longer outweighs the
increase risk of bleeding
Risk factors for increased bleeding
■ Uncontrolled hypertension
■ Age >75 years
■ Renal impairment
■ Anaemia
■ Recent major bleeding
Thrombolytic agents
■ tissue plasminogen activator (tPA) and streptokinase.
■ indicated in massive PE.
■ Tissue plasminogen activator is the agent of choice as it is clots pecific.
■ The dose for streptokinase is 250,000IU IV bolus followed by 100,000 IU/hr for 24
hours.
■ The dose for tPA is 100mg IV over 2 hours followed by therapeutic heparin infusion
THROMBOLYTIC THERAPY
Venous thrombectomy
■ Where DVT threatens leg viability through venous gangrene, the leg should be elevated,
anticoagulation commenced and consideration given to venous thrombectomy
■ prevent severe complications of postthrombotic syndrome.
■ indicated in impending venous gangrene of the lower limbs due to phlegmasia caerulea
dolens, which is associated with considerable morbidity (50% amputation rate and 12 to
14% PE) and a 20% mortality rate
Pulmonary embolectomy
■ very rarely done
■ high perioperative morbidity and mortality rates (30-50%).
■ However, the long term outcome for survivors is good.
■ indicated in massive PE (proven by imaging modalities) with haemodynamic compromise.
■ done as an emergency procedure following failed conservative measures including
thrombolysis
percutaneous cathether directed embolectomy device
■ quicker and easier to perform.
■ This can be augmented by the administration of thrombolytic drugs, which speeds up clot
fragmentation.
Vena Caval Filters
■ absolute contraindication : complete IVC thrombosis
■ prevent pulmonary embolism secondary to DVT.
■ inserted through the internal jugular or femoral vein, and placed in the IVC under fluoroscopic or
ultrasound guidance
■ Temporary
■ should be safely removed once there is no risk of emboli.
■ Can be removed between 14 to 25 days of insertion
■ newer filters can be left in situ for up to 90 days
PREVENTION OF POSTTHROMBOTIC
SYNDROME
■ most common complication of VTE: chronic venous insufficiency (CVI) leading to post
thrombotic syndrome (PTS).
■ Results in debilitating pain, swelling, and ulceration and is a significant cause of loss of
working days.
■ can contribute to an increase in recurrent DVT and PE
ThromboEmbolic Deterent Stockings
■ graduated elastic compression stockings with an ankle pressure greater than 23 mmHg
following a proximal DVT
■ continue wearing the stockings on the affected leg for at least 2 years
■ replaced 2 to 3 times per year
HEPARIN INDUCED THROMBOCYTOPENIA and
THROMBOSIS
■ All patients receiving any heparin should have a baseline platelet count
■ caused by the development of IgG antibodies directed against a complex of platelet
factor 4 (PF4) and heparin.
■ The IgG/ PF4/ heparin complexes bind to and activate platelets through their Fc
receptors resulting in a prothrombotic condition that is associated with venous and
arterial thrombosis
■ incidence of HITT is greater with unfractionated heparin than with LMWH (5% vs.
0.5%).
Diagnosis and management of HIT/T
■ platelet count typically begins to fall 5 to 10 days after starting heparin, although in patients
who have received heparin in the previous 3 months it can have a rapid onset due to preexisting
antibodies.
■ If the platelet count falls by 30% or more and/or the patient develops new thrombosis or skin
allergy or any of the other rarer manifestations of HITT between days 4 to 14 of heparin
administration, HITT should be considered and heparin should be stopped and an alternative
anticoagulant started in full dosage
■ clinical diagnosis.
■ Tests for HIT antibodies e.g. platelet activation assays and antigen assays are time consuming
and have limited sensitivity and specificity
therapeutically anticoagulated
■ for 3 months after HIT with a thrombotic complication
■ for 4 weeks following HIT without a thrombotic complication.
MANAGEMENT OF OVERANTICOAGULATION
■ risk for bleeding increases with age, history of past bleeding, specific comorbid
conditions and the level of the INR.
■ 50% of bleeding episodes when the INR < 4.0
Warfarin reversal
Vitamin K
■ ampoules for IV administration (more rapid correction, preference in bleeding)
■ given orally mixed with a glass of juice or water.
■ Not recommended for subcutaneous/ intramuscular use as the response is unpredictable with a
risk of haematoma formation
■ 1.0 to 2.0 mg of oral vitamin K is sufficient
■ optimal intravenous dose for partial reversal of overwarfarinisation is 0.5 to 1.0 mg
■ If the INR is particularly high, 5 mg may be required, and then INR can usually be normalized
within 24 hours
Prothrombin Complex Concentrate
■ made from pooled donor plasma
■ undergone viral inactivation
■ contains clotting factors II, IX and X with variability in their factor VII content.
■ Concentrates with little factor VII (3factor PCC) produce poor correction of the INR and are
not recommended
■ Patients on warfarin have reduced levels of factors II, VII, IX and X and rapid correction
involves replacement of these 4 factors.
■ This is achieved with the 4factor PCC: octaplex and beriplex
■ achieve factor levels between 80 to 100% within 10minutes in life threatening bleeding
■ Four factor PCCs are able to completely reverse warfarin induced anticoagulation within 10
minutes but the infused clotting factors have a finite half life, the shortest of which is factor
VII at 6 hours.
■ 5 mg of intravenous vitamin K should be given with the PCC.
HEPARIN AND BLEEDING
■ Overheparinisation may occur in conditions such as ‘heparin resistance’ in pregnancy or
accidental heparin overdose as a result of drug error, with 5000 units/mL vials being
mistaken for 50 units/mL vials.
Fresh frozen plasma
■ cannot provide a rapid and complete correction of warfarin induced
coagulopathy.
■ At doses of 15 to 20 mL/kg, factor levels rise no more than 30%,
■ Not recommended for life threatening bleeding
References
■ CPG Prevention and Treatment of Venous Thromboembolism
■ https://www.slideshare.net/smcmedicinedept/a-case-of-dvt-for-discussion
■ https://www.youtube.com/watch?v=JK72NIPg9xA
■ https://litfl.com/ecg-changes-in-pulmonary-embolism/
