➢ Deep Vein Thrombosis -Clinical manifestations and Diagnosis ➢ Pulmonary Embolism -Clinical manifestations and Diagnosis ➢ Diagnostic algorithm in acute VTE ➢ Anti-coagulants ➢ Treatment of DVT & LMWH ➢ Treatment of PE -UFH and newer anti-coagulants -Thrombolysis - IVC Filters ➢ Maintenance Therapy ➢ Intrapartum management

1. DR. SHUBHI DUBEY
BATCH OF JANUARY 2021
DEPARTMENT OF OBSTETRICS AND GYNAECOLOGY
VENOUS
THROMBOEMBOLISM IN
PREGNANCY

2. ACUTE VTE
IN PREGNANCY

3. CONTENTS
 Deep Vein Thrombosis
-Clinical manifestations and Diagnosis
 Pulmonary Embolism
-Clinical manifestations and Diagnosis
 Diagnostic algorithm in acute VTE
 Anti-coagulants
 Treatment of DVT & LMWH
 Treatment of PE -UFH and newer anti-coagulants
-Thrombolysis
- IVC Filters
 Maintenance Therapy
 Intrapartum management
 Postpartum management – Warfarin and NOACs
 Contraception in VTE

5. CLINICAL MANIFESTATIONS OF DVT
SYMPTOMS IN DEEP VEIN THROMBOSIS (DVT)
Pain in the extremity
Swelling in the extremity
Redness in the extremity

6. CLINICAL MANIFESTATIONS OF DVT
EXAMINATION FINDS IN DEEP VEIN THROMBOSIS (DVT)
 Calf swelling
 Tenderness
 Rise in temperature
 Cyanosis
 Phlegmasia alba dolens
 Phlegmasia cerulea dolens
 Homan’s sign
 Mose’s sign
 Pratt’s sign

7. COMPRESSION DUPLEX
ULTRASOUND
IS THE
PRIMARY DIAGNOSTIC
TEST
FOR DVT (RCOG 2015)
DIAGNOSIS OF DVT
COMPRESSION
ULTRASONOGRAPHY
InitialdiagnostictestrecommendedbyACOG
(2020)

8. COMPRESSION DUPLEX ULTRASOUND
 Sensitivity of serial compression
ultrasonography – 99.5%
 Negative predictive value – 99.5%

9.  Clinical suspicion of DVT  Compression Duplex Ultrasound
 Duplex ultrasound positive  Treat
 Duplex Ultrasound Negative :
 Low level of clinical suspicion  Discontinue anticoagulants
 High level of clinical suspicion  Continue anticoagulants
 Repeat ultrasound on day 3 and 7
DIAGNOSIS OF ACUTE DVT

10. In case of suspected Iliac vein thrombosis:
 Doppler ultrasound of the iliac vein
 Magnetic resonance venography
 Contrast venography
DIAGNOSIS OF ACUTE DVT

11. MRI
Useful for diagnosis of iliofemoral and pelvic vein thrombosis
Sensitivity- 100%
Specificity- 90%
Also helps establish non thrombotic differential diagnosis:
-Cellulitis
-Myositis
-Hematoma
-Superficial Phlebitis

12. CLINICAL PRESENTATION
PULMONARY EMBOLISM
SYMPTOMS IN PULMONARY EMBOLISM (PE)
 Loss of consciousness
 Cough
 Hemoptysis
 Shortness of breath
 Wheezing
 Dull chest pain
 Calf/ thigh pain

13. CLINICAL FINDINGS IN
PULMONARY EMBOLISM
EXAMINATION FINDINGS IN PULMONARY EMBOLISM (PE)
 Tachypnea
 Tachycardia
 Desaturation
 Raised JVP
 Reduced breath sounds
 Loud P2
 Calf swelling and tenderness

14. DIAGNOSIS OF ACUTE PE
 CHEST X- RAY
 Normal (50%)  V/ Q scan
 Atelectasis
 Effusion
 Pulmonary edema
Suggestive of Pulmonary Embolism  CTPA

15. DIAGNOSIS OF ACUTE PE
ELECTROCARDIOGRAM abnormalities (41%)
 T wave inversion (21%)
 S1Q3T3 pattern (15%)
 Right bundle branch block (18%)

16. ECHOCARDIOGRAM
 RIGHT HEART
- RV dilatation
- RV dysfunction
(global or regional hypokinesia)
- Tricuspid regurgitation
 LEFT HEART
- Normal/ hyperdynamic function
- Paradoxical septal motion
DIAGNOSIS OF ACUTE PE

17. DIAGNOSIS OF ACUTE PE
 ARTERIAL BLOOD GAS ANALYSIS:
 Arterial pO2 < 60 mm of Hg (10%)
 Oxygen saturation < 90% (2.9%)
 Limited role of ABG in diagnosis of acute PE

18. CTPA
most commonly used modality to
diagnose pulmonary embolism outside
pregnancy

19. SIMILARNPV-100%V/S99%
(RCOG2015)
V/Q SCAN CTPA
RADIATION EXPOSURE FETAL- 0.5 mGy
MATERNAL- < 10 mGy
FETAL- 0.1 mGy
MATERNAL- 10-70 mGy
ALTERNATIVE DIAGNOSIS Identifies Pulmonary edema/
Pneumonia/ Aortic dissection
DEFINITIVE DIAGNOSIS High negative predictive value Better sensitivIty and specificity
INVASIVENESS Requires IV injection of Technetium 99m
macroaggregated albumin and radionuclide
inhalation
IV injection of contrast
INTERPRETATION Standardized Interobserver variation (+)

20. D- DIMER
should not be performed
in the investigation of acute VTE in pregnancy

21. D- DIMER SCREENING TEST
FALLACY IN PREGNANCY:
-D-dimer levels can be elevated in pregnancy
-Higher levels in multifetal gestation
-Elevated levels in abruption/ pre-eclampsia/ sepsis
FIBRIN  FIBRIN DEGRADATION PRODUCT (D-DIMER)
ACOG (2020) recommends against the use of D-DIMER assays
AMERICAN THORACIC SOCIETY/ SOCIETY OF THORACIC RADIOLOGY
recommends against use of D-DIMER assays

22. DIAGNOSIS OF ACUTE PE
 Signs/ symptoms of acute PE  Chest X-Ray + ECG
 Suspected PE + signs/symptoms of DVT Compression duplex ultrasound
 Suspected PE + No signs/symptoms of DVT  V/Q SCAN or CTPA
 CTPA > V/Q SCAN - If Chest X-Ray is abnormal
 Suspected PE + normal CTPA or V/Q SCAN  repeat alternative testing
 continue anti-coagulants

23. DIAGNOSIS
OF
ACUTE VTE
SIGNS AND SYMTPOMS OF DVT
PRESENT
COMPRESSION DUPLEX
ULTRASOUND POSITVE
CONTINUE THERAPEUTIC DOSE
OF LMWH

24. DIAGNOSIS OF ACUTE VTE
CHEST X-RAY
ABNORMAL
CTPA
PE NOT CONFIRMED-
ALTERNATIVE TESTING
+ LMWH BASED ON
CLINICAL SUSPICION
CHEST X-RAY
NORMAL
V/ Q SCAN PE CONFIRMED-
CONTINUE
LMWH
IN CASE OF
ABSENCE OF
SIGNS/
SYMTPOMS
OF DVT-
PERFORM
CHEST X- RAY
>PE CONFIRMED-
CONTINUE
LMWH
>PE NOT
CONFIRMED-
ALTERNATIVE
TESTING + LMWH
BASED ON
CLINICAL
SUSPICION

25. Baseline investigations before
initiating anticoagulants :
 Complete blood count
 Coagulation profile
 Renal function tests
 Liver function tests
 Thrombophilia screen – not recommended

26. THROMBOPHILIA
TESTING
Women with thrombosis
should be evaluated for
antiphospholipid antibodies
and inherited thrombophilia
ACOG 2018- PRACTICE BULLETIN 197- INHERITED
THROMBOPHILIAS IN PREGNANCY

28. Initial treatment of acute VTE in pregnancy:
Any women with symptoms/ signs suggestive of acute VTE
should have objective testing performed
and treatment with LMWH given immediately,
until the diagnosis is excluded by objective testing,
unless treatment is strongly contraindicated.

29. UNTREATED DVT
PULMONARY EMBOLISM (15-24%)
> FATALITY (15%)
> MORTALITY WITHIN 30 MINUTES
OF EMBOLISM (66%)

30. LMWH V/S UFH
LMWH UFH
SAFE IN PREGNANCY
EFFICACY MORE EFFECTIVE
HAEMORRHAGE 1.2% 2%
MORTALITY 4.5% 6%
RECURRENCE/ EXTENSION 3.6% 5.4%

31. Why LMWHpreferredover IH?
Do not cross placenta
More predictable anticoagulant response  fewer
bleeding complications
Longer half-life  prohibits neuraxial analgesia in
labour
Renal clearance  to be used cautiously in case of
renal dysfunction
Better bioavailability
More predictable anticoagulant response  fewer
bleeding complications
Longer half-life  prohibits neuraxial analgesia in
labour
Lower risk of osteopenia/thrombocytopenia

32. ANTICOAGULATION IN PREGNANCY
 40-50% increase in maternal blood volume
 Increase in glomerular filtration  increased renal excretion of heparin
 Increase in protein binding of heparin
 Shorter half- life
 Lower peak plasma concentration
REQUIRES HIGHER AND MORE FREQUENT DOSING

33. LOWMOLECULARWEIGHTHEPARIN
ENOXAPARIN/DALTEPARIN/
TINZAPARIN
Derivatives of UFH (molecular weight of 4000-5000
v/s 12,000-16,000)
MECHANISM OF ACTION:
- Inhibits factor Xa
- Activates prothrombin

34. ABSORPTION Tmax HALF LIFE
ANTI Xa/
ANTI IIa
ENOXAPARIN 100% 3 hours 4.4 hours 4
DALTEPARIN 90% 3-4 hours 4 hours 2.6
TINZAPARIN 90% 4-6 hours 1.5 hours 1.5
LOW MOLECULAR WEIGHT HEPARIN
ENOXAPARIN/DALTEPARIN/TINZAPARIN

35. LOW MOLECULAR WEIGHT HEPARIN
ENOXAPARIN/DALTEPARIN/TINZAPARIN
ACOG 2018- PRACTICE BULLETIN 197- INHERITED THROMBOPHILIAS IN PREGNANCY
-ACOG 2020-TARGET anti- Xa LEVEL: 0.6-1UNIT/mL
(4 hours after last injection)
- American Society of Hematology- anti Xa levels monitoring not justified
THERAPEUTIC LMWH - ENOXAPARIN 1MG/KG SC Q12H
- DALTEPARIN 200u/KG SC OD
- TINZAPARIN 175U/KG SC OD

36. CONTRAINDICATIONS
TOHEPARIN
 Active antepartum/ postpartum haemorrhage
 History of haemorrhagic stroke in the past 4 weeks
 Thrombocytopenia
 Hemophilia
 Von Willebrand disease
 Uncontrolled hypertension
 Severe hepatic/ renal disease

37. MONITORING OF LMWH THERAPY
Routine measurement of peak
anti- Xa activity for patients on
therapeutic LMWH for
management of acute VTE in
pregnancy/ postpartum is not
recommended.
Routine platelet count
monitoring is not
recommended

38. MANAGEMENT OF DVT
Once leg pain resolves (7-10 days) :
-Continue anti-coagulation
-Graded ambulation (pain and swelling resolves faster compared to immobilisation)
-Elastic stockings (ankle pressure >23 mm of Hg)
(upto 2 years- to reduce Post-thrombotic Syndrome)

39. MANAGEMENT OF PE
 Experienced clinicians (multidisciplinary)
- Physicians
- Obstetricians
- Radiologists
 Individualised management:
- Intravenous Unfractionated Heparin
- Thrombolysis
- Thoracotomy and surgical embolectomy

40. In case of cardiac arrest:
 Left lateral position
 Follow resuscitation principles : Airway  Breathing  Circulation
 Perimortem caesarean section within 5 minutes of unsuccessful resuscitation
(if pregnancy more than 20 weeks)
MANAGEMENT OF PE

41. MASSIVE PE
Intravenous Unfractionated Heparin
is the preferred initial treatment in
massive PE with cardiovascular compromise

42. UNFRACTIONATED
HEPARIN
MECHANISM OF ACTION:
- Increases anti-thrombin activity
- Increases factor XA inhibitor activity
- Inhibits platelet aggregation

43. UNFRACTIONATED HEPARIN
Doesn’t cross placenta  safe in pregnancy
Higher dose and frequency of administration required in pregnancy
Higher volume of distribution
Lesser peak plasma concentration
Half-life – 1 hour

44. UNFRACTIONATED HEPARIN
Used in initial management of DVT (immediate onset of action)
In cases in which delivery/ surgery/ thrombolysis maybe required (ACOG 2020)
ROUTES OF ADMINISTRATION:
-Initial IV dose followed by adjusted-dose UFH SC dose (12th hourly)
-Adjusted dose UFH- SC (12th hourly)
Adjusted dose UFH- dose adjusted to prolong the aPTT into a thereupatic range (6
hours post injection)

45. UNFRACTIONATED HEPARIN
Bolus IV dose of 70-100 U/kg (5,000-10,000U)
Followed by continuous IV infusion- 15-20U/kg/hr (1000U/hr)
IV regimen for 5-7 days followed by SC UFH
Target aPTT- 1.5-2.5 (6 hours after injection)
ACOG 2018- PRACTICE BULLETIN 197- INHERITED THROMBOPHILIAS IN PREGNANCY

46. DOSE ADJUSTMENT OF
UNFRACTIONATED HEPARIN

47. UNFRACTIONATED HEPARIN- MONITORING
Patients on unfractionated heparin should have platelet monitoring every 2- 3 days
Late pregnancy  apparent Heparin resistance
Increased fibrinogen and Factor VIII  deranged aPTT  high dose of Heparin
Determine anti- Xa levels
Target anti- Xa levels- 0.35- 0.7 u/ mL

48. COMPLICATIONS OF HEPARIN
BLEEDING
- Incidence: upto 5.5% - UFH>>LMWH
HEPARIN INDUCED
THROMBOCYTOPENIA
- Usually within 5-10 days of
initiation of therapy
- Rare in pregnancy
SKIN NECROSIS
- Rare. Occurs in fat-rich
areas
- Erythema  Bruising
Necrosis
OSTEOPOROSIS
- When used for >6months
- Can cause pathological
fractures
- Reversible
- UFH >> LMWH
(less osteoclastic activation)

49. HEPARIN-INDUCEDTHROMBOCYTOPENIA
Drop in platelet count by >50%
Thrombosis beginning 5-10
days after start of heparin with
appearance of platelet-
activating antibodies
INCIDENCE: 3%
TYPE 1 HIT TYPE 2 HIT
- Non- immune
- Occurs within first
few days of therapy
and resolves by Day 5
- Results from IgG
antibodies against
PLATELET FACTOR 4
and HEPARIN
- Occurs between day
5-14

50. HEPARIN- INDUCED THROMBOCYTOPENIA
 Incidence in Obstetric patients: <0.1% (ACOG 2020)
 In suspected cases- evaluate for anti-platelet
antibodies / functional assays
 Management:
- Stop heparin and start alternative anticoagulants
(Fondaparinux- ASH)
- Avoid platelet transfusion

51. In massive life-threatening PE with hemodynamic compromise,
thrombolytic therapy should be started
to reduce the obstruction in the circulation
ALSO SUGGESTED BY THE AMERICAN SCOEITY OF HEMATOLOGY

52. NON-FIBRIN SPECIFIC FIBRIN SPECIFIC
 Streptokinase
 Urokinase
 Anistreplase
 Alteplase
 Reteplase
 Tenecteplase
THROMBOLYSIS

53. THROMBOLYSIS
 Cause rapid lysis of clots compared to
heparin
improvement in pulmonary
hypertension
 Lowers risk of mortality
 2% risk of fatal haemorrhage
 Complication rates similar to non-pregnant
state
should not be withheld in pregnancy

54. THROMBOLYSIS

55. IVC FILTERS IN VTE
Temporary IVC filters
can be considered in the peripartum period
for patients with Iliac vein VTE
or proven DVT with recurrent PE despite anticoagulants
to reduce the risk of PE

56. VENA CAVAL FILTERS
In case of patients with recent DVT(<2 WEEKS)
In case of patients developing PE despite heparin
therapy
In case of patients with massive emboli not fit for
thrombolysis
Placed in the IVC through jugular/ femoral vein
Not proven to be beneficial- similar complication rates
when compared to heparin therapy alone
COMPLICATIONS:
-Migration
-Bleeding/ thrombosis at site of
insertion
-Erosion of IVC wall
-Obstruction of IVC

57. MAINTENANCE TREATMENT OF DVT/ PE
Therapeutic dose of subcutaneous
LMWH should be given
for the remaining duration of
pregnancy
and for at least 6 weeks postnatally
and until at least 3 months of
treatment has been given in total
THERAPEUTIC
ANTICOAGULATION
FOR 3-6 MONTHS
followed by
PROPHYLACTIC THERAPY OF THE
DURATION OF PREGNANCY AND
PUERPERIUM

58. Newer anticoagulants
(Fondaparinux, Argatroban, Hirudin)
should be considered in pregnant women
unable to tolerate heparin but requiring
continued anticoagulation

59. NEWER ANTI-COAGULANTS
CLASS DRUG ROUTE MONITORING COMMENT
HEPARINOID DANAPAROID
IV BOLUS 
SC INJECTION Q12H
ANTI-Xa LEVELS
-Safe
-Expensive
-HIT
DIRECT
THROMBIN
INHIBITOR
LEPIRUDIN
IV INFUSION
PTT
- HIT safe
BIVALIRUDIN
PT/ aPTT
- Preliminary
studies show that
drug is safe in
pregnancy
ARGATROBAN PTT
ANTI- Xa
INHIBITOR
FONDAPARINUX SC INJECTION Q24H
ANTI-Xa LEVELS
-Limited placental
transport
- Used in HIT
HEPATIC CLEARANCE
RECOMMENDED BY THE PREGNANCY AND THROMBOSIS WORKING GROUP

60. ANTICOAGULANTS IN LABOUR
VTE at term  IV Unfractionated Heparin (easily manipulated)
Discontinue LMWH 24 hours prior to planned delivery (vaginal/ caesarean)
Regional anaesthesia should not be undertaken for at least 24 hours after the last
dose of LMWH
Do not remove epidural cather for at least 12 hours after the last dose of LMWH
LMWH should not be given for 4 hours after the use of spinal anaesthesia/
removal of epidural catheter

61. INTRAPARTUM MANAGEMENT
 Switch from LMWH to UFH in the last month of pregnancy/ when delivery is
imminent
 Blood loss increased (cervical/ vaginal lacerations >> uterine bleeding)
SOCIETY FOR OBSTETRIC ANAESTHESIA AND PERINATOLOGY:
- Withhold prophylactic UFH for 4-6 hours
- Withhold prophylactic LMWH for 12 hours
* Withhold therapeutic UFH/ LMWH for 24 hours

62. INTRAPARTUM MANAGEMENT
 If in labour while taking heparin- measure aPTT
- reversal with PROTAMINE SULPHATE
 UFH- completely reversible
 LMWH- partially reversible
 1% risk of anaphylaxis (in case of NPH exposure) 1:1000 epinephrine should be
available
 DOSAGE- 1mg protamine sulphate/ 100U Heparin
- 1mg protamine sulphate/ 1mg Enoxaparin

63. ANTICOAGULANTS AND CAESAREAN SECTION
In patients receiving therapeutic doses of LMWH,
wound drains (abdominal and rectus sheath) should be considered
and skin incision should be closed with interrupted sutures
(to allow drainage of any hematoma)

64. POSTPARTUM MANAGEMENT
Restart UFH/LMWH
4-6 hours after vaginal delivery
and 6-12 hours after LSCS
(ACOG 2020)

65. POSTNATAL ANTICOAGULATION
Therapeutic dose of subcutaneous LMWH should be given
for at least 6 weeks postnatally
and until at least a total of 3 months of treatment is given

66. POSTNATAL ANTICOAGULATION
 Counsel patient regarding need of blood tests to monitor warfarin, for at least 10
days, and offer the choice between LMWH and oral anticoagulants
WARFARIN COMPOUNDS
Vitamin K antagonist
Blocks post-translational modification of prothrombin and factor VII, IX, X,
Protein C and S

67. WARFARIN COMPOUNDS

68. VITAMIN K ANTAGONISTS
should not be used in management of VTE antenatally
due to their adverse effects on the fetus

69. What are the features of WARFARINEMBRYOPATHY?
 Nasal and midface hypoplasia
 Microphthalmia
 Mental retardation
 Maximum teratogenicity:
6-12 weeks of gestation

70. WARFARIN COMPOUNDS
 Safe in lactation
 Avoid warfarin until day 5  increased risk of bleeding
 POSTPARTUM THROMBOSIS- IV Heparin + Oral Warfarin
 Max. absorption in 1 hour
 Half-life- 35 hours
 Max. effect in 2-3 days
 Initial dose of Warfarin- 5-10mg for 2 days
 Maintenance dose titrated to target INR:2-3
 UFH/LMWH given for 5 days to avoid paradoxical thrombosis/ skin necrosis (ACOG
2020) – half-life of Protein C shorter than coagulation factors VII, IX, X
 After discontinuation- effect last for ~5 days

71. DIRECT THROMBIN INHIBITORS
 Dabigatran
FACTOR XA INHIBITORS
 Rivaroxaban
 Apixaban
 Edoxaban
NON-VITAMINK ANTAGONISTS
ORALANTI-COAGULANTS
 DRUG OF CHOICE FOR NON-PREGNANT PATIENTS
 HUMAN REPRODUCTIVE RISKS NOT KNOWN (LIKELY TO CROSS PLACENTA)
 EXCRETED IN BREAST MILK TO USE ALTERNATIVE AGENTS/ AVOID
BREASTFEEDING

72. CONTRACEPTION IN VTE
IUCD LNG- IUD DMPA
PROGESTERONE
ONLY PILLS
COMBINED ORAL
CONTRACEPTIVE
PILLS
HISTORY OF
VTE
1 2 2 2 4
CURRENT
VTE
1 2 2 2 4

73. RCOG ACOG ASH
CHOICE OF ANTICOAGULANT
IN PREGNANCY
LMWH > UFH
ORAL ANTI-COAGULANTS
LMWH > UFH LMWH > UFH
DURATION
TOTAL- 3 MONTHS
PREGNANCY+ 6 WEEKS
POSTPARTUM
TOTAL- 3-6 MONTHS
PREGNANCY+ 6 WEEKS
POSTPARTUM
MECHANICAL PROPHYLAXIS
AFTER ACUTE SYMTPOMS
RESOLVE
PNEUMATIC COMPRESSION
DEVICES
VENA CAVAL FILTERS
ILIAC DVT
RECURRENT DVT
RECURRENT DVT
THROMBOLYSIS
PE WITH HEMODYNAMIC
INSTABILITY
IN PE WITH HEMODYNAMIC
INSTABILITY
DURING LABOUR
UFH
WITHHOLD LMWH 24 HR
UFH
WITHHOLD LMWH 24 HR
PRIOR DISCONTINUATION
CHOICE OF
ANTICOAGULATION DURING
LACTATION
LMWH/ UFH UFH/ LMWH/ WARFARIN AGAINST ORAL ANTI-
COAGULANTS
POSTPARTUM
ANTICOAGULATION
LMWH/ UFH
WARFARIN
WARFARIN/ ORAL ANTI-
COAGULANT

74. THANK
YOU