Venous thromboembolism during pregnancy

1. `
VENOUS THROMBOEMBOLISM DURING PREGNANCY
1A-MOWAFY 2013
VTE = Venous thromboembolism
Includes; Deep venous thrombosis DVT, Pulmonary embolism PE
INCIDENCE :
 2-3 in 1000 pregnancies
 DVT 80% PE 20%
 2/3 of DVT are antepartum
 Caesarean section increases the risk 3-5 fold than vaginal delivery
PATHOGENESIS
Virchow’s triade =
1. Circulatory stasis
2. Vascular damage
3. Increased blood co-agulation
AETIOLOGY
Risk factors:
1. Pregnancy itself is a risk factor
2. Previous VTE in patient on hormonal contraception
3. Previous VTE during pregnancy ( risk is 12 % )
4. Rheumatic heart disease and patients with heart prosthesis
5. Thrombophilias (congenital and acquired?!)
6. Age ˃ 35 years old
7. Obesity ; BMI ˃ 30
8. Multiparity ; parity ˃ 4
9. Recurrent miscarriage
10. Bed rest and physical immobility
11. Hyperemesis gravidarum
12. Shock and dehydration
13. Infections
Venous thromboembolism
during pregnancy
Venous thromboembolism during pregnancy

2. `
VENOUS THROMBOEMBOLISM DURING PREGNANCY
2A-MOWAFY 2013
14. Pregnancy-induced hypertension
15. Excessive blood loss
16. Prolonged labour
17. Instrumental delivery
18. Cesarean section
19. Pelvic surgery in peri-partum period
20. Sickle cell anemia
21. Gross varicose veins
22. Fetal demise with remaining viable fetus
23. Intra-uterine gross restriction IUGR
Q: What is thrombophilia?
It is abnormalities in the blood co-agulation that is increases the risk of thrombosis;
(congenital, Acquired?)

3. `
VENOUS THROMBOEMBOLISM DURING PREGNANCY
3A-MOWAFY 2013
RISKY GROUPS AND THEIR MANAGEMENT:
Very high risk
Criteria  Previous VTE with thrombophilia
 Long term warfarin therapy
Antepartum  High prophylactic dose or therapeutic dose of LMWH
Postpartum  LMWH for 5 days + Warfarin
High risk
Criteria  Previous recurrent VTE
 VTE once with thrombophilia
 VTE once with positive family history
 Diagnosed important thrombophilia
 Valvular mechanical prosthesis
Antepartum  prophylactic dose LMWH
Postpartum  LMWH for 5 days + Warfarin for 6 weeks
Moderate risk
Criteria  Single provoked VTE without thrombophilia
 Thrombophilia + Anti-thrombin III deficiency
 Mitral stenosis
Antepartum  Antenatal aspirin
Postpartum  LMWH for 5 days + Warfarin for 6 weeks
Low risk
Criteria Two or more of the following :
 Obesity
 Age ˃ 35
 Parity ˃ 4
 Gross varicose veins
 Recurrent hypertensive disorders
Antepartum  Antenatal aspirin
Postpartum  Warfarin for 6 weeks

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VENOUS THROMBOEMBOLISM DURING PREGNANCY
4A-MOWAFY 2013
ANTI-COAGULANT DRUGS:
Heparin
Types I. Unfractionated heparin → UFH “Cal-heparin”
II. Low molecular weight heparin → LMWH “Clexan”
Onset Within 10 minutes
Half-life 6 hours
Doses
I. Unfractionated heparin
 Normal body weight → 5000 IU/day
 Body weight ˂ 50 kg → 2500 IU/day
 Body weight ˃ 90 kg → 5000 IU/12 h
 High prophylactic dose→ 100 IU/kg/12h
II. Low molecular weight heparin
 Normal body weight → 40 mg/day
 Body weight ˂ 50 kg → 20 mg /day
 Body weight ˃ 90 kg → 40 mg / 12h
 High prophylactic dose→ I mg/kg/12h
Monitoring 1. Activated partial thromboplastin aPPT twice weekly
2. Plattlets concentration monthly
3. Bone mineral density every 3 months
Advantages
1. No effect on the fetus ( does not cross placental blood barrier )
2. Not secreted on milk ( no effect on lactation )
N.B : advantages of LMWH over UFH
o Fewer side effect
o Prolonged half-life
o Greater inhibitory effect on factor X
o Prophylactic dose once daily
o No need for continuous laboratory monitoring
Drawbacks  Increase bleeding tendency
 Osteoporosis ( improved by adding calcium , hence name “ Cal-heparin “
 Fat necrosis at site of injection
 Alopecia
Anti-dot Protamine sulphate 1mg/100IU

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VENOUS THROMBOEMBOLISM DURING PREGNANCY
5A-MOWAFY 2013
Oral anti-coagulant drugs
Types I. Coumarine → Warfarin sodium “Marevan”
II. Indandione → phenoidione “Dindevan”
Onset Full effect after 5 days
Half-life  Warfarin → 44 hours
 Phenoidione → 5 hours
Doses 2 to 5 mg/day
Monitoring 1. INR = “ international randomized ratio “→ should be 2 to 3
2. PT = “ prothrombine time “→ 30–50 % of normal control
Advantages Oral route , potent and long acting
Drawbacks  Maternal :
1. Skin: allergy, fever, rash, urticarial and dermatitis
2. Blood: agranulocytosis
3. Liver: liver disturbances; jaundice
4. Renal: renal disturbances; hematuria
5. Over dose → bleeding tendency
 Fetal :
1. Warfarin embryopathy; nasal hypoplasia, depression of nasal bone, mental
retardation, optic atrophy, skeletal defect ‘ bone splitting’
2. Can cross placental-blood barrier; bleeding tendency and increases the risks
of intracranial hemorrhage and accidental hemorrhage
 Drug interactions :
1. drugs increases the effect : salicylates, quinine, steroids
2. drugs decreases the effect : hepatic enzyme inducers
Anti-dot  Vitamin K IM. , SC.
 For rapid effect :
1. Fresh blood , fresh frozen plasma
2. Vitamin K to the mother and baby
PROTOCOLS FOR ANTI-COAGULATION DURING PREGNANCY
Frist trimester → only heparin for fear of warfarin embryopathy
Second trimester → warfarin starting from 13 weeks
Continue till:
 33 weeks if risk of preterm laobour exist
 36 weeks if no risk of preterm labour
However, oral anti-coagulants are not absolutely safe as delayed warfarin
embryopathy is recorded
Late in pregnancy: at 33 – 36 weeks → shift to heparin again
Postpartum: Vitamin K to the mother and baby and readjust the dose