We know that during pregnancy, women have a five-
fold risk of VTE as compared to non-pregnant
Absolute risk of group VTE during pregnancy is
between 0.5-3/100 women, based on studies using
As we know that PE is one of leading cause of
maternal death in U.S. The prevalence and severity of
this condition warrant consideration of anticoagulant
therapy in pregnancy for women at risk for VTE.
Numerous changes in the coagulation system
account for the hypercoagulation state associated
Virchow’s triad factor (Fibrinogen, we will
brand, Ristocetin co-factor activity) anticoagulant
(AI, UI, S,C) marked mean term and post delivery.
Recently, it has been recognized that up to ½ of
women who have thrombotic events during
pregnancy possess an underlying congenital or
Most common thrombophilias in occasion:
– FSLM – prevalence of 5% of this population.
– PGM – 2% of 5% of this population.
In approximately 50% of patient with hereditary
thrombophilia, the initial thrombotic event occurs
in the presence of an additional risk factor e.g.
pregnancy ocp orthopedic trauma, and major
Traditionally, it was believed that the risk of VI was
greatest in the 3rd trimester and immediately
Most recent studies have found that antepartum DVT is at
least as common as postpartum and occurs with equal
frequency in all 3 trimester.
However, PE is a common postpartum.
Recurrence: Women with history of TE have an risk of
recurrence when they become pregnant.
The estimate recurrence 7.5 – 12% were based only on 2
random secondary trials.
But no studies differentiated between the risk of
recurrence based on underlying risk factor (but most of the
estimate of recurrence are based on women who had their
initial event day OCP use).
? Other familial hypercoagulation state
These are some of the clinical consideration and
recommendation that might assure some of these
question which we needed in our clinical practice.
How should be tested?
1. Hx of thrombosis esp. if it will affect man.
2. Family hx of thrombosis without personal but strong family hx of
thrombosis. History of thrombosis control, e.g. first degree
relative with AT deficiency homozygous factor 5LM or PGM.
May benefit from testing, e.g. – antepartum prophylaxis. – They
are more likely to have multiple inherited risk factors with risk
of thrombosis (4-40%), e.g. 15% C + 39% S positive FSLM
with markedly risk of thrombosis.
APS (pt with history of T, RDL, early or severe PET or
unexplained IUGR) prophylactic anticoagulation may
improve the pregnancy outcome.
Hereditary thrombophilia C, S, AT, FSL, PGM, Meth.
Severe early PET, unexplained fetal loss or still birth
Abruption No RCT supporting the efficacy of
anticoagulation Rx in preventing these conditions.
So, it is important to discuss with the patient the
implication of Positive test and to determine whether the
patient management would be altered during pregnancy
3. Also test AT, PC&S with extensive ____,
Warfarin and Heparin use – may result in falsely
4. DNA test for FSLM, PGM, THFR are reliable in
So after we identified our patient
candidate for Rx, what are the type of
What test should we order?
These are the test that we order to evaluate the risk of
thromboembotic events in female with history of
thrombosis FHx 1st degree relative with specific
1. Given the law prevalence of AT-III and consideration should
variable pathogenicity of Protein C & S) be given to test only
when all other studies have yielded with negative results.
Normal physiological changes in pregnancy result in marked
2. In Prot S & C, so the test should be deferred until after
pregnancy, e.g. Prot S by 40% in pregnancy.
– in pregnancy p. volume
in Heparin binding Protein
Heparin deg. by the placenta
Bioavailability of Hep.
No prospective trials that have determined adequate
prophylactic doses in pregnancy.
Still the major concerns with use of Heparin during
pregnancy are not fetal but maternal include
OST, Bleeding, skin necrosis
- 2 P.T. of pregnant women exposed to Heparin
confirmed a mean bone loss of 5%, complete
reversability of this process has not been clearly
established nor the dose response relationship.
- Some found that selected patient with FHx of
osteoporosis, smoker – p. evaluation of bone density
may have therapeutic implication.
• Common - Less common
• Reversible - >severe
• Less severe - D 5-14 of full dose
• Occur in 1st few days of Rx of Heparin
• Not require cessation of Rx - 3% of patient may
have wide spread
DVT and PE are the most frequent presentation
Rx should discontinue
It is recommended to measure Platelets on Day 5
and periodically for the 1st 2 weeks of treatment.
1. Advantages over standard Heparin
– It may reduces the 3 complications associated
with standard Heparin – (Bleeding,
– It crosses the placenta into fetal circulation.
– It has better bio-availability over the standard
Heparin because of H binding process.
– It can be restricted to once or twice daily dosing.
2. Dose same reason R. clearance and p.
3. No need for laboratory monitoring but peak
antifactor – Q4-6 weeks should be utilized
especially in patient receiving twice daily dose.
Relatively C.I. in pregnancy, because it crosses the
placenta into fetal circulation.
It is use mainly pp and antipartum should be
restricted to selected patient – RhD, vulv. HD, AF –
those with prolonged high dose Heparin Rx is
After we knew the type of anticoagulant, what do we
use for them?
Adjusted dose not frequently used mainly used in
selected patient those with vulvular heart disease
Certain high risk condition that require dosage
adjustment to achieve higher therapeutic level.
Because of the absence of adequate prospective
trials, number of different prophylactic regimen was
offered by various consensus panel.
One study determined that during pregnancy, a
doubling of the dose of Heparin was required to
achieve same anticoagulant response of non-
pregnant patient – Taley 5u 2t/d.
Pregnant ladies who require adjusted dose
prophylactic, may benefit from higher bio-
availability of LMWH.
After 3 months of therapeutic heparinization,
experts differ as to what should be done for rest
of the pregnancy.
Some recommend using L.D. of S.C. Heparin
and others in continuing therapeutic
anticoagulant for the rest of prgnancy.
LMWH may be an alternative Rx for acute
event but actual dose is not clear yet.
INTRAPARTUM & POSTPARTUM
Intrapartum care is complicated, and Rx
It is helpful to consult with personnel who have
expertise in the intrapartum management of
Low dose – varies widely, although all agree that
the postpartum period is one of high risk.
The use of spinal or epidural in patient may receiving
thromboembolic prophylaxis is controlled.
Safety of LMW, or oral anticoagulant – before the
procedure is unclear (because no studies addressing
anticoagulant in pregnancy relative to use of conduction
Although, FDA – reported cases of
Finally, the American Society of _______ anesthesia
6-12 Wks. Mid Trimester
- Skeletal embryopathy - optic atrophy
- Stippled epiphysis - microcephaly
- Nasal & limb hypoplasia - developmental delay
Bleeding and fetal loss may occur at anytime.