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Thrombophilic dimension of recurrent fetal loss
in Indian patients
Sonal Vora, Shrimati Shetty and Kanjaksha Ghosh
We studied the prevalence of acquired and genetic
thrombophilia in 198 women with recurrent fetal loss who
were having three or more than three abortions. Seventy-
nine women had only early pregnancy losses, that is, first
trimester abortions, 30 women had only late pregnancy
losses, that is, second and third trimester abortions
whereas 89 had both early and late pregnancy losses. The
control group included 100 age-matched fertile parous
women who did not have any obstetric complications and
had at least one normal healthy child. Several genetic and
acquired thrombophilia markers were studied. The
strongest association was observed with anticardiolipin
(odds ratio 22.6, confidence interval 5.7 – 89, P U 0) followed
by lupus anticoagulant, anti-b2 glycoprotein-1, antiannexin.
Association of antiphospholipid antibody syndromes was
detected with the time of pregnancy loss in anticardiolipin,
lupus anticoagulants, which was significantly associated
with early pregnancy loss as compared with second and
third trimester loss. In case of b2 glycoprotein-1,
antiannexin it was less significantly associated with early
pregnancy loss as compared with second and third
trimester loss. The risk of fetal loss with protein S deficiency
was the highest risk observed for any heritable
thrombophilia, followed by protein C, factor V Leiden,
endothelial protein C receptor, antithrombin III deficiency
and b448 fibrinogen polymorphism. Modest risks were also
observed with 5,10-methylenetetrahydrofolate reductase,
plasminogen activator inhibitor 4G/4G polymorphisms and
b448 fibrinogen polymorphism. A combination of two or
more than two genetic risk factors were observed in
55 (27.7%), whereas the genetic and acquired risk factors
were observed in 107 (54%) of the cases. Thrombophilia is
an important contributing factor for both early and late
pregnancy losses; approximately two-thirds of our cases of
unexplained fetal losses could be explained by acquired or
heritable thrombophilia or both, which is in line with
other western studies. Blood Coagul Fibrinolysis 19:581–
584 ß 2008 Wolters Kluwer Health | Lippincott Williams &
Wilkins.
Blood Coagulation and Fibrinolysis 2008, 19:581–584
Keywords: antiphospholipid antibodies, inherited thrombophilia, recurrent
spontaneous abortion
National Institute of Immunohaematology (ICMR), KEM Hospital, Parel, Mumbai,
India
Correspondence to Dr Kanjaksha Ghosh, MD, MRCP, MRCPI, FRC Path
Director, National Institute of Immunohaematology (ICMR) KEM Hospital, Parel,
Mumbai 400012, India
Tel: +91 22 24138518 19; fax: +91 22 24138521;
e-mail: kanjakshaghosh@hotmail.com
Received 22 August 2007 Revised 23 April 2008
Accepted 30 April 2008
Introduction
Pregnancy loss is one of the leading problems in women’s
health issues, that is, 9–13% of women in the reproductive
age group are reported to have one clinically recognized
fetal loss, 5% experience two or more losses whereas 1–2%
suffer three or more losses [1–3]. Up to 50% of these cases
remain unexplained after the standard investigations for
habitual fetal losses, which include the gynecological,
hormonal and karyotypic analyses. Thrombophilia, both
acquired and genetic, that is, the principal risk factors for
maternal thromboembolism have been implicated for
increased susceptibility to adverse pregnancy outcomes
such as fetal loss, recurrent spontaneous abortions (RSAs),
abruptio placentae, intrauterine growth retardation
(IUGR) and preeclampsia [4,5].
There is no comprehensive data on the prevalence of
both acquired and genetic risk factors in cases of unex-
plained fetal loss from India.
Material and methods
Patients
Among the 198 patients tested, 79 had only early pregnancy
loss (EPL), 30 had late pregnancy loss (LPL) whereas
89 patients had both EPL and LPL. Patients were included
in the study only if theconventional etiological factors were
found to be normal. If the patients presented immediately
after abortion, the samples were collected at least 4 months
after the abortion. If the patients were pregnant at the time
of presentation the tests for protein C (PC), protein S (PS)
and antithrombin (AT) III were repeated again 4 months
after delivery and only the confirmed postdelivery results
were considered. PC and PS were both measured to rule
out low activity of these proteins in the presence of
antiphospholipid antibodies.
Controls
One hundred age-matched normal healthy women who
had at least one normal healthy child and did not have any
Original article 581
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