Hypercoagulability

Question 1

What percentage of population have inherited thrombophilia? What pecentage of people with VTE have inherited thrombophilia?

Answer 1

10% 50%

Question 2

Most common inherited thrombophilias?

Answer 2

• 6% of population have Factor V Leiden - white people • 2% of population have Prothrombin gene mutation - white people • 0.4% of population have Protein C deficiency - asian people • 0.1% of population have Protein S deficiency • 0.02% of population have antithrombin III deficiency Black people more affects by elevated factor 8 & sickle cell disease

Question 3

when should you test for hereditary thrombophilia?

Answer 3

with unprovoked DVT or PE and it is planned to stop treatment.

Question 4

what is Factor V leiden mutation?

Answer 4

It is due to a gain of function mutation in the Factor V Leiden protein. The result of the mis-sense mutation is that activated factor V (a clotting factor) is inactivated 10 times more slowly by activated protein C than normal. This explains the alternative name for factor V Leiden of activated protein C resistance

Question 5

Risk of VTE with Factor V Leiden?

Answer 5

4-fold heterzygous 10-fold homozygous

Question 6

Relative risks of VTE with COCP, in pregnancy and in post-partum?

Answer 6

Normal: 1/5,000 risk (RR=1) COCP: RR=2.5 Pregnancy: RR=15 Post-partum: RR= 150

Question 7

when to stop COCP and HRT before elective surgery?

Answer 7

4 weeks

Question 8

Anti-VTE measures for surgery (non-pharm)?

Answer 8

Anti-embolism stockings mobilise early hydration intermittent pneumatic compression

Question 9

Length of time on LMWH for acute medical patients, elective hip, elective knee, chest/abdo surgery?

Answer 9

7 days 28 days 14 days 7 days

Question 10

LMWH in pregnancy?

Answer 10

Previous unprovoked VTE or 4 risk factors: LMWH from booking to 6 weeks pp Previous provoked VTE, thrombophilia, medical conditions or 3 risk factors: LMWH from 28 weeks to 10 days pp 2 risk factors: 10 days pp LMWH Admission to hospital, or >3 days postnatally, LMWH Risk factors worth 1 point: BMI>30, age>35, parity >3, smoker, C/S, varicose veins, PET, immobility, FH, IVF, twins, prolonged labour.

Question 11

Warfarin in pregnancy causes?

Answer 11

○ Hypoplasia of nasal bridge ○ Congenital heart defects ○ Ventriculomegaly ○ Agenesis corpus callosum ○ Stippled epiphyses

Question 12

Pregnancy risks of VQ scan vs CT scan?

Answer 12

• In women with suspected PE without symptoms and signs of DVT, a ventilation/perfusion (V/Q) lung scan or a computerised tomography pulmonary angiogram (CTPA) should be performed. [New 2015] • When the chest X-ray is abnormal and there is a clinical suspicion of PE, CTPA should be performed in preference to a V/Q scan. [New 2015] • Alternative or repeat testing should be carried out where V/Q scan or CTPA is normal but the clinical suspicion of PE remains. Anticoagulant treatment should be continued until PE is definitively excluded. Women with suspected PE should be advised that, compared with CTPA, V/Q scanning may carry a slightly increased risk of childhood cancer but is associated with a lower risk of maternal breast cancer; in both situations, the absolute risk is very small. [New 2015]

Question 13

What anticoagulants can be used in breastfeeding?

Answer 13

warfarin and LMWH

Question 14

Generally, by what percentage does warfarin reduce risk of VTE event?

Answer 14

by two-thirds from 3.7% of people to 1.2% with CHADVASC of 3

Question 15

Generally, by that percentage does warfarin increased risk of serious bleeding event?

Answer 15

by two-thirds from 0.9% of people to 1.5% of people with HASBLED of 3

Question 16

When you start warfarin, how do you monitor?

Answer 16

INR test on day 5 and 8 (so can only start on Mon, Thurs, Fri)

Question 17

How does bleeding present with warfarin?

Answer 17

nose bleeds, black faeces, bruises, haemoptysis, menorrhagia more serious: intracranial

Question 18

general advice for warfarin

Answer 18

keep diet steady, esp greens, eggs avoid cranberry juice, OTC don’t take NSAID, can take paracetamol stick to alcohol limits, be consistent avoid contact sports beware antibiotics

Question 19

NOAC as alternative advice?

Answer 19

○ NOACs less risk of bleeding ○ Must not miss any NOAC dose because of shorter half-life ○ NOACs have less monitoring ○ NOACs do not have reversibility antidote

Question 20

MOA of anticoagulants?

Answer 20

Rivaroxaban is a direct factor Xa inhibitor. Apixaban is also a direct factor Xa inhibitor. Dabigatran is a direct thrombin inhibitor. Heparin activates antithrombin III (which inhibitis Xa and thrombin). Warfarin inhibits activation of clotting factors II, VII, IX and X (and protein C&S) by inhibiting vitamin K epoxide reductase.

Question 21

contraindicaionts for DOACs?

Answer 21

renal failure heart valves

Question 22

RF for blood clots?

Answer 22

• Previous VTE • Cancer • Age • Obesity • Male • HF • Thrombophilia • Inherited: Mutated Factor V Leiden, Protein C deficiency, Protein S deficiency, Anti-thrombin deficiency • Acquired: Antiphospholipid syndrome, Primary and Secondary Polycythaemia, Thrombocytosis (essential and secondary to bleeding, infection, malignancy, vasculitis, surgery) • Smoking • Chronic low-grade injury to vascular wall • Vasculitis • Venous stasis • Chemotherapy TEMPORARY • Immobility • Trauma • HRT • Pregnancy and postpartum • Dehydration

Question 23

DDx for DVT

Answer 23

• Trauma • Thrombophlebitis • Post-thrombotic syndrome (ie after previous DVTs) • Baker’s cyst • Cellulitis • Dependent oedema

Question 24

Sx for DVT

Answer 24

• Unilateral • Generalized Pain • Generalized Swelling • Skin colour change: erythema / purple • Temperature normally up • Vein distension - “palpable cord”

Question 25

two places to check when examining DVT

Answer 25

• Check between two heads of gastrocnemius • Check Hunter’s canal (femoral canal)

Question 26

Aide memoire for Wells score for DVT?

Answer 26

Tender swollen auld collaterals can stand still before 3 big pittbulls (all 1 point except -2 for alternative cause. 2 or more means it’s likely) Active cancer Paralysis, paresis, plaster immob Bedridden >3 days or major surgery in last 12 weeks Localized tenderness along distribution of deep veins Entire leg is swollen Calf swelling >3cm than asymptomatic leg (measure it 10 cm below tibial tuberosity) Pitting oedema confined to symptomatic leg Collateral superficial veins Previously documented DVT Alternative cause more likely

Question 27

If likely DVT what next and what time frame?

Answer 27

• Refer for proximal leg Duplex USS within 4 hours • If not possible: ○ D dimer ○ 24 hour dose of parenteral anticoagulant (LMWH) ○ USS within 24 hours

Question 28

What blood tests if likely DVT and why?

Answer 28

INR LFT U&E all for future anticoagulation

Question 29

treatment of DVT?

Answer 29

anticoagulate for 3 months if provoked, 6 months if unprovoked, indefinite if recurrent either LMWH bridge and warfarin or DOAC advice: walk, elevate, don’t travel for 2 weeks

Question 30

further Ix if unprovoked?

Answer 30

investigate for cancer (CXR, blood, urine, abdo-pelvic CT) investigate for thrombophilia (hereditary or acquired Abs)

Question 31

how to prevent a DVT (7)?

Answer 31

LMWH/fondaparinux hydrate early mob after surgery pneumatic compression intraoperatively stockings stop COCP one month before surgery IVC filters for high risk cancer

Question 32

complication of DVT?

Answer 32

post-thrombotic syndrome - basically chronic venous insufficiency • Venous hypertension causing pain swelling hyperpigmentation dermatitis, venous gangres • Lipdermatosclerosis • Affects 20-40% of people post-DVT

Question 33

Describe the venous system of the leg

Question 34

Well’s score for PE?

Answer 34

Deep auld hearts stand still before bloody cancer

3 3 1.5 1.5 1.5 1 1

>4

DVT -3

Alternative Diagnosis - 3

Tachycardia 1.5

Three days immobile (or surgery 4 weeks) 1.5

Thromboembolism previous -1.5

Coughing up blood 1.5

Cancer

Question 35

SX PE?

Answer 35

Pleuritic chest pain

Dyspnoea

Presyncope

Feeling of apprehension

Calf tenderness

Haemoptysis

Tachypnoea

Fever

tachycardia

Hypotension

Raised JVP

Sternal heave

S2 - loud pulmonary

Question 36

Ix for PE?

Answer 36

Bedside:
ECG

ABG

Blood:

BC - cancer, platelet count for treatment, contributory factor

Clotting

U&E - for anticoagulant therapy adjustment in renal

D-dimer is Wells score is unlikely, if positive then CTPA or LMWH if not immediately available

Troponin

Thrombophilia screen

CRP

Imaging:

CXR first to rule out other causesNot specific or sensitive for PE but can show:

Wedge shaped infarction

Effusion

Enlarged pulmonary artery

CTPA if Wells score says PE is likelyContraindicated in pregnancy renal failure , kids

Use V/Q scan instead for renal failure, or patients with allergy to contrast media

Use doppler scan of leg for pregnant women (RCOG 2015)

If CTPA is not immediately available, offer LMWH

Question 37

ECG features of PE?

Answer 37

S1Q3T3

presence of S wave in lead I and Q wave and inverted T wave in lead III.

RAD, V1/`V2 R-wave dominant /ST dep

Tachy

Question 38

Mx of PE?

Answer 38

Haemodynamically unstable

A-E

Haemodynamically stable:

O2

Acute NOAC or (LMWH bridge + Warfarin)

LMWH in pregnancy at therapeutic dose

When confirmed, continue anti-coag for 3-6 months provoked, 6 months unprovoked (no RFs), indefinite if recurrent

Consider IVC filter if doing embolectomy

Thrombolysis if massive - Alteplase

IVC filter if recurrent