VTE Flashcards
What are the three parts of Virchow’s triangle?
How are they affected in pregnancy?
- Stasis - vasodilation of pregnancy, reduced venous return
- Hyper-coagulability - increase in prothrombotic factors, and a reduction anticoagulant factors
- Vessel damage - occurs during CS and vaginal birth, and pregnancy is an inflammatory state so endothelial cell are activated
What is the incidence of VTE in pregnancy and the puerperium?
2:1000
SOMANZ
What is the relative risk of VTE in pregnancy, compared to the non-pregnant state?
RR 4-5 x
SOMANZ
When is the highest risk for VTE
Postpartum
- 30-50% VTE associated with pregnancy occur postpartum
- 3-5 x risk of antenatal VTE
In women that have PE in pregnancy, what % will have a fatal result?
15%
What are the guidance for LMWH VTE prophylaxis in pregnancy for women with a previous Hx VTE?
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)
Should a D-dimer be performed in pregnancy?
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.
Should the WELLS score / PERC score be used in pregnancy?
No
There are currently no validated pretest scoring systems for pregnancy
What is the sensitivity of Serial compression duplex USS in assessing DVT?
94%
What is the NPV of Serial compression duplex USS in assessing DVT?
99.5%
If a DVT remains untreated, how many patients will develop a PE?
15-24%
If suspecting DVT and the Compression Duplex USS is negative, what is the next step?
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.
What ECG changes are seen with a PE?
- 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
What CXR findings are seen with a PE?
Atelectasis, effusion, focal opacities, regional oligaemia, pulmonary oedema, hamptons hump
Is an ABG useful in diagnosing a PE in pregnancy?
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.
Why is breast tissue especially sensitive to radiation exposure during pregnancy?
Hormonally increased glandular cavity, increased mitotic rate
What is the duration of treatment for a PE / DVT diagnosed in pregnancy?
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
How do patients present with massive life threatening PE?
Shock, refractory hypoxaemia, RV dysfunction on Echo
What is the preferred treatment for massive life-threatening PE and why?
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
What is post-thrombotic syndrome?
Chronic persistent leg swelling Pain Feeling of heaviness Dependent cyanosis Telangiectasis Chronic pigmentation Eczema Associated varicose veins Venous ulceration (most severe cases)
What are risk factors for post-thrombotic syndrome?
Smoking Maternal age > 33 Obesity Proximal postnatal thrombosis Recurrent ipsilateral DVT
What are INTRAPARTUM risk factors for VTE
CS (particularly EmCS) Prolonged labour > 24h PPH > 1L / requiring RBC Stillbirth Mid-cavity / rotational operative delivery PTB
What are PRE-PREGNANCY and ANTENATAL risk factors for VTE?
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
What are medical comorbidites that increase risk for VTE?
Cancer Active SLE, IBD or inflammatory polyarthropathy Nephrotic syndrome T1DM with nephropathy Heart failure IVDU Sickle cell disease
What are contraindications to LMWH?
Active bleeding Allergy Severe renal / liver disease Thrombocytopenia, Plt < 75 Known bleeding disorder Acute stroke in previous 4 weeks (Haemorrhagic / ischaemia) Uncontrolled HTN
What are the advantages of UFH compared to LMWH?
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
What are the risks of Warfarin in pregnancy
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
What is the guidance around a family Hx of VTE?
- 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)
What is the guidance around inherited thrombophilias?
- 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)
Compare V/Q, Q-only and CTPA scanning for diagnosis of PE in pregnancy.
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)
What is the sensitivity and NPV of CTPA and V/Q scanning?
CTPA
- NPV = 100%, sensitivity 83%
V/Q
- NPV = 100%, sensitivity 100%
What is the current guidance regarding the best modality of scanning in suspected PE?
- 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
What steps can be taken to reduce breast tissue exposure in CTPA?
- Choose V/Q scan instead or perfusion-only
- bismuth protective shield for breasts ( reduces by 50%)
- Reduced contrast monitoring component of CTPA
What is the public health importance of PE?
- Most common cause of direct maternal death in Aus
- 3rd most common cause of direct maternal death in NZ
How long before birth/CS, epidural placement, epidural removal should PROPHYLACTIC dose LMWH be stopped?
And for UFH?
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
How long before birth/CS, epidural placement, epidural removal should THERAPEUTIC dose LMWH be stopped?
And for UFH?
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
What additional steps should happen if woman is on therapeutic LMWH or UFH and needs urgent delivery.
- 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
What is the mechanism of action for heparin?
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.
