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INTRODUCTION: -
Pre-eclampsia is a syndrome complex specific to man which
induces hypertension & prorteinurea or edema in pregnant
females. It has been traditionally thought to occur late in
pregnancy (1). This may be true for majority of cases. However,
clinicians and academicians of the subject know very well that
pre-eclampsia can occur as early as 20 weeks of pregnancy. This
was a subject of scientific investigations for many workers in
the field. Thus pre-eclampsia at or before 28 weeks was
classified as one remote from term (2).
A DISTINCT ENTITY: -
The behavior of pre-eclampsia remote from term was much more
furious and devastating than its older counterpart. We started
investigations in this area and found that pre-eclampsia remote
from term is a distinct entity. This paper of ours which was
subsequently published (3), proved to be a prize winning paper
at the All India Conference of O. & G. at Jaipur. After this
paper we embraced upon a much more challenging and difficult
course of following up these cases who had pre-eclampsia remote
from term as regards their behavior in subsequent obstetrics. We
found that these mothers have a significantly higher risk of
developing pre-eclampsia in subsequent pregnancy. The disease
runs a furious course in these mothers, resulting in higher
incidence of renal failures, IUGR and still birth. These mothers
had a higher chance of developing hypertension, subsequently in
life. This work was also subsequently published (4).
OBSTETRICS CONSEQUENCES OF ANTIPHOSPOLIPID ANTIBODY SYNDORME:
-
It was during the time that papers on this entity started
getting published. Antiphospholipid Antibodies or APA were
identified to be of six types. Of these six, (5) three were
important for us clinicians:
A) Anticardiolipin antibodies ( ACA)
B) Lupus anti coagulant ( LAC)
C) Biologically False Positive Serological Test For Syphilis (BFPSTS).
These three are inter-related and presence of one may indicate
the presence of other as well. However, the international
recommendation today suggests that if one is interested in using
LAC as a test for Antiphospholipids than it must fulfill the
following criteria:
1) Prolongation of APTT
2) That the abnormality is caused by inhibition
3) That this inhibitor is directed against phospholipids.
In the same way for BFPSTS to be exclusively used for testing
antiphosplolipids, the following are the criteria:
· Person should serologically test continuously positive for
syphilis for 6 months without treponemal infection.
No such recommendations are made for ACA and thus this is the
test primarily involved in picking up APA cases. However, what
clinical significant has the testing of IgM and IgG have in ACA,
bearing their cross reactivity in mind, is a matter currently
under investigation.
Soon a host of obstetric consequences were attributed to APA
(6). These include:
1) Recurrent miscarriage
2) Intra Uterine Growth Retardation
3) Pre eclampsia remote from term
4) Recurrent still births and others (6)
When these results were flowing in, we started investigating cases of
Recurrent Spontaneous Abortions (RSA) cases for APA. These were
essentially late first and second trimesters. We found a strong
association between these cases of RSA and APA syndrome (7).
Other workers in this field soon confirmed similar results, as
well.
APA SYNDROME AND PE REMOTE FROM TERM: -
Intrigued by the strange and distinctly different behavior
of P.E. remote from term, we were seeking explanations for the
same. Encouraged by the reports of investigations in this field
(8) we now started investigating the association between APA
syndrome and P.E. remote from term. To our happiness we could
achieve a breakthrough. A close association emerged between the
two (9). Soon it became a routine for us to request APA testing
for cases of P.E. remote from term.
PATHOPHYSIOLOGY INVOLVED: -
APA are antibodies with, a strong activity against vascular
tree. APA are a diverse family of auto antibodies which share a
common reactivity with negatively charged phospholipids (5). The
most common theories for their mechanism of action may be
divided into:
1) Those that ascribe APA to disrupt platelet function and
2) Those that postulate that APA interfere with the function of
endothelial cells.
A major advance was made by the demonstration that both LA and
ACA require plasma protein cofactors to exert their action. They
are charged particles (5). By this virtue they have a tendency
to interact with the decidual-placental interface. They tend to
bring about changes in vascular endothelium in such a way that
it reduces the caliber of the vessels. The vascularity is
affected and the effective number of vessels decline. This is
known as a state of decidual vasculopathy (10-11). Immunological
staining methods have shown a clear deposition of immune
complexes at the vessels of the deciduo-placental interface so
affected. These vascular changes in turn produce the resultant
manifestations of pre eclampsia.
Once the vasospasm and vasculopathy occurs,
the BP rises to compensate for the poor vascularity. It is a
natural mechanism to maintain the placental blood flow. This
produces hypertension. Individual organs being so affected
causes the manifestations specific to these organs. This
includes renal proteinurea, intracranial hemorrhage, IUGR,
recurrent still births, accidental hemorrhage.
Seemingly diverse clinical conditions like R.S.A. of missed
type, I.U.G.R. recurrent still births, accidental hemorrhage,
etc are all explainable by the vasculopathy of APA. No wonder
these cases also consistently test positive for APA.
DIAGNOSIS: -
A strong index of suspicion and a good laboratory back up
can make the diagnosis of APA syndrome in a given case of P.E.
remote from term, not at all difficult. Cases presenting as full
blown pre-eclampsia or even eclampsia at 28 –30 weeks, can be
conveniently brushed aside as not being of P.E. remote from term
type. However, the actual process of manifestation of APA has
started much earlier in these subjects. Most of the time these
cases have never got their B.P. checked during pregnancy. In our
set up, where 60% of obstetrics service is for unbooked cases,
this problem becomes all the more pertinent. A strong index of
suspicion is therefore very valuable in these cases. Diagnosis
is also helped by asking a history of allied complications of
APA like RSA of missed type, Recurrent still births, Recurrent
IUGR, etc.
As regards, the actual testing for APA, we rely on the ELIZA
technique with samples of maternal blood collected when the
mother has not taken any thing by month for at least 2 hours.
The standard classification used is:
Negative ® < 10 GPL units
Low positive ® 10-20 GPL units
Mod. Positive ® 20-100 GPL units
Strong positive ® > 100 GPL units.
Once the diagnosis is well established
treatment plans are instituted.
PREVENTION: -
It is strange but true that once a full-blown picture of
P.E. remote from term has developed, it is not possible to
influence the course of the disease significantly. So,
prevention has gained much more pertinence than cure.
There are two sets of clinical situations wherein these measures
require to be taken: In the first set, the subject might come in
the interval period (Non pregnant) or in early pregnancy and has
a strong positive history of one or more of the obstetric
consequences, forth coming. In these immediate measures can be
instituted. In the other set of situations the subject presents
with P.E. remote from term in its full clinical manifestation.
In these, measures can be instituted only in subsequent interval
period or the next obstetric performance.
The protocol that we follow in cases of P.E. remote from term
testing positive for APA is as follows: -
· In interval period :
® For low and moderate positive, Aspirin in a dose of 1.2
mg/kg./day for three months – Allow a conception – Restart
aspirin in the same dose upto 36 weeks.
®For High positive, Prednisolone in a dose of 10 mgms./day for 3
months in the interval period. Allow conception- start aspirin
from 12 weeks upto 36 weeks.
· In Pregnancy:
® For these cases we give only the post-conception protocol of
aspirin specified above.
We have satisfactory results that are
written in the section to follow.
RESULTS: -
In our study (12), 154 subjects testing positive for APA were
given the above treatment protocols. In the group where
treatment could be given pre conception as well as post
conception, full term delivery rates achieved were 88.3%. In the
group where only post conception treatment could be given, the
same rate was 72.3% .The incidence of P.E. remote from term
declined from 26.7% to 3.3 %.
CONCLUSIONS: -
It is therefore clear now that pre eclampsia remote from
term is a distinct entity. It has a much more devastating
outcome. It has a strong association with Antiphospholipid
Antibodies. Immune suppressive and immune modulatory treatment
protocols are able to thwart the adverse effects of this
condition, satisfactorily.
REFRENCES: -
1) Jack Pritchard, Mac Donald P, Gant N: H.T. disorders of
pregnancy. Williams Obstetrics : 17th Ed.,
2) Purwar M, Bhattacharya P, Sanyal P: Jr. O. & G. India, 43: 5
714 : 1993.
3) Desai P., Hazra M: Jr. O. & G. India 38: 5: 548: 1988.
4) Desai P., Desai M: Jr. O. & G. of India 44:6: 855: 1994.
5) Pattison NS, Birdsall MA, Charley L.W.: Rec. Adv. In O. & G.
18:23:1994
6) Rai R, Reagan L: Prog. In O. & G. 12: 136:1996.
7) Hams E N.: Br J. Rheumatol: 26: 324:1987
8) Branch DW, Andres R, Digre KB: Obst. & Gyn.: 73:544:1989.
9) Desai P, Desai M, Modi D: Jr. O. & G. of India:48:1:1998
10) De Wolf F, Correras L.O, Moerman P: Am Jr. O. & G.;142:
829:1982
11) Qut H.J, Koorjman C.D.: Eur. Jr. O. & G.:41:179:1991
12) Desai P, Desai M: Jr. O. & G. Research:24:3:67:1998
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