Transcript Slide 1

A MASTERCLASS IN:
VENOUS THROMBOEMBOLISM
(VTE)
Dr. Tom Heaps
Consultant Acute Physician
LEARNING OUTCOMES AND FORMAT
 By the end of this session you should be familiar with the
presentation, investigation and management of both routine
and complex aspects of venous thromboembolic disease
 Interactive case-based discussion format based on recent
national clinical guidance and my own clinical experience and
learning
CASE 1: INVESTIGATION OF DVT
 45-year-old male presents to AEC with acute left leg swelling
 no significant PMH
 FY1 clerks patient and asks you whether to take a d-dimer or not
HOW DO YOU RESPOND AND HOW SHOULD YOU
PROCEED FROM HERE?
CASE 1: INVESTIGATION OF DVT
 Assess clinical pre-test probability
 Wells score
 Low clinical probability or ‘DVT unlikely’ (modified Wells Score)
 Check d-dimer
 USS if d-dimer positive
 Intermediate/High clinical probability or ‘DVT likely’ (modified Wells score)
 USS (do not check d-dimer)
 Compression doppler USS
 Sensitivity 98.7% and specificity 100% for above-knee DVT
 Sensitivity 85.2% and specificity 98.2% for below-knee DVT
CASE 1: INVESTIGATION OF DVT
WHAT ARE YOUR OPTIONS IF USS IS INCONCLUSIVE
OR NEGATIVE WITH A HIGH PERSISTING CLINICAL
SUSPICION FOR DVT?
 administer LMWH for 1/52 and recall patient for repeat USS
 CT or MR venogram
 invasive venography
CASE 2: INVESTIGATION OF PE
 76-year-old female
 no previous Hx of VTE
 never smoked
 referred to ED with acute onset pleuritic chest pain
 CXR NAD
 heart rate 102/min, other observations NAD
IS HER CLINICAL PRESENTATION SUGGESTIVE OF PE?
HOW WOULD YOU PROCEED FROM HERE?
CASE 2: PRESENTATIONS OF PE
1.
pleuritic chest pain, tachycardia, haemoptysis +/abnormal CXR
• peripheral PE
2.
unexplained dyspnoea and/or hypoxaemia
• moderate or chronic PE
3.
acute cor pulmonale and syncope
• massive PE with RV outflow obstruction
CASE 2: CLINICAL FEATURES IN PE
CLINICAL FEATURES ALONE ARE UNRELIABLE (have a low
threshold for suspicion);
 Major risk factors for VTE absent in 40%
 Signs of coexistent DVT in ≤15%
 Triad of pleuritic pain, dyspnoea and haemoptysis <10%
 Normal A-a gradient in 6%
 No dyspnoea, tachypnoea, pleuritic pain or hypoxaemia in 3%
SUSPECT DIAGNOSIS OF PE;
 COPD patients with acute dyspnoea and no/minimal signs of infection
 Any unwell patient with cancer
 Younger patients with unusually severe ‘pneumonia’
 Recurrent unexplained syncope
 Sudden deterioration as an inpatient or post-surgery
CASE 2: INVESTIGATION OF PE
ASSESS THE CLINICAL PRE-TEST PROBABILITY AS FOR DVT
 Wells score
 Geneva score
 BTS guideline
 Pulmonary
embolism
(PERC)
1. patient has
clinicalrule-out
features criteria
compatible
with PE – breathlessness and/or
with or without pleuritic chest pain and/or haemoptysis plus;
 tachypnoea
age <50 years
 pulse <100bpm
2. absence
of another
SpO2 >94%
on air reasonable clinical explanation and/or;
 no unilateral leg swelling
IF ALL SATISFIED, RISK OF PE <2%
3. presence of a major risk factor for VTE
 no haemoptysis
 no 2.
recent
trauma
or surgery
Where
and 3.
are both
true the probability is high; if only one is true the
 probability
no prior PEisor
DVT
intermediate;
and if neither is true the probability is low
 no hormone use
CASE 2: INVESTIGATION OF PE
 Low or intermediate pre-test probability or ‘PE unlikely’
 Check d-dimer
 if hospital uses SimpliRED assay only check d-dimer if low
probability
 if d-dimer positive proceed to imaging (V/Q or CTPA)
 High pre-test probability or ‘PE likely’ (modified Wells)
 DO NOT check d-dimer
 Proceed straight to definitive imaging
D-DIMERS
 Only measure AFTER assessment of pre-test clinical probability: LOW OR INTERMEDIATE
 High sensitivity (>95%) ELISA-based d-dimer assays (Vidas, MDA)

low specificity (40% in outpatients)

negative in <30% of outpatients
 Moderate sensitivity (80-94%) d-dimer assays (SimpliRED)

more specific (70%)

can only be used to exclude VTE in patients with low clinical pre-test probability
 Llimited value in patients with HIGH clinical pre-test probability of PE


50% will have a positive result due to the presence of PE

negative predictive value greatly reduced by high prevalence of disease i.e. if d-dimer <0.5μg/ml;

post-test probability for PE <2% if low pre-test probability but 19-28% if high pre-test probability
specificity reduced by age, pregnancy, cancer, inflammatory conditions, trauma and surgery
 using age-adjusted upper limits of normal (age/10) for patients aged >50 may increase
specificity without affecting sensitivity
CASE 2: INVESTIGATION OF PE
 76-year-old female
 no previous Hx of VTE
 never smoked
 referred to ED with acute onset pleuritic chest pain
 CXR NAD
 heart rate 102/min, other observations NAD
 patient has a Wells score of 1.0 = low clinical probability
 d-dimer 498ng/ml (>243ng/ml considered positive)
WHAT INVESTIGATION SHOULD YOU REQUEST NEXT?
DIAGNOSIS OF PE – V/Q SCANS
 less radiation than CTPA
 overall sensitivity low at 55%
 normal perfusion scan in only 25% of people without a PE
 only useful if young, non-smoker, no respiratory disease
 consequently up to 70% of scans non–diagnostic
 CTPA required after V/Q
 do not show alternative pathologies
LIKELIHOOD OF PE BASED ON POSITIVE
V/Q SCAN (PIOPED)
Clinical Probability of PE
Scan Result
High
Intermediate
Low
High Probability
95
86
56
Intermediate Probability
66
28
15
Low Probability
40
15
4
Normal
0
2
2
DIAGNOSIS OF PE - CTPA
 Higher radiation dose (women of child-bearing age)
 Overall sensitivity of 86% and specificity of 96% in PIOPED II
 Positive predictive value varies with
 extent of PE; 97% for main/lobar c/w 25% subsegmental
 clinical pre-test probability; 96% if high c/w 58% if low
 Overall sensitivity increased to 90% with addition of lower limb CT venogram
 Sensitivity probably higher with modern multi-detector CT scanners
 May miss subsegmental clot
 mortality <1% if anticoagulation witheld
 94% with subsegmental clot have evidence of more proximal PE
 May assist in diagnosing alternative/coexisting pathologies (e.g. pneumonia, lung cancer)
and provide information on thrombus burden and RV strain
DIAGNOSIS OF PE – CXR
Hampton’s Hump

abnormal CXR in 84% in PIOPED e.g. atelectasis, pleural effusion

main role of CXR is to
 rule out alternative or coexisting pathology e.g. pneumothorax
 assist in determining suitability for V/Q
Westermark’s Sign
Fleischner’s Sign
DIAGNOSIS OF PE – OTHER TESTS
 ECG abnormal in 70%
 Sinus tachycardia most common
 Atrial arrhythmias
 T wave inversion V1-3 and inferior leads
 ST depression or elevation
 S1Q3T3
 RBBB
 ECHO abnormal in up to 40%
 Useful in emergency situation, pulmonary HTN, RV strain/dilatation
 Troponin and BNP
 Elevated levels in significant PE correlate with prognosis
CASE 3: MANAGEMENT OF VTE
 58-year-old male
 Acutely breathless 10d post-right total knee replacement
 Multiple segmental PE confirmed on CTPA
 No significant PMHx and no previous VTE
 Haemodynamically stable with normal ECG and hs-TnI
WHAT TREATMENTS ARE YOU GOING TO PRESCRIBE?
HOW MIGHT YOUR PRESCRIPTION CHANGE IF THE PATIENT
WAS MUSLIM?
FOR HOW LONG ARE YOU GOING TO RECOMMEND
ANTICOAGULATION?
CASE 3: MANAGEMENT OF VTE - WARFARIN
 Start LMWH immediately once diagnosis confirmed (before scan if high CPTP or
anticipated delay in imaging >4h)
 SC Enoxaparin (Clexane®) 1.5mg/kg OD (1mg/kg OD if GFR <30)
 continue for 48h once INR >2 and for a minimum of 5d in total
 SC Fondaparinux 5-10mg OD is alternative if objection to porcine products
 Start warfarin after diagnosis confirmed by imaging aiming for INR 2.0-3.0
1.
Isolated calf vein thrombosis with transient (reversible) risk factor
≥6weeks
2.
Proximal DVT or PE with transient (reversible) risk factor
≥3months
3.
Isolated calf vein thrombosis which is unprovoked (idiopathic)
≥3months
4.
Proximal DVT or PE which is unprovoked (idiopathic)
≥6months*
5.
Recurrent (second or subsequent) DVT or PE
indefinite
*consider longer-term or indefinite anticoagulation in all patients
CASE 3: MANAGEMENT OF VTE
 patient states that he is needle-phobic
 will not agree to regular blood tests for INR monitoring
 asks about ‘some new tablets for treating blood clots’ that he
has read about on the internet
WHAT NOVEL ANTICOAGULANTS ARE AVAILABLE
FOR THE TREATMENT OF VTE?
WHAT ARE THE PROS AND CONS OF THESE
AGENTS?
CASE 3: MANAGEMENT OF VTE – NOVEL
ANTICOAGULANTS
 PO rivaroxiban (Xarelto®) is a factor Xa inhibitor
 15mg BD for 21d then 20mg OD (no need for LMWH)
 Currently licensed for acute Rx of DVT/PE and prevention of recurrent
DVT/PE, need GFR >30mL/min
 PO dabigatran (Pradaxa®) is a direct thrombin inhibitor
 110-150mg OD AFTER 5d initial treatment with LMWH
 Currently only licensed for prophylaxis of VTE after hip or knee surgery
in adults
 PO apixaban and edoxaban are alternative factor Xa inhibitors
CASE 3: MANAGEMENT OF VTE – NOVEL
ANTICOAGULANTS
PROS
 Non-inferiority to warfarin (VTE recurrence rates and all-cause mortality)
demonstrated in recent meta-analyses
 Non-significant trends towards lower rates of major haemorrhage overall (less ICH,
more UGIB)
 No requirement for regular monitoring/blood tests/dose changes
CONS
 Expensive £75.60 for 60 tablets of dabigatran and £112.00 for 60 tablets of rivaroxaban
(c/w £1.84 for 60 tablets of warfarin)
 Higher incidence of SE esp. GI (nausea, dyspepsia, diarrhoea)
 Long-term effects/efficacy unknown; higher rates of ACS with dabigatran
 No reliable method for rapid reversal of anticoagulation (discontinue drug, supportive
care, activated charcoal, PCC, rFVIIa, FEIBA)
CASE 4: THROMBOLYSIS FOR PE
 75-year-old female admitted acutely breathless
 Previous PE post-THR aged 62
 Looks unwell
 RR 31, SpO2 90% on air, HR 104, BP 130/67
 CTPA large volume thrombus in main pulmonary arteries bilaterally with
some RV dilatation
 Signs of RH strain on ECG and hs-TnI 48
SHOULD SHE RECEIVE THROMBOLYSIS?
CASE 4: THROMBOLYSIS FOR PE
 Alteplase 10mg stat then 90mg over 2h then IV UFH (no loading dose) once APTT <2x ULN
 Massive PE with hypotension (sBP <90mmHg or fall in sBP ≥40mmHg for ≥15 minutes once
other causes excluded)
 accelerates clot lysis and has short-term haemodynamic benefits
 no meta-analysis conclusively showing reduction in mortality or recurrent PE
 consistent non-significant trends towards improved long-term outcomes
 recommended by NICE if not high risk for bleeding
 Submassive PE (normal BP but evidence of RV dysfunction on ECHO, RV dilatation on CTPA,
RV strain on ECG and/or raised troponin)
 reduces risk of in-hospital death and clinical/haemodynamic deterioration requiring escalation





(PEITHO)
no effect on risk of recurrent PE or overall mortality
Excess risk of major haemorrhage 9% vs 6% (may be confined to certain subgroups)
Lower rates of pulmonary hypertension with similar bleeding risk using low-dose alteplase 10mg
bolus followed by 40mg infusion (MOPPET)
not recommended by NICE
consider on case-by-case basis with second (senior) opinion
CASE 5
 39-year-old male with no PMHx
 Referred from ED with acutely swollen left arm
 Decorating house 2 days prior to onset
WHAT IS THE DIAGNOSIS?
HOW WILL YOU CONFIRM THIS?
HOW WILL YOU TREAT?
CASE 5: UPPER EXTREMITY DVT
Primary (20%)
 venous thoracic outlet syndrome (1st rib, clavicle, subclavius, anterior scalene band)
 effort-related thrombosis (Paget-Schroetter syndrome)
 acquired/hereditary thrombophilia
Secondary (80%)
 catheter associated (indwelling central venous catheter, PPM, defibrillator)
 cancer-related
 surgery/trauma to arm/shoulder
 pregnancy/use of OCP
 compression US, CTA/MRA, conventional venogram, CXR/CT thorax
 anticoagulate for >3m with warfarin
 catheter-directed thrombolysis for clinically massive UEDVT
 SVC filter or surgical thrombectomy if treatment failure or CI to anticoagulation
CASE 6
 68-year-old female
 PMHx varicose veins
 Referred to Acute Medical Clinic ‘swollen painful R leg ?DVT’
 OEx prominent distal long saphenous vein on R, associated erythema,
hardness and tenderness, minimal R leg swelling
WHAT IS THE DIAGNOSIS?
DOES SHE REQUIRE AN ULTRASOUND?
HOW SHOULD SHE BE TREATED?
CASE 6: SUPERFICIAL THROMBOPHLEBITIS
 up to 20% with proximal superficial thrombophlebitis have an underlying DVT at
presentation
 risk of progression to DVT in a further 3-4%
 compression USS if proximal superficial thrombophlebitis
 topical NSAIDs or hirudoid for symptomatic relief
 TEDS
 prophylactic dose LMWH for 30d (or fondaparinux 2.5mg for 45d) for
proximal superficial thrombophlebitis
 treatment dose LMWH for 6-12w if proximal thrombophlebitis approaching
or at saphenofemoral junction
 oral NSAIDs for 10d if distal superficial thrombophlebitis (or proximal and
anticoagulation CI (less effective than LMWH)
CASE 7
 27-year-old male
 Current IVDU and alcohol abuse
 Presents to ED with extensive L leg swelling
 Immediate therapeutic dose of LMWH given
 Doppler USS confirms extensive L ileofemoral DVT
WHAT IS THE MANAGEMENT?
CASE 7:VTE AND IVDU
 Limited evidence available
 Difficult venous access for INR checks
 Poor compliance with warfarin and attendance at anticoagulation clinics due
to chaotic lifestyle
 Co-existing alcohol misuse common
 LMWH for ≥6w (ideally 6m) is treatment of choice (consider rivaroxaban)
 Shortly after returning from scan patient becomes pale and clammy,
hypotensive, significant haematemesis witnessed
HOW SHOULD HE BE MANAGED NOW?
CASE 7: IVC FILTERS
 most IVC filters are retrievable and licensed for short-term use only;
 anticoagulation contraindicated
 interruption of anticoagulation required e.g. for surgery or
delivery within 4w of extensive proximal DVT
 recurrent PE from continuing DVT despite adequate anticoagulation
 pulmonary vascular bed compromised such that another embolic event
would be poorly tolerated (e.g. massive PE, severe pulmonary
hypertension due to chronic thromboembolic disease, severe COPD)
 effective short-term in preventing PE
 do not reduce mortality or recurrent symptomatic PE in the long-term
 increase incidence of recurrent DVT
CASE 8
 31-year-old female
 Confirmed R ileofemoral DVT
 History of DVT in mother at age 52
 No other significant RF for VTE
HOW LONG SHOULD SHE BE ANTICOAGULATED FOR?
SHOULD SHE BE TESTED FOR HERITABLE THROMBOPHILIA?
CASE 8: DURATION OF ANTICOAGULATION
FOLLOWING FIRST UNPROVOKED
(IDIOPATHIC) PROXIMAL DVT/PE
 risk of recurrent VTE approximately double that if thrombosis was distal or provoked
 10% risk of recurrence at 1y and 30% by 5y following discontinuation of warfarin
 indefinite warfarin therapy reduces risk by 90% to ≤1% per year
 risk of recurrence and case fatality rate with recurrence decrease with time from initial
event (highest in first 6m) whereas risk of major bleeding increases with age
 factors increasing risk of recurrence
 idiopathic/unprovoked VTE
 presentation with PE or proximal DVT (rather than distal DVT)
 male sex (?influence of oestrogens)
 duration of anticoagulation <3m
 ongoing risk factors (e.g. obesity, immobility, malignancy, IBD, thrombophilia)
 residual venous obstruction/thrombus on ultrasound
 persistently elevated d-dimer/thrombin levels after period of anticoagulation
 consider long-term or indefinite anticoagulation on an individual patient basis
 take into account patient values/preferences and annual risk of bleeding with warfarin
 potential role for newer oral anticoagulants?
CASE 8: THROMBOPHILIA SCREENING
 Thrombophilia screening tests for commonest heritable thrombophilias;
 Activated Protein C resistance
 Factor V Leiden (if APCR positive)
 Protein C and Protein S deficiency
 Prothrombin gene mutation
 Antithrombin III deficiency
 Lupus anticoagulant and Anticardiolipin antibodies
 Thrombophilia screening is CI if
 obvious provoking factor for VTE
 active/acute thrombosis
 on anticoagulation therapy
 pregnant
 taking OCP or HRT
CASE 8: THROMBOPHILIA SCREENING
 no clear international consensus on who should be tested
 NICE Clinical Guideline CG144 (June 2012)
 do not test patients who have decided to continue indefinite anticoagulation
 consider testing for antiphospholipid antibodies only in patients with unprovoked
DVT/PE if they are planning to stop anticoagulation
 consider full testing in patients with unprovoked DVT/PE and a 1⁰ relative who has
had DVT or PE if they are planning to stop anticoagulation
 do not test patients who have had provoked DVT or PE
 do not routinely test 1⁰ relatives of people with VTE and thrombophilia
 other potential indications for thrombophilia testing
 young patients with atypical VTE (cerebral venous sinus, axillary, mesenteric)
 young patients with unexplained arterial thromboses
 patients with a history of recurrent miscarriage, pre-eclampsia, placental abruption,
IUGR or unexplained stillbirth
CASE 8: THROMBOPHILIA SCREENING CAVEATS
 negative test does not exclude a heritable thrombophilia
 positive test after unprovoked VTE rarely affects management
 no overall difference in rates of VTE recurrence
 biggest risk for recurrence is prior episode of VTE itself
 no evidence that testing improves outcome for asymptomatic family
 significant costs involved and potential for creating unnecessary anxiety
 may influence decision to continue anticoagulation long-term
CASE 9
 65-year-old male
 diagnosed with PE 4 weeks after elective THR
 no significant PMHx
 observations all stable
 no RV strain on CTPA or ECG
CAN HE BE SAFELY MANAGED AS AN OUTPATIENT?
Prognostic Variable
Points
CASE 9: OUTPATIENT
MANAGEMENT
OF
PE
age
+ age
 no national clinical guidance
 locally agreed protocols
 use of scoring systems
 Pulmonary Embolism
Severity Index (PESI)
 Geneva Risk Score (GRS)
male sex
cancer
heart failure
chronic lung disease
pulse ≥110 per minute
systolic BP <100mmHg
respiratory rate ≥30 per minute
temperature <36ºC
altered mental status
arterial oxygen saturation <90%
+10
+30
+10
+10
+20
+30
+20
+20
+60
+20
Class
Risk
Total Points
30-Day Mortality
(%)
I
very low
<65
0-1.6
II
low
66-85
1.7-3.5
III
intermediate
86-105
3.2-7.1
IV
high
106-125
4.0-11.4
V
very high
>125
10.0-24.5
CASE 10
 64-year-old female
 admitted with cellulitis L leg
 3rd admission this year
 L leg swollen and painful following
extensive proximal DVT 3 years
ago (6/12 warfarin)
WHAT IS THE DIAGNOSIS?
HOW COULD THIS HAVE
BEEN PREVENTED?
CASE 10: POST-THROMBOTIC SYNDROME (PTS)
 persistent venous obstruction, valvular incompetence and reflux
 affects 43% of patients with DVT by 2y (30% mild, 10% moderate, 3% severe)
 higher incidence in those with proximal (ileofemoral) DVT (only 20% recanalization)
 extensive clot, persisting obstruction, previous ipsilateral DVT, high BMI, older age, female
 painful heavy oedematous leg, parasthesiae, cramps, pruritus, varicosities, hyperpigmentation,
ulceration and recurrent infections (significant impact on QOL)
 immediate mobilization and grade II-III (20-40mmHg) below-knee graduated compression
stocking (NOT TEDS) on affected side for ≥2y after proximal DVT
 reduces incidence of PTS by up to 50%
 consider catheter-directed thrombolysis within 14d of symptomatic ileofemoral DVT in
patients with good functional status, life expectancy >1y and low risk of bleeding (NICE CG144)
 reduced risk of PTS from 78% to 27% and improved QOL in one study
CASE 11
 72-year-old male
 admitted with ‘unprovoked’ proximal DVT R leg
 ex-smoker
 nil specific on systems review
 physical examination unremarkable
HOW AGGRESSIVELY SHOULD HE BE SCREENED FOR OCCULT
MALIGNANCY?
CASE 11: SCREENING FOR MALIGNANCY
 3-fold increased risk of occult cancer (incidence 20% by 2y) in those with ‘idiopathic’ VTE
 no high quality evidence for cost effectiveness or improved survival with aggressive diagnostic
testing for occult malignancy
 diagnosis of cancer would result in change to pharmacological treatment and duration of
anticoagulation
 evaluation recommended by NICE CG144 for patients with unprovoked VTE
 focused history
 thorough physical examination (including DRE)
basic screening detects cancer in ~10% of
 CXR
patients with idiopathic/unprovoked VTE
 urinalysis
 FBC, LFTs, calcium (not PSA routinely)
 if all above are normal consider CT abdomen/pelvis (plus mammogram in women) if age >40
}
 more aggressive screening may be warranted in those with recurrent ‘idiopathic’ VTE
CASE 11 CONTINUED
 CXR reveals a large soft tissue mass at the right lung base
 CT and biopsy confirms metastatic small cell lung cancer
 commenced on long-term LMWH for his DVT and scheduled for
chemoradiotherapy as an outpatient
 readmitted 10d after discharge with acutely ischaemic L leg
 platelet count 63 (189 on discharge)
WHAT IS THE DIAGNOSIS?
HOW IS THIS CONFIRMED AND TREATED?
CASE 11: HEPARIN-INDUCED THROMBOCYTOPENIA (HIT)
Score 2
Score 1
Score 0
 antibody mediated thrombocytopenia (fall in platelet count >30% from baseline) in the
presence of new venous or arterial thrombosis occurring 5-10d after starting LMWH
Thrombocytopenia
(acute)

estimate
pre-test
Platelet nadir 20-100
Platelet nadir 10-19
(or any platelet fall 30–
(or
any
platelet
fall
>50%)
probability of HIT using the ‘four Ts’50%)
Platelet nadir <10
(or any platelet fall <30%)
Day 4 if
 send blood (2x red top and 2x pink top) to haematology lab for transfer to<Bristol
iming of onset of
Days
5–10
high (6-8) or intermediate (4-5) pre-test probability
>Day 10 orscore
timing unclear
(no recent heparin)
platelet fall (or other
sequelae of HIT)
 liaise with haematology regarding management
T
Proven new thrombosis;
 discontinuation of LMWH
skin necrosis; or acute
hrombosis or other
systemic reaction after IV
sequelae
 use IV lepirudin infusion until UFH
platelet count
T
Progressive or recurrent
thrombosis;
erythematous skin
lesions; suspected
>100
and warfarin
or
thrombosis
(not proven)
anticoagulant (e.g. SC fondaparinux) can be started
T
O her cause(s) of
platelet fall
None evident
Possible
None
alternative
Definite
CASE 12
 24-year-old female
 28 weeks pregnant (first pregnancy)
 pleuritic chest pain and dyspnoea
 ECG sinus tachycardia, S1Q3T3
 respiratory alkalosis on ABG
HOW WOULD YOU INVESTIGATE FOR PE?
HOW WOULD YOU TREAT IF PE CONFIRMED?
CASE 12:VTE AND PREGNANCY
 VTE is a leading cause of preventable maternal death (2/100,000 pregnancies)
 failure to take symptoms seriously and under-investigation are common
 VTE is 6x more common in pregnancy than outwith pregnancy
 risk maximal in late pregnancy/early puerperium (1st trimester - 3m postpartum)
 up to 50% with VTE in pregnancy have heritable thrombophilia (esp. FVL)
 other RF include previous VTE, obesity, dehydration, smoking, age >35, twins, multiparity,
pre-eclampsia, ovarian hyperstimulation syndrome
 85% of DVTs occur on left (55% outside of pregnancy)
 72% of DVTs are ileofemoral/proximal (9% outside of pregnancy)
 leg oedema and calf pain are common in normal pregnancy
 long-term complications in young healthy women
 severe PTS (10%) and chronic pulmonary HTN (4%)
CASE 12:VTE IN PREGNANCY – DIAGNOSIS
 d-dimer positive in 80% by 2nd trimester and 100% by 3rd trimester
 negative d-dimer should not be used to exclude VTE in pregnancy
 sinus tachycardia, rightward axis and S1Q3T3 on ECG and respiratory alkalosis on
ABG are NORMAL findings in pregnancy
 CXR <0.01mGy to foetus = 9d background radiation (1.8mGy/y) or transatlantic
flight
 bilateral leg USS
 low yield in the absence of clinical DVT and 3% risk of false +ve in pregnancy)
CASE 12:VTE IN PREGNANCY – DIAGNOSIS
 V/Q perfusion only 0.5mGy + ventilation (0.1mGy) if positive
 inconclusive scans in only 20% (70% in general population)
 CTPA 1/10 radiation of V/Q (0.05mGy) to foetus but 20x more to maternal breast
 lifetime risk of breast cancer for females ~1/8
 excess lifetime risk of breast cancer 1/3500 at age 40, 1/1200 at age 20
 overall increased relative lifetime risk of breast cancer 1.004
 risk may be reduced further by use of breast shields and modified protocols
 CXR, V/Q, CTPA and conventional pulmonary angiography combined gives <9/12
background radiation to foetus
CASE 12:VTE IN PREGNANCY - TREATMENT
 warfarin is teratogenic in (early) pregnancy (safe during breastfeeding)
 LMWH is safe during pregnancy
 different dosing e.g. enoxaparin 1mg/kg BD
 check platelet count after 2 weeks of Rx (HIT)
 anti-factor Xa monitoring needed only if ↓↓ or ↑↑ BMI or GFR <30ml/min
 discontinue LMWH temporarily 24h prior to delivery; restart after 6-12h
 continue anticoagulation for ≥6w after delivery and for ≥6m in total
 switch to warfarin 1w after delivery
 prophylactic LMWH antenatally in subsequent pregnancies
CASE 13
 36-year-old female
 3m post-partum (C-section) uncomplicated pregnancy
 No history of VTE
 Left leg severely swollen/oedematous to groin, 1/52 Hx
 No cellulitis, lymphadenopathy or pelvic mass
 D-dimer 579ng/mL
 USS left leg no evidence of proximal DVT
WHAT NEXT?
CASE 13 CONT.
 Treated with LMWH for 1/52
 Recalled for repeat USS L leg plus abdomen/pelvis
 USS NAD
 L leg more swollen with blue discolouration
 R leg also starting to swell
 CT venogram abdomen and pelvis
 L iliac vein thrombosis extending into IVC
CASE 13: PELVIC DVT
 USS will miss isolated pelvic (iliac) DVT and IVC thrombosis
 Risk factors for pelvic DVT
 Hormonal therapy
 Pregnancy
 Pelvic trauma or surgery (including C-section)
 IBD, diverticulitis
 Pelvic malignancy
 High index of suspicion in patients with otherwise unexplained
unilateral/bilateral leg swelling and risk factors for VTE if USS negative
 Diagnosis with CTV or MRV
CASE 14
 42-year-old Chinese male
 Idiopathic proximal L leg DVT age 34
 warfarin for 6/12
 Recurrent unprovoked proximal L leg DVT 3/12 ago
 indefinite warfarin therapy
 Now presents with acutely increasing pain and swelling
affecting left leg ‘? recurrent DVT on warfarin’
WHAT DO YOU NEED TO KNOW?
CASE 14: ‘RECURRENT’ VTE
1.
Has his INR consistently been in target range?
2.
Are his symptoms due to residual/chronic thrombus and/or
PTS or a ‘new’ episode of VTE?
 often impossible to distinguish on USS
 low recanalization rates (<20%) in proximal DVT
 USS still abnormal in 50% after 1y of Rx for proximal DVT
 persistent thrombus/obstruction and/or elevated d-dimer
may influence decision to continue warfarin
CASE 14: RECURRENT VTE
3.
4.
Will confirmation of recurrent DVT or PE change my management?

may influence duration of anticoagulation if first episode

diagnosis of PE in patient being treated for DVT may affect risk stratification
and follow-up (ECHO)

if recurrent distinct episodes of VTE despite optimal anticoagulation options;

switching to long-term LMWH

higher target INR e.g. 3.0-3.5 (increased bleeding risk)

IVC filter (risk of complications, will not prevent DVT)
Am I missing thrombophilia, occult malignancy or something else?

patient underwent CTV to r/o malignancy/venous obstruction

compression of left iliac vein by right internal iliac artery (May-Thurner
syndrome); stented
VTE: KEY LEARNING POINTS
 Low threshold of suspicion for PE – cannot rely on clinical features alone
 Assess clinical pre-test probability in ALL patients before taking d-dimer
 Thinking should not stop once diagnosis made – why, what, how?
 Ix for cancer and consider long-term/indefinite anticoagulation after single
episode of idiopathic/unprovoked VTE
 Thrombophilia testing rarely indicated
 Consider CDT in younger patients with massive proximal DVT
 Limitations of novel anticoagulants
 Special cases – pregnancy, UEDVT, IVDU, malignancy, isolated pelvic DVT,
thrombophlebitis, recurrent VTE
 Follow-up patients for long-term complications – PTS, pHTN
ANY OTHER QUESTIONS?