Author Information
Chakre Shila*, Pardeshi Sachin*, Mayadeo NM
(* Assistant Professor, **
Professor, *** Third Year Resident. Department of Obstetrics and Gynecology, Seth G.S. Medical College
and K.E.M Hospital ,
Mumbai , India
Abstract
Antiphospholipid antibody syndrome in obstetric is clinically
defined by repeated unexplained abortion
before 10th weeks, unexplained fetal loss at or after 10th
week, premature birth before 34 weeks due to preeclampsia.[1] In Antiphospholipid
antibody syndrome placental mediated complications such as mild to severe
pregnancy induced hypertension, intrauterine growth restriction, intrauterine
fetal demise, missed abortion, antepartum hemorrhage and threatened abortion
are high and hence the rate of cesarean section is also high.[2] Antiphospholipid antibody syndrome management is based on combined
medical-obstetric high risk management and treatment with aspirin and injection
heparin but still there are refractory cases to treatment in which there are obstetric
complications. We present a case report of different obstetric outcomes in a
same patient with two separate pregnancy, one year apart in a treated Antiphospholipid
antibody syndrome.
Introduction
Antiphospholipid antibody syndrome is defined by the presence of pregnancy
morbidity and thromboembolic complications in presence of persistently
increased titers of Antiphospholipid antibodies.[3] There are
subtypes of antibodies in Antiphospholipid antibody syndrome. These are
antibody against lupus anticoagulant, anticardiolipin antibody and anti β2
glycoprotein-1 antibodies. In Antiphospholipid antibody syndrome, pathogenesis
for thrombosis is binding of Antiphospholipid antibodies to endothelial cells
which stimulate an up regulation of adhesion molecule increasing leucocyte
adhesions and thus thrombosis.[2] Anticardiolipin antibodies
interfere with anticoagulation pathway. Lupus anticoagulant lead to
thromboembolic event rather than clinical bleeding.[3]
Case Report
A 28
years old gravida 7, abortion 5, IUFD1, presented to antenatal OPD, with one
and half month of amenorrhea with urine pregnancy test positive. Patient
previous records were checked. She had consecutive five missed abortion before
10 weeks of gestation. She was evaluated for recurrent pregnancy loss. When she
was pregnant for 6th time, 2 years back her thrombophilia profile
showed lupus anticoagulant positive. During that pregnancy, she was started on
low dose aspirin 75 mg OD and low molecular weight heparin 40 mg subcutaneous
daily in prophylactic doses as there was no history of thrombotic events.
Patient was monitored throughout pregnancy for Antiphospholipid antibody syndrome
related complications. There was no complication noticed. At around 35 weeks of
gestation there was sudden intrauterine fetal demise despite of being on treatment.
The cause of intrauterine fetal demise was not explained. Patient delivered
vaginally, 2.6 kg, female baby. Placenta was sent for histopathology which
revealed no obvious placental thrombosis. Patient was advised to repeat lupus
anticoagulant after 6 weeks which again was positive. Patient conceived seventh
time after one year. Again she was started on low dose aspirin 75mg OD and low
molecular weight injection heparin 40 mg subcutaneous 24 hourly from 8 weeks of
gestation after cardiac activity was documented on ultrasonography. She was
monitored again for Antiphospholipid antibody syndrome complications by daily
fetal kick count, non stress test and obstetric Doppler. Obstetric Doppler at
32 weeks of gestation was suggestive of mild uteroplacental but no
fetoplacental insufficiency. Patient was followed up with Doppler after four
weeks which was showing the same changes.
Patient
delivered by cesarean section in view of precious pregnancy with baby weight of
2.7 kg, male child. Patient was discharged and was advised to continue low
molecular weight heparin for 6 weeks at dose of 40 mg subcutaneous 24 hourly.
The postpartum period was uneventful.
Discussion
Antiphospholipid
antibodies causes activation of endothelial cells, monocytes and platelets
causing overproduction of tissue factor, thromboxane A2 and complement
activation.[2] All these lead to change in hemostatic system during
normal pregnancy which results in hypercoagulable state. This leads to
thrombosis and then to pregnancy complications associated with Antiphospholipid
antibody syndrome. Antiphospholipid antibody trigger inflammatory response
leading to trophoblast damage and so abnormal placentation.[4] Abnormal
placentation which leads to obstetric
complication such as recurrent miscarriage, preterm delivery, oligohydramnios, prematurity,
intrauterine growth restriction, fetal distress, fetal or neonatal thrombosis, preeclampsia,
eclampsia, HELLP syndrome, arterial or venous thrombosis and placental
insufficiency.[2] Obstetric Antiphospholipid antibody syndrome
without thrombosis is currently managed by giving low dose aspirin and heparin.[5]
Unfractionated heparin and low molecular heparin act by binding to antithrombin,
to catalyze the molecule binding and altering the activity of serine protease
procoagulants. There are more adverse outcomes with antibody against lupus
anticoagulant.[6] Anticardiolipin antibody is associated with
clinical bleeding. In our patient lupus anticoagulant was positive which might
have lead to sudden intrauterine death even on treatment with low molecular heparin.
There is continued occurrence of late pregnancy complications like
preeclampsia, intrauterine growth restriction, prematurity and intrauterine
fetal demise despite treatment which
suggest the need for strict monitoring of the disease and treatment-related
complications throughout pregnancy.[7] In this pregnancy there was
only uteroplacental insufficiency on low molecular weight heparin.
Lastly to
conclude that severity of obstetric complications and thrombosis can be reduced
by giving thromboprophylaxis with heparin, a close watch should be kept in the
late pregnancy to prevent adverse outcomes though on heparin treatment. There
might be a need of more dose effective regimen of heparin treatment.
References
1.
Ruiz-Irastorza G, Crowther M, Branch W, Khamashta MA. Antiphospholipid
syndrome.
Lancet
2010;376(9751):1498-1509.
2.
Fosca A. F. Di Prima, Oriana
Valenti, Entela Hyseni, Elsa Giorgio4, Marianna Faraci, Eliana Renda, Roberta
De Domenico, Santo Monte. Antiphospholipid Syndrome during pregnancy: the state
of the art. Journal of Prenatal Medicine 2011;5(2):41-53.
3. Henry Namme Luma,
Marie-Solange Doualla, Elvis Temfack, Servais Albert Fiacre, Eloumou Bagnaka,
Emmanuella Wankie Mankaa, Dobgima Fofung. The antiphospholipid antibody syndrome: a case
report.International Medical Case Reports Journal
2012:563–67.
4.
Stone S, Khamashta MA, Poston L. Placentation, Antiphospholipid syndrome and
pregnancy outcome. Lupus 2001; 10: 67-74.
5.
Sylvie Bouvier, E´ va Cochery-Nouvellon, Ge´ raldine Lavigne-Lissalde, E´ rick
Mercier, Tess Marchetti, Jean-Pierre Balducchi, Pierre Mar`es and
Jean-Christophe Gris. Comparative incidence of pregnancy outcomes in treated
obstetric antiphospholipid syndrome: the NOH-APS observational study. Blood
2014;123(3):404-413.
6.
Galli M, Luciani D, Bertolini G, Barbui T. Lupus anticoagulants are stronger
risk factors for thrombosis than anticardiolipin antibodies in the
Antiphospholipid syndrome: a systematic review of the literature.Blood 2003;
101: 1827-32.
7. Dadhwal V, Sharma AK
Citation
Chakre
S, Pardeshi S, Mayadeo NM