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MRCOG PART 2 SBAs and EMQs

MRCOG Part 2, MRCOG 2

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SBA	2115

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ESSAY 149 - ANTI-D

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		Posted by Nibedita R. Mon Feb 21, 2005 05:53 am
Rh-isoimmunisation can occur from feto-maternal haemorrhage (75%), when a Rh-negative women carrying a RhD positive fetus, produces antibodies against RhD antigen; which may then cross the placenta in future pregnancies and cause haemolytic disease in the RhD positive fetus (in severe form causes hydrops, stillbirth or neonatal death from anaemia and jaundice). Sensitising events are spontaneous miscarriage or elective TOP, amniocentesis or other invasive procedures, ectopic pregnancy, APH, ECV, closed abdominal trauma, fetal death and transfusion of RhD positive blood or blood products like platelet. Frequency of FMH increases with gestation from 3% in first trimester to 45% in third trimester. Before immunoprophylaxis became available, the incidence of HDN was 1% of all births and HDN was responsible for the death of 46/100,000 births. The introduction of anti-D prophylaxis in the UK in 1969 prevents Rh-isoimmunisation in approximately 97% of cases; this has significantly reduced the incidence. Anti-D prophylaxis, small family norm and advances in the neonatal surveillance (Doppler, USS and intrauterine fetal transfusion facilities) have reduced death from HDN to 1.6/100,000. Anti-D is recommended after any potentially sensitising event or procedures (mentioned above). In early pregnancy, anti-D is recommended after therapeutic termination of pregnancy or evacuation of uterus (RPOC) after spontaneous miscarriage, threatened or spontaneous miscarriage after 12weeks and after an unsensitised ectopic pregnancy. Before 12weeks gestation routine anti-D is not recommended for threatened or spontaneous miscarriage unless complicated by repeated or heavy bleeding and associated with pain. After 12weeks if intermittent bleeding continues, anti-D should be administered every 6weeks. After transfusion of Rh-positive blood or blood products, anti-D is recommended. Dose should be administered subcutaneously instead of IM, in severe thrombocytopaenia to avoid haematoma formation. Routine antenatal prophylaxis recommended at 28 and 34weeks gestation, has shown to effectively prevent iso-immunisation and is also cost effective (NICE guidelines). Should be administered irrespective of previous anti-D administration for sensitising event. At least 500iu of anti-D Ig must be given to every non-sensitised Rh-D negative woman within 72 hrs following delivery of Rh-positive infant and additional dose adjustment in large FMH>4ml (traumatic deliveries including CS, twin pregnancy and manual removal of placenta). The recommended dose is 500iu after 20weeks and 250iu before 20weeks gestation. Appropriate dose adjustment by kleihauer test, which can identify FMH over 4ml RBCs and who require extra dose. Anti-D should be given by IM injection into deltoid muscle within72hrs of sensitising event, although, when given within 9-10 days, may still offer protection. Perinatal mortality is still continuing because of other fetal antigens like C, c, E, e, K, k and M from which isoimmunisation is still possible and is not preventable by anti-DIg. Occult FMH causing sensitisation, failed prophylaxis or omitted prophylaxis are the few causes of continuing sensitisation. In suspected sensitised pregnancy, referral to a tertiary centre where expertise available for improved fetal surveillance and intra uterine transfusion facilities would reduce perinatal mortality further. The health professional (obstetrician, midwife or GP) responsible for care of a non sensitised Rh-D-negative woman should discuss the purpose of anti-D prophylaxis, the recommendations available and the difference between RAADP and prophylactic anti-D, and must indicate that it is a blood product- all should be clearly explained to the woman to make an informed choice about Rh-prophylaxis and should be provided with information leaflet. The discussion should include the circumstances where RAADP would be neither necessary nor cost effective, such as: opted to be sterilised after childbirth, when a stable relationship exists with the father of the child who is known Rh-negative, or is certain that she will not have another child after her current pregnancy.
		Posted by Sarwat F. Mon Feb 21, 2005 08:08 am
The introduction of anti D in 1960s has dramatically reduced the incidence of perinatal morbidity and mortality associated with rhesus isoimmunization. Rhesus isoimmunization occurs when a Rh negative mother carrying a Rh positive baby gets sensitized and starts producing antibodies against Rh positive fetal blood cells which result in hemolysis and later hydrops, fetal death, still birth or neonatal death. Sensitizing events include delivery, miscarriage, termination of pregnancy, invasive prenatal testing, external cephalic versionand antepartum hemorrhage. The dose of anti D is 250 iu before 20 weeks and 500 iu after 20weeks and kleihauer testing is recommended after 20 weeks. Regarding spontaneous first trimester miscarriages it is recommended that anti D is given after 12 weeks of gestation. In this case accurate dating of pregnancy is essential by ultrasound scanning in first trimester. Problems occur when women do not attend antenatal clinic and are not sure of their LMP giving wrong dates so that anti D is missed and this results in sensitization. Ideally kleihauer test should be done in those Rh negative women in whom gestational age can not be ascertained. Also more education of general practitioners is needed for realization of the fact that sensitization can occur and kliehauer testing is indicated as they may strictly adhere to guidelines not giving anti D before 12 weeks. Recent Guidelines also suggest that for threatened first trimester miscarriage anti D is given with heavy and repeated bleeding or with abdominal pain. The problem with this guideline lies in its implementation as the criteria for defining heavy bleeding is vague and there are different pain threshold for different women. These women are again candidate for kleihauer testing. Again in later stages of pregnancy and delivery the dose of anti d that is required may be higher and routine administration of 500 iu without assessing the size of fetomaternal hemorrhage may result in sensitization. Strict adherence to the point that anti D is effective for 72 hrs after sensitizing event also results in failing to prevent isoimmunization as some protection can still be provided if anti d is administered uptill 10 days. Routine administration of anti D at 28 and 34 weeks as recommended in recent guidelines will help in reducing Rh sensitization in these later stages of pregnancy when the chances of sensitization is higher. This is likely to cover silent fetomaternal hemorrhages. However not all units have implemented this the reason being high cost of the immunoglobulin. Then there are some patients who will not accept anti Das this is a human product and also because of the new variant creudz feld Jacobs disease. This problem can however be overcome by the use of monoclonal product. Women need to make an informed decision and she is counseled regarding the fact that this immunoglobulin is a blood product and should be provided information leaflets. Then there are circumstances when a woman may not need anti D for example when she is having sterilization following delivery or is in a stable relationship with a partner who is Rh negative. There are other antigens as well like C, E which can also result in sensitization and anti D does not confer protection against these. Although use of anti D has reduced the incidence of hemolytic disease of newborn, various factors like failure of administration, failure to use correct dose and failure to protect despite administration will remain a factor in eradicating this problem. Recent guidelines have addressed some of these problems but the problem lies in the implementation of guidelines as only proper implementation can effectively reduce the incidence of hemolytic disease.
		Posted by SWATI M. Mon Feb 21, 2005 05:17 pm
Rh issoimmunisation occur when woman with Rh negative blood group carries Rh positive fetus produces antibodies due to feto-maternal haemorrhage, which cross the placenta and destroys fetal red blood cells.Depending on the severity of haemolysis, disease is manifested as neonatal anaemia,jaundice,still birth,hydrops fetalis.Anti-D immunoglobulin prophylaxis prevents Rh ?isoimmunisation . Mortality due to haemolytic diseases of newborn has fallen since the prophylaxis use of anti D in 1969. To reduce risk of isoimmunisation ,anti-D should be recommended for potential sensitising events such as spontaneous miscarriage after 12 weeks ,induced abortion, evacuation of retained products of conception ,ectopic pregnancy, CVS,amniocentesis, ECV, APH,abdominal trauma.In threatened miscarriage before 12 weeks,it is indicated only if bleeding is heavy/recurrent or associated abdominal pain.It is not indicated for spontaneous miscarriage before 12 weeks who does not require evacuation. The recommended doses before 20 weeks is 250 iu and after 20 weeks 500iu followed by Kleihauer test to identify FMH >4ml for additional doses. For the postpartum prophylaxis,500iu of anti-D should be given to unsensetised Rh negative woman preferably within 72 hours of delivery of Rh positive baby .But if it is not given in 72 hours,should be administered as it may offer some protection if given within 9-10 days.Additional doses should be given if large FMH (>4ml) calculated by Kleihauer test which may occur during caesarean delivery,manual removal of placenta. Routine antenatal prophylaxis is recommended at 28 and 34 weeks of gestation which reduces risk of sensitization due to silent FMH from 1.5% to 0.2%.It is cost effective and administered irrespective of previous administration for potential sensetising events. The postnatal administration of anti-D is not affected by antenatal use. Anti-D is also indicated if inadvertent infusion of Rh positive blood or Rh positive platelets. Anti-D should be given by IM injection on deltoid muscle.Administration is not necessary if woman is opted for sterlisation,stable relation with Rh negative partner,will not have another child but it may be difficult to be certain of these factors. Anti-D will not prevent haemolytic diseases caused by other red cell antigens such as C,c,E,e,K,k .Since it is a blood product,can transmit infections.Isoimmunisation still occur due to omitted or failed prophylaxis and all health professionals involved in care of Rh negative woman should discuss prophylaxsis with her and follow guidelines.
		Posted by Iman B. Tue Feb 22, 2005 05:47 pm
Rh immunoglobulin is necessary to prevent sensitization of an Rh negative mother from the Rh positive blood of her fetus.It will not prevent the occurence of a sensitising event from other blood groups as the kell or C or E antigens. About 99.2-99.3 % of fetomaternal hemorrhages (FMH)of about 4 ml occur following normal vaginal delivery. However, 0.7-0.8 % of Rh negative women will have larger FMHs. Many europian countries do not estimate the degree of FMH, but give a post natal dose of 1500 IU of anti D. This if followed in the UK would lead to about 200 women yearly not receiving adequate doses of anti D immunoglobulin. The Kleihaur test detects fetal Hb in maternal blood, it will indicate large FMHs that may need further assessment by either flow cytometry or the rosette technique. The majority of FMHs now occur antepartum from sensitizing events. These sensitizing events include threatened miscarriages after 12 weeks, ectopic pregnancies, therapeutic termination of pregnancy either by surgery or medically, spontaneous miscarriages after 12 weeks, interventional techniques as chorion villus sampling, cordocentesis or amniocentesis, interventional procedures as shunts or transfusion, antepartum haemorrhage, abdominal trauma, external cephalic version, nonimmune hydrops fetalis, intrauterine death, and difficult deliveries as cesarian section or manual separation of the placenta. In all these cases if the event occurs before 20 weeks 250 IU units of anti D are given, and 500 IU of anti D after 20 weeks, unless the kleihaur test proves a larger FMH, in which case the dose is estimated such that 4ml of fetal Rh +ve blood will be suppressed by 500IU of anti D. In the absence of sensitizing events a dose given at 28 and 34 weeks each 500 IU has been found to prevent antenatal spontaneous sensitization. These doses are equal to the 1500 IU dose at 28 weeks previously recommended, givng equal benefit but more cost effective. The cost effectiveness of these recommendations have been calculated as opposed to the treatment of sensitized patients in tertiary care. Pregnanct women should receive information leaflets and handouts explaining the benefit of Rh immunoglobulin and the difference between the routine prophylactic dose at 28 and 34 weeks and the doses given on occurrence of any sensitizing event. She should be informed that the anti D is a blood product, and the chance of any one person receiving any recognizable infection from this immunoglobulin is in the order of 1 in every 10 000 billion cases. The postnatal dose should not be affected by any antenatal doses taken, and the presence of weak anti D globulin in her blood from previous anti D doses antenatally should not prevent her receiving a full dose post natally. N the event that an Rh negative woman requires platelet transfusion, three units of platelets require a 250 IU dose to suppress any inadvertent RH positive RBCs. The dose in this case will be given subcutaneously rather than intramuscularly in the deltoid muscle, to avoid hematoma formation. Patients who receive Rh positive blood must have the amount of blood received calculated and a sufficient dose of anti D given, this may be up to exchange transfusion if more than two units of Rh positive blood is given. The NICE guidelines suggest that it will not be cost effective to give anti D to pregnant women in a stable relationship with the father of the child who is also Rh negative. Or if the patient is certain that she will no longer have any more children or those who wish for tubal sterilization after delivery.
		Posted by narmin B. Thu Feb 24, 2005 01:48 am
Rhesus Iso immunisation disease of the fetus and newborn, is caused by feto-maternal bleeding in a Rhesus negative mother who is carrying a Rhesus positive fetus. This disease is associated with increased fetal mortality and morbidity. Anti D immune globulin is used to prevent this disease in unsensitised Rhesus negative mothers. Every unit should have a clear protocol with regard to anti D use which should be based on national guidelines. The recommended dose of anti D is intramuscular injection of 250 units of anti D before 20 weeks and 500 units after that. This dose is adequate for feto maternal bleeding up to 4 mls. Whenever there is a possibility that the bleeding is more than 4 mls, a Kleihaure test should be performed to estimate the amount bleeding and extra dose should be given if required. Anti D should be given after any sensitising event during pregnancy. After procedures such as chorionic villous sampling, amniocentesis and cordocentesis anti D is required. Also after antenatal bleeding, administration of anti D is required. In the case of frequent antenatal bleeding a Kleihaure test and administration of anti D accordingly is required. Other procedures like external cephalic version also can cause feto maternal bleeding and anti D injection is necessary. In spite of this protocol for anti D administration, still there may be occult feto maternal bleeding which has no obvious signs or symptoms. For this reason, nowadays two prophylactic injections are given to Rhesus negative mothers at 28 and 34 weeks. Although this policy has its own costs and staff requirements but it has been shown that this can reduce the rate of iso immunisisation diseases even further. Anti D also should be used after delivery or termination of pregnancy. In addition to antenatal prophylactic regime, it is recommended that anti D should be administered to Rhesus negative mothers with Rhesus positive fetuses within 72 hours after delivery. If for some reason administration of anti D is not possible within 72 hours, there is some evidence that shows administration of anti D even after 72 hours has some benefit. In the case of manual removal of the placenta or severe abruption where the amount of fetomaternal bleeding can be more than normal Kleihaure test and extra dose may be required. After termination of pregnancy in Rhesus negative women at any stage of pregnancy also anti D use is necessary. Of course the mother can be sensitised by events in early weeks of pregnancy such as threatened miscarriage with sever pain and bleeding, evacuation of retained products of conception and ectopic pregnancy. Therefore clear protocols in gynaecology departments are required to prevent sensitisation of mothers at this stage of pregnancy.