Hematological and

Thromboembolic
Disorders in
Pregnancy
TAGUD, LYZEL
CSU-MEDICINE

Normal Pregnancy
Hypervolemic state
Physiologic/ Dilutional Anemia
Increase WBC
Mild thrombocytopenia

Hypercoagulable state
Diminished fibrinolysis

Blood volume

HYPERVOLEMIC
STATE

Plasma Volume

Red Cell Volume

DILUTIONAL
ANEMIA

Dilutional/
Physiological Anemia
Defined by CDC as:
- 11 g/dL in the first and third
trimesters, and
- 10.5 g/dL in the second trimester

low hgb level

low hct level

Leukocyte Count

During active labor there may be another

normal increase, even in the absence of
infection 25,000/uL

Platelet Count
GESTATIONAL THROMBOCYTOPENIA
Typically defined as below the 2.5th percentile
or 116,000/uL
partially due to the hemodilutional effect
also due to increased platelet consumption

Coagulation and
Fibrinolysis

Coagulation and
Fibrinolysis
Fibrinogen, Factors II, VII, X, XII, and XIII increase
Von Willebrand factor increases
Antithrombin, Protein C, Factor V, and Factor IX
levels remain unchanged or increased slightly
Fibrinolytic activity is reduced in normal
pregnancy

HYPERCOAGULABLE STATE

Hematologic
Disorders

I. RED BLOOD CELL

A. Anemia
a.
b.

Acquired
Hereditary

B. Polycythemia

II. PLATELET DISORDERS

C.
D.
E.
F.

Inherited Thrombocytopenia
ITP
Thrombocytosis
Thrombotic Microangiopathies

III. INHERITED COAGULATION DEFECTS

G.
H.
I.
J.

Hemophilia
Factor VII or IX Inhibitor Defects
Von Willebrand disease
Other Coagulation Factor Defects

ANEMIA

Clinical picture
SYMPTOMS:

SIGNS

Lethargy
SOB
Palpitations
Chest pain
Headaches
Dizziness and fainting

Pallor
Tachycardia
Soft Ejection Systolic
murmur

Effects on Pregnancy
preterm birth
low birthweight
small-for-gestational age infants
Lower mental development

Anemia from Acute Blood

Loss
The two most common causes of anemia
during pregnancy and the puerperium are
iron deciency and acute blood loss
Anemia is much more common postpartum
from obstetrical hemorrhage.
Conditions wherein blood transfusions are not
indicated, instead iron therapy is given for at least
3 months:
moderately anemic woman (hgb 7 g/dL)
hemodynamically stable,
able to ambulate without adverse symptoms
not septic

Iron Deciency Anemia

In a typical singleton gestation, the
maternal need for iron averages close to
1000 mg:
a. 300 mg is for the fetus and placenta
b. 500 mg for maternal hemoglobin mass
expansion
c. 200 mg that is shed normally through the gut,
urine, and skin

consequence primarily of expansion of

plasma
volume
without
normal
expansion of maternal hemoglobin
mass.

Iron Deciency Anemia

Diagnosis
erythrocyte hypochromia and microcytosis
is less prominent in the pregnant woman.
The initial evaluation of a pregnant woman with
moderate anemia:
hemoglobin, hematocrit, and red cell indices
measurement of serum iron, ferritin, or both
careful examination of a peripheral blood smear

Bone marrow biopsy- lack of stainable iron

Iron Deciency Anemia

Treatment
Daily oral supplementation with
30- 60 mg of elemental iron
400 ug of folic acid

Simple iron compounds (200 mg)daily:

ferrous sulfate, fumarate, or gluconate

parenteral iron:
Ferrous sulfate is safer than iron-dextran

Megaloblastic Anemia
characterized by blood and bone-marrow
abnormalities from impaired DNA synthesis.
Rare
Includes:
Folic Acid Deficiency
Vit. B12 Deficiency

Megaloblastic Anemia

Folic Acid Deciency

pernicious anemia of pregnancy
Recommended requirement of folic acid
nonpregnant women- 50 to 100 ug/day
pregnant- 400 ug/day

Treatment:
a. folic acid (1mg p.o daily)
b. nutritious diet
c. Iron
Prevention: A diet sufficient in folic acid

Hemolytic Anemia
There is accelerated erythrocyte
destruction which can be due to:
Autoimmune
Drug- induced
Pregnancy Induced
Paroxysmal Nocturnal Hemoglobinuria
Inherited Erythrocyte Membrane Defect
Hereditary Spherocytosis
Non- Hereditary Spherocytosis

Hemolytic Anemia

Drug- induced Hemolytic Anemia

usually occurs as a result of drug-mediated
immunologic red cell injury.
more often related to a congenital erythrocyte
enzymatic defect, such as glucose-6-phosphate
dehydrogenase (G6PD) deciency
Hemolysis is mild in most cases
Resolves with drug withdrawal
can be prevented by avoidance of the drug.

Hemolytic Anemia

Severe Preeclampsia and

Eclampsia
Fragmentation or microangiopathic hemolysis
with thrombocytopenia is relatively common.
Mild degrees are likely present in most cases of
severe disease
may be referred to as HELLP syndrome
hemolysis,
elevated liver enzymes,
low platelet.

Hemolytic Anemia

Acute Fatty Liver in Pregnancy

Associated with moderate to severe hemolytic
anemia
The most fulminant acquired hemolytic
anemia encountered during pregnancy is
caused by:
Exotoxin of Clostridium
Group A -hemolytic streptococcus

APLASTIC AND
HYPOPLASTIC ANEMIA
Characterized by pancytopenia and
markedly hypocellular bone marrow.
It is rare in pregnancy
Some of the pregnancy induced
hypoplastic anemia:
a. Diamond- blackfan anemia
b. Gauchers disease

Definitive tx: bone marrow transplant

Polycythemia
EXCESSIVE ERYTHROCYTOSIS

I. Secondary Polycythemia
during pregnancy is usually related to chronic
hypoxia due to maternal congenital cardiac
disease or a pulmonary disorder
If polycythemia is severe, the probability of a
successful pregnancy outcome is low.

II. Polycythemia Vera

myeloproliferative hemopoietic stem cell
disorder
characterized by excessive proliferation of
erythroid, myeloid, and megakaryocytic
precursors.
Symptoms are related to increased blood
viscosity, and thrombotic complications are
common.
Fetal loss has been reported to be high in
women
pregnancy outcome may be improved with
aspirin therapy

HEMOGLOBINOP
ATHIES
SICKLE CELL AND THAL ASSEMIAS

I. Sickle Cell
Hemoglobinopathies
Hemoglobinopathies with Sickle cell
syndrome:
Sickle cell anemia (HbSS)
Sickle cell- hemoglobin c dse (HbSC)
Sickle cell- - thalassemia dse (Hb S/B0 or Hb
S/B+)
Sickle- cell E dse (Hb SE)

PATHOPHYSIOLOGY
RBC w/ hgb S
(deoxygenated)
sickling & hemoglobin aggregates
(constant sickling and de-sickling)
Membrane damage
slow erythrocyte transit through the microcirculation
vaso-occlusion
endothelial cell adhesion
erythrocytic dehydration
vasomotor dysregulation

Sickle Cell
Hemoglobinopathies

In Pregnancy
Rare but a serious burden
Common maternal morbidity:
a.
b.
c.
d.

Ischemic necrosis of multiple organs

Pyelonephritis
Pneumonia
Acute Chest Syndrome

Possible perinatal outcome

Hemoglobin SS and SC disease
a. FGR
b. Stillbirth
c. Neonatal Death

in

women

with

Sickle Cell
Hemoglobinopathies

Management during
Pregnancy
necessitates close observation, Women are kept comfortable
but not overly sedated
IVF, opioids, and oxygen therapy
Prenatal folic acid supplementation with 4 mg/day (ACOG,
2007)
Fetal assessment.
Labor: epidural analgesia is ideal
Delivery: PRBC transfusion
Vaginal delivery not contraindicated
Others: Prophylactic red cell transfusion

Pneumococcal vaccine

II. Thalassemias
characterized by impaired production of
one or more of the normal globin peptide
chains.
The two major forms involves
impaired production or instability either of peptide chains ( thalassemia)
or of -chains ( thalassemia)

Alpha- Thalassemias

Alpha- Thalassemias

In Pregnancy.
Hemoglobin H disease ( 4)
compatible with extrauterine life
The neonate appears well at birth but soon
develops hemolytic anemia.
Anemia in these women usually is worsened
during pregnancy

Alpha- Thalassemias

Pregnancy
Hemoglobin Bart Disease
deletion of all four -globin chain genes
(/)
homozygous thalassemia
Hemoglobin Bart : has an appreciably
increased affinity for oxygen
Causes stillbirths

-THALASSEMIA MAJOR OR
COOLEY ANEMIA
Homozygous
the neonate is healthy at birth, but as the
hemoglobin F level falls, the infant becomes
severely anemic and fails to thrive.
Prognosis is improved by iron chelation
therapy with deferoxamine

Platelet
Disorders

Platelet Disorders

Inherited Thrombocytopenias
Bernard-Soulier syndrome
characterized by lack of platelet membrane
glycoprotein (GPIb/IX)
May-Hegglin anomaly
autosomally dominant
characterized by thrombocytopenia,
platelets, and leukocyte inclusions

giant

Platelet Disorders

Immune Thrombocytopenic
Purpura
Also called idiopathic thrombocytopenic purpura
(ITP)
usually results from a cluster of IgG antibodies
directed
against
one
or
more
platelet
glycoproteins
Antibody-coated
platelets
are
destroyed
prematurely in the reticuloendothelial system,
especially the spleen.

Acute vs. Chronic

Acute ITP

Chronic ITP

often a childhood disease

Adults (young women)

resolve spontaneously

rarely resolves spontaneously

Secondary forms of chronic thrombocytopenia

appear in association with:
a. systemic lupus erythematosus
b. Lymphomas
c. Leukemias
d. systemic diseases.

Platelet Disorders

Immune Thrombocytopenic
Purpura
Treatment
Prednisone - 1 mg/kg/day PO (for improvement)
Corticosteroid therapy usually produces
amelioration.
high-dose immunoglobulin : IV

Platelet Disorders

Immune Thrombocytopenic
Purpura
In pregnant women with no response to
steroid or immunoglobulin therapy:
open or laparoscopic splenectomy may be
effective.
In late pregnancy, cesarean delivery may be
necessary for exposure.
Intravenous anti-D IgG
There usually is improvement by 1 to 3 days with
a peak at approximately 8 days.

Fetal and Neonatal Effects

Platelet-associated IgG antibodies cross the
placenta and may cause thrombocytopenia in
the fetus-neonate.
May cause:
Fetal death from hemorrhage
increased risk for intracranial hemorrhage with
labor and delivery

Thrombocytosis
(thrombocythemia )
defined as persistent platelet counts > 450,000/L.
usually is asymptomatic, but arterial and venous
thromboses may develop
a. secondary or reactive thrombocytosis
Common causes:

- iron deficiency
- infection
- inflammatory diseases
- malignant tumors
b. essential thrombocytosis

Thrombocytosis in Pregnancy
Normal pregnancies have been described in
women whose mean platelet counts were >
1.25 million/L
complicated by spontaneous abortion, fetal
demise, and preeclampsia (Niittyvuopio and
colleagues, 2004)
Treatment during pregnancy includes:
aspirin,
dipyridamole,
heparin,
platelet pheresis, or combinations thereof

THROMBOTIC MICROANGIOPATHIES
1.THROMBOTIC THROMBOCYTOPENIC
PURPURA
Pentad of thrombocytopenia (Moschcowitz)
Fever
Neurological abnormalities
Renal impairment
Hemolytic anemia

Deficiency of a von Willebrand factor - clearing protease

ADAMTS-13

2.HEMOLYTIC UREMIC SYNDROME

With more profound renal involvement and fewer neurological
aberrations
Usually due to endothelial damage incited by viral or bacterial
infections

THROMBOTIC MICROANGIOPATHIES

CLINICAL PRESENTATION
Thrombocytopenia, fragmentation hemolysis, and
variable organ dysfunction
Preceding viral prodrome (40 % cases)
Neurological symptoms develop in up to 90 %

Headache
Altered consciousness
Fever
Stroke

Renal failure
Severity: HUS > TTP

THROMBOTIC MICROANGIOPATHIES

Treatment
Plasmapheresis with fresh-frozen plasma
replacement
not indicated for preeclampsia-eclampsia complicated
by hemolysis and thrombocytopenia

Red cell transfusions

Prednisone
For those with mild neurological symptoms
200 mg orally, daily
Plasma exchange with FFP

THROMBOTIC MICROANGIOPATHIES

PREGNANCY
Severe
preeclampsia
and
ecclampsia
complicated
by
thrombocytopenia
and
overt
hemolysis have been confused with
TTP and vice versa
Hemolytic anemia is rarely seen in
preeclampsia, even with HELLP syndrome
Hepatocellular necrosis is not described in
TTP
Delivery does not improved TTP

THROMBOTIC MICROANGIOPATHIES

LONG TERM PROGNOSIS

Pregnant women with thrombotic
microangiopathy have a number of
long-term complications:
renal disease requiring dialysis ,
transplantation, or both
severe hypertension
transfusion-acquired infectious diseases

Non-pregnant women who have

recovered from TTP:
Persistent cognitive defects

INHERITED COAGULATION
DEFECTS

von Willebrand Disease

Heterogenous group of approximately 20 functional
disorders
Most commonly inherited bleeding disorders
prevalence is as high as 1 to 2 percent

Involves aberrations of factor VIII complex and

platelet dysfunction
Most variants are inherited as autosomal dominant
traits
a. Types I and II - most common variants (Type I accounts
for 75% of vWD)
b. Type III - most severe and is phenotypically recessive

Pathogenesis: von Willebrand

Disease

Aberratio
ns in vWF

Impaired
platelet
adhesion
to
subendothelial
collagen
Impaired formation of
a primary hemostatic
plug at the site of
blood vessel injury
Impaired stabilization
of the
coagulant
properties of factor VIII

Bleeding
problems

CLINICAL MANIFESTATION
LABORATORY FEATURES:

Characterized clinically
by :
1.Easy bruising
2.Epistaxis
3.Mucosal hemorrhage
4.Excessive bleeding with
trauma, including
surgery

Prolonged bleeding
time
Prolonged PTT
Decreased vWF
antigen levels
Decreased factor VIII
immunological as well
as coagulationpromoting activity
Inability of platelets in
plasma from an
affected person to
react to a variety of
stimuli

Pregnancy and vWD

Normal pregnancy
Maternal levels of both factor VIII as well as vwf antigen increases

Pregnant women with vWD

Develop normal levels of factor VIII coagulant activity as well as
vwf antigen

If factor VIII activity is very low or if there is bleeding:

Treatment is recommended
Desmopressin by infusion may transiently increase factor viii and
vwf factor levels, especially in patients with type I disease

With signicant bleeding

15 or 20 units or "bags" of cryoprecipitate are given every 12 hours

Pregnancy outcomes are generally good

Postpartum hemorrhage is encountered in up to 50 percent of
cases

THROMBOEMBOLIC
DISORDERS

Introduction

The risk of venous thrombosis and

pulmonary embolism:
6x higher during the 3rd trimester,
22x higher in the 1st 6 wks postpartum (Sultan,
2011, UK)

Incidence of thromboembolic events

averages approximately 1/ 1000
pregnancies.
DVT is more frequent antepartum,
Pulmonary embolism is more common in the
rst 6 wks postpartum (Jacobsen et.al., 2008,
Norway)

Pathophysiology
Predisposing factors for thrombosis
development that is further increased
during pregnancy (R. Virchow):
a.Stasis
Most constant predisposing risk factor

b.Local trauma
c. Hypercoagulability

Table 52-1. Some Risk Factors Associated

with an Increased Risk for
Thromboembolism

Table 52-1. Some Risk Factors Associated

with an Increased Risk for
Thromboembolism General
Obstetrical
Prior history of
embolism
The most important

35 y/o andrisk
above

Cancer
factor

CSD

Diabetes

Hemmorrhage & anemia

Hyperemesis

Immobility

Connective tissue dse

15 25 % of all venous
Dehydration

Immobility
thromboembolism
cases
Multifetal gestation

Infection
during pregnancy
are and inflammatory dse
Multiparity

Myeloproliferative
recurrent events
(ACOG, dse
Preeclampsia

Nephrotic syndrome
Puerperal infection
2011).

Obesity

Oral contraceptive use

Orthopedic surgery

Paraplegia

Sickle cell dse

Smoking

Thrombophilia

Table 52-1. Some Risk Factors Associated

with an Increased Risk for
Thromboembolism General
Obstetrical

CSD

Diabetes

Prior history of embolism

The next most important

35 y/o and above

individual risk
factor

Cancer

Connective tissue dse

Orthopedic surgery

Paraplegia

Sickle cell dse

Smoking

20- 50% of women

who

Dehydration
Hemmorrhage & anemia
develop a venous
thrombosis

Immobility
Hyperemesis
during pregnancy
or
Immobility

Infection and inflammatory dse

an
Multifetal gestation postpartum have

Myeloproliferative dse
Multiparity
identiable underlying

Nephrotic syndrome
Preeclampsia
genetic disorder
(ACOG,

Obesity
Puerperal infection
2011.

Oral contraceptive use

Thrombophilia

Thrombophilias
Inherited or acquired deficiencies on
proteins
that
inhibit
coagulation
cascade
which
can
lead
to
hypercoagulability and recurrent VTE.
Obstetrical complications associated
with thrombophilias:
Pregnacy loss
Preeclampsia
Placental Abruption
FGR

Thrombophilias
Inherited Thrombophilias:
a. Antithrombin Deficiency
b. Protein C Deficiency
c. Protein S Deficiency
d. Activated Protein C Resistance Factor V
Leiden Mutation G20210A
e. Hyperhomocystenemia

Acquired Thrombophilias:
a. Antiphospholipid antibody
b. Heparin induced thrombocytopenia
c. cancer

Inherited thrombophilias

Antithrombin Deciency
The most thrombogenic
heritable coagulopathies.

of

the

Rare 1 in 2000 to 5000 individual.

Thrombosis risk during pregnancy without
personal or family history is

3- 7%.

Thrombosis risk during pregnancy with

personal or family history is 11- 40%.
Almost always autosomal dominant and
homozygous and is lethal.

Inherited thrombophilias

Antithrombin Deciency
Antithrombin
Synthesized in the liver.
Binds and inactivate thrombin and the activated
coagulation factors IXa, Xa, XIa, and XIIa.
Accelerated by heparin.

TYPE I Antithrombin Deciency

result of reduced synthesis of biologically
normal antithrombin

TYPE II Antithrombin Deciency

Characterized by normal levels of antithrombin
with reduced functional activity.

Inherited thrombophilias

Antithrombin Deciency
Untreated women had a 50% risk of
stillbirth and FGR.
Management:
a. Heparin- for affected women during pregnancy
with or without prior thrombosis.
b. Recombinant human antithrombin- If
anticoagulation must be necessarily withheld
(surgery, delivery).
c. Antithrombin concentrate infusion +
therapeutic coagulation- pregnant woman
with antithrombin deficiency who developed
thrombosis during 3rd trimester.

Inherited thrombophilias

Protein C Deciency
Prevalence: 2 to 3 per 1000
6 to 12 fold increased risk for
VTE.
Protein C
Activated by binding of thrombin to
thrombomodulin
inactivating factor Va and VIIIa.
Also
inhibits
the
synthesis
plasminogen- activator inhibitor 1.
Largely unchanged in pregnancy.

of

Inherited thrombophilias

Protein S Deciency
Prevalence: 2 per 1000
Measured antigenically determined
free, functional and total S levels.
All three decline during normal
gestation thus diagnosis is difficult in
pregnant women

For screening: measure free S

Protein during 2nd or 3rd trimester.

 Purpura Fulminans
Associated with neonatal
homozygous protein C or S
Deficiency.
Characterized by extensive
thromboses in microcirculation soon
after birth leading to skin necrosis.

Inherited thrombophilias

Activated Protein C Deciency /

Factor V Leiden Mutation
The most prevalent of the known
thrombophilia syndrome
Heterozygous inheritance of factor V
leiden is the most common heritable
thrombophilia.
Accounts for 40% of VTE cases in
pregnancy
characterized by resistance of plasma to the
anticoagulant effects of activated protein C.
Causes:
a. Missense mutation in factor V gene

Inherited thrombophilias

Activated Protein C Deciency /

Factor V Leiden Mutation
The abnormal factor V retains its
procoagulant activity thus predisposed to
thrombosis.
Diagnosis: DNA analysis

Inherited thrombophilias

Prothrombin G20210A Mutation

missense mutation in prothrombin gene

There is excessive accumulation of

prothrombin which can be converted to
thrombin.
For heterozygous carrier with history, the
risk exceeds 10 %.

Inherited thrombophilias

Hyperhomocysteinemia
There is elevated levels of plasma
homocysteine and is a weak risk factor.
Autosomal recessive
Causes:
C667T thermolabile mutation of 5,10methylene-tetrahydrofolate reductase
(MTHFR)- the most common cause
Deficiency in the enzymes involved in
methionine metabolism.
Nutritional deficiencies: folic acid, Vitamin
B6, or Vitamin B12.

Overview of inherited thrombophilias and their effect on coagulation cascade.

Antithrombin Deciency

G2021A
mutatio
n

Dec.
thrombin
neutralization

nc. Prothrombin level

ROTHROMBIN

THROMBIN

Factor V
leiden
Mutation

Thrombin binds to
thrombomodulin
on endothelial
cells

Factor V
resistant to
degradation
by protein C

Protein
S

Inactivat
es factor
Va
Protein S

Inactivat
es factor
VIIIa

COAGULATION

Protein
C
decie
ncy

Protein S
Activated protein C

Protein C

Hyperhomocysteinem
ia

Acquired thrombophilias

Antiphospholipid Antibodies
Autoantibodies
directed
against
cardiolipin or against phospholipid
binding
proteins
such
as
2glycoprotein I.
Commonly but not always found in
patients with SLE
5-12% risk of thrombosis during
pregnancy and puerperium (ACOG,
2012).

Acquired thrombophilias

Antiphospholipid Antibodies
Defined by the following features (ACOG,
2012):
1. At least 1 unexplained fetal death at or
beyond 10 wks.
2. At least one preterm birth before 34 wks
because of pre- eclampsia, severe
eclampsia, or placental insufficiency.
3. At least 3 unexplained consecutive
spontaneous abortion before 10 wks.
In
women
with
this
state,
thromboembolism
most
commonly
involves the lower extremities.

Deep- Vein Thrombosis

Clinical Presentation:
most venous thromboses are
conned to the deep veins of
lower extremities.
a. Iliofemoral- 70 %
b. Iliac vein- 17 %
c. Calf veins- 6%

Most cases during pregnancy

are left sided.

DEEP VEIN THROMBOSIS

Clinical Presentation
Abrupt in onset, with pain and edema
of the leg and thigh
Reflex arterial spasm pale, cool
extremity with diminished pulsations
Homans sign- calf pain in response
to squeezing or to Achilles tendon
stretching.
30- 60 % of women with DVT are
asymptomatic.

DEEP VEIN THROMBOSIS

Diagnosis
A. Compression Ultrasonography

Recommended by ACOG as initial

diagnostic test

Non-invasive technique that is

currently the most used rst line test
to detect DVT.

normal findings with venous UTZ result do

not always exclude pulmonary
embolism.

Thrombosis assoc. with PE during pregnancy

frequently originates in the iliac veins.

DEEP VEIN THROMBOSIS

Diagnosis
A. Compression Ultrasonography
B. MRI

Immensely useful for diagnosis of

iliofemoral and pelvic thrombosis.

C. D-Dimer Screening Tests

Their use in pregnancy is uncertain but

negative result is reassuring.

D. Venography
Gold standard to exclude lower
extremity DVT.

Complications: fetal exposure, thrombosis,

time consuming.

DEEP VEIN THROMBOSIS

Management
Anticoagulation and limited activity!
During pregnancy: heparin
(unfractionated/ LMWH) is continued
Post- partum : begun simultaneously with
warfarin.
After symptoms have abated: graded
ambulation, elastic stockings &
anticoagulation continued.
Compression stockings is continued for 2
yrs to reduce incidence of Posthrombotic
Syndrome ( chonic leg paresthesial pain,
intractable edema, skin change, leg ulcer)

DEEP VEIN THROMBOSIS

Management: Anticoagulation

ACCP suggest preferential use of

LMWH during pregnancy because of:
Better bioavailability
Longer plasma half-life
More predictable dose response
Reduced risks of osteoporosis and
thrombocytopenia
Less frequent dosing

DEEP VEIN THROMBOSIS

Management: Anticoagulation
Unfactionated Heparin
Should be considered initial treatment of
thromboembolism and in situation in which
delivery, surgery, or thrombosis maybe
necessary.
Safe during breastfeeding.

LMWH
Derivatives of UFH
Cannot cross placenta
Activates antithrombin, greater activity against
factor Xa

Should be avoided in women with renal failure

DEEP VEIN THROMBOSIS

Management: Anticoagulation
Warfarin
Generally contraindicated during pregnancy
Used during
heparin

postpartum together with

Therapeutic doses of UFH/ LMWH are

maintained for 5 days & unitl INR is maintained
at 2-3 for 2 consecutive days (ACOG, 2010).
This is to prevent the anti- protein C effect of
warfarin leading to paradoxical thrombosis
and skin necrosis.
Safe during breastfeeding

DEEP VEIN THROMBOSIS

Management: Anticoagulation
During Labor
Anticoagulation should be converted from
LMWH to shoter half- life UFH to avoid epidural
or spinal hematoma during neuraxial blockade.
ACCP- for planned delivery discontinue 2x daily
SQ UFH or LMHW 24 hours before labor
induction or CSD.
ACOG- adjusted dose SQ LMWH of UFH can be
discontinued 24-36h before labor induction or
CSD.

DEEP VEIN THROMBOSIS

Management: Anticoagulation
During Labor
ASRAP- withholding neuraxial blockade
for 10- 12h after last prophylactic dose of
LMHW or 24h after the last therapeutic
dose.
If labor begins while taking UFH,
clearance can be verified by aPTT
Protamine sulfate.
For women in whom anticoagulation
therapy
has
temporarily
been
discontinued, pneumatic compression
devices are recommended (ACOG, 2011)

DEEP VEIN THROMBOSIS

Management: Anticoagulation
During Delivery
Heparin therapy is generally stopped
during labor and delivery
ACOG and AAP- recommend restarting
UFH or LMHW no sooner than 4-6h after
vaginal delivery, or 6-12h after CSD.
Slow IV administration of protamine
sulfate generally reverses the effect of
heparin

DEEP VEIN THROMBOSIS

Management: Anticoagulation
Complication
Hemorrhagecomplication

most

serious

Thrombocytopenia (HIT)
Osteoporosis
The latter two can be reduced with
LMHW

DEEP VEIN THROMBOSIS

Management: Anticoagulation
Heparin Induced Thrombocytopenia
Two types
a.

Most common- nonimmune, benign, reversible

that develops within 1st few days of therapy and
resolves ~5 days w/o therapy cessation.

b.

Severe form- result from an immune reaction

involving IgG antibodies direstec against
complexes of platelet factor 4 and heparin.

Incidence: < 0.1%

Management: stop heparin therapy!

initiate alternative anticoagulation.
a.

LMHW

b.

Danaparoid (ACPP)

c.

Fondaparinux and argatroban

And

DEEP VEIN THROMBOSIS

Management: Anticoagulation
Heparin Induced Osteoporosis
Bone loss may develop within 6 months
or longer of heparin therapy and more
prevalent with cigarette smoker.
Women treated with any haeparin should
be encouraged to take 1,500 mg calcium
supplement.

Supercial Venous Thrombophlebitis

Strictly limited to the superficial veins of

saphenous system typically seen with
varicosities or sequela to an indwelling IV
catheter.

Heparin is given when DVT is involved

Pulmonary Embolism

causes 10% of maternal death but is

uncommon in pregnancy

Incidence: 1 in 7000 pregnancies

30- 60 % of women with DVT will have
coexisting silent Pulmonary embolism.

PULMONARY EMBOLISM

Clinical Presentation
Dyspnea, chest pain
Cough
Syncope
Hemoptysis
Tachypnea, apprehension, tachycardia
Pulmonic closure sound, rales, friction
rub
ECG: right axis deviation, T
inversion in anterior chest leads

wave

Alveolar-arterial difference of >20 mmHg

PULMONARY EMBOLISM

Massive Pulmonary Embolism

Defined
as
embolism
hemodynamic instability.

causing

Most likely caused by a saddle embolism.

It is important to infuse crystalloids
carefully and to support BP with
vasopressor.
O2
treatment,
ET
intubation
and
Mechanical ventilation are completed
preparatory
to
thrombolysis,
filter
placement, or embolectomy.

PULMONARY EMBOLISM

Diagnosis
CT Pulmonary Angiography
Ventilation- Perfusion Scintigraphy- Lung
scan
Magnetic Resonance Angiography
Intravascular Pulmonary Angiography
There is controversy regarding the best
imaging method to be used in pregnancy.

PULMONARY EMBOLISM

Management
Immediate
treatment
anticoagulation.

is

full

Complementary procedures
a. Vena Caval Filters- can be used in
pregnant women who recently suffered PE
and must undergo CSD.
b. Thrombolysis- provide more rapid lysis
than heparin. (eg. Tissue plasminogen
activator)
c. Embolectomy- stillbirth rate is 20-40 %

Thromboprophylaxis

ACOG- recommended placement of pneumatic

compression devices before CSD for all women not
already receiving thromboprophylaxis.

ACCP- recommends risk- adjusted approach to

thromboprophylaxis

See table 52-8

ACCP Recommendation for

thromboprophylaxis following CSD
Minor Risk
Factors

Major Risk
factors

Immobility

Previous VTE

Antithrombin Deficiency

Factor V leiden

Prothrombin G20210A

SLE

Heart Disease

Sickle Cell Anemia

Multifetal pregnancy
Postpartum
hemorrhage >1L
Smoking > 10
cigarettes/day

Medical condition

Thrombophilia

BMI > 30 kg/m2

Postpartum hemorrhage > 1 L with surgery

Thrombophilia

Blood transfusion
Postpartum infection

Concurrent malignancy

FGR

Protein C deficiency

Protein S deficiency

Preeclampsia