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Perinatal management of fetal hemolytic disease due to Rh incompatibility combined with fetal alloimmune thrombocytopenia due to HPA-5b incompatibility.

We report out experience in the perinatal management of a complex case of fetal hemolytic disease primarily due to Rhesus incompatibility combined with fetal alloimmune thrombocytopenia. The lowest fetal hemoglobin and platelet levels were 2.6 g/dl and 13,000/microliter, respectively. Intrauterine treatment consisted of six transfusions of packed red cells into the umbilical vein and one transfusion of platelets. The neonate required four transfusions of packed red cells to correct her hyporegenerative erythropoiesis. Postnatal management also included one platelet transfusion, intravenous immunoglobulins and erythropoietin. Although some degree of fetal thrombocytopenia may invariably be found in fetal red cell incompatibility, other rare causes need to be excluded.

Adult↗

Middle cerebral artery peak systolic velocity in the prediction of fetal anemia.

OBJECTIVE: The fetal middle cerebral artery peak systolic velocity (MCA PSV) has been suggested as a potential test to predict the fetal hematocrit level. We tested the hypothesis that a low fetal hematocrit is associated with an increase in MCA PSV in a prospective study of normal and alloimmunized pregnancies. METHODS: Fetal hematocrit and MCA PSV were obtained in 26 alloimmunized fetuses, immediately before their first fetal blood transfusions between 15 and 35 weeks. Results were compared with the MCA PSVs from 170 control fetuses not at risk of alloimmune anemia between 13 and 37 weeks. RESULTS: In control fetuses, PSV varied with gestation (PSV = 0.56 - 0.032 GA + 0.00086 GA2, where GA is gestational age; R2 = 0.41). The correlation between PSV and hematocrit Z scores (Pearson correlation coefficient r = -0.69) was highly significant (P = 0.0001). Using a PSV > 1 SD, the sensitivity of the test in predicting a fetal hematocrit < 2 SD below the mean was only 64% but the specificity was 100%. However, the sensitivity of the test in predicting a fetal hematocrit < 3 SD and < 4 SD rose to 73% and 83%, while the specificity was still good (93% and 80% respectively). CONCLUSIONS: MCA PSV and fetal hematocrit are highly significantly correlated. The sensitivity of the test was good and the high positive predictive value indicates that the presence of a raised PSV (defined as > 1 SD) is a strong indicator of fetal anemia. In conclusion, MCA PSV is a useful test in clinical practice for the detection of fetal anemia.

Adult↗

Resolution by erythrocytapheresis of the exposure of an Rh-negative person to Rh-positive cells: an alternative treatment.

Acute trauma with severe bleeding caused the unavoidable transfusion of Rh-positive red cells (RBCs) to a young, childless, Rh-negative woman during surgery. Of the 10 units of RBCs given, 6 were Rh positive. An alternative treatment for large-volume exposure involves the removal of some of the Rh-positive cells transfused at a time when the patient's condition could not be jeopardized by the shortage of Rh-negative RBCs. It is believed that the combination of erythrocytapheresis followed by Rh immune globulin treatment was successful, when immunoprophylaxis alone might not have been. It is strongly recommended that partial RBC exchange for the removal of the unwanted RBCs be considered in addition to Rh immune globulin treatment in cases of large-volume exposure such as the one presented.

Adult↗

Lack of alloimmunization to D antigen in D-negative immunosuppressed liver transplant recipients.

BACKGROUND: Orthotopic liver transplantation (OLT) sometimes requires large amounts of blood. An adequate supply of Rh-negative blood for Rh-negative patients is not always available. STUDY DESIGN AND METHODS: Seventeen Rh-negative patients, out of 327 receiving OLT in this hospital, received from 5 to 41 units of Rh-positive red cells during surgery. Each of the 17 patients was followed for 7 weeks to 70 months after OLT for detection of unexpected antibodies. Cyclosporin A and prednisone, azathioprine, and adjunctive rabbit antilymphocyte globulin or monoclonal OKT3 antibody were used to prevent graft rejection. RESULTS: Evidence of immunization, either to D or to antigens in the rest of the red cell antigen systems, did not appear in any patients. CONCLUSION: It is hypothesized that cyclosporin A affects the immune humoral response, inhibiting lymphocyte activation and the primary immune response; consequently, Rh-positive blood may be transfused to Rh-negative OLT recipients so treated with little or no risk of alloimmunization.

Adult↗

Clinical evaluation of a solid-phase test for red cell antibody screening of pregnant women.

BACKGROUND: The aims of this study were to evaluate the results of a new solid-phase screening test for detecting atypical red cell (RBC) antibodies in a large number of pregnant women and to compare these results to the clinical outcome of the newborn. STUDY DESIGN AND METHODS: A total of 38,700 infants born in Stockholm were studied retrospectively. Of these infants, 18,500 were born to pregnant women screened with the solid-phase test. Data were collected on all newborns with a positive direct antiglobulin test (DAT) and on infants requiring an exchange transfusion or a blood transfusion. These data were correlated to the screening results for the mothers. RESULTS: Of 409 DAT-positive newborns, a serologic explanation for the positive DAT was found in 349. Three hundred four cases were due to ABO incompatibility between mother and child; 19 of these infants needed an exchange transfusion. Forty-two cases were due to unexpected maternal RBC antibodies; 11 of these infants were given an exchange transfusion. All 11 were identified before birth. Three other infants had DAT-positive tests due to ABO incompatibility and to unexpected maternal RBC antibodies. CONCLUSION: ABO incompatibility is a major indication for exchange transfusion in DAT-positive newborns. There was no evidence that the solid-phase screening test had failed to detect any clinically significant RBC antibodies. Finally, the results of this study do not indicate a need for routine screening of D+ women more than once during each pregnancy.

ABO Blood-Group System↗

Primary anti-D immunization by weak D type 2 RBCs.

BACKGROUND: D is the most immunogenic blood group antigen. In about 0.4 percent of whites, D is expressed on RBCs in a weak form. Recently, it was found that the weak D phenotypes are caused by a large number of distinct RHD alleles generally encoding altered D proteins. No particular molecular weak D type has yet been shown to induce anti-D. The threshold of D antigen density required for anti-D immunization is not known. CASE REPORT: A 72-year-old D- white man received apparently D- RBCs. Nineteen days later, he developed a positive DAT, and anti-D was found in his serum and an eluate from his RBCs. One donor was found to be D+ with a weak D type. The weak D type was determined by RHD exon 9-specific nucleotide sequencing from genomic DNA. The transfusion recipient showed alloanti-D. Ten months later, anti-D but no other antibody was detectable; the DAT was negative and the eluate was nonreactive. The donor of the incriminated unit was D+ (ccDEe) with weak D due to the weak D type 2 allele, expressing about 450 D antigens per RBC. CONCLUSION: This case provides formal proof that RBCs of weak D type 2 phenotype may cause alloanti-D immunization. Among the more prevalent weak D types in whites, weak D type 2 has the lowest D antigen density. Thus, units of blood from donors of the weak D type 2 phenotype should be labeled D+; the weak D type 2 phenotype may be useful for quality assurance.

Aged↗

Detection of multiple passively acquired alloantibodies following infusions of IV Rh immune globulin.

BACKGROUND: Passively acquired blood group alloantibodies are detected regularly after infusions of IV Rh immune globulin (RhIG) for the treatment of immune thrombocytopenic purpura (ITP) in D+ patients. STUDY DESIGN AND METHODS: Blood samples from 16 D+ patients with ITP were tested after treatment with IV RhIG for the presence of passively acquired alloantibodies. Similar studies were conducted for three D- patients after injections of IM RhIG for Rh immunoprophyl-axis. Four production lots of IV RhIG and 2 lots of IM RhIG were tested for the presence of alloantibodies. RESULTS: All 16 D+ patients with ITP developed a positive DAT, as well as positive antibody detection test results, after infusions of IV RhIG. All postinfusion plasma samples contained anti-D, as well as one or more additional antibodies, usually anti-C, -E, -G, -V, or -Fy(a). Eluates from patients' RBCs with positive DAT results contained multiple passively acquired alloantibodies. Multiple alloantibodies were detected in samples of different production lots of IV RhIG or IM RhIG. No acute transfusion reactions were observed in five D+ patients with ITP who had been treated with IV RhIG and had been given serologically incompatible D+ RBCs. After injections of IM RhIG, the only passively acquired alloantibody detected was anti-D. CONCLUSION: Plasma samples from D+ patients with ITP treated with IV RhIG regularly contained anti-D and multiple other passively acquired Rh, Duffy, or Kidd system alloantibodies. Postinfusion RBC samples all had positive DAT results with eluates containing anti-D and multiple other Rh, Duffy, or Kidd system antibodies. The consistent detection of multiple passively acquired alloantibodies after IV RhIG, in contrast to the detection of anti-D only after IM RhIG, reflects the immediate effect of the entire (bolus) dose of RhIG by the IV route, the dose for treating ITP that is approximately 10 times the dose for Rh immunoprophylaxis, and the expected serologic incompatibility with recipients' D+ RBCs.

Erythrocyte Transfusion↗

RBC alloimmunization and autoimmunization among transfusion-dependent Arab thalassemia patients.

BACKGROUND: Thalassemia major is a common hemoglobinopathy in the Arabian Gulf region. However, limited data are available on the frequency of RBC alloimmunization and autoimmunization in transfusion-dependent Arab thalassemia patients. STUDY DESIGN AND METHODS: A total of 190 thalassemia major patients were classified as Kuwaiti Arab and non-Kuwaiti Arab. Pretransfusion investigation records were reviewed for the presence of RBC alloantibody and autoantibody, and the age at which RBC alloantibody was developed. RESULTS: Fifty-seven (30%) patients developed RBC alloantibodies. The most common clinically significant alloantibodies were directed against antigens in the Kell and Rh systems. Anti-K developed in 41 (72%) patients followed by anti-E in 26 (45.6%). RBC autoantibodies developed in 21 (11%) patients with and without underlying RBC alloantibodies. Sixty-six (49.6%) RBC alloantibodies developed between the ages of 2 and 10 years. CONCLUSION: Several factors might have contributed to the high alloimmunization and autoimmunization rate observed in this study, including the heterogeneity of the population living in Kuwait, lack of better-matched donors for those patients, and the use of poststorage leukodepleted blood. It is recommended that thalassemia patients receive blood matched for Rh and Kell antigens and prestorage leukodepleted RBCs.

Adolescent↗

Red blood cell alloimmunization in pregnancy.

Red blood cell (RBC) alloimmunization in pregnancy continues to occur despite the widespread use of both antenatal and postpartum Rhesus immune globulin (RhIG), due mainly to inadvertent omissions in administration as well as antenatal sensitization prior to RhIG given at 28 weeks' gestation. Additional instances are attributable to the lack of immune globulins to other RBC antigens. Evaluation of the alloimmunized pregnancy begins with the maternal titer. Once a critical value [32 for anti-Rh(D) and other irregular antibodies; 8 for anti-K and -k] is reached, fetal surveillance using serial Doppler ultrasound measurements of the peak velocity in the fetal middle cerebral artery (MCA) is standard. In the case of a heterozygous paternal phenotype, amniocentesis can be performed to detect the antigen-negative fetus that requires no further evaluation. MCA velocities greater than 1.5 multiples of the median necessitate cordocentesis, and if fetal anemia is detected, intrauterine transfusion therapy is initiated. A perinatal survival of greater than 85% with normal neurologic outcome is now expected. Future therapies will target specific immune manipulations in the pregnant patient.

Algorithms↗

Patient refusal of treatment in obstetrics.

During the later half of the previous century, Clinical Ethics evolved from the iconoclastic and murky realm of philosophical dissertation into a practical and useful discipline to be applied to clinical dilemmas occurring in everyday practice. We have explored a brief exposition of prevailing ethical theories that are most commonly recognized. These include Consequentialism and Principlism, and we have applied them to actual cases as they might occur in clinical practice. It is our hope that this will help us all to facilitate decisions with which we will be comfortable and which will be compatible with the beliefs and values of our patients.

Adult↗

A case of extreme unconjugated fetal hyperbilirubinemia.

We present an unusual case of severe unconjugated hyperbilirubinemia and normal hemoglobin at birth in a premature newborn with Rh incompatibility. We speculate that the possible mechanism is due to placental dysfunction. To our knowledge, this is the highest reported unconjugated bilirubin level at birth.

Adult↗

[Fetal plasma erythropoietin concentration during intrauterine transfusion therapy in isoimmunohemolytic anemia due to rhesus incompatibility].

PURPOSE: Prenatal plasma concentrations of erythropoietin in fetuses with Rh disease should contribute information to the clinical course and therapeutic control of this disease. METHOD: Fetal plasma erythropoietin (Epo) and haemoglobin (Hb) concentrations were measured in 145 umbilical venous blood samples of 30 fetuses with Rh disease at 20 to 38 weeks' gestation. RESULTS: Both Epo and Hb concentrations were independent of the gestational age in red blood cell-isoimmunised pregnancies. The Hb concentration correlated significantly with Epo concentration without intrauterine transfusion (IUT) (r = -0.519, p = 0.005) and after IUT (i = -0.212, p = 0.01). A haemoglobin deficit of 3 g/dl at 20 weeks' gestation increased to 6 g/dl at 38 weeks' gestation in spite of IUT (p = -0.354, p < 0.001). CONCLUSION: Even with IUT, Epo concentrations increase with gestational age during these pregnancies. This is due to increasing Hb deficits indicating fetal hypoxia which might be prevented by increasing volumes of transfusion.

Adult↗

[Antibody detection after antepartal rhesus prophylaxis: normal values or sensitization].

Antibody screening tests were performed in 29 unsensitized pregnant women after antepartum Rh immune prophylaxis, using the indirect Coombs test (ICT) and a more sensitive ID-microtyping-system (IDM). With the ICT, anti-D antibodies were detected in 85% for at least 4 weeks and at most 8 weeks after immunisation. The maximum titer was 1:8. With the IDM, 97% showed antibodies against 'D' for at least 4 weeks and at most 11 weeks with a maximum of 1:16. The IDM titer was always 1 to 3 steps more sensitive than the ICT. After postpartum Rh immune prophylaxis, anti-D titers were again positive in many of the patients (ICT: 42%; IDM: 60%). In conclusion, it is nearly always possible to measure antibodies against 'D' after antepartum Rh immune prophylaxis and IDM was superior in comparison to ICT. However, maternal isoimmunisation to the rhesus antigen cannot be excluded for sure and patients have then to be controlled. As isoimmunisation could not be confirmed in any of our patients, postpartum Rh immune prophylaxis has to be administered even after detection of an antibody titer against 'D' after antepartum Rh prophylaxis.

Coombs Test↗

[Clinical and immune hematologic problems in prenatal prevention of Rhesus sensitization].

Various studies have provided impressive evidence of the efficacy of antenatally administered anti-D in the prevention of rhesus (D) alloimmunisation in rhesus-negative women. However, possible clinical and immunohaematological problems associated with this prophylactic therapy have received little attention. We describe perinatal and immunohaematological problems, which occurred in four cases after antenatal rhesus prophylaxis. Classical immunohaematological techniques were employed, to detect and specify irregular red cell antibodies. It was found, that the antenatal administration of anti-D could mask sensitization to other red cell antigens or the production of maternal immune anti-D antibodies later in pregnancy. A further problem encountered was that of neonates with a positive direct Coombs' test (the uncertainty in the individual case being, whether this is a result of the antenatal administration of anti-D) and marked hyperbilirubinaemia. Antenatal immunoprophylaxis for rhesus disease can give rise to immunohaematological and clinical findings, of which the interpretation is extremely difficult and requires intensive cooperation between the obstetrician, neonatologist, and haematologist/clinical biochemist.

Adult↗

[Monitoring umbilical cord puncture and intravascular transfusions with Doppler ultrasound].

Complications of percutaneous umbilical blood samplings and intravascular transfusions can be detected rapidly, easily and efficiently by Doppler ultrasound and therefore the operator can react as early as possible. In addition to real-time sonography Doppler ultrasound allows for assessment of haemodynamical changes due to intravascular transfusions both on the venous and arterial side of umbilical perfusion. Because of immediate recognition of bradycardia and other fetal cardiac frequency alterations as well as increase of resistance to blood flow on the arterial side the operator can react promptly. On the venous side correct application of transfused volume is monitored continuously by changes of flow velocity waveforms during injection and allows to assess dislocation of the needle.

Blood Flow Velocity↗