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Severe hemolytic disease of the newborn due to anti-c
73
Int. J. Gynecol. Obstet., 1990,33: 73-X International Federation of Gynecology and Obstetrics
Severe hemolytic disease of the newborn due to anti-c Z. Appelman,
S. Lurie,
A. Justera and R. Borenstein
Department of Obstetrics and Gynecology and “Neonatal Intensive Care Unit, Kaplan Hospital, Rehovot (Israel) (Affiliated to the Medical School of the Hebrew Univerity and Hadassah. Jerusalem) (Received March 9th, 1989) (Revised and accepted June 3Oth, 1989)
Abstract Two cases of severe hemolytic disease of the newborn due to c-isoimmunization are presented. Both women were multiparous, had previous blood transfusion and high maternal titers of anti-c (I:1024 and 1:4036, respectively).
Keywords: Rh isoimmunization. Introduction Since the introduction of Rh immune globulin (RhIgG) the incidence of hemolytic disease of the newborn (HDN) has dramatically decreased [2]. About 26 antigens related to the Rh locus have been described [7]. The incompatibility associated with irregular antigens including Rh subtypes other than Rh(D) remains a continuing problem. The first case of HDN caused by c-isoimmunization was described in 1944 [5]. The c-gene frequency is about 0.58 in the Caucasian population [4], but only a limited number of cases of cincompatibility have been described [ 1,3,9] and severe presentation is quite rare. Although there is a suggestion that c-incompatibility may cause severe HDN most cases 00%7292/90/$03.50 0 1990 International Federation of Gynecology and Obstetrics Published and Printed in Ireland
in the literature were not severe. We present two case reports of severe c-isoimmunization. Case reports Case 1 A healthy 31-year-old gravida 3, para 2, abortion 0, presented at 39.5 menstrual weeks because of reduction in fetal movements a few hours prior to admission. Her previous pregnancies had resulted in full-term deliveries, one spontaneous and one by vacuum extraction. The infants were healthy and did not have neonatal jaundice. She had had a laparotomy for resection of simple ovarian cyst, receiving two units of whole blood at that operation, for excessive blood loss at surgery. Her blood type was A Rh(D) positive, and the indirect antiglobulin test (Coombs) at the time of her previous pregnancies and operation was negative and had not been performed in the current pregnancy. On admission the Bishop’s score was three, she had no contractions, fetal heart rate monitoring showed no accelerations, and no fetal movements were seen on ultrasonic examination. Labor was induced by oxytocin infusion and amniotomy. Three hours later type 2 (late) decelerations appeared and cesarean section was performed. While crossCase Report
14
Appelman et al.
er’s phenotype was found to be c-negative. The baby did not have clinical signs of HDN, but his blood type was B Rh(D) positive, c positive and his direct antiglobulin test was positive. In her third pregnancy, she was followed in an outpatient clinic. Her physician was not aware of her previous problems and therefore no indirect antiglobulin test was performed until after the fetal demise. The anti-c titer was found to be 1:4036. At 17 weeks of her third pregnancy maternal serum a-fetoprotein of 5.5 MOM was found and an amniocentesis for genetic studies was performed. The karyotype was 46Xx. At the same time detailed sonographic examination did not reveal any abnormal findings. On admission the diagnosis of fetal death was confirmed. The ultrasonic measurements were compatible with 24 menstrual weeks. An induction by extra-amniotic infusion of prostaglandins was performed. The infant was a stillborn female, weighing 900 g. The placenta was preterm with severe congestion, focal infarcts, hemorrhage and intervillous fibrin deposition. The cord had three vessels. On autopsy the fetus was found to have severe edema and maceration of the skin and all internal organs. No congenital malformations were found.
matching blood for transfusion during the operation an anti-c maternal titer of 1: 1024 was found. The patient received 350 ml of cnegative packed cells during the operation and the postoperative period was normal. The baby was a male, weighing 2920 g, with a I-min Apgar score of 3. He was extremely pale, respiration was poor and he was immediately intubated. No heart murmurs were heard, no spleen or liver enlargement was found, and he did not have signs of peripheral edema. His blood pressure was 43/ 20. At birth the capillary blood gases were pH = 6.95, PCO, = 67 mmHg, Pco, = 43 mmHg, and the bicarbonate was 12 mequiv/l giving a base excess of -16 mequiv. His hemoglobin was 4 g%, hemotocrit 16%, white blood cell count 47,000, and platelet count 216,000. His blood type was A Rh c, D positive and the direct antiglobulin test was positive. On X-ray examination the heart was not enlarged, the lungs were clear and no ascites was seen. Appropriate fluid and respiratory support was introduced; 195 ml of cantigen negative packed cells were transfused. At 8 h of age the infant developed clinical jaundice with a total bilirubin rising to 16.2 mg% at 24 h of age. Total volume blood exchange was performed. The infant made a good recovery, was extubated at 36 h of age and discharged on the 12th day of life.
Discussion
Case 2 A healthy 30-year-old gravida 3, para 2, abortion 0, presented at 27 menstrual weeks because of fetal death noted on routine ultrasonic examination. Her first pregnancy resulted in cesarean section for breech presentation. Her blood type was noted to be AB Rh(D) positive, and the indirect antiglobulin test (Coombs) was negative. She received one unit of whole blood during the operation which was not screened for c-antigen. The reason for blood transfusion was excessive blood loss during surgery. Her second pregnancy resulted in a full-term spontaneous vaginal delivery. The indirect antiglobulin test at delivery was positive for anti-c. The moth-
The immune hemolytic disease of the newborn is caused by red blood cell antigen incompatibility and may occur in forms ranging from mild anemia to hydrops fetalis and in utero death [8]. The clinician usually recognizes the possibility of isoimmunization by routine blood typing of pregnant women. Routine antibody screening on all pregnant women is advocated by some authors [6,10] and carried out in some countries, irrespective whether they are Rh(D) positive or Rh(D) negative. In Israel, only in Rh(D) negative women is the indirect antiglobulin test (Coombs) performed. With the c antigen this policy may be misleading, because Rh(D) negative genotypes capable of producing anti-
Int J Gynecol Obstet 33
Anti-c isoimmunization
c occur in only approximately 0.01% of the population [9]. Therefore, most c negative Rh(D) positive women fail to be detected or further tested. Kornstad [l] states that most cases of anti-c erythroblastosis are mild to moderate. In his data only 9 out of 32 neonates required an exchange transfusion and only one had less than 10 gVo hemoglobin. He suggested that severe cases with intrauterine anemia may occur. Our cases present such a severe form of anti-c isoimmunization. The first case had a hemoglobin of 4 g% which required transfusion and was followed by exchange transfusion. The second case presented as an intrauterine death with extremely high titers of maternal anti-c (1:4036). In the cases presented, both women were multiparous, had previous blood transfusions and high maternal titers of anti-c (1:1024, 1:4036). Those factors are associated with a high probability of developing HDN [1,9, lo]. Perhaps caution should be taken about using blood transfusions that may not be needed. The reason for the high maternal serum afetoprotein measured in the second case could be imminent fetal death or a recent fetomaternal transfusion, which could have accelerated the isoimmunization process. No fetal chromosomal aberrations or malformations were found. In our opinion the intrauterine death was caused by c-isoima fact compatible with the munization, autopsy findings. The cases presented demonstrate the occurrence of severe forms of anti-c isoimmunization, and those patients who have anti-c antibody should be treated with appropriate attention in order to prevent grave HDN. The
cost of irregular adds an ing the patients.
15
performing antibody screening for antibodies in all obstetric patients insignificant expense when considertotal cost of follow-up of such
References 1
2
3
4
5
6
Astrup J, Komstad L: Presence of anti-c in the serum of 42 women giving birth to c positive babies: serological and clinical findings. Acta Obstet Gynecol Stand 56: 185, 1977. Centers for Disease Control: Rh Hemolytic disease Connecticut, United States 1970-1979. MMNR 30(Z): 13,198l. Hiehle WW, Altmirano MD, Kurlman HH, Saxton LA: Hemolytic disease of the newborn due to anti-c. A case report. Am J Obstet Gynecol79: 601,196O. Kornstad L: New cases of irregular blood group antibodies other than anti-D in pregnancy. Acta Obstet Gynecol Stand 62: 43 1,1983. McCall AJ, Race RR, Taylor CL: Rhesus antibody in Rh positive mother causing hemolytic disease of newborn. Lancet i: 214,1944. Parer JT: Severe Rh isoimmunization - current methods of in utero diagnosis and treatment. Am J Obstet Gynecol 158: 1323, 1988. Rote Neal S: Pathophysiology of Rh isoimmunization. Clin Obstet Gynecol25: 243.1982. Scott JR: Isoimmunization in pregnancy. In: Obstetrics and Gynecology, 5th edn (ed DN Danforth, JR Scott), p 419, JP Lippincott, Philadelphia, 1986. Tripton RH. Speller DCE, Mucklow ES: The occurrence of anti-c antibodies in maternal blood. Obstet Gynaecol Br Commonw 74: 563,1%7. Weinstein L: Irregular antibodies causing hemolytic disease of the newborn: a continuing problem. Clin Obstet Gynecol25(2): 321, 1982.
Address for reprints: Z. Appelmrn Department of Obstetrics and Gynecology Kaplan Hospital 76100 Rehovot, Israel
Case Report
Int. J. Gynecol. Obstet., 1990,33: 73-X International Federation of Gynecology and Obstetrics
Severe hemolytic disease of the newborn due to anti-c Z. Appelman,
S. Lurie,
A. Justera and R. Borenstein
Department of Obstetrics and Gynecology and “Neonatal Intensive Care Unit, Kaplan Hospital, Rehovot (Israel) (Affiliated to the Medical School of the Hebrew Univerity and Hadassah. Jerusalem) (Received March 9th, 1989) (Revised and accepted June 3Oth, 1989)
Abstract Two cases of severe hemolytic disease of the newborn due to c-isoimmunization are presented. Both women were multiparous, had previous blood transfusion and high maternal titers of anti-c (I:1024 and 1:4036, respectively).
Keywords: Rh isoimmunization. Introduction Since the introduction of Rh immune globulin (RhIgG) the incidence of hemolytic disease of the newborn (HDN) has dramatically decreased [2]. About 26 antigens related to the Rh locus have been described [7]. The incompatibility associated with irregular antigens including Rh subtypes other than Rh(D) remains a continuing problem. The first case of HDN caused by c-isoimmunization was described in 1944 [5]. The c-gene frequency is about 0.58 in the Caucasian population [4], but only a limited number of cases of cincompatibility have been described [ 1,3,9] and severe presentation is quite rare. Although there is a suggestion that c-incompatibility may cause severe HDN most cases 00%7292/90/$03.50 0 1990 International Federation of Gynecology and Obstetrics Published and Printed in Ireland
in the literature were not severe. We present two case reports of severe c-isoimmunization. Case reports Case 1 A healthy 31-year-old gravida 3, para 2, abortion 0, presented at 39.5 menstrual weeks because of reduction in fetal movements a few hours prior to admission. Her previous pregnancies had resulted in full-term deliveries, one spontaneous and one by vacuum extraction. The infants were healthy and did not have neonatal jaundice. She had had a laparotomy for resection of simple ovarian cyst, receiving two units of whole blood at that operation, for excessive blood loss at surgery. Her blood type was A Rh(D) positive, and the indirect antiglobulin test (Coombs) at the time of her previous pregnancies and operation was negative and had not been performed in the current pregnancy. On admission the Bishop’s score was three, she had no contractions, fetal heart rate monitoring showed no accelerations, and no fetal movements were seen on ultrasonic examination. Labor was induced by oxytocin infusion and amniotomy. Three hours later type 2 (late) decelerations appeared and cesarean section was performed. While crossCase Report
14
Appelman et al.
er’s phenotype was found to be c-negative. The baby did not have clinical signs of HDN, but his blood type was B Rh(D) positive, c positive and his direct antiglobulin test was positive. In her third pregnancy, she was followed in an outpatient clinic. Her physician was not aware of her previous problems and therefore no indirect antiglobulin test was performed until after the fetal demise. The anti-c titer was found to be 1:4036. At 17 weeks of her third pregnancy maternal serum a-fetoprotein of 5.5 MOM was found and an amniocentesis for genetic studies was performed. The karyotype was 46Xx. At the same time detailed sonographic examination did not reveal any abnormal findings. On admission the diagnosis of fetal death was confirmed. The ultrasonic measurements were compatible with 24 menstrual weeks. An induction by extra-amniotic infusion of prostaglandins was performed. The infant was a stillborn female, weighing 900 g. The placenta was preterm with severe congestion, focal infarcts, hemorrhage and intervillous fibrin deposition. The cord had three vessels. On autopsy the fetus was found to have severe edema and maceration of the skin and all internal organs. No congenital malformations were found.
matching blood for transfusion during the operation an anti-c maternal titer of 1: 1024 was found. The patient received 350 ml of cnegative packed cells during the operation and the postoperative period was normal. The baby was a male, weighing 2920 g, with a I-min Apgar score of 3. He was extremely pale, respiration was poor and he was immediately intubated. No heart murmurs were heard, no spleen or liver enlargement was found, and he did not have signs of peripheral edema. His blood pressure was 43/ 20. At birth the capillary blood gases were pH = 6.95, PCO, = 67 mmHg, Pco, = 43 mmHg, and the bicarbonate was 12 mequiv/l giving a base excess of -16 mequiv. His hemoglobin was 4 g%, hemotocrit 16%, white blood cell count 47,000, and platelet count 216,000. His blood type was A Rh c, D positive and the direct antiglobulin test was positive. On X-ray examination the heart was not enlarged, the lungs were clear and no ascites was seen. Appropriate fluid and respiratory support was introduced; 195 ml of cantigen negative packed cells were transfused. At 8 h of age the infant developed clinical jaundice with a total bilirubin rising to 16.2 mg% at 24 h of age. Total volume blood exchange was performed. The infant made a good recovery, was extubated at 36 h of age and discharged on the 12th day of life.
Discussion
Case 2 A healthy 30-year-old gravida 3, para 2, abortion 0, presented at 27 menstrual weeks because of fetal death noted on routine ultrasonic examination. Her first pregnancy resulted in cesarean section for breech presentation. Her blood type was noted to be AB Rh(D) positive, and the indirect antiglobulin test (Coombs) was negative. She received one unit of whole blood during the operation which was not screened for c-antigen. The reason for blood transfusion was excessive blood loss during surgery. Her second pregnancy resulted in a full-term spontaneous vaginal delivery. The indirect antiglobulin test at delivery was positive for anti-c. The moth-
The immune hemolytic disease of the newborn is caused by red blood cell antigen incompatibility and may occur in forms ranging from mild anemia to hydrops fetalis and in utero death [8]. The clinician usually recognizes the possibility of isoimmunization by routine blood typing of pregnant women. Routine antibody screening on all pregnant women is advocated by some authors [6,10] and carried out in some countries, irrespective whether they are Rh(D) positive or Rh(D) negative. In Israel, only in Rh(D) negative women is the indirect antiglobulin test (Coombs) performed. With the c antigen this policy may be misleading, because Rh(D) negative genotypes capable of producing anti-
Int J Gynecol Obstet 33
Anti-c isoimmunization
c occur in only approximately 0.01% of the population [9]. Therefore, most c negative Rh(D) positive women fail to be detected or further tested. Kornstad [l] states that most cases of anti-c erythroblastosis are mild to moderate. In his data only 9 out of 32 neonates required an exchange transfusion and only one had less than 10 gVo hemoglobin. He suggested that severe cases with intrauterine anemia may occur. Our cases present such a severe form of anti-c isoimmunization. The first case had a hemoglobin of 4 g% which required transfusion and was followed by exchange transfusion. The second case presented as an intrauterine death with extremely high titers of maternal anti-c (1:4036). In the cases presented, both women were multiparous, had previous blood transfusions and high maternal titers of anti-c (1:1024, 1:4036). Those factors are associated with a high probability of developing HDN [1,9, lo]. Perhaps caution should be taken about using blood transfusions that may not be needed. The reason for the high maternal serum afetoprotein measured in the second case could be imminent fetal death or a recent fetomaternal transfusion, which could have accelerated the isoimmunization process. No fetal chromosomal aberrations or malformations were found. In our opinion the intrauterine death was caused by c-isoima fact compatible with the munization, autopsy findings. The cases presented demonstrate the occurrence of severe forms of anti-c isoimmunization, and those patients who have anti-c antibody should be treated with appropriate attention in order to prevent grave HDN. The
cost of irregular adds an ing the patients.
15
performing antibody screening for antibodies in all obstetric patients insignificant expense when considertotal cost of follow-up of such
References 1
2
3
4
5
6
Astrup J, Komstad L: Presence of anti-c in the serum of 42 women giving birth to c positive babies: serological and clinical findings. Acta Obstet Gynecol Stand 56: 185, 1977. Centers for Disease Control: Rh Hemolytic disease Connecticut, United States 1970-1979. MMNR 30(Z): 13,198l. Hiehle WW, Altmirano MD, Kurlman HH, Saxton LA: Hemolytic disease of the newborn due to anti-c. A case report. Am J Obstet Gynecol79: 601,196O. Kornstad L: New cases of irregular blood group antibodies other than anti-D in pregnancy. Acta Obstet Gynecol Stand 62: 43 1,1983. McCall AJ, Race RR, Taylor CL: Rhesus antibody in Rh positive mother causing hemolytic disease of newborn. Lancet i: 214,1944. Parer JT: Severe Rh isoimmunization - current methods of in utero diagnosis and treatment. Am J Obstet Gynecol 158: 1323, 1988. Rote Neal S: Pathophysiology of Rh isoimmunization. Clin Obstet Gynecol25: 243.1982. Scott JR: Isoimmunization in pregnancy. In: Obstetrics and Gynecology, 5th edn (ed DN Danforth, JR Scott), p 419, JP Lippincott, Philadelphia, 1986. Tripton RH. Speller DCE, Mucklow ES: The occurrence of anti-c antibodies in maternal blood. Obstet Gynaecol Br Commonw 74: 563,1%7. Weinstein L: Irregular antibodies causing hemolytic disease of the newborn: a continuing problem. Clin Obstet Gynecol25(2): 321, 1982.
Address for reprints: Z. Appelmrn Department of Obstetrics and Gynecology Kaplan Hospital 76100 Rehovot, Israel
Case Report