anti-D prophylaxis programme, there has been very little ... A 30 year old staff nurse , presented in her sixth ... At 32 weeks onwards, mild polyhydramnios was.
Pak J Med Res Vol. 44, No. 3, 2005
CASE REPORT
Severe RhD-alloimmunisation: A Miraculous Suppression of Immunogenicity Riffat Shaheen, Fazli Subhan, Faheem Tahir Department of Obstetrics and Gynecology, Federal Governmet Services Hospital, Department of Reproductive Physiology/Health, Public Health laboratories Division, National Institute of Health, Islamabad.
INTRODUCTION
R
hesus blood group system was the fourth system to be discovered and yet it is second most important blood group from the point of view of transfusion1. Perinatal deaths due to RhD alloimmunisation have fallen a hundred fold since the introduction in 1969 of a policy to administer anti-D IgG to RhD-negative women after sensitising events in pregnancy and the birth of RhDpositive neonates. In 1990s pregnancy loss and death in the first week after delivery due to RhD alloimmunisation was 50 per year in the UK2. In spite of great efforts for anti-D prophylaxis programme, there has been very little change in the incidence of failures of anti-D prophylaxis which remain constant in the region of 1-2%2. This appears to be for two main reasons: i) some women do not receive the benefit of the anti-D prophylaxis policy; ii) women are sensitized by small bleeds from the fetus, mainly in the last 12 weeks of pregnancy which go undetected. On the other hand, major advances have occurred in the monitoring and management of affected fetuses in utero, and in neonatal intensive care which has resulted in a very significant reduction in reported mortality associated with RhD haemolytic disease to the extent that it is not perceived as a problem any more3. RWe managed a case of severe RhD alloimmunisation who had previous two hydrops fetalis and one early termination of pregnancy. She refused all the available medical treatment including intrauterine transfusion because of high cost of therapy in specialized centres.
CASE REPORT A 30 year old staff nurse , presented in her sixth pregnancy. She was a diagnosed case of severe Rhalloimmunisation with a history of previous two 'immune hydrops fetalis' babies and one early termination of pregnancy. Her blood group was B-Negative while, her husbands' blood group was homozygous A- Positive. Her
Pak J Med Res
Rh- antibody titre remained very high during her previous three pregnancies. It was I in 500 during first trimester in her last pregnancy. In 1989, her first pregnancy was uneventful and she had a full term normal vaginal delivery of a live male baby. Prophylactic injection anti-D was given within 24 hours. After two years, she had an incomplete abortion for which she underwent Evacuation & Curettage. However, administration of prophylactic injection anti-D was missed. The following year in January 1992, she presented in her third pregnancy and was admitted in first trimester with severe hyperemesis gravidarum. On investigations she was diagnosed as a case of Rhalloimmunisation with a rapidly rising titre of Rhantibodies on serial testing. In early mid-trimester, she started developing polyhydramnios and pre-eclampsia with deterioration of her condition. Ultrasonography confirmed 'hydrops fetalis'. After counseling with the couple, induction of labour was, carried out at 28 weeks of pregnancy and she gave vaginal birth to a hydrops fetalis male baby who died after 12 hours. In December 1992, she presented in her fourth pregnancy very shortly within a few months after the last delivery as if she was desperate to have a healthy baby. Unluckily, the same events occurred even more severely and earlier than the previous mishap. In fact, the severity of the disease was of such a degree that the Rh antibody titre was very high in early mid-trimester. Prospects of amniocentesis and intra-uterine transfusion seemed very poor. Counseling was done and the couple did not agree for any procedure. At 26 weeks gestation, fundal height was 34 weeks and on USG, it was confirmed as 'hydrops fetalis'. Termination of pregnancy had to be carried out at 26 weeks of gestation and a hydrops fetalis fresh stillborn male baby was delivered. After delivery, detailed counseling was done with the couple and different options were discussed including referral to a hospital having specialized management such as plasmaphresis and early intra-uterine therapy. She consulted a number of obstetricians, however, did not opt for any of the
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procedures. The only thing that she did, was strict contraception for about four years with the logic that it might suppress the pathology. Then, in June 1996, she presented in early pregnancy with severe hyperemesis gravidarum. Rh antibody titre was very high, 1 in 500 and counseling was done for termination of pregnancy that she agreed. In first week of September 1999, she presented with a history of amenorrhea of 28, weeks gestation (LMP: 02/ 28/ 99 ). Astonishingly, on clinical and ultrasonic examination, there was no abnormality found. Qualitative Rh antibody test was negative. She did not agree for Rh antibody titre because she was frightened about it. On friendly discussion, she told that she had been taking some herbal medicine (Vernonia anthelmintica, commonly known as kali zeeri, 16 seeds daily) for the last one year on advice of a herb specialist. She did not come earlier for pre-natal check-up because of fear of a bad news. At 32 weeks onwards, mild polyhydramnios was observed, but no evidence of hydrops fetalis. Rh antibody titre was advised which she refused.. At 37+3 weeks gestation (11/ 17/ 99 ) clinically, slightly more increase in liquor volume was observed, but no evidence of hydrops fetalis on ultrasound. She was advised to get Rh-titre done and her husband was also involved. The titre came out to be 1 in 32. Emergency lower segment caesarean section was performed on 18.11.99. The liquor was markedly yellow. A live male baby with yellowish staining of the skin weighing 3200g was delivered with Apgar score 5/10 at 1 minute and 7/10 at 5 minutes. The bay was transferred to neonatology intensive care unit (NICU) for observation. The cord blood was taken for blood group, hemoglobin (Hb) % and unconjugated bilirubin. The blood group was B+, Hb was 9.0 gm% and unconjugated bilirubin was 280 µ mol / L (16mg/l00ml). Exchange transfusion was done with cross matched a-negative blood on the same night at 12 hours age. Phototherapy was given. The condition of the baby remained satisfactory and. Jaundice improved markedly after exchange transfusion. Unconjugated bilirubin decreased to 30 µ mol / L (1.8 mg%) after 48 hours. The baby was handed over to the mother after 72 hours. On fifth post-operative day the mother and the baby were discharged home. Regular follow-up of the baby showed no complications. In June, 2001 she presented in pre-natal clinic in her seventh pregnancy with a history of amenorrhea of six months (LMP was 12/10/2000). Clinically, there were no abnormal features. There was no evidence of increased liquor, and hydrops fetalis. Rh- antibody qualitative test was negative. She had been continuously taking the herbal medicine but slightly lesser amount that she decided on her own. This time, she was more confident
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and was complying regarding investigations and decisions about management. At 32 weeks gestation, clinically, there was slightly increased liquor. USG confirmed it, but excluded any evidence of hydrops fetalis. Rh-antibody titre was 1 in 28. She was admitted for maternal and fetal monitoring. Plan of emergency caesarean section was discussed with her, but she refused and wanted to wait till maturity. Regular monitoring was continued. Daily cardiotocography was done. Weekly USG showed no evidence of hydrops fetalis. Fetal echocardiotocography was normal. Weekly Rh- antibody titre was done that was static till 35 weeks gestation when it came out as 1 in 32. Counseling was done and emergency caesarean section was performed on 8/13/01. The liquor was markedly yellowish. A live female baby weighing 3075 g was delivered with Apgar score 6/10 at one minute and 7/10 at 5 minutes. The cord blood Hb was 8.7 gm % and unconjugated bilirubin was 295 µ mol / L (17 mgi100 ml).Exchange transfusion with a-negative blood group was given twice. After 48 hours, unconjugated bilirubin was 35 µ mol / L (2 mgi100ml).. Both mother and the baby were discharged home on 5th post-operative day. Both babies are healthy having normal mile stones, neurological development and physical growth up till now, the boy is about 4 1/2 years old and girl is 2 3/4 years.
DISCUSSION Hemolytic disease of the newborn (HDN) is a condition in which the lifespan of the fetal or. newborn s' red blood cells is shortened by the action of maternal antibodies against antigens present on red cells. Anti-D is by far the commonest cause of mild, moderate and severe HDN. This is due to the high immunogenicity of the RhD antigen compared with all other red cell antigens. In pregnancy, antibodies are made in the maternal immune system when fetal red cells bearing antigen foreign to the mother enter her circulation. To start with IgM antibodies are formed that are converted to IgG. Maternal IgG antibodies can cross the placenta and enter fetal circulation; the passage is an active mechanism that involves interaction between the Fc fragment of IgG and Fc receptors on the placenta. Red cell destruction begins in intrauterine life and may lead to severe anemia and even hydrpos fetalis and death in utero. An interesting fact is that the herbal specialist is a female and totally ignorant of the disease HDN. She prescribed this medicine as she was doing it earlier on, to women with a history of fertility deprivation or recurrent pregnancy losses. Extensive follow-up of this case was possible because the patient was a staff , nurse working in the
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same hospital. From her case history, it appears that she responded to this herbal medicine and had two successful pregnancies. However, a further evaluation of this medicine is required. Detailed review of literature has not revealed any case of spontaneous resolution where by a patient who was strongly Rh-alloimmunised, later had two successful pregnanci.es without intra-uterine blood transfusion through cordocentesis or paracentesis. This herbal medicine suppressed the immunogenicity already proven in this patient by previous two hydrpos fetalis and high Rh-antibody titre. It indicated that the same medicine may be helpful in other immunological disorders. As the seeds of this plant have no harmful steroids so, it is speculated that the seeds have some role in suppression of the antibodies against antigens. This medicine may suppress the sensitivity of B and T cells to the antigens by changing the nature of the receptors specific to the antigens, or may block both T and B cells to undergo blast formations. It also appears that the seeds may alter the blast transformation and did not allow them to differentiate into antibodies forming cells. In the present study the seeds of the Vernonia anthelmintic a have shown remarkable property for its use in managing RhD alloimmunisation in patients, which will certainly attract other scientists also. It seems to be a potential drug in future. There is a need of randomized double blind controlled trials under strict quality control with the objective of finding its role in numerous immunological disorders.
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Molison PL . Blood transfusion in clinical medicine. 6th ed. Oxford: Blackwell Scientific Publication; 1979. Urbaniak SJ. Consensus conference on anti-D prophylaxis, April 7 & 8, 1997: final consensus statement. Royal College of Physicians of Edinburgh/Royal College of Obstetricians and Gynaecologists. Transfusion. 1998 Jan;38:97-9. Gallot D, Boiret N, Vanlieferinghen P, Laurichesseh H, Micorek JC, Berger M, et al. The peritoneal route as a safe pathway for early in utero therapies illustrated by a 12 year follow-up after conservative management of severe Rh alloimmunisation. Fetal Diagn Ther 2004;19(2): 170-3.
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