[Music]
hi I'm Matt beniker the director of
clinical virology and vice-chair up
practice in the Department of Laboratory
Medicine and pathology at Mayo Clinic
did you know that venous thromboembolism
or blood clots is one of the leading
causes of death among pregnant women
fortunately this condition can be
successfully managed if identified and
treated appropriately in this month's
hot topic my colleague dr. Ariela
Marshall will provide an overview of
venous thromboembolism including its
risk factors treatment and prevention I
hope you enjoyed this month's hot topic
and I personally want to thank you for
allowing male medical laboratories the
opportunity to be a partner in your
patients healthcare
thank so much for the opportunity to
speak today my name is Ariela Marshall
I'm one of the senior associate
consultants here in the division of
hematology and Mayo Clinic Rochester and
a member of the coagulation and our core
and consultative hematology groups and
one of my specific interest is
coagulation and bleeding disorders in
women's health so I'd like to talk about
that today
I do not have any disclosures so looking
at the presentation overall we just like
you to consider some of the following
important points about how testing and
diagnosis are used in management when
should test be use and how a result of
testing impact patient management we
like to start with the keys this is a 31
year old woman who I saw in our
coalition clinic she has a history of
venous thromboembolism and she wishes to
become pregnant for a second time so
she's 31 she's previously been pregnant
she's pre menopausal and she does have a
history of polycystic ovarian syndrome
in 2011 she presented with a queued
right leg pain and swelling after a long
drive she was also an active smoker at
the time and was using a nuvaring for
contraception she did not have imaging
that were aware of this is all diagnosed
as an outside facility but she was
treated empirically for a possible DVT
with an ox Oparin and her symptoms
resolved she did well between 2011 and
2015 during this period of time she used
both as a mini pill which is a progestin
containing contraceptive as well as
combined oral contraceptives containing
estrogen 2015 she had a successful
pregnancy and after her pregnancy she
restarted the NuvaRing
which is an estrogen containing type of
contraceptive three weeks postpartum she
awoke with lower extremity pain and to
see on exertion she's diagnosed with a
left lower extremity DVT as well as
bilateral pulmonary emboli she was
transitioned to laufen ox and then to
warfarin she did undergo thrombophilia
testing at that time it's essentially
unremarkable so negative for factor v
leiden and proton and gene mutations
negative for antiphospholipid antibodies
as well as did not show any evidence of
deficiencies of protein c
or anti Robin at the time she saw us in
clinic she'd been on warfarin for one
month she also noted some increased
menstrual bleeding but is otherwise
tolerating it well and she wanted to
discuss the role of her anticoagulation
therapy and her risk of VTE in future
pregnancies including what to do about
the risk of hormone stimulation if she
needed it for infertility related to her
PCOS as well as the role of prophylactic
anticoagulation so talking about Venus
or mo Maalik disease and pregnancy in
general about one to two per 1,000
pregnancies are complicated by VTE the
risk is higher and all pregnant women
but there's a difference between
antenatal and postnatal periods so in
the antenatal period the risk was about
fivefold higher than a non pregnant
women and DVT is more common however in
the postnatal period the risk was
actually increased up to twenty fold
higher compared to non pregnant women
and this is the time when pulmonary
emboli are more common in terms of
consequences pregnancy related VTE is
one of the leading causes of pregnancy
related death in the developed world and
the mortality is as high as 1 in 100,000
in the United States in Europe so the
risk factors primarily are what we've
all learned about in terms of virchow's
triad
so the first being stasis so this is a
may Turner physiology with compression
of the left iliac vein by the right
iliac artery or ovarian artery this
innovation is actually exacerbated in
pregnancy by compression due to the
gravity uterus and in pregnancy this
explains why we see about 90% of DVT s
on the left side versus essentially
equivocal between left and right and non
pregnant women we also see a
predilection towards more proximal VTE
in pregnancy so 70% of DVT s are
actually in iliofemoral veins or more
proximal veins versus only about 10% in
the non pregnant population less than
10% of VTE in pregnancy are isolated
calf DVTs
versus a much higher proportion in the
non pregnant women there's also a
hypercoagulability and endothelial
injury in terms of hypercoagulability we
see increases in many of the coagulation
factors that predispose towards
thrombosis we also see D
creased anticoagulant factors so
decrease protein s and acquired
resistance to activated protein C
furthermore those reduced for analysis
via reduced TPA and increased
plasminogen activator inhibitor which is
placental there's also an acquired
antithrombin deficiency this can be seen
in the setting of preeclampsia leading
to protein area and loss of antithrombin
that way until eventual Sileo injury we
see compression by the uterus as well as
the deema during pregnancy and finally
during delivery there's actually a quite
a bit of vascular damage which occurs
there are multiple other risk factors
varying both between the ande partum and
the postpartum period so antepartum we
do see that advanced age in terms of the
mother as well as just a tional diabetes
and in some cases assisted reproduction
can lead to increased risk with the
sister reproduction this is primarily
due to ovarian hyperstimulation syndrome
which we see in women who are given
hormones to promote ovulation in the
postpartum period we see VTE related to
things that have essentially happened
during delivery so preeclampsia and
eclampsia
for cental previa and abruption as well
as either plan or emergency c-sections
can all increase the risk of VTE and
finally we know the woman who have
hereditary thrombophilia is and also any
woman who's had a prior VTE before the
current pregnancy these are risk factors
for V T at all times during pregnancy in
terms of treatment for women in general
we're pregnant and have VTE related to
pregnancy we prefer use of low molecular
weight heparins unfresh innate heparin
in front of parents there are other
alternatives we do avoid warfarin due to
the risk of fetal malformation and at
this point we're actually recommending
against the use of the direct oral
anticoagulants and this is because we
don't have enough evidence for their
safety and efficacy in pregnancy we have
some of the recommended doses here in
terms of prophylactic and therapeutic
dosing so in terms of prophylaxis after
a woman has had a prior VTE
we know that any patient with a prior
VTE is at higher risk of recurrent VTE
in subsequent pregnancy
interestingly a woman's lifetime risk of
recurrent VTE is lower if her first VTE
was pregnancy associated but the risk is
actually higher in subsequent
pregnancies of her first VTE was
pregnancy associated and this happens
because estrogen was likely the
provoking risk factors of any situation
in which the woman is exposed to
estrogen again would increase her risk
of a future VTE so these recommendations
here are for women who do not have a
known hereditary thrombophilia so this
is for a woman who has a prior history
of VTE if it was provoked in a non
estrogen associated situation and this
would be things like surgery or trauma
in the antepartum setting we recommend
clinical vigilance but no prophylactic
anticoagulation ORS in the postpartum
setting we do recommend prophylactic
anticoagulation from only set a prior VT
which was estrogen associate and this
could be a prior VTE related to
pregnancy or to or contraceptives
we recommend both antepartum as well as
postpartum prophylaxis and this is also
true for women who've had a prior
unprovoked VTE and women who are on
warfarin at baseline for instance for
mechanical heart valves are switched to
low molecular weight heparin during the
antepartum setting and restarted on
warfarin in the postpartum setting
I'd like to talk a little bit about the
hereditary thrombophilia so we know that
about 50% or even even higher percentage
of women who have VTE in pregnancy have
at least one inherited thrombophilia and
so there's a difference in management
for these women who have the inherited
thrombophilia is in terms of antepartum
and postpartum prophylaxis compared to
women who do not have these
thrombophilia x' and this really depends
not only on the woman's personal history
but also on the specific thermo philia
that she has as well as her family
history so as many different situations
that I'll talk through and I think
really for most of them we do recommend
postpartum anticoagulation and the
differences are more and whether we
recommend antepartum anticoagulation or
not so the high-risk situation is a
woman who has a homozygous factor v
leiden or proton and gene mutation also
in the high-risk situation we would
consider women who have
pound heterozygosity for factor v leiden
and a program and gene mutation so these
are the highest risk for pregnancy
associated VTE and so if a woman has one
of these high risk mutations does not
have a prior history of VTE but has a
family history of VTE we recommend both
antepartum and postpartum
anticoagulation if a woman has these
high risk mutations but did not have a
personal or a family history of VTE
would recommend antepartum clinical
vigilance and postpartum prophylaxis for
prior VTE and women who have homozygous
factor v leiden a prothrombin gene
mutation or compound heterozygotes
because i've had a prior VTE
regardless of family history recommend
both antepartum and postpartum
prophylaxis for all the other form
affiliates and this would be protein c
or protein s deficiency as well as
heterozygous for factor v leiden or
proton a gene mutation if the woman has
a family history of VTE we'd recommend
postpartum prophylaxis and if there's no
family history of VTE we recommend
clinical vigilance both antepartum and
postpartum and for any woman who's had a
prior VTE or any other thrombophilia we
recommend a m-- Department postpartum
prophylaxis and this is really for the
history of prior VTE more so than for
the samel philia itself I would like to
mention that these are official
recommendations however in the real
world
bounine called clinical setting there
are variations among practitioners and
if a woman has a high risk from
Ophelia's a friend since homozygous for
factor v leiden even if there's no
family history of VTE many practitioners
would use antepartum prophylaxis for
these women and similarly even a woman
with a somewhat lower risk of VTE such
as a factor v leiden heterozygosity if
there's a family history of VTE some
practitioners would recommend antepartum
as well as postpartum prophylaxis so
it's really a very good practitioner
dependent situation and one that
requires careful discussion with the
patient about risks and benefits of
antepartum prophylaxis so returning to
our case kind of summarizing the
findings here we felt that this patients
first DVT was likely provoked in a set
hormone exposure as well as smoking and
physical inactivity her second DVT in
the poner Emily we followed her likely
provoked in the postpartum setting so in
the setting of estrogen exposure going
forward she does have this history of
polycystic ovarian syndrome and meaning
hormone therapy to become pregnant so we
recommended considering full dose
warfarin or directoral and Jacqueline
during this time of hormonal stimulation
and this is based on evidence that was
published recently that suggests that
women who are on therapeutic
anticoagulation do not have an increased
risk of recurrent VTE when they're
exposed to hormones even if they do have
a hormone related VTE historically in
the past once a pregnancy is attained in
the future we did recommend antepartum
prophylaxis with an ox Oparin for the
complete duration of pregnancy as well
as postpartum prophylaxis with an ox
Oparin or with warfarin therapy for at
least six weeks after delivery and some
practitioners would actually recommend
up to eight weeks if a woman had a
caesarean section because this would
give additional risk factors for VTE so
kind of summarizing the overall thoughts
about pregnancy related VTE I would say
that the most important things to
consider what an individual patient's
risk factors are for thrombosis what
we're going to test for if there's a
family history of VTE you might consider
testing for hereditary thrombophilia
since this would have impact on
recommendations for prophylaxis in the
future and depending on results of
thermo philia testing as well as a
woman's personal and family history
making specific recommendations about
antepartum and postpartum prophylaxis
and certainly we'd also want to take
into account the method of delivery the
woman's other risk factors and the
specific situation that she may have had
a VTE in the initial situation so that
is what I wanted to talk about today and
I hope this was helpful for everyone