VTE

Question 1

What are the three parts of Virchow’s triangle?

How are they affected in pregnancy?

Answer 1

1. Stasis - vasodilation of pregnancy, reduced venous return
2. Hyper-coagulability - increase in prothrombotic factors, and a reduction anticoagulant factors
3. Vessel damage - occurs during CS and vaginal birth, and pregnancy is an inflammatory state so endothelial cell are activated

Question 2

What is the incidence of VTE in pregnancy and the puerperium?

Answer 2

2:1000

SOMANZ

Question 3

What is the relative risk of VTE in pregnancy, compared to the non-pregnant state?

Answer 3

RR 4-5 x

SOMANZ

Question 4

When is the highest risk for VTE

Answer 4

Postpartum

• 30-50% VTE associated with pregnancy occur postpartum
• 3-5 x risk of antenatal VTE

Question 5

In women that have PE in pregnancy, what % will have a fatal result?

Answer 5

15%

Question 6

What are the guidance for LMWH VTE prophylaxis in pregnancy for women with a previous Hx VTE?

Answer 6

LMWH prophylaxis once pregnancy confirmed, till 6 weeks postpartum if:
- PE in or outside of pregnancy
- Proximal/extensive DVT
- VTE associated with pregnancy or COCP
- Recurrent or unprovoked VTE
 (SOMANZ 2012, 2021)

Previous provoked DVT after surgery/trauma has low association with PA-VTE:

• No need for antenatal prophylaxis unless addition risk factors
• Extended 6 week postpartum prophylaxis

Women on long-term oral anticoagulation for any reason: - stop it on diagnosis of pregnancy and commence therapeutic LMWH after 1-3 days, transfer to warfarin postpartum

Therapeutic dose required if previous VTE with:

• antithrombin deficiency
• APS
• Recurrent VTE (intermediate dose)

Question 7

Should a D-dimer be performed in pregnancy?

Answer 7

NO.
Some evidence that higher pregnancy specific levels may be helpful, but not validated at present.
May have some benefit in excluding VTE. BUT poor negative predictive value, up to 40% VTE cases may be missed in pregnancy by using a negative D-dimer for reassurance.

Question 8

Should the WELLS score / PERC score be used in pregnancy?

Answer 8

No

There are currently no validated pretest scoring systems for pregnancy

Question 9

What is the sensitivity of Serial compression duplex USS in assessing DVT?

Answer 9

94%

Question 10

What is the NPV of Serial compression duplex USS in assessing DVT?

Answer 10

99.5%

Question 11

If a DVT remains untreated, how many patients will develop a PE?

Answer 11

15-24%

Question 12

If suspecting DVT and the Compression Duplex USS is negative, what is the next step?

Answer 12

If low clinical suspicion, discontinue LMWH

If high clinical suspicion, discontinue LMWH but REPEAT USS on day 3 and 7

If suspicious for pelvic vein DVT consider MRV.

Question 13

What ECG changes are seen with a PE?

Answer 13

• Sinus tachycardia
• T wave inversion
• S1Q3T3 pattern - deep S wave in lead I, Q wave in III, inverted T wave in III, “classic” finding but is actually low in sensitivity and specificity
• RBBB

Question 14

What CXR findings are seen with a PE?

Answer 14

Atelectasis, effusion, focal opacities, regional oligaemia, pulmonary oedema, hamptons hump

Question 15

Is an ABG useful in diagnosing a PE in pregnancy?

Answer 15

SOMANZ endorses it use for risk stratification, but

not a sensitive or specific marker for PE and should not be measured by a normal a-a gradient.

Question 16

Why is breast tissue especially sensitive to radiation exposure during pregnancy?

Answer 16

Hormonally increased glandular cavity, increased mitotic rate

Question 17

What is the duration of treatment for a PE / DVT diagnosed in pregnancy?

Answer 17

At least 3 months, to 6 months of therapeutic dose LMWH
Can be reduced to a prophylactic dose after this time
Continue until at least 6/52 postpartum

Postnatally, can be offered warfarin if still taking therapeutic doses

Question 18

How do patients present with massive life threatening PE?

Answer 18

Shock, refractory hypoxaemia, RV dysfunction on Echo

Question 19

What is the preferred treatment for massive life-threatening PE and why?

Answer 19

IV Unfractionated Heparin

• rapid effect
• extensive experience in this area
• can be adjusted more readily if thrombolytic therapy is administered

Thrombolysis can be considered for life threatening PE
- high risk for significant bleeding, miscarriage, still birth

Question 20

What is post-thrombotic syndrome?

Answer 20

Chronic persistent leg swelling
Pain
Feeling of heaviness
Dependent cyanosis
Telangiectasis
Chronic pigmentation
Eczema
Associated varicose veins
Venous ulceration (most severe cases)

Question 21

What are risk factors for post-thrombotic syndrome?

Answer 21

Smoking
Maternal age > 33
Obesity
Proximal postnatal thrombosis
Recurrent ipsilateral DVT

Question 22

What are INTRAPARTUM risk factors for VTE

Answer 22

CS (particularly EmCS)
Prolonged labour > 24h
PPH > 1L / requiring RBC
Stillbirth
Mid-cavity / rotational operative delivery
PTB

Question 23

What are PRE-PREGNANCY and ANTENATAL risk factors for VTE?

Answer 23

PRE-PREGNANCY: 
Previous VTE
Previous 1st degree relative with VTE
Inherited Thrombophilia ( high risk and low risk)
APS
Age > 35
Parity > 3
Smoker
Medical comorbidities (T1DM with nephropathy, cancer, etc)
Gross varicose veins

ANTENATAL:
Hyperemesis
OHSS
ART
Admission or immobility
Surgery e.g. appendicectomy 
Sepsis
APH
Multiple pregnancy 
PET

Question 24

What are medical comorbidites that increase risk for VTE?

Answer 24

Cancer
Active SLE, IBD or inflammatory polyarthropathy
Nephrotic syndrome
T1DM with nephropathy 
Heart failure
IVDU
Sickle cell disease

Question 25

What are contraindications to LMWH?

Answer 25

``` Active bleeding Allergy Severe renal / liver disease Thrombocytopenia, Plt < 75 Known bleeding disorder Acute stroke in previous 4 weeks (Haemorrhagic / ischaemia) Uncontrolled HTN ```

Question 26

What are the advantages of UFH compared to LMWH?

Answer 26

Shorter half life - required interval between prophylactic UFH and regional anaesthesia is less ( 4 hours c.f. 12 hours with LMWH) More complete reversal with Protamine sulphate Less concern regarding neuraxial haematomas

Question 27

What are the risks of Warfarin in pregnancy

Answer 27

Crosses placenta Embryopathy in approx 5% of fetuses exposed between 6-12/40 Dose dependent, higher incidence if >5mg/ day ``` C-ongenital heart defects H-ypoplasia of nasal bridge V-entriculomegaly A-genesis of corpus callosum S-tipple epiphysis ``` ``` Other adverse effects Miscarriage Stillbirth Neurological impairment Fetal and maternal haemorrhage ```

Question 28

What is the guidance around a family Hx of VTE?

Answer 28

- Significant family Hx is only for 1st degree relatives - Correlated with increased risk of VTE in pregnancy/postpartum - Risk stratified to high risk and low risk thrombophilias LOW RISK - Antenatal LMWH not usually required - Extended LMWH postpartum should be considered if other risk factors HIGH RISK - factor V leiden homozygous, protein c or protein s deficiency, multiple inherited thrombophilias - consider antenatal prophylactic LMWH AND prolonged 6 week postpartum course - Antithrombin (factor Xa) deficiency particularly high risk therefore consider intermediate/therapeutic dose antenatally and for 6 weeks postpartum (SOMANZ)

Question 29

What is the guidance around inherited thrombophilias?

Answer 29

- The majority of inherited thrombophilias have minimal increased risk of VTE - The high risk conditions: antithrombin deficiency, factor V leiden homozygous, protein c and protein s deficiency, >1 thrombophilic marker Low risk thrombophilia - no need for antenatal or extended postnatal LMWH High risk thrombophilia and no FHx VTE - extended 6 week postnatal prophylaxis only High risk thrombophilia and positive FHx VTE - consider antenatal prophylaxis - extended 6week postnatal prophylaxis Antithrombin deficiency - The most high risk thrombophilia, 11% risk antenatal VTE and 29% risk postnatal VTE, which increases significantly if FHx of VTE - Antenatal prophylaxis with intermediate of therapeutic dose LMWH - extended 6week postnatal prophylaxis (SOMANZ)

Question 30

Compare V/Q, Q-only and CTPA scanning for diagnosis of PE in pregnancy.

Answer 30

CTPA - NPV 100%, sensitivity 83% - Higher dose of radiation and therefore higher risk for future breast cancer (1/2000 lifetime risk - though likely lower now with modern radiology techniques) - Useful in detecting other lung pathology - More widely available, less delay in diagnosis - Can continue breast feeding after - Can lead to over diagnosis - More sensitive to detecting SSPE - but these are of little clinical significance with no increase in mortality or recurrence if treated or not V/Q - NPV 100%, sensitivity 100% - Nuclear imaging not as widely available - Lower dose of radiation and lower risk of future breast cancer (1/40,000 lifetime risk - though likely lower with modern radiology techniques) - Lower rate of non-diagnostic studies, particularly in the third trimester - Must avoid breast feeding for at least 12 hours due to increased passage of radioactive contrast in breast milk Both studies give negligible doses of radiation to the fetus (<1mSv), well below the threshold (10mGy) for increased risk of miscarriage, genetic damage or congenital malformation. Even if this threshold is exceeded the risk of additional childhood cancer is roughly 2/1000. Perfusion only scanning is generally not recommended due to the relatively low levels of radiation and risks associated. - NPV 83%, sensitivity 60% - If abnormal perfusion scan, then need to do a ventilation scan after - 1/4 - 1/2 studies are inconclusive (SOMANZ 2021)

Question 31

What is the sensitivity and NPV of CTPA and V/Q scanning?

Answer 31

CTPA - NPV = 100%, sensitivity 83% V/Q - NPV = 100%, sensitivity 100%

Question 32

What is the current guidance regarding the best modality of scanning in suspected PE?

Answer 32

- Do not avoid doing necessary scan due to concerns about radiation - the radiation exposure is minimal with both CTPA and V/Q scanning and is far outweighed by the potential risks of PE. - Both CTPA and V/Q are safe and acceptable options - In clinically stable women with a normal CXR - preference is for V/Q scan - If clinically unstable women or with CXR abnormalities, a CTPA is preferred Others: - Echo can be considered in unstable women to assess evidence of right heart strain and aid risk stratification - If multiple scans are performed calculate the breast and fetal radiation exposure - If radiation contraindication non-gadolinium MRA can be considered if available

Question 33

What steps can be taken to reduce breast tissue exposure in CTPA?

Answer 33

- Choose V/Q scan instead or perfusion-only - bismuth protective shield for breasts ( reduces by 50%) - Reduced contrast monitoring component of CTPA

Question 34

What is the public health importance of PE?

Answer 34

- Most common cause of direct maternal death in Aus | - 3rd most common cause of direct maternal death in NZ

Question 35

How long before birth/CS, epidural placement, epidural removal should PROPHYLACTIC dose LMWH be stopped? And for UFH?

Answer 35

LMWH - 12 hours CS - 12 hours epidural placement or removal - Can restart 4 hours after epidural removal - Can restart 6-12 hours after delivery UFH - 4-6 hours CS - 4-6 hours epidural placement or removal - Can restart 1 hour after epidural removal

Question 36

How long before birth/CS, epidural placement, epidural removal should THERAPEUTIC dose LMWH be stopped? And for UFH?

Answer 36

LMWH - 24 hours CS - 24 hours epidural placement or removal - Can restart 4 hours after epidural removal - Can restart 12-24 hours after delivery UFH - 24 hours CS BUT 4-6 if given IV - 24 hours epidural placement BUT 4-6 if given IV - 4-6 hours before removal - Can restart 1 hours after epidural removal

Question 37

What additional steps should happen if woman is on therapeutic LMWH or UFH and needs urgent delivery.

Answer 37

- All routine care and work-up - Senior obs review and senior anaesthetic review - Stop anticoagulation - Decision re. timing - can delivery be delayed till reversal of thromboprophylaxis - Ensure IV access, FBC and G&H - Measure anti-Xa levels for LMWH, and APTT for UFH - Liase with haematology and Consider administration of protamine (more effective for reversal of UFH) - Ensure plan in place for recommencing anticoagulation postpartum

Question 38

What is the mechanism of action for heparin?

Answer 38

Binds to antithrombin causing structural change and increasing its activity, thus: - inhibits factor Xa cleavage of prothrombin to thrombin (factor IIa), and acts directly to inhibit thrombin - which is required for cleavage of fibrinogen to fibrin involved in stable clot formation.