Last update in thromboprophylaxis and methods of assessment and prevention

1. Thromboprophylaxis in
gynecology
A review of current evidence
Dr. Athraa J. Mohammed
Source :
TOGS ARTICLE
Green-top guideline No. 37a

2. Introduction
• VTE is a major cause of morbidity & mortality.
• Its a largely preventable complication following surgery.
• Without thromboprophylaxis the incidence of confirmed DVT in major
abdominal surgery ranges from 17-40%.
• the risk of VTE following surgery exist for the first 12 wk, with likelihood of
admission with VTE being greatest in the first 6 wk
• HAT(hospital acquired thrombosis) is defined as any venous thromboembolic
event occurring in hospital or within 90 days of hospital admission, it account
for 50-60% of all thromboembolic event

3. pathophysiology
• The basis for
thrombosis is
explained by the
Virchow’s triad:
endothelial injury;
stasis and
hypercoagulability.

4. Thromboprophylaxis in early pregnancy
• The risk for VTE increases from the first trimester
• Thrombin generation increase in women as early as 5 wk of gestation
• VTE is the 2nd commonest cause of maternal death
• Women at high risk of thrombosis should be started on thromboprophylaxis
as early as possible in pregnancy (primary care, prepregnancy)
• Hyperemesis gravidarum is a recognized risk factor for VTE (due to
dehydration with resultant hemoconcentration and immobility caused by
fatigue ), it’s a transient risk.
• OHSS show a 100-fold increased risk of VTE in pregnancies achieved by IVF,
as opposed to 5-fold increased risk due to IVF pregnancy without OHSS
• In OHSS thromboprophylaxis can be discontinued at the time of withdrawal
bleeding

5. • Some women with previous recurrent VTE require higher doses of LMWH.
• Women on long-term warfarin or other oral anticoagulants should be
counselled about the risks of these agents to the fetus and advised to stop
their oral anticoagulant therapy and change to LMWH as soon as pregnancy is
confirmed, ideally within 2 weeks of the missed period and before the sixth
week of pregnancy.
• All women with a previous history of confirmed VTE should be offered
thromboprophylaxis with LMWH or warfarin for at least 6 weeks postpartum
regardless of the mode of delivery.
• All women who have had caesarean sections should be considered for
thromboprophylaxis with LMWH for 10 days after delivery apart from those
having an elective caesarean section who should be considered for
thromboprophylaxis with LMWH for 10 days after delivery if they have any
additional risk factors

6. • If UFH is used after caesarean section (or other surgery), the platelet count
should be monitored every 2–3 days from days 4–14 or until heparin is
stopped.
• Warfarin use in pregnancy is restricted to the few situations where heparin is
considered unsuitable, e.g. some women with mechanical heart valves.
• Women receiving long-term anticoagulation with warfarin can be converted
from LMWH to warfarin postpartum when the risk of haemorrhage is
reduced, usually 5–7 days after delivery
• Non-vitamin K antagonist oral anticoagulants (NOACs) should be avoided in
pregnant women.
• Aspirin is not recommended for thromboprophylaxis in obstetrical patient
• Wafarin is safe in breast feeding

7. thromboembolism in pregnancy and the
puerperium
Pre-existing Previous VT
Thrombophilia Heritable
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
Medical comorbidities e.g. cancer; heart failure; active SLE, inflammatory polyarthropathy or IBD; nephrotic
syndrome; type I diabetes mellitus with nephropathy; sickle cell disease;49 current intravenous drug use
Age > 35 years
Obesity (BMI ≥ 30 kg/m2 ) either prepregnancy or in early pregnancy
Parity ≥ 3 (a woman becomes para 3 after her third delivery)
Smoking
Gross varicose veins (symptomatic or above knee or with associated phlebitis, oedema/skin changes)
Paraplegia

8. Risk factors for venous thromboembolism in pregnancy and the
puerperium
Obstetric risk factors Multiple pregnancy
Current pre-eclampsia
Caesarean section
Prolonged labour (> 24 hours)
Mid-cavity or rotational operative delivery
Stillbirth
Preterm birth
Postpartum haemorrhage (> 1 liter/requiring transfusion)

9. Risk factors for venous thromboembolism in pregnancy and the
puerperium
New onset/transient
These risk factors are potentially
reversible and may develop at later
stages in gestation than the initial
risk assessment or may resolve and
therefore what is important is an
ongoing individual risk assessment
Any surgical procedure in pregnancy or puerperium except immediate
repair of the perineum, e.g. appendicectomy, postpartum sterilization
Bone fracture
Hyperemesis, dehydration
Ovarian hyperstimulation syndrome
(first trimester only)
Assisted reproductive technology
(ART), in vitro fertilization (IVF)
Admission or immobility (≥ 3 days’
bed rest)
e.g. pelvic girdle pain restricting
mobility
Current systemic infection (requiring
intravenous antibiotics or admission
to hospital)
e.g. pneumonia, pyelonephritis,
postpartum wound infection
Long-distance travel (> 4 hours)

11. Risk assessment for venous thromboembolism
(VTE)
• 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.
For patients with an identified bleeding risk, the balance of risks of bleeding
and thrombosis should be discussed in consultation with a hematologist with
expertise in thrombosis and bleeding in pregnancy

13. Suggested thromboprophylactic doses for
antenatal and postnatal LMWH
Weight Enoxaparin Dalteparin Tinzaparin (75 u/kg/day)
< 50 kg 20 mg daily 2500 units daily 3500 units daily
50–90 kg 40 mg daily 5000 units daily 4500 units daily
91–130 kg 60 mg daily 7500 units daily 7000 units daily
131–170 kg 80 mg daily 10 000 units daily 9000 units daily
> 170 kg 0.6 mg/kg/day 75 u/kg/day 75 u/kg/day
High prophylactic dose for
women weighing 50–90 kg
40 mg 12 hourly 5000 units 12 hourly 4500 units 12 hourly

15. Summary of guideline for thromboprophylaxis in women with previous
VTE and/or thrombophilia
Very high risk Previous VTE on long-term oral anticoagulant
therapy
Recommend antenatal high-dose LMWH and at least
6 weeks’ postnatal LMWH or until switched back to
oral anticoagulant therapy
Antithrombin deficiency Antiphospholipid
syndrome with previous VTE
These women require specialist management by
experts in haemostasias and pregnancy
High risk Any previous VTE (except a single VTE related to
major surgery)
Recommend antenatal and 6 weeks’ postnatal
prophylactic LMWH
Intermediate risk Asymptomatic high-risk thrombophilia
homozygous factor V Leiden/compound
heterozygote
Protein C or S deficiency
Refer to local expert Consider antenatal LMWH
Recommend postnatal prophylactic LMWH for 6
weeks
Single previous VTE associated with major surgery
without thrombophilia, family history or other
risk factors
Consider antenatal LMWH (but not routinely
recommended) Recommend LMWH from 28 weeks of
gestation and 6 weeks’ postnatal prophylactic LMWH
Low risk) Asymptomatic low-risk thrombophilia
(prothrombin gene mutation or factor V Leiden
Consider as a risk factor and score appropriately
Recommend 10 days’ if other risk factor postpartum
(or 6 weeks’ if significant family history) postnatal
prophylactic LMWH

16. Thromboprophylaxis for gynecological surgeries
• Patient related risk factors
• Risk with underlying malignancy
• Risk with combined hormonal contraception
• Risk with hormonal replacement therapy HRT
• Thrombotic risk with covid 19
• Procedure related risk factors
• Effect of anesthesia &length of surgery
• Rout of surgery (laparoscopy versus laparotomy )
• Rout of surgery ( vaginal versus abdominal )
• Duration of hospital stay & risk of thrombosis

17. • Risks with underlying malignancy:
• Cancer is a recognized risk factor for VTE specially gynecological cancer patient who underwent
surgery.
• LMWH (+IPC) should be given for 28 days if there is current diagnosis of cancer, unless
contraindicated
• Risks with OCP (combined contraception)
• The risk of VTE is greatest among new users in the first year of use, with highest risk in the first
few months
• Following this period, risk reduces & then stabilizes, frequent stopping & starting is therefore
discouraged
• The prothrombotic factors with use of OCP last for at least 4-6wk after stopping OCP & hence
cessation of OCP is recommended 4wk before surgery
• Risk of VTE is higher among women using OCP with drospirenone or 3rd generation progesterone
(desogestrel, gestodene), with the exception of norgestimate that had a similar action to 2nd
generation progesterone
• BNF recommends stopping combined hormonal contraception 4 wks before elective surgery &
restarting pills at least 2 wks after regaining full mobility following surgery
• POP may be offered as an alternative
• In emergency situation when patient on OCP thromboprophylaxis should take this in to account.

18. • Risk with HRT :
• Studies shows that transdermal HRT is the safest in context of VTE
• Estradiol was associated with lower risk than conjugated EE in estrogen containing
preparation
• when considering combination the lowest risk is with Estradiol- dydrogesterone and
the max risk is with conjugated EE-medroxyprogesterone acetate
• HRT doesn’t need to be stopped prior to surgery, but it should be considered as a factor
while assessing risk for VTE
• Risk with covid 19:
• Covid 19 has identified as a risk factor for VTE so the hypercoagulability should be
consider when assessing the risk
• Effect of anesthesia & length of surgery:
• Incidence of DVT ↑ progressively with ↑duration of surgery
• Regional anesthesia associated with a lower risk of DVT than general anesthesia

19. • Rout of surgery:
• Minimally invasive surgery was associated with lower risk of VTE due to early
ambulation, faster post operative recovery & early discharge from hospital.
• Vag. Surgery was associated with very low rate of VTE
• In patient undergoing urogynecological surgery by all routes, laparotomy was
associated with ↑thrombotic event than other route

20. Modes of thromboprophylaxis
• Early ambulation
• Mechanical thromboprophylaxis
• Anti-embolic stocking /graduated compression stocking GCS:
• the recommended ankle pressure for primary prophylaxis was 18 mmhg
• Proper fit of the stocking is recommended as tourniquet effect could promote venous stasis
• Patient adherence was noted to be better with knee length stocking than thigh high stocking
• Intermittent pneumatic compression:(IPC) it reduce incidence of DVT by 60% & may be
used in combination with other method
• Pharmacological thromboprophylaxis
• Low molecular wt. heparin LMWH
• Low dose unfractionated heparin
• Fondaparinux (arixtra)
• Direct oral anticoagulant (apixaban, dabigatran, rivaroxaban & edoxaban)

22. Pharmacological thromboprophylaxis
• LMWH is the preferred agent of choice in many countries
• LMWH have increased risk of hematoma (about 2%) following c-section
• Prolong use of UFH in pregnancy may associated with osteoporosis &
fracture
• the required interval between a prophylactic dose of UFH & regional
analgesia or anesthesia (4 hrs.) is < with LMWH (12hrs.) & there is less
concern regarding neuraxial hematoma with UFH
• Women receiving antenatal LMWH should be advised that if they have any
vaginal bleeding or once labour begins they should not inject any further
LMWH.
• When a woman presents while on a therapeutic regimen of LMWH, regional
techniques should be avoided if possible for at least 24 hours after the last
dose of LMWH.

23. VTE risk scores for patient undergoing gynecological surgeries
Patient related risk factors Score
Age ≤40 years 0
41-60 years +1
61-74 years +2
≥75 years +3
BMI ≥30 +1
≥40 +2
Combined hormonal contraception /oral HRT +1
Pregnancy or 6wk following delivery (any GA) or
miscarriage
+3
Varicose veins +1
Pelvic mass of significant mass (eg fibroid > 12wk in
size)
+1
Personal hx of VTE +3
Family hx of unprovoked VTE +3
Known high risk of inherited thrombophilia +3
Mobility currently on bed rest +1
Patient confined to bed > 72 hrs +2
Medical condition (acute MI, COPD, iflam bowel dis,
heart failure, sepsis, pneumonia, DM require insulin)
+1
Major surgery in the past month +1
Hip, pelvis or leg fracture, stroke, multiple trauma,
acute spinal cord injury causing paraplegia
+5
Active cancer / cancer treatment +2
smoking +1
Immobilizing plaster cast +2
Blood transfusion +1
Procedure – related risk factors score
Duration of surgery ( total anesthetic & surgical time)
<60 min
+1
>60 min +2

24. Thromboprophylaxis based on VTE SCORE (adopted from
Caprini score)
Risk score Risk strata Thromboprophylaxis
0 Low risk Ambulation alone or IPC or GCS during hospitalization
1-4 Moderate risk IPC +/- GCS during hospitalization
5-8 High risk IPC + LMWH or LMWH alone for 7-10 days
>9 Highest risk IPC + LMWH or LMWH alone for 30 days

25. Contraindications/cautions to LMWH use
Known bleeding disorder (e.g. hemophilia, von Willebrand’s disease or acquired
coagulopathy)
 Active antenatal or postpartum bleeding
 Women considered at increased risk of major haemorrhage (e.g. placenta previa)
Thrombocytopenia (platelet count < 75 × 10⁹ /l)
 Acute stroke in previous 4 weeks (hemorrhagic or ischemic)
Severe renal disease (glomerular filtration rate [GFR] < 30 ml/minute/1.73m2 )
Severe liver disease (prothrombin time above normal range or known varices)
 Uncontrolled hypertension (blood pressure > 200 mmHg systolic or > 120 mmHg
diastolic)
Procedure related risk (procedure with high risk of bleeding or related to anesthesia
12 hrs. before & 4 hrs. after lumber puncture /epidural /spinal anesthesia)
Clinical and laboratory thresholds are taken from the Department of Health’s guidelines based on evidence from the
nonpregnant population.

26. Complication & contraindication to thromboprophylaxis
• GCS is contraindicated in
• Peripheral art. Disease
• Peripheral art. Bypass grafting
• Peripheral neuropathy
• Leg edema
• Allergy to material
• sever leg deformity preventing a
correct fit
• IPC is contraindicated in
• Allergy to the material of compression
sleeve
• Localize leg problem like cellulitis
• Wound infection
• Edema from congestive heart failure
• Venous problem like active phelibitis or
DVT
• Significant arterial insufficiency
• Adverse event of mechanical
compression
• Skin irritation
• Discomfort & pain
• Forefoot edema & lymphedema
• Allergic skin reaction
• Bact. & fungal infection
• Soft tissue damage or necrosis
• Arterial insufficiency, nerve damage
• VTE (improper application)
• Cardiac decompensation

27. Well leg compartment syndrome
• Acute lower leg compartment syndrome(condition in which compartment
pressure exceed perfusion pressure causing tissue ischemia & necrosis)
occurring in the absence of trauma & may occur without pre-existing
vascular disease
• Risk factors
• Prolonged Abd pelvic surgeries lasting > 4hrs. With patient in lithotomy position
• Age < 45 years old
• BMI > 25
• Presence of vascular disease & intraoperative hypotension
• Measures used to reduce leg compartment are periodic lowering(every 4
hrs.) of the legs to horizontal position, reducing intraoperative hypotension
and adequate padding

28. Ethical issues
• Patient should be informed that LMWH is porcine- derived, where
this is may be significant to them, & alternative therapy (fondaparinux
or DOAC) should be offered.
• Non compliance to the medication is a major issue, so patient
education & appropriate counselling may help to reduce risk of VTE
• Clinician must convinced to accept evidence based practice, as
hesitance to instituting thromboprophylaxis as a routine practice
following surgery can pose a considerable constraint to
implementation.