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Venous Thromboembolism
VTE
VTE is most common cause of maternal mortality in UK.
Pregnancy is hypercoagulable state because of:
1. alteration in thrombotic & fibrinolytic system.
2. There is increase in clotting factors VIII, IX, X & fibrinogen level.
3. There is reduction in protein S & antithrombin III (AT III)concentration.
The net result is :
1. to reduce the likelihood of haemorrhage following delivery.
2. at same time predispose women to thromboembolism that exacerbated by venous
stasis in lower limb due to weight of gravid uterus placing pressure on IVC in late
pregnancy & puerperium.
More common in Left side due to compression of left iliac vein by left iliac artery
Thrombophilia:
Acquired or hereditary.
Deficiency of anticoagulant protein C, protein S & AT III.
Associated with several pregnancy complication: recurrent fetal loss, placental abruption
, IUGR & thromboembolism.
Antiphosphlipid syndrome:
APS: is acquired form of thrombophilia.
Diagnosis of APS require at least one of following:
3 or more unexplained consecutive spontaneous abortion before 10th of pregnancy with
maternal anatomical or hormonal abnormalities & paternal and maternal chromosomal
abnormalities excluded.
1 or more unexplained death of morphological normal fetus at or beyond 10th week of
gestation.
1 or more premature birth of morphological normal neonate at or before 34th week
because of PE orE or placental insufficiency .
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In addition persistent abnormality of one of following tests when measured at least twice
more than 6 wk apart :
- Lupus anticoagulant
- Anticardiolipin antibody
Risk factors for VTE
Pre-existing:
1-Maternal age ˃ 35
2-Thrombophilia
3-Obesity ˃ 80 kg
4-Previous th.embolism
5-Severe varicose veins
6-Smoking
7-Malignancy
Specific to pregnancy:
1-Multiple gestation
2-Pre-eclampsia
3-Grand multiparity
4-CS , especially emergency
5-Damage to pelvic veins
6-Sepsis
7-Prolonged bed rest
DX of acute VTE:
DVT:
1- Symptoms : calf pain with redness & swelling especially unilateral, calf is tender to
touch
2- Doppler ultrasound
3- venography : is invasive require injection of contrast medium & use of x-ray
Pulmonary embolism:
1. symptoms : mild breathlessness, inspiratory chest pain, tachycardia , mild pyrexia 37.5
massive PE there will be acute cardio-respiratory collapse.
2. ECG, CXR, & arterial blood gas analysis to exclude other condition.
3. Lower limb ultrasound for evidence of DVT .
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4. If all tests are normal with high clinical suspicion, a ventilation-perfusion scan or
pulmonary angiography should be performed.
5. D- dimer: in pregnancy low level exclude DVT or PE, while increase level of D-dimer
suggest thrombosis , D –dimer level may be elevated in normal pregnancy due to
physiological changes of pregnancy.
Treatment of VTE:
1-Warfarin cross the placenta & cause warfarin embryopathy (limb & facial defect) in 1st trimester
& fetal intracerebral haemrrhage in 2nd & 3rd trimester.
2-heparin (LMWH or unfractionated) are treatment of choice , not cross placenta . Prolonged use
may cause bleeding , osteoparosis, thrpmbocytopenia & allergy.
The potential advantages of LMWH over UFH is less risk of bleeding .
UFH cause dose dependent loss of bone , if administered for more than one
month . LMWH carry a much lower risk of osteoparosis.
Heparin induced thrombocytopenia HIT is another complication of UFH , this
risk is lower with LMWH.
Allergy to UFH or LMWH take the form of itchy, erythematous lesion at injection
site. Changing preparation or shifting to other type may help.
The woman taking LMWH therapy should be advised that once she is established in
labour or thinks that she is in labor, she should not inject any further heparin.
Where delivery is planned, LMWH maintenance therapy should be discontinued 24 hours
before planned delivery.
Regional anesthetic or analgesic techniques should not be undertaken until at least 24
hours after the last dose of therapeutic LMWH .
Heparin anticoagulation (LMWH or UFH) may be restarted 3–6 h after vaginal delivery
and 6–8 h after cesarean. Warfarin anticoagulation may be started postpartum day 1.
Following delivery women can convert to warfarin with checking of INR or remain on
LMWH. Both are safe in breast feeding mother .
If spontaneous labor occurs while receiving LMWH, anticoagulant effect depends on
timing of last dose, Avoid epidural, Protamine can be considered.
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Antenatal thromboprophylaxis:
high risk-----antenatal LMWH:
1-Single previous VTE +
2-Thrombophilia
3-Family history
4-Estrogen related previous recurrent VTE.
intermediate risk -- antenatal LMWH
1-Single previous VTE with no family HX or thrombophilia
2-Thrombophilia & no HX of VTE
3-Medical co-morbidity: SLE, cancer, inflammatory condition, nephrotic syndrome, sickle
cell disease , iv drug user
4-Surgical procedure: appendicectomy.
Age ˃ 35 yr
Obesity BMI ˃ 30 kg\m2
Parity 3 or more
Smoker
Gross varicose vein
Current infection
Immobility eg long distance travel, paraplegia
Preeclampsia
Dehydration , hyperemesis gravidarum.
Multiple pregnancy
→ 3 or more risk factors----high risk ----antenatal prophylaxis
→˂ 3 risk factors----intermediate----mobilization & avoidance of dehydration.
Postnatal thromboprophylaxis:
1-Any previous VTE.
2-Any one requiring antenatal LMWH.
→High risk : at least 6 wk postnatal prophylactic LMWH
CS in labour
Asymptomatic thrombophilia
BMI ˃40 kg\ m2
Prolonged hospital admission
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Medical co-morbidity: heart or lung disease, SLE, cancer, inflammatory condition,
nephrotic syndrome, sickle cell disease , iv drug user.
→intermediate risk : 7 days postnatal LMWH, if more than 3 risk factors, consider
extended px with LMWH.Thyroid Disease In Pregnancy
Age ˃ 35 yr
Pariry ≥ 3
Obesity BMI ˃ 30 kg\m2
Smoker
Elective CS
Elective surgical procedure in puerperium
Gross varicose vein
Current systemic infection
Immobility
Preeclampsia
Mid cavity rotational forceps delivery
Prolonged labour ˃24 hr
PPH
→2 or more risk factors--- 7 days px LMWH
˂ 2 risk factors-----low risk : mobilization & avoidance of dehydration
Normal physiology in pregnancy
in pregnancy threre is decrease in level of iodine due to increase in renal
excretion of (increase in GFR ), plasma vol. expansion .
TSH fall ,serum level of total T3 & total T4 increased, fT4 rise in 1
st
trimester followed by fall in advancing gestation (due to increased TBG )&
is the only accurate measure for estimation of TF in pregnancy.
Fetal thyroid function
By 11- 12 wk the fetal thyroid is able to produce T4 & by 12-14 wk , it is
able to concentrate iodine
Placental transfer of thyroid hormones
Iodine cross placenta
T4 minimally cross placenta & appear to be important in fetal neuronal
development in 1
st
trimester before fetal thyroid function begins.
ATD such as propylthiouracil & methimazole cross placenta & can cause
fetal hypothyroidism
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Maternal hyperthyroidism
Increase risk of prematurity, IUGR, PE, stillbirth, neonatal M & M.
Most common cause is Graves disease , which is an Auto- immune disease
characterize by TSH receptor stimulating antibodies . Patient with graves
disease tend to have remission during pregnancy & relapse postpartum.
Clinical features: clinical DX is difficult during pregnancy , because many of
S & S of hyperthyroidism are present in normal pregnancy. PR more than
100 b\m which fail to slow with valsalva manoeuvre, eye changes, wt loss
& heat intolerance are helpful in making DX.
Investigation : increase in serum free T4 & Suppressed TSH level
Treatment :
1. radio-active iodine is contraindicated in pregnancy.
2. Anti thyroid drugs are main stay of treatment: thiomides block synthesis
of thyroid hormones, such as propylthiouracil & methimazole , in the
lowest effective dose should be used to keep fT3 & fT4 at upper normal
range. B-blocker can be used also. During breast feeding PTU can be used
because execretion in breast milk is minimal.
3. Surgical treatment : if medical Rx is failed ,or if there is suspicion of
malignancy can be done in 2
nd
trismester
Neonatal thyrotoxicosis
1% of pregnant women with graves disease give birth to babies with
thyrotoxicosis due to transplacental transfer of thyroid stimulating
antibodies.
Transient lasts less then 2-3 months .
Can be suspected if baseline FHR more then 160 b\m & ULS can identify
fetal goitre.
Is associated with high PNM&M , after delivery TF should be measured in
cord Bd & should be treated pre & postnatally.
Hypothyroidism
Pregnant women with appropriate thyroid replacement can expect normal
outcome.
Untreated cases are associated with spontaneous miscarriage, PE,
abruption ,LBW, low IQ in offspring.
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Dx : elevated TSH.
Rx : levothyroxine , full thyroid replacement & biochemical euothyroidism
is the aim. TFT should be performed each trimester with appropriate
adjustment of the dose
Neonatal hypothyroidism
Thyroid hr deficiency in fetal & early neonatal period lead to generalized
developmental retardation.
Etiology: thyroid dysgenesis , inborn error of thyroid function, drug
induced hypothyroidism.
BY:TWANA NAWZAD