A MASTERCLASS IN VENOUS THROMBOEMBOLISM VTE Dr Tom

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 FY 1 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 1. patient has clinical features compatible with PE – breathlessness and/or Pulmonary embolism rule-out criteria (PERC) with or without pleuritic chest pain and/or haemoptysis plus; tachypnoea age <50 years pulse <100 bpm 2. absence of another reasonable clinical explanation and/or; Sp. O 2 >94% on air no unilateral leg swelling IF ALL SATISFIED, RISK OF PE 3. presence of a major risk factor for VTE <2% no haemoptysis Where 2. and 3. are both true the probability is high; if only one is true the no recent trauma or surgery probability is intermediate; and if neither is true the probability is low no prior PE or DVT no hormone use

CASE 2: INVESTIGATION OF PE Low or intermediate pre-test probability or ‘PE unlikely’ Check d-dimer if hospital uses Simpli. RED 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 (Simpli. RED) 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 498 ng/ml (>243 ng/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 Westermark’s Sign main role of CXR is to rule out alternative or coexisting pathology e. g. pneumothorax Fleischner’s Sign assist in determining suitability for V/Q

DIAGNOSIS OF PE – OTHER TESTS ECG abnormal in 70% Sinus tachycardia most common Atrial arrhythmias T wave inversion V 1 -3 and inferior leads ST depression or elevation S 1 Q 3 T 3 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 10 d 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-Tn. I 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 >4 h) SC Enoxaparin (Clexane®) 1. 5 mg/kg OD (1 mg/kg OD if GFR <30) continue for 48 h once INR >2 and for a minimum of 5 d in total SC Fondaparinux 5 -10 mg 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 ≥ 6 weeks 2. Proximal DVT or PE with transient (reversible) risk factor ≥ 3 months 3. Isolated calf vein thrombosis which is unprovoked (idiopathic) ≥ 3 months 4. Proximal DVT or PE which is unprovoked (idiopathic) 5. Recurrent (second or subsequent) DVT or PE indefinite *consider longer-term or indefinite anticoagulation in all patients ≥ 6 months*

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 15 mg BD for 21 d then 20 mg OD (no need for LMWH) Currently licensed for acute Rx of DVT/PE and prevention of recurrent DVT/PE, need GFR >30 m. L/min PO dabigatran (Pradaxa®) is a direct thrombin inhibitor 110 -150 mg OD AFTER 5 d 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, r. FVIIa, FEIBA)

CASE 4: THROMBOLYSIS FOR PE 75 -year-old female admitted acutely breathless Previous PE post-THR aged 62 Looks unwell RR 31, Sp. O 2 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-Tn. I 48 SHOULD SHE RECEIVE THROMBOLYSIS?

CASE 4: THROMBOLYSIS FOR PE Alteplase 10 mg stat then 90 mg over 2 h then IV UFH (no loading dose) once APTT <2 x ULN Massive PE with hypotension (s. BP <90 mm. Hg or fall in s. BP ≥ 40 mm. Hg 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 10 mg bolus followed by 40 mg 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 (1 st 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 >3 m 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 30 d (or fondaparinux 2. 5 mg for 45 d) for proximal superficial thrombophlebitis treatment dose LMWH for 6 -12 w if proximal thrombophlebitis approaching or at saphenofemoral junction oral NSAIDs for 10 d 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 ≥ 6 w (ideally 6 m) 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 4 w 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

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 1 y and 30% by 5 y 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 6 m) 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 <3 m 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 CG 144 (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?

CASE 9: OUTPATIENT MANAGEMENT OF Prognostic Variable Points age + age PE male sex +10 cancer +30 +10 +20 +30 +20 +60 +20 no national clinical guidanceheart failure locally agreed protocols use of scoring systems Pulmonary Embolism chronic lung disease pulse ≥ 110 per minute systolic BP <100 mm. Hg respiratory rate ≥ 30 per minute temperature <36ºC altered mental status arterial oxygen saturation <90% Severity Index (PESI) Geneva Risk Score (GRS) 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 3 rd 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 2 y (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 -40 mm. Hg) below-knee graduated compression stocking (NOT TEDS) on affected side for ≥ 2 y after proximal DVT reduces incidence of PTS by up to 50% consider catheter-directed thrombolysis within 14 d of symptomatic ileofemoral DVT in patients with good functional status, life expectancy >1 y and low risk of bleeding (NICE CG 144) 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 2 y) 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 CG 144 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 10 d 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 -10 d after Platelet nadir 10 -19 Platelet nadir <10 starting LMWH Platelet nadir 20 -100 Thrombocytopenia (acute) (or any platelet fall >50%) (or any platelet fall 30– 50%) (or any platelet fall <30%) estimate pre-test probability of HIT using the ‘four Ts’ < Day 4 T iming of onset of Days 5– 10 send blood (2 x red top and 2 x pink top) to haematology lab for transfer to Bristol >Day 10 or timing unclear platelet fall (or other if high (6 -8) or intermediate (4 -5) pre-test probability score sequelae of HIT) (no recent heparin) liaise with haematology regarding management Proven new thrombosis; skin necrosis; or acute or other hrombosis discontinuation of LMWH systemic reaction after IV sequelae UFH T Progressive or recurrent thrombosis; erythematous skin lesions; suspected thrombosis (not proven) None use IV lepirudin infusion until platelet count >100 and warfarin or alternative anticoagulant (e. g. SC fondaparinux) can be started T O her cause(s) of platelet fall None evident Possible Definite

CASE 12 24 -year-old female 28 weeks pregnant (first pregnancy) pleuritic chest pain and dyspnoea ECG sinus tachycardia, S 1 Q 3 T 3 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 6 x more common in pregnancy than outwith pregnancy risk maximal in late pregnancy/early puerperium (1 st trimester - 3 m 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 2 nd trimester and 100% by 3 rd trimester negative d-dimer should not be used to exclude VTE in pregnancy sinus tachycardia, rightward axis and S 1 Q 3 T 3 on ECG and respiratory alkalosis on ABG are NORMAL findings in pregnancy CXR <0. 01 m. Gy to foetus = 9 d background radiation (1. 8 m. Gy/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. 5 m. Gy + ventilation (0. 1 m. Gy) if positive inconclusive scans in only 20% (70% in general population) CTPA 1/10 radiation of V/Q (0. 05 m. Gy) to foetus but 20 x 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 1 mg/kg BD check platelet count after 2 weeks of Rx (HIT) anti-factor Xa monitoring needed only if ↓↓ or ↑↑ BMI or GFR <30 ml/min discontinue LMWH temporarily 24 h prior to delivery; restart after 6 -12 h continue anticoagulation for ≥ 6 w after delivery and for ≥ 6 m in total switch to warfarin 1 w after delivery prophylactic LMWH antenatally in subsequent pregnancies

CASE 13 36 -year-old female 3 m 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 579 ng/m. L 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 1 y of Rx for proximal DVT persistent thrombus/obstruction and/or elevated ddimer 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, p. HTN

ANY OTHER QUESTIONS?