1. VTE in OBGYN practice DR ANBU SUBBIAN
DGO, DNB, MRCOG, Fellowship in Gyne Oncology CONSULTANT GYNECOLOGIST/GYNE ONCOLOGIST BANGALORE

2. Aim of this session -
Prevention of VTE in pregnancy – Risk assessment and prophylaxis
Diagnosis and treatment of VTE in pregnancy
Management of women on LMWH in labour
Prevention of VTE in gynaecology patients

3. Incidence in pregnancy – 4 fold increase.
40% of women develop an acquired resistance to activated protein C
Reduction in the concentration of protein S, a cofactor required for functioning of activated Protein C
Increase in coagulation factors I, VII, VIII, X and XII and vWF
Increased circulating concentrations of plasminogen activator inhibitor type 1 (PAI-1), produced in the endothelium and the liver.
Reduced fibrinolysis is by the secretion of plasminogen activator inhibitor type 2 (PAI-2) by the placenta
Venous stasis in the pelvis is partly due to the enlarging uterus impeding blood
flow and the reduced venous return from the lower limbs
Changes in the coagulation system begin with conception and do not return to baseline until more than eight weeks postpartum

4. Risk factors for VTE - Preexisting
Previous VTE (except a single event related to major surgery) 4
Previous VTE provoked by major surgery 3
Known high-risk thrombophilia
Medical comorbidities e.g. cancer, heart failure; active systemic lupus erythematosus, inflammatory polyarthropathy or inflammatory bowel disease; nephrotic syndrome; type I diabetes mellitus with nephropathy; sickle cell disease; current intravenous drug user
Family history of unprovoked or estrogen-related VTE in first-degree relative 1
Known low-risk thrombophilia (no VTE)
Age (> 35 years)
Obesity
1 or 2
Parity ≥ 3
Smoker
Gross varicose veins
RCOG Green-top Guideline No. 37a

5. Transient risk factors
Obstetric risk factors
Pre-eclampsia in current pregnancy 1
ART/IVF (antenatal only)
Multiple pregnancy
Caesarean section in labour 2
Elective caesarean section
Mid-cavity or rotational operative delivery
Prolonged labour (> 24 hours)
PPH (> 1 litre or transfusion)
Preterm birth < 37+0 weeks in current pregnancy
Stillbirth in current pregnancy
Transient risk factors
Any surgical procedure in pregnancy or puerperium except immediate repair of the perineum, e.g. appendicectomy, postpartum sterilisation 3
Hyperemesis
OHSS (first trimester only) 4
Current systemic infection 1
Immobility, dehydration

6. Risk assessment Pre pregnancy or early pregnancy
Admitted to hospital or develops intercurrent problems
Labour and immediate post partum

7. Thrombophilias Heritable Acquired Antithrombin deficiency
Protein C deficiency
Protein S deficiency
Factor V Leiden
Prothrombin gene mutation
Acquired
Antiphospholipid antibodies
Persistent lupus anticoagulant and/or persistent moderate/high titre anticardiolipin antibodies and/or β2-glycoprotein 1 antibodies
No evidence for universal screening
Selective screening in women with a personal or family history of thrombosis (if known antithrombin deficiency or unknown) or a history of poor pregnancy outcome (for APS)
(Around 50% of such women will have a thrombophilia)
The Obstetrician & Gynaecologist 2006;8:215–221

8. Antepartum thromboprophylaxis
May be on oral anticoagulants - warfarin
Need to be switched over to LMWH prior to pregnancy ( preferably)
Very High risk group
Antithrombin deficiency
APS associated with VTE
Prev VTE with long term anticoagulation
Thromboprophylaxis with higher dose LMWH (either 50%, 75% or full treatment dose)
Started antenatally and for 6 weeks postpartum
Require specialist management by experts

9. Asymptomatic thrombophilias
Heterozygosity for factor V Leiden or prothrombin gene mutation or antiphospholipid antibodies
+ three other risk factors - antenatal thromboprophylaxis,
+ two other risk factors thromboprophylaxis - prophylaxis from 28 weeks
+ one other risk factor postnatal thromboprophylaxis for 10 days
Asymptomatic Antithrombin deficiency, Protein C or S deficiency, combination of defects
Antenatal + post natal 6 weeks prophylaxis

10. Intermediate risk

11. INTERMEDIATE RISK
If total score ≥ 4 antenatally, consider thromboprophylaxis from the first trimester.
• If total score 3 antenatally, consider thromboprophylaxis from 28 weeks.
• If total score ≥ 2 postnatally, consider thromboprophylaxis for at least 10 days.
• If admitted to hospital antenatally consider thromboprophylaxis.
• If prolonged admission (≥ 3 days) or readmission to hospital within the puerperium consider thromboprophylaxis.

12. LMW Heparin Antenatal and postnatal prophylactic dose
Weight < 50 kg = 20 mg enoxaparin/2500 units dalteparin/3500 units tinzaparin daily
Weight 50–90 kg = 40 mg enoxaparin/5000 units dalteparin/4500 units tinzaparin daily
Weight 91–130 kg = 60 mg enoxaparin/7500 units dalteparin/7000 units tinzaparin daily
Weight 131–170 kg = 80 mg enoxaparin/ units dalteparin/9000 units tinzaparin daily
Weight > 170 kg = 0.6 mg/kg/day enoxaparin/ 75 u/kg/day dalteparin/ 75 u/kg/day tinzaparin

13. Adjuvant measures Ambulation Adequate hydration
GCS are specialized hosiery that provide graduated pressure on the lower legs and feet to help prevent thrombosis.
Tightest at the ankles and gradually become less constrictive towards the knees and thighs.
Little evidence supporting the efficacy in the prevention of VTE.
May be used in women who undergo elective CS / long travel > 4 hours
Ambulation
Adequate hydration
Graduated compression stockings

14. Aim of this session -
Prevention of VTE in pregnancy – Risk assessment and prophylaxis
Diagnosis and treatment of VTE in pregnancy
Management of women on LMWH in labour
Prevention of VTE in gynaecology patients

15. DVT in pregnancy
Occurs with equal frequency in each trimester and postpartum
Diagnosing is difficult during pregnancy.
Clinical suspicion confirmed in 10 percent of pregnant women, compared with 25 percent of nonpregnantpatients.
Typical symptoms are unilateral leg pain and swelling
Left leg Iliofemoral
Pregnant to 90% %
Nonpregnant % %
Initial management
Leg elevation
Graduated elastic compression stocking to reduce oedema
Mobilisation with graduated elastic compression stockings should be encouraged.
Volume 77, Number 12 ◆June 15, 2008

17. Diagnosis of VTE / PE Acute PE ECG/ CHEST X Ray
Compression duplex ultrasound (if DVT suspected)
Spiral CTPA Vs V/Q scan

18. CT PA
V/Q scan

19. Treatment of DVT/ PE
LMWH is the treatment of choice
Safety and efficacy is proven
Dosage is based on booking pregnancy weight
Routine platelet / aPTT/ PT/ INR / Factor Xa follow up monitoring not required
Continued throughout pregnancy and 6 weeks post partum ( or atleast 3 months of total therapy)
Full blood count, coagulation screen, urea and electrolytes, liver function tests.
Thrombophilia screen prior to therapy not recommended

20. Unfractionated heparin
Used in
VTE close to term
Post operative patients with risk of haemorrhage
Massive PE with cardiovascular collapse
Loading dose of 80 units/kg, followed by a continuous iv infusion of 18 units/kg/hour
Mandatory to measure activated partial thromboplastin time (APTT) level 4–6 hours after the loading dose, 6 hours after any dose change and then at least daily
Therapeutic target APTT ratio is usually 1.5– 2.5 times the average laboratory control value
Platelet counts every 2-3 days

21. Additional therapies Leg elevation Thrombolytic therapy
Graduated compression stockings
IVC filters – recurrent PE with massive DVT
Thrombolytic therapy
Reserved for patients with severe pulmonary thromboembolism with haemodynamic compromise
Massive iliofemoral thrombosis with limb/life threatening complications

22. Management in labour First of all, “ Do not inject if in labour”
Prophylactic LMWheparin
In planned delivery, discontinue 12 hours prior
NO regional anaesthetic or analgesic until at least 12 hours after the last dose
No LMWH for 4 hours after the use of spinal anaesthesia or after the epidural catheter has been removed
Epidural catheter should not be removed within 12 hours of the most recent injection
Therapeutic LMWheparin
In planned delivery, discontinue 24 hours prior
NO regional anaesthetic or analgesic until at least 24 hours after the last dose
No LMWH for 4 hours after the use of spinal anaesthesia or after the epidural catheter has been removed
Epidural catheter should not be removed within 12 hours of the most recent injection.

23. Post natal management
Continued for at least 6 weeks postnatally and until at least 3 months of treatment has been given in total.
Before discontinuing treatment the continuing risk of thrombosis should be assessed.
May be switched over to oral anticoagulant for postnatal therapy
Postpartum warfarin should be avoided until at least the fifth day and for longer in women at increased risk of postpartum haemorrhage.
Heparin (unfractionated or LMWH) and warfarin NOT contraindicated in breastfeeding.
LMWH (more than 12 weeks) is associated with a significantly lower chance of developing post-thrombotic syndrome.

24. Aim of this session -
Prevention of VTE in pregnancy – Risk assessment and prophylaxis
Diagnosis and treatment of VTE in pregnancy
Management of women on LMWH in labour
Prevention of VTE in gynaecology patients

25. VTE in gynecologic surgery
The diagnosis of DVT is approximately 3% when diagnosed clinically, and fatal PE occur in 0.2–0.9% of patients.1
Death from a PE occurs rapidly, with most patients succumbing within 30 minutes of the first clinical symptoms.
By I125 fibrinogen leg scanning, about 14% of patients having surgery for benign indications develop thromboembolism compared to 38% of gynecologic oncology patients.

26. Risk Classification for VTE in Pre op patients
Level of Risk
Low Surgery lasting <30 minutes in patients younger than 40 years with no additional
risk factors
Moderate Surgery lasting <30 minutes in patients with additional risk factors;
Surgery lasting <30 minutes in patients aged 40 to 60 years with no additional risk factors;
Major surgery in patients younger than 40 years with no additional risk factors
High Surgery <30 minutes in patients older than 60 years or with additional risk factors
Major surgery in patients older than 40 years or with additional risk factors
Highest Major surgery in patients older than 60 years plus prior venous thromboembolism, cancer, or
hypercoagulable state
Modified from Geerts WH et al. Prevention of venous thromboembolism: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004;126(suppl):338S–400S.

27. Venous Thromboembolism Risk Factors
Surgery
Trauma (major or lower extremity)
Immobility, paresis
Malignancy
Cancer therapy (hormonal, chemotherapy, or radiotherapy)
Previous venous thromboembolism
Increasing age
Pregnancy and the postpartum period
Estrogen-containing oral contraception or hormone therapy or SERMSs
Acute medical illness
Heart or respiratory failure
Inflammatory bowel disease
Myeloproliferative disorders
Paroxysmal nocturnal hemoglobinuria
Nephrotic syndrome
Obesity
Smoking
Varicose veins
Central venous catheterization
Inherited or acquired thrombophilia

28. Highest risk
Alternatives for prophylaxis for highest-risk patients include the following:
Combination prophylaxis (such as the combination of pneumatic compression and either low dose unfractionated heparin or low molecular weight heparin)
Consideration of continuing low molecular weight heparin prophylaxis as an outpatient for up to 28 days postoperatively
If administration of low molecular weight heparin 12 hours before surgery is impractical, initial dosing should commence 6 to 12 hours postoperatively.
From NGC-5947

29. High risk patients Moderate risk patients
Pneumatic compression devices placed before surgery and continued until hospital discharge
Unfractionated heparin (5,000 units) administered subcutaneously 2 hours before surgery and every 8 hours postoperatively and continued until discharge
LMWH (dalteparin 5,000 units or enoxaparin 40 mg) subcutaneously, hours before surgery / once daily postoperatively until discharge
Pneumatic compression devices or GCS placed before initiation of surgery and continued until the patient is fully ambulatory
Unfractionated heparin (5,000 units) subcutaneously 2 hours before surgery and every 12 hours after surgery until discharge
LMWH(dalteparin, 2,500 units, or enoxaparin, 40 mg) subcutaneously, hours before surgery / once a day postoperatively until discharge

30. Low-risk patients - No specific prophylaxis other than early ambulation.
Laparoscopic surgery should be stratified by risk category (and provided prophylaxis) similar to patients undergoing laparotomy

31. Agnelli G et al. A clinical outcome-based prospective study on venous thromboembolism after cancer surgery: project. Ann Surg Jan;243(1):89-95.
2000 patients with cancer undergoing surgery
80% of patients received in-hospital prophylaxis
2% rate of clinical VTE
Total mortality was 1.72% within 35 days of surgery
Despite prophylaxis, 46% of the deaths were caused by VTE. 
It is important to identify and treat high-risk patients, as consistent, systematic thromboprophylaxis will help to decrease the risk of a potentially fatal VTE