WRITE UPS - OBSTETRIC VASCULOPATHY - The Auto Immunity Of Pre Eclampsia Remote From Term



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).


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).


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.


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.


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.


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.


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.


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 %.


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.


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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