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Two cases of nontraumatic fetal-maternal bleeding occurred in the second trimester. Both presented with mild, lower quadrant tenderness similar to round ligament pain, illustrating the potential for a misdiagnosis.

Study Objective: To determine the practice of emergency physicians with regard to the issue of Rh isoimmunization., Design: A retrospective chart review., Setting: A university-affiliated tertiary care hospital emergency department., Type of Participants: Pregnant women presenting with a risk factor for Rh sensitization., Measurements and Main Results: One hundred thirty-eight patient encounters were analyzed descriptively as to whether they were candidates for Rh immune prophylaxis, and if so, whether it was given. Most (68%) were hospitalized. Of those, all were Rh typed, but two patients were not given Rh immune globulin (RhIG) when indicated. Of those discharged from the ED, most (86%) were not Rh typed, and none was administered RhIG., Conclusion: This study demonstrates a need for increased attention to the potential for Rh isoimmunization in patients presenting to the ED.

Previous studies of sensitization to RhD by RhD-positive platelet transfusions in RhD-negative cancer patients have shown different frequencies of alloimmunization (max. 19%). We studied 37 RhD-negative patients who received RhD-incompatible platelet transfusions and simultaneously anti-D-immune globulin. We provide evidence that in this setting RhD-prophylaxis is highly effective in preventing alloimmunization due to RhD antigen, since none of the patients studied developed anti-D. Detection of other red blood cell antibodies than anti-D proves the possibility of immunization in these patients. Prevention of isoimmunization in patients with malignant diseases is recommended especially in young females, since an increasing number of patients are having successful pregnancies, despite prior or even during cytotoxic therapy.

Transcervical chorionic villus sampling (CVS) was performed in 174 patients between 7 & 12 menstrual weeks of pregnancy opting for prenatal diagnosis. Advanced maternal age was the most common indication for CVS (39.7%). The sampling success rate was 95.4% (166/174), representing 88.9% at 7 to 8 weeks, 98.9% at 9 to 10 weeks & 92.7% at 11 to 12 weeks gestation. In 139 of 174 patients (80%), successful sampling was accomplished in one or two catheter passages only. Four spontaneous fetal losses (2.3%) occurred. The cytogenetic analysis routinely used was the direct overnight & long-term culture methods which revealed 4 abnormalities (2.4%). To date, 90 of the women have been delivered & all infants are doing well and the remaining 65 pregnancies are continuing uneventually. Maternal serum alphafetoprotein (MSAFP) concentration was determined in 72 patients immediately before & after CVS. A significant increase of 20% or more, comparable to pre CVS levels, was noted immediately after sampling in 56 of 72 patients (77.8%). The increase in MSAFP concentration correlated with the amount of villi sampled (r = 0.498, p less than 0.001) & with the number of sampling attempts (p less than 0.05). Estimated CVS related fetomaternal hemorrhage (FMH) ranged from 0.005 to 0.1552 ml and in 5 of 72 patients (6.90%) 0.06 ml or more of FMH was noted. Two of the 5 patients had FMH of 0.1 ml or more.

Appropriate postpartum administration of Rh immune globulin relies on sensitive detection and accurate quantitation of fetomaternal hemorrhage (FMH). Recently, the microscopic Du test (micro Du) enhanced with polyethylene glycol (PEG Du) and flow cytometry (FC) have been advocated for this purpose. Three qualitative methods (micro Du, rosette test, and PEG Du) and two quantitative methods (acid elution and FC) for assessing FMH were evaluated with particular attention given to PEG Du and FC. In vitro studies comprised 10 series of dilutions of D+ cord cells in D- adult cells to yield D+ cell concentrations of 0.06, 0.12, 0.25, 0.50, 0.75, 1.0, and 2.0 percent. Additionally, 26 postpartum samples were tested. Of the qualitative techniques, the micro Du test was the least sensitive with 20 percent false-negative results occurring at 0.5 percent fetal cells. The PEG Du test was only slightly more sensitive and offered no clinical advantage. The rosette test was the most sensitive, consistently detecting fetal cells at concentrations of 0.25 percent or greater. FC and acid elution showed similar results, with good correlation obtained between measured and expected quantities of fetal cells (r = 0.99 and 0.96, respectively). One of 26 postpartum samples was positive by all screening techniques; acid elution and FC detected 0.3-percent concentrations of fetal cells and 0.17-percent concentrations of D+ cells, respectively. Although acid elution is a more commonly used method for quantitating FMH, FC offers an acceptable alternative that is capable of analyzing large numbers of cells with objectivity and reproducibility.

In the course of 13 years (1977-1989) 223 of 223,121 liveborn infants in the district of Erfurt suffered from haemolytic disease due to Rh-isoimmunization, 0.1 per cent died. An initial drop of morbidity from 1.6 to 0.6 of 1000 newborns was followed by stagnation and further increase during the last years. More than 50% of the affected babies were delivered by women who had to be protected from sensibilization by immune prophylaxis. The cause for the immunization were deliveries (75%), miscarriages and interruptions (23%). The most important reason for the insufficient decrease of the Rh-morbidity is the failure of immune prophylaxis in the case of ABO-incongruence between mother and child. Our results support the demands for a general immune prophylaxis without taking into consideration the main blood groups and the number and result of the pregnancy. The quantity of severe erythroblastosis (7 stillborn and 5 hydropic liveborn) demonstrates the necessity to improve the prenatal management of these babies.

Intravenous drug abuse causes many health problems. From March 1989 to January 1990 of 27 Rh-negative women (28 pregnancies) referred to our centre, 4 women (5 pregnancies) were Rh immunized due to the sharing of needles and blood with their Rh-positive partners. Severe hydrops was present in 4 of their 5 fetuses when they were first seen at 17-35 weeks of gestation. Only the fetus first seen at 35 weeks survived. That infant was moribund at birth and now has evidence of leukomalacia and porencephaly. The fifth fetus, not hydropic, required two intravascular fetal transfusions in order to survive. A fifth woman, immunized in a similar manner, had a spontaneous abortion. These fetuses represent some of the earliest and severest examples of hydrops fetalis ever seen at our centre. The severity of their fetal hemolytic disease is probably due to the fact that their mothers' exposure to Rh(D) antigen by blood sharing was continuous and ongoing. Because of their aberrant behaviour, these women have suffered irreversible reproductive damage.

Reported here is the first example of a partial D antigen stimulating the production of anti-D: stimulation was of fetal origin. During her second pregnancy, anti-D developed in the serum of a D-negative mother who had received Rh immunoglobulin after the birth of her first D-positive child. Her second baby had moderate neonatal jaundice and was successfully treated by phototherapy. Subsequently the red cells of the father and of the first child were shown to carry a partial D antigen of category DVa type. Six available batches of Rh immunoglobulin reacted with DVa cells.

33 bone allotransplants (cryopreserved) of AB0- and Rh-incompatible (donor-recipient) patients were performed to evaluate the question which AB0 Rh-incompatibility leads to immunization of the bone transplant recipient. Several different antibodies were tested pre- and postoperatively in the recipient. Regarding the Rh-system no immunization was demonstrable; however, a significant increase of antibody leads was found regarding the AB0-system. Thus, in bone bank techniques AB0 compatibility is important for allogeneic bone transplantation in young women. Otherwise, there is a risk for the development of MHN in case of pregnancy. Blood group-typing is not necessary in other patient groups. Although no Rh-antibodies were demonstrable, a similar mechanism can be postulated for the Rh-system. We, thus, conclude that in allogeneic bone tx in young women the Rh-system has to be taken into consideration.

Described is a pregnancy complicated by severe Rh sensitization and hydrops fetalis which was managed aggressively with frequent intrauterine transfusions initiated at 21 1/2 weeks of gestation. No improvement or only temporary improvement of the fetal hydrops was observed after each intrauterine transfusion. Postmortem examination of the infant revealed the additional presence of nonimmunologic factors involved such as pulmonic atresia and lung hypoplasia. In cases of severe Rh sensitization associated with persistent fetal hydrops despite frequent intrauterine transfusions, the presence of coexistent factors for nonimmunologic fetal hydrops should be considered.

Of 655 Rh negative women without anti-D antibody in their serum at genetic amniocentesis, 361 delivered a Rh positive infant. Prophylactic treatment with anti-D immunoglobulin was not given at amniocentesis. The women were followed prospectively, being given a screening test for antibody after amniocentesis, at delivery, and six months later. Five of these 361 women yielded a positive test result due to anti-D antibody. The immunisation rate after genetic amniocentesis was no higher than the spontaneous immunisation rate during pregnancy. Four women who had two amniocenteses in the same pregnancy and 34 women who had amniocentesis in two consecutive pregnancies with Rh positive fetuses were not immunised. Among six women with anti-D antibody in their serum before amniocentesis the titre of antibody increased in three. Amniocentesis may have worsened the outcome of these pregnancies. These results suggest that the risk of immunisation in Rh negative women is small.

Only a few cases of Rhesus blood-type immunization after bone allografting have been reported (Hill et al. 1974, Johnson et al. 1985). Rhesus immunization in girls or fertile women may have severe consequences. We report a case of Rhesus-antibody production after bone allografting for an aneurysmal bone cyst.

After several transfusions with D-negative blood, an O Rh-negative women was apparently sensitized to the C and D antigens. In her prenatal workup, it became evident that she had in fact not been sensitized to D but to G, which initially appeared as anti-D plus anti-C. This sensitization pattern is an unusual occurrence in itself. Moreover, the fetus was affected significantly and was delivered at 32 1/2 weeks with moderate hemolytic disease of the newborn. Consideration is given to points regarding current methods of screening Rh-negative women for transfusion, the use of anti-Rh immune globulin in patients sensitized to anti-C and anti-G, medicolegal implications, and continuous attention to the risk-benefit ratio in decisions to use transfusions.

Choriocarcinoma of the uterus developed in an Rh0(D)-negative woman six weeks after delivery of a normal Rh0(D)-positive child. Although the patient's medical history did not show any previous sensitization, a strong anti-Rh0(D) antibody was detected during evaluation preceding surgical removal of the tumor. The tumor was considered the most probable cause of the Rh0(D) sensitization, since large Rh0(D)-positive areas of tumor were demonstrated by the immunoperoxidase method. This finding indicates that the Rh0(D) antigen is not restricted to erythrocytes, as commonly assumed, but can also be expressed on other tissue, such as tumor tissue.

Fetomaternal hemorrhage can result from different types of trauma and may be followed by fetal anemia, fetal death, or isoimmunization. We prospectively studied the frequency and volume of fetomaternal hemorrhage, fetal well-being, abruptio placentae, and fetal outcome in 32 pregnant patients suffering recent trauma. Fetomaternal hemorrhage occurred in nine of 32 trauma patients (28%) with a mean volume of 16 ml +/- 14.3(SD). There was a statistically significant difference in the frequency and mean volume of fetomaternal hemorrhage in this group over that in gestational-age-matched controls. Neither the nature of the trauma nor the gestational age was related to the frequency or volume of fetomaternal hemorrhage. The outcome in three of the nine trauma patients who sustained fetomaternal hemorrhage was poor; fetal anemia, paroxysmal atrial tachycardia, and fetal death occurred in each one. Maternal trauma remains a significant cause of maternal and fetal morbidity and death, and the use of the Kleihauer-Betke analysis is indicated to identify fetomaternal hemorrhage. Rh-immune globulin therapy should be given to Rh-negative patients with fetomaternal hemorrhage.

Isoimmune neonatal thrombocytopenia is an unusual problem with significant morbidity and mortality. Though it is often self-limited, it is potentially fatal due to hemorrhage. Specific therapy with compatible platelets is indicated. In previously unrecognized cases, platelet antigen and antibody studies delay therapy unacceptably. Therefore, maternal platelets are used, which also aid in establishing a therapeutic diagnosis. A case of isoimmune neonatal thrombocytopenia is reported, and the etiology, clinical and laboratory implications, and methods of management are discussed.

Rh-immunization of a male recipient was observed following the transplantation of two kidneys from Rh-pos donors. Immunosuppression consisted of azathioprine, prednisone and antilymphocyte globulin (1st transplantation) and cyclosporin A and prednisone (2nd transplantation). The immunization was probably caused by the residual blood in the cadaver kidneys. The use of cyclosporin A might increase the risk of Rh-immunization.

Transfusion of one unit or more of Rh-positive red blood cells normally causes circulating anti-D antibody to appear 2-6 months later in 80-95% of Rh- persons. We asked whether transplant immunosuppression with cyclosporine and corticosteroids affects Rh immunization. Nineteen Rh- liver, heart, and heart-lung transplant recipients received 3-153 (median: 10) units of Rh+ RBCs at surgery and were tested for anti-D greater than 2 months later. Three patients developed anti-D at 11-15 days; one may have had an unusually rapid primary immune response and two were secondary to previous exposure by pregnancy. None of the other 16 patients had anti-D when tested 2.5-51 months later (13 patients, greater than 11.5 months). This low rate of Rhesus immunization in association with cyclosporine immunosuppression allows greater flexibility in meeting the transfusion needs of Rh- liver and heart transplant patients. Caution is still advised in young females and in patients who may have been previously exposed to Rh+ RBCs by transfusion or by pregnancy prior to the availability of perinatal Rh immune globulin twenty years ago. Other humoral immune responses to some vaccines or infectious agents may also be impaired in transplant patients.

Three primigravidas developed Rh sensitization after unexplained third-trimester fetal death. One patient manifested sensitization after the diagnosis of fetal death had been made but before delivery occurred. The other two demonstrated anti-D antibodies early in the next pregnancy, despite having received postpartum Rh immunoglobulin. Unsensitized Rh-negative women with unexplained third-trimester fetal death should be screened routinely for fetomaternal hemorrhage when fetal death is discovered, so that adequate prophylaxis against Rh sensitization can be given.

The emergency blood needs of 449 patients were met by supplying 1,717 uncrossmatched units of either red blood cells (RBC) type specific Whole Blood or group O RBC. The RBC were all Rh positive, and 601 units were transfused to 262 untyped patients. None of the patients presented with anti-Rh antibodies. Only 20 patients who were Rh negative received group O Rh positive RBC, and most of these patients were male. There were no acute hemolytic reactions or sensitizations of young females. Group O Rh positive RBC is our first choice to support patients with trauma who cannot wait for type specific or crossmatched blood. Those who do survive the emergency conditions can be reverted to blood of their own type without problem. Acceptance of Rh positive emergency transfusions by physicians giving emergency care can prevent unbalanced shortages in a regional blood supply system.

Maternal serum alpha-fetoprotein concentrations were determined by radioimmunoassay in 72 patients immediately before and after chorionic villus sampling for prenatal diagnosis. Fifty percent showed a rise of greater than or equal to 5 ng/ml. Assuming such rises represent fetal blood crossing the intervillous space, in 14% of the cases greater than or equal to 60 microliters of fetal blood was transferred at the time of chorionic villus sampling. A positive correlation was found between the magnitude of rise in maternal serum alpha-fetoprotein levels and the amount of villi removed (r = 0.39, p less than 0.001). When cases were examined by number of passes, a greater rise in maternal serum alpha-fetoprotein levels was noted with multiple passes than with single passes for a given sample size. The transfer of greater than or equal to 60 microliters of fetal blood suggests that maternal sensitization to fetal antigens may occur after chorionic villus sampling. During biopsy, as small a sample of villi as necessary for diagnosis should be taken with as few catheter passes as possible.

Since immune memory in Rh(D)-negative isoimmunized subjects remains through life, even in the absence of measurable anti-Rh(D), we investigated the transformation of lymphocytes from such donors by Rh(D) antigen. The time lapse from the last stimulus was up to 13 years. Mononuclear cells from immunized women were stimulated by Rh(D)-positive erythrocyte stroma. Maximum transformation was observed on the sixth day of culture, with a stroma protein concentration of 8 micrograms/mL of culture medium. The stimulation index (SI) in cells from 11 immunized women was 6.8 +/- 3.1 (mean +/- SD), with a range from 3.1 to 15.0. In five different sets of control cultures, the SI ranged from 0.9 +/- 0.2 to 1.3 +/- 0.4. There was no overlap between stimulated and control cultures. No anti-D could be demonstrated in the serum of four of the 11 immunized cases studied. Also, transformation was observed in mononuclear cells from Rh(D)-negative immunized women with Rh(D)-positive erythrocytes. The findings demonstrate that lymphocytes from isoimmunized Rh(D)-negative subjects maintain the immune memory and are transformed in vitro by the Rh(D) isoantigen.

From the experience accumulated in less than 4 years of chorionic villus sampling activity, much has been learned about the advantages of prenatal diagnosis in the first trimester. The safety of the procedure during this developmental stage has been extremely good. The record in this centre with over 2700 cases sampled and over 2000 deliveries has demonstrated a fetal loss rate similar to that observed in amniocentesis studies. It appears that fetal loss that may be attributed to the procedure is not more than 1% and may be less. Some of that loss appears to be correlated with avoidable trauma to the chorionic membrane area. If this conclusion is valid, then avoidance of this pattern even in the occasional difficult case may further improve the already acceptable safety record of the procedure.

A retrospective survey of Winnipeg Rh laboratory data from January 1, 1981 to December 31, 1984 determined that, despite placental localization, 2.6% of 974 women having amniocenteses performed at 16 to 18 weeks' gestation for genetic reasons and 2.3% of 1215 women having amniocenteses performed between 32 and 38 weeks' gestation had fetal-maternal transplacental hemorrhages greater than or equal to 0.1 mL of fetal red cells due to placental trauma. In 1.6 and 1.8%, respectively, the fetal transplacental hemorrhages were greater than or equal to 1 mL. Four of 99 alloimmunized women undergoing 257 amniocenteses for determination of severity of fetal erythroblastosis had fetal transplacental hemorrhages all greater than 5 mL of fetal red cells. The 1.9% incidence of fetal transplacental hemorrhages after amniocentesis in alloimmunized women is 83% less than the 11.2% incidence that occurred in the authors' institution from February 1963 to December 1966. However, in three of the four women, there was a very rapid rise in Rh antibody titer and increased severity of Rh fetal disease. Only the alloimmunized woman who meets strict criteria, indicating that her fetus is at risk of fetal death, should be subjected to amniocentesis, and then only after careful placental localization by ultrasound. Because fetal transplacental hemorrhages occur after amniocentesis despite ultrasound placental localization, 300 micrograms of Rh immune globulin should be administered to all unimmunized Rh negative women after amniocentesis.

In 944 Rh-negative patients who received rhesus immunoglobulin (anti-D) following genetic amniocentesis, not a single case of Rh sensitization occurred. Routine administration of a small dose (100 micrograms) of anti-D is effective in preventing Rh sensitization after midtrimester amniocentesis.

Acute exacerbation of Rh isoimmunization following abdominal trauma is a rare complication of pregnancy. The report describes a case of a mild case of erythroblastosis fetalis following maternal exposure to massive fetal-maternal transfusion, occurring after abdominal injury in motoring accident. Abruptio placenta 7 days following the trauma indicated emergency cesarean section, at which a severely affected fetus (erythroblastosis fetalis) was delivered. Late abruption--in the presence of no other risk factor--is considered to call for prolonged surveillance. Any abdominal trauma in a Rh-negative woman should alert one to the possibility of massive transplacental hemorrhage and augmentation of the maternal immune response.