1. THROMBOPHILIA &
THROMBOEMBOLISM DURING
PREGNANCY &
PUERPERIUM-PREVENTION &
MANAGEMENT
Dr. Jagannath Mishra
Chair-Person-Dr. Sasmita Swain,
Associate Prof. Dept. of O&G
Co-chairperson-Dr. Utkal Naik,
SR, Dept. of O&G

2. DEFINITIONS
• Homeostasis- Process that maintain blood in a
fluid, clot-free state.
• Thrombosis- the formation of blood clot
(thrombus) within vessels.
• Embolus- Dislodged thrombus within vessels.
• Thrombophilia- Group of inherited and
acquired disorders that has increased risk of
thrombosis.

3. The Three Factors……

5. Anticoagulant and Fibrinolytic
Pathways
IXXI / platelets IXa VIIIa
Xa
X
TF/ VII
- )APC/S(
X
TFPI-
Va
IIIIa - )APC/S(
FDP
FXIII Fibrin
Fibrinogen
+tPA
Plasmin
- Antithrombin
PAI-1
Antiplasmin
-
-
5

6. VTE in Pregnancy
Epidemilogy
1.Affects 1 in 100,000 women of child bearing
age.
2.10 times more common in pregnancy.
3.Age <35 = 1/1000 pregnancy
4.Age >35 = 2.4/1000 pregnancy
5.10%-20% of VTE are PE

7. Mortality
• PE remains third most common cause of
maternal death after hypertension and
hemorrhage.
• Most common direct cause maternal death in
devloped countries.
• 62% of women with fatal VTE die in 1st
trimester although highest risk is immediately
after delivery.

8. Risk Factors…..

9. 1. Pregnancy

10. Pregnancy-Associated Changes in
Haemostatic and Fibrinolytic
Proteins
1. Increase in Clotting Factors:
• 20 to 200% increase in levels of
fibrinogen,
• factors II, VII, VIII, IX, X and
• vWF
• Progressive platelet activation

11. Pregnancy-Associated Changes in
Haemostatic and Fibrinolytic
Proteins
2. Decrease in Anticoagulant and Fibrinolytic
Activity:
• Protein S levels (free and total) decrease by
60% to 70%
• PAI-1 and PAI-2 levels increase two to
three-fold in pregnancy

12. • Some women are at even higher
risk during pregnancy because
they have one or more additional
risk factors

13. Additional risk factors for venous
thromboembolism (VTE)
Pre-existing risk factors
• Previous recurrent VTE
• Family history of VTE
• Known thrombophilia

14. Pre-existing risk factors-contd..
• Medical co-morbidities(e.g. heart or lung
disease, SLE, cancer, inflammatory conditions,
nephritic syndrome, sickle cell disease,
intravenous drug user, Surgical procedure,
• Age (> 35 years)
• Obesity
• Smoker
• Gross varicose veins

15. Obstetric risk factors
• Parity ≥3
• Pre-eclampsia
• Dehydration/ hyper emesis/ OHSS
• Multiple pregnancy
• Caesarean section in labor
• Elective caesarean section
• Prolonged labor (> 24 hours)
• PPH (>1 liter or transfusion)

16. Acute presentation
DVT
• Usually U/L, most commonly left leg.
• a red and hot swollen leg.
• swelling in entire leg or just part of it.
• pain and/or tenderness
• or it may just feel heavy.

17. PE
• sudden unexplained difficulty in breathing
• tightness in the chest or chest pain
• Haemoptysis
• Faintness or collapse
• Tachypnoea
• Raised JVP
• ABG= Hypoxemia

18. Diagnosis
• Compression duplex ultrasound
• Chest x-ray
• Ventilation-perfusion lung scan
• Computed tomography pulmonary angiogram
Note: D-dimer testing was considered but not
recommended.

19. MANAGEMENT
Offer either:
• proximal leg vein ultrasound scan (within 4 hours)
or
• if proximal leg vein scan not available within 4
hours, D-dimer test and an interim 24-hour dose of a
parenteral anti-coagulant followed by proximal leg
vein ultrasound within 24 hours .
NICE

20. • Repeat proximal leg vein ultrasound scan
6–8 days later for all patients with
positive D-dimer test and negative
proximal leg vein ultrasound scan.
NICE

21. FOR ACUTE PRESENTATION
Choice is LMWH- as soon as possible
except in
1.Renal failure
2.High risk of bleeding
3.Hemodynamic instability
• In these conditions UFH is safer than LMWH
NICE

22. For patients with hemodynamic
unstability
• Urgent CTPA within one hour but t/t shouldn’t
be delayed
• Thrombolysis if possible (Golden period=1st
hour)
• IV UFH 5000iu bolus followed by 1000-
2000iu/hr infusion with daily monitoring of
aPTT
• Gradually switch over to LMWH

23. Confirmed PE or proximal DVT
Continue LMWH for remainder
of pregnancy + 6 weeks post-
partum.
NICE

24. Mechanical interventions
Temporary inferior vena caval filters:
•offer to patients with proximal DVT or PE
who cannot have anticoagulation treatment.
•consider for patients with recurrent proximal
DVT or PE despite adequate anticoagulation
treatment.
NICE

25. Mechanical interventions
Offer below-knee graduated compression stockings
(ankle pressure greater than 23 mmHg) to patients with
proximal DVT a week after diagnosis or when swelling
is reduced sufficiently, and:
•advise patients to continue wearing the stockings for
at least 2 years
•ensure that the stockings are replaced 2 or 3 times per
year
•advise patients that the stockings need to be
worn only on the affected leg or legs.
NICE

26. THROMBOPROPHYLAXIS

27. • Women at high risk of VTE,
including those with previous
confirmed VTE, should be offered
pre-pregnancy counseling with a
prospective management plan.
Pre-pregnancy Counseling

28. • Is important because thrombotic
risk exists from the beginning of
the first trimester and often the
antenatal booking visit is at the end
of the first trimester.

29. • All women should undergo an
assessment of risk factors for
VTE in early pregnancy or
before pregnancy.
C

30. • A retrospective comparison of the overall
risk of recurrence of VTE during
pregnancy and the non-pregnant period
revealed risks of 10.9% during and 3.7%
outside pregnancy.
Evidence level III

31. • However, the risk was higher if the
woman had thrombophilia or if the
previous VTE was in an unusual site.
Evidence level III

32. scenarios
1. Women with previous VTE and no
thrombophilia
2. Women with previous VTE who have
thrombophilia
3. Women without previous VTE or
thrombophilia

33. •Women with a previous
VTE and no thrombophilia

34. Women with a previous VTE and no
thrombophilia
• Women with single previous VTE and no
thrombophilia should be offered
prophylaxis with low molecular weight
heparin (LMWH) for six weeks after
delivery.
• Whether they also require antenatal
thromboprophylaxis is controversial.

35. • Although pregnancy may be associated
with a more than three-fold increase in
the risk of recurrent VTE, the evidence is
conflicting.

36. • It may be reasonable not to use antenatal
thromboprophylaxis with heparin in
women with a single previous VTE
associated with a temporary risk factor
that has now resolved.
C

37. Women who have had :
1. more than one previous episode of VTE,
2. who have had one episode and in
addition have a family history of VTE in
a first degree relative or
3. whose episode of VTE was in an unusual
site
should be considered for antenatal
thromboprophylaxis with LMWH and for at
least six weeks postpartum.

38. Women with a previous
VTE who have thrombophilia

39. Women with a previous VTE who have
thrombophilia
• Women with thrombophilias have an
increased risk of VTE in pregnancy,
but this risk varies
depending upon the specific
thrombophilia.

40. High Risk
• Antiphospholipid syndrome
• Anti-thrombin deficiency

41. Medium Risk
• Protein C deficiency
• Protein S deficiency
• Homozygosity for Factor V Leiden
mutation
• Homozygosity for PT G20210A mutation
• Combined heterozygosity (Factor V
Leiden and PT 20210A)

42. Low Risk
• Heterzoygosity for Factor V Leiden
mutation
• Heterozygosity for PT G20210A
mutation

43. WHO DO WE SCREEN ?
• Studies suggests that all patients with a
history of prior venous thrombotic events
and those with adverse pregnancy events
such as fetal loss, abruptions, severe intra-
uterine growth restriction and early onset
severe preeclampsia, should be evaluated for
thrombophilias.
• Screening tests for inherited and acquired
thrombophilias

44. LABORATORY TESTS FOR
TROMBOPHILIAS SCREENING
A. Acquired Thrombophilias
• Lupus anticoagulants
•Anticardiolipin antibodies
•ß2-glycoprotein antibodies
•Anti-nuclear antibodies

45. LABORATORY TESTS FOR
TROMBOPHILIAS SCREENING
B. Inherited Thrombophilias
•Activated protein C resistance (APCR)
•Protein S
•Protein C
•Ant thrombin III (AT III)
•Factor V Leiden mutation
•Prothrombin gene mutation

46. • Women should be stratified according to the level of risk
associated with their thrombophilia.
• Since the risk of VTE is lower in women with no history
of VTE,
antenatal thromboprophylaxis is not always necessary,
except in:
1. those with combined defects,
2. those homozygous for defects or
3. those with anti-thrombin deficiency.
Women with a previous VTE who haveWomen with a previous VTE who have
inherited thrombophiliainherited thrombophilia

47. Women with acquired
thrombophilia
(antiphospholipid syndrome)

48. Antiphospholipid syndrome (APS)
is defined as:
the presence of lupus anticoagulant or anticardiolipin
antibodies of medium–high titer on two occasions 12
weeks apart, found in association with a history of:
• Thrombosis (arterial or venous) or
• Adverse pregnancy outcome :
1. Three or more unexplained miscarriages before ten
weeks of gestation,
2. Fetal death after ten weeks of gestation or
3. Preterm birth {less than 34 weeks} due to severe
pre-eclampsia or intrauterine growth restriction.

49. • The risk of recurrent thromboses in
women with APS is up to 70% and may
be even higher in pregnancy.
• Therefore, pregnant women with APS and
previous thromboses should receive
antenatal and postnatal
thromboprophylaxis with LMWH.

50. • Low-dose aspirin has been shown to
improve pregnancy outcome in APS and
is recommended for all women with APS.

51. Women without previous
VTE or thrombophilia

52. • The combination of either of (Age over 35 years
and BMI greater than 30/body weight greater
than 90 kg )with any other risk factor for VTE
(such as pre-eclampsia or immobility) or
• The presence of two other persisting risk factors
should lead the clinician to consider the
use of LMWH for three to five days
postpartum.
GPP
Women without previous VTE or
thrombophilia

53. Timing and duration
of
thromboprophylaxis

54. Ante partum
• As VTE during pregnancy has an
equal distribution throughout
gestation , if a decision is made to
initiate thromboprophylaxis
antenatally, this should begin as
early in pregnancy as practical.

55. • Once antenatal treatment is
initiated it should continue until-
1.Labour pain occurs
2.Elective induction of labour
starts

56. BEFORE LSCS
• last heparin injection should be 24 hours
before the planned caesarean delivery.
• If by emergency caesarean section within 24
hours of last injection
Need general anesthesia

57. Very High Risk
• Women with recurrent VTE associated
with either
1. On long term oral anti-coagulation
2. Anti-thrombin deficiency or
3. Antiphospholipid syndrome
Requires antenatal prophylaxis with LMWH
(high dose 40 mg 12-hourly)

58. High Risk
• Women with
1. Single previous VTE with
a)Thrombophilia or family history
b) Unprovoked/estrogen-related
2. Previous recurrent VTE (> 1)
require thromboprophylaxis with LMWH
antenatally

59. Intermediate Risk
Women with
1.Single previous VTE with no family
history or thrombophilia
2.Thrombophilia without VTE
3.Medical co-morbidities
LMWH prophylaxis can be considered
antenatlly

60. • Age > 35 years, Obesity (BMI > 30kg/m2)
• Parity ≥ 3, Pre-eclampsia
• Smoker
• Gross varicose veins, Immobility
• Dehydration/hyper emesis/OHSS
• Multiple pregnancy or ART
-More than 3 risk factors- consider LMWH antenatally
-Less than 3 risk factors- do not require LMWH
antenatally ( mobilization & prevention of
dehydration)

61. Postpartum
• Postpartum thromboprophylaxis should
be given as soon as possible after
delivery, provided that there is no
postpartum hemorrhage.
• Those with postpartum hemorrhage
should be fitted with thromboembolic
deterrent stockings.

62. • If the woman has been given regional
analgesia, LMWH should be withheld
until four hours after insertion or
removal of the epidural catheter (or six
hours if either insertion or removal were
traumatic).
Postpartum

63. • The combined oral contraceptive
pill should not be prescribed
during the first three months
postpartum for women with other
risk factors for VTE.

64. High Risk
• Any previous VTE
• Anyone requiring antenatal LMWH
At least 6 weeks postnatal prophylactic
LMWH

65. Intermediate Risk
• Caesarean section in labor
• Asymptomatic thrombophilia
• BMI > 40 kg/m2
• Medical co-morbidities
At least 7 days postnatal prophylactic LMWH

66. • Age > 35 years, Obesity (BMI > 30kg/m2)
• Parity ≥ 3, Pre-eclampsia
• Smoker
• Elective caesarian section
• Gross varicose veins, Immobility
• Prolonged labor (> 24 hours)
• PPH > 1 liter or blood transfusion
-2 or more risk factors-At least 7 days postnatal
prophylactic LMWH
-Less than 2 risk factors-Mobilization and
avoidance of dehydration

67. Agents for thromboprophylaxis

68. • Regardless of their risk of VTE,
immobilization of women during
pregnancy, labour and the
puerperium should be minimized
and dehydration should be
avoided.
Good Practice Point (GPP)

69. Low molecular weight heparin
• Low molecular weight heparins are
the agents of choice for antenatal
thromboprophylaxis.
• They are as effective as and safer
than unfractionated heparin in
pregnancy.
B

70. Advantages of LMWH over UFH
1. No need for laboratory monitoring-
-Experience indicates that, provided that
the woman has normal renal function,
monitoring of anti-Xa levels is not required
when LMWH is used for
thromboprophylaxis.

71. Continued……..
2.Higher bioavailability - 90% vs 30%
3.Longer plasma half-life
– 4 to 6 hours vs 0.5 to 1 hour
– renal (slower) vs hepatic clearance
4. Less inhibition of platelet function
– potentially less bleeding risk, but not shown in
clinical use

72. Continued……
5.Lower incidence of thrombocytopenia and
thrombosis (HIT syndrome)
– less interaction with platelet factor 4
– fewer heparin-dependent IgG antibodies
current guidelines still recommend
checking the platelet count one week
after starting LMWH

73. 6. Prolonged unfractionated heparin use during
pregnancy may result in osteoporosis and
fractures but this risk is low with LMWH.
Continued……

74. • Experience of enoxaparin in the
puerperium reports no adverse effects on
the baby resulting from breastfeeding.
Low molecular weight heparin

75. Thromboprophylactic doses for antenatal and
postnatal LMWH
Weight (kg) Enoxaparin Dalteparin Tinzaparin
<50 20 mg daily 2500U daily 3500U daily
50-90 40 mg daily 5000U daily 4500U daily
90-130 60 mg daily 7500U daily 7000U daily
>130 80 mg daily 10,000U daily 9000U daily
High
prophylactic
40 mg 12-
hourly
5000 units 12-
hourly
4500 units 12-
hourly
Treatment
dose
1 mg/kg/12
hourly
antenatal;1.5
mg/kg/daily
100
units/kg/12
hourly
175 u/kg/daily
(antenatal
and postnatal)

76. Low-dose aspirin
• Low-dose aspirin is safe in pregnancy,
although its use for thromboprophylaxis
in this setting has never been assessed by
a controlled trial.

77. • The use of low-dose aspirin
(75 mg daily) may be appropriate in
situations where the risk of VTE is
increased but is not deemed high
enough to warrant the use of
antenatal LMWH.
Low-dose aspirin

78. Warfarin
• Warfarin should be avoided if possible
during pregnancy, especially between 6 and
12 weeks of gestation, because it is
associated with an up to :
1. 5% risk of teratogenesis and
2. increases the risk of miscarriage,
3. fetal and maternal hemorrhage,
4. neurological problems in the baby and
stillbirth.

79. • Warfarin is safe after delivery and
for breastfeeding, although it
requires :
1. Close monitoring,
2. Frequent visits to an anticoagulant
clinic
Warfarin

80. Warfarin carries an increased risk of:
1. Postpartum hemorrhage and
2. Perineal hematoma compared with
LMWH.
Warfarin

81. Dextran
Dextran should not be used primarily because
of the risk of anaphylaxis, which has killed
fetuses by causing :
• Massive histamine release and
• Uterine hyper tonus.

82. Graduated elastic compression stockings
• There are no trials to support such practice but the
British Society for Hematology guidelines give a
grade C recommendation (evidence level IV) that:
All women with previous VTE or a thrombophilia
should be encouraged to wear
class-II graduated elastic compression
below knee stockings throughout their
pregnancy and for 6–12 weeks after delivery.