Lecture by Dr Sujoy Dasgupta in BOGSCON 2015, the Annual Conference of Bengal Obstetric and Gynaecological Society, held at Hotel Novotel, Kolkata in January, 2015; where he had been invited as FACULTY to deliver his lecture

1. THROMBO-PROPHYLAXIS
IN
OBSTETRICS
SUJOY DASGUPTA
MBBS (Gold Medalist, Hons),
MS (OBGY- Gold Medalist), DNB (OBGY)
Senior Resident, Deptt of Gynaecological Oncology,
Chittaranjan National cancer Institute (CNCI), Kolkata

3. Venous Thromboembolism (VTE)
• Incidence- 2.3 per 1000 pregnancy
• Risk increases 4-6 fold in pregnancy
• Risk increases further in puerperium (especially the 1st
week)
• Overall case fatality rate- 3.5%
• The mortality rate of PE is 11% within an hour of presentation
and a further 30% among survivors if not recognized.
• Often no time for diagnosis and treatment
• Globally- 3% of maternal deaths (WHO, 2014)
Prevention- THROMBO-PROPHYLAXIS

5. Risk Factors for VTE*
Pre-existing Previous venous thromboembolism
Thrombophilia: Hereditary (Deficiency of antithrombin, Protein S, Protein C; Mutation of Factor V Leiden,
Prothrombin G20210A), Acquired (Anti-Phospholipid Syndrome)
Medical comorbidities (e.g. heart or lung disease, SLE, cancer, inflammatory conditions , nephrotic
syndrome (proteinuria > 3 g/day), sickle cell disease, intravenous drug user
Age > 35 years
Obesity (BMI > 30 kg/m2) either pre-pregnancy or in early pregnancy
Parity ≥ 3
Smoking
Gross varicose veins (symptomatic or above knee or with associated phlebitis, oedema/skin changes)
Paraplegia
Obstetric Multiple pregnancy, assisted reproductive therapy
Pre-eclampsia
Caesarean section
Prolonged labour, mid-cavity rotational operative delivery
PPH (> 1 litre) requiring transfusion
New-onset/transient)
Potentially reversible
Surgical procedure in pregnancy or puerperium (e.g. ERPC, appendicectomy, postpartum
sterilisation)
Hyperemesis, dehydration
Ovarian hyperstimulation syndrome
Admission or immobility (≥ 3 days’ bed rest) e.g. symphysis pubis dysfunction restricting mobility
Systemic infection (requiring antibiotics or admission to hospital)
Long-distance travel (> 4 hours)
*
RCOG Green-top Guidelines No. 37a, November 2009 Reducing the risk of thrombosis and embolism during pregnancy and the puerperium

6. When to Assess
• Preconceptional Care
• First Antenatal visit
• Intrapartum period
• Immediate postpartum
• If admitted to hospital for any reason
• If develops intercurrent problems (e.g.,
infection)

7. Risk Scoring
Pre-existing Score Obstetric Score Transient Score
Previous recurrent VTE 3 Pre-eclampsia 1 Any Surgery 2
Previous VTE – unprovoked/
estrogen related
3 Dehydration/
Hyperemesis/OHSS
1 Current
Infection
1
Previous VTE – provoked 2 Multiple pregnancy/ ART 1 Immobility 1
Family history of VTE 1 CS in labour 2
Known thrombophilia 2 Elective CS 1
Medical comorbidities 2 Mid-cavity/ rotational
forceps
1
Age (> 35 years) 1 Prolonged labour (>24 hrs) 1
Obesity (BMI >40 kg/m2
) 2 PPH (>1 litre or transfusion) 1
Obesity (BMI >30kg/m2
) 1
Parity ≥3 1
Smoker 1
Gross varicose veins 1

8. Methods of Prophylaxis

9. Heparin
Unfractionated
Heparin (UFH)
Low Molecular Weight
Heparin (LMWH)
Molecular weight 12,000-16,000 Da 3000-7000
Inhibitory effect F Xa, F IIa F Xa mainly
Bioavailability 20-30% 70-80%
aPTT Prolonged Not prolonged
Complications (Bleeding,
Osteoporosis)
Common Rare
Heparin Induced
Thrombocytopenia (HIT)
3-5% Never occurs de novo
Half life 30 min 3 hour
Anticoagulant action Shorter Prolonged (Once daily
dose)
Cost Cheaper Expensive

10. Prophylactic Dose Calculation
Weight (Kg) Enoxaparin Dalteparin Tinzaparin
(75 U/kg/day)
<50 20 mg OD 2500 U OD 3500 U OD
50-90 40 mg OD 5000 U OD 4500 U OD
91-130 60 mg OD*
7500 U OD*
7000 U OD*
131-170 80 mg OD*
10,000 U OD*
9000 U OD*
>170 0.6 mg/kg/day*
75 U/kg/day*
75 U/kg/day*
*
May be given in two divided doses

11. Higher dose
• Recurrent VTE, who were on long term oral anticoagulants
• Antithrombin III deficiency
• Homozygous Factor V Leiden Mutation
• Homozygous Prothrombin G20210A Mutation
• Double heterozygous defect (FVL, G20210A)
• APLA syndrome with H/O VTE
Enoxaparin Dalteparin Tinzaparin
High
Prophylactic/
Intermediate
Dose
40 mg 12 hourly 5000 U 12 hourly 4500 U 12 hourly
(Weight 50-90 kg)
Adjusted/
Therapeutic Dose
Antenatal-
1 mg/kg/ 12
hourly
Postnatal-
1.5 mg/kg/daily
Antenatal-
100 U/kg/12
hourly
Postnatal-
200 U/kg/daily
175 /kg/daily
(Antenatal and
Postnatal)

12. Monitoring
1. Platelet
count
•No previous exposure
to UFH
Not required
•Past/ recent use of
UFH
Every 2-3 days from D4-
D14
2. Anti-Xa •Prophylactic dose Not required
if renal function is normal
(Creatinine clearance >30
ml/min)
•Therapeutic dose •Extreme of body weight
(<50 kg, >90 kg)
•Renal compromise
•Risk factors for bleeding

13. Delivery and anaesthesia
• To stop further injection if she feels labour
pain/ vaginal bleeding

14. 1. Gap between last dose of
UFH/ LMWH and
Regional anesthesia
 12 hours (prophylactic
dose)
 24 hours (therapeutic
dose)
2. Restart LMWH/ UFH-
 4 hours after removal of
epidural catheter or SA
 4 hours after operation
Sunday
6 PM
LMWH 40
mg SC
}>12 hrsMonday
8 AM
Elective CS
under EA
Monday
2 PM
Remove
epidural
catheter
}4 hrs
Monday
6 PM
LMWH 40 mg
SC

15. Alternative to Heparin
Danaparoid Preferred drug in HIT
Lepirudin •Antenatal- Better avoided
•Postnatal- Alternative to danaparoid
Fondaparinux Better to be avoided
Warfarin •Antenatal- 5% risk of embryopathy, if used in 6-9
weeks, at dose >5 mg/day
•Postnatal- Preferred to LMWH, if prophylaxis is
needed for >7 days
Rivaroxaban
Apixaban
Inadequate data
Dabigatran
Ximelgatran
Inadequate data
Dextran Can cause anaphylaxis

16. Special Cases

17. Thrombophilia and Thrombosis

18. Previous history of RECURRENT episodes of VTE
Antenatal Postnatal
On long term anticoagulant Adjusted or 75% Therapeutic
dose of LMWH
Long term anticoagulants
Not on long term
anticoagulant
Prophylactic or Intermediate
dose LMWH
6 wk LMWH/ Warfarin
Previous history of SINGLE episode of VTE
Antenatal Postnatal
1. Unprovoked
2. Estrogen related
3. Hereditary
thrombophilia
4. Positive family H/O VTE
Prophylactic dose LMWH 6 wk LMWH/ Warfarin
Associated APLA syndrome Adjusted or 75%
Therapeutic dose of LMWH
+ Aspirin
Long term anticoagulants
Related to transient risk
factors no longer present
Vigilance 6 wk LMWH/ Warfarin

19. Asymptomatic Thrombophilia (no previous history of VTE)
Antenatal Postnatal
Antithrombin III deficiency Adjusted or 75% Therapeutic
dose of LMWH
Long term anticoagulants
1. Homozygous
Factor V
Leiden
2. Homozygous
Prothrombin
G20210A
3. Double
heterozygous
defects (FVL +
G20210A)
Positive
Family
H/O VTE
Prophylactic/ Intermediate
dose LMWH
6 wk LMWH/ Warfarin
No family
H/O VTE
Vigilance 6 wk LMWH/ Warfarin
Other hereditary
thrombophilia
Vigilance 7 days LMWH
APLA syndrome (with H/O
Obstetric complications)
Prophylactic dose LMWH +
Aspirin
6 wk LMWH/ Warfarin
APLA seropositivity only, no
Obst H/O, no thrombosis
Vigilance 7 days LMWH

20. Artificial Mechanical Heart Valves
• Thrombosis vs fetal risk
• Individualization and informed risk consent

21. • 1st
trimester:
1. If on low dose warfarin (<5 mg/day)- Consider
continuation of warfarin (ESC, 2011)
2. High risk of VTE (Older generation in mitral
position, past H/O VTE)- Continue Warfarin
(ACCP, 2012)
3. In other cases- Consider replacement of warfarin
by LMWH or UFH (ACCP, 2012)
• 2nd
and 3rd
trimester:
1. Warfarin and replace by UFH close to term (ESC,
2011)
2. Any one of Warfarin, LMWH or UFH (ACCP,
2012)
• After delivery:
Resume anticoagulant 4-6 hour after delivery
(ACCP 2012, ESC 2011)

22. INDIAN SCENARIO

23. Indian J Urol 2009;25:11-16
REVIEW ARTICLE
Venous thromboembolism: A
problem in the Indian/Asian
population?
Sunil Agarwal, Arvind Dhas Lee, Ravish
Sanghi Raju, Edwin Stephen
Conclusion- Venous thromboembolism (VTE) is a
common and potentially life threatening condition. It
continues to be under diagnosed and undertreated.
Awareness among Indians
regarding this potentially life-
threatening disease is low.
Contrary to earlier belief, the
incidence of VTE in Asia and
India is comparable to that in
Western countries. The prevailing belief
that VTE in the Asian population is less than in the
Western population has essentially been disproved
and there appears no reason to believe that it should
be any different in India.
Pulmonary Thromboembolism:
Indian Scenario
BNBM Prasad
CONCLUSION- In India, VTE is a common cause of
mortality and morbidity in patients hospitalized for
surgical or medical illnesses. It is often misdiagnosed and
not treated in time. Worldwide it ranks among three big
cardiovascular killers. Though the exact
magnitude of problem is not known in
India, the clinical relevance and
incidence is not expected to be
different from Western countries. Signs
and symptoms are nonspecific and high degree of clinical
suspicion with right application of diagnostic tools both
imaging and nonimaging are vital for definitive
diagnosis. pFuture will witness almost total prevention of
VTE in hospitalized patients and application of novel
pharmacological and interventional techniques for
optimizing therapy. .

24. International Journal of Biological & Medical Research
Journal homepage: www.biomedscidirect.com
Original Article
Maternal Mortality at a Tertiary Care Teaching Hospital of Rural India: A
Retrospective Study
Vidyadhar B. Bangal, Purushottam A. Giri, Ruchika Garg
Pulmonary embolism is the third most common direct cause of
maternal mortality (10.59% deaths) after haemorrhage and
eclampsia

25. Original Article
Deep venous thrombosis in the
antenatal period in a large
cohort of pregnancies from
western India
Sonal Vora, Kaniaksha Ghosh,
Shrimati Shettv, Vinita Salvi, and
Purnima Santoskar
Conclusion- We conclude that
the prevalence of DVT in
India is more or less similar
to other reports published (1
in 1000) and both acquired and
heritable thrombophilia show
strong association with DVT
associated with pregnancy.
Thromb J. 2007; 5: 9
J Obstet Gynaecol India.
Dec 2013; 63(6): 373–377
Original Article
Safety and Efficacy of Low
Molecular Weight Heparin
Therapy During Pregnancy:
Three Year Experience at a
Tertiary Care Center
Nilanchali Singh, Priva Varshnev, Reva
Tripathi, Y. M. Mala, and Shakun
Tyagi
Conclusion- Low molecular
weight heparin can be used in
pregnancy for various
indications as an alternative to
unfractionated heparin or
warfarin as it is efficacious and
safe.

26. Conclusion
• Pregnancy itself is a
thrombogenic condition
• Every woman should be
assessed for risk factors
• Decision for
thromboprophylaxis should be
individualized
• LMWH is the drug of choice
• Threshold for recommending
thromboprophylaxis should be
lower because the risk is higher
and the duration is shorter

27. THANK YOU