Mitigation strategies for anti-D alloimmunization by platelet transfusion in haematopoietic stem cell transplant patients: a survey of NCCN® centres.

BACKGROUND AND OBJECTIVES: D-negative patients are at risk of developing an alloantibody to D (anti-D) if exposed to D during transfusion. The presence of anti-D can lead to haemolytic transfusion reactions and haemolytic disease of the newborn. Anti-D alloimmunization can also complicate allogeneic haematopoietic stem cell transplantation (HSCT) with haemolysis and increased transfusion requirements. The goal of this study was to determine whether cancer centres have transfusion practices intended to prevent anti-D alloimmunization with special attention in patients considered for HSCT. METHODS AND MATERIALS: To understand transfusion practices regarding D-positive platelets in D-negative patients with large transfusion needs, we surveyed the 28 cancer centres that are members of the National Comprehensive Cancer Network® (NCCN® ). RESULTS: Nineteen centres responded (68%). Most centres (79%) avoid transfusing D-positive platelets to RhD-negative patients when possible. Four centres (21%) avoid D-positive platelets only in D-negative women of childbearing age. If a D-negative patient receives a D-positive platelet transfusion, 53% of centres would consider treating with Rh immune globulin (RhIg) to prevent alloimmunization in women of childbearing age. Only one centre also gives RhIg to all D-negative patients who are HSCT candidates including adult men and women of no childbearing age. CONCLUSION: There is wide variation in platelet transfusion practices for supporting D-negative patients. The majority of centres do not have D-positive platelet transfusion policies focused on preventing anti-D alloimmunization specifically in patients undergoing HSCT. Multicentre, longitudinal studies are needed to understand the clinical implications of anti-D alloimmunization in HSCT patients.

Neonatal hyperbilirubinemia secondary to combined anti e and anti C isoimmunisation: a literature review.

A term male infant was admitted at 48 h of postnatal life to the neonatal unit for jaundice. The investigation showed total serum bilirubin (TSB) of 17.1 mg/dl, haemoglobin of 11 g/dl, reticulocyte count of 9.5% and peripheral smear was suggestive of macrocytic, normochromic red blood cell (RBC) with target cells and multiple spherocytes with occasional nucleated RBC. The infant's blood group was B positive. Direct antiglobulin test was strongly positive by gel method (3+). Mother's blood group was B positive and indirect antiglobulin test was positive when tested postnatally. Extended minor blood grouping and cross matching showed this as a case of combined anti e and anti C antibodies isoimmunisation. Infant was treated with phototherapy for 72 h and was shifted to mother side. Infant was serially monitored with TSB level every sixth hourly and American Academy of Pediatrics (AAP) phototherapy charts were followed to see for rebound hyperbilirubinemia. The neonate was discharged and there was no readmission for hyperbilirubinemia. It is very rare and we report the third case of its type till date.

Isolated anaemia as a manifestation of Rh isoimmunisation.

Rh isoimmunisation leads to haemolytic anaemia and hyperbilirubinaemia in the first h of life. Isolated early onset neonatal anaemia has rarely been reported. The authors describe the case of a term infant, born to an 'A' negative, second gravida mother. On the second day of life, pallor was noticed. His haemoglobin (Hb) was 6.8 g/dl, he had reticulocytosis and a positive direct antiglobulin test. However, he did not have a high total serum bilirubin (TSB) (87.2 µmol/l). He was transfused with red blood cells and kept under phototherapy for 3 days. Three weeks later, he received another transfusion for severe anaemia (Hb 6 5 g/dl). During this period, he was never jaundiced and the maximum level of TSB was 122 µmol/l. On follow-up, his Hb stabilised and he had no further problems. This report highlights the possibility of early onset anaemia without jaundice as the sole manifestation of Rh isoimmunisation.

Hemolytic disease of the newborn- anti c antibody induced hemolysis.

Hemolytic disease in the newborn, as a cause of early jaundice, is not uncommon. This is mostly due to Rh (D), ABO incompatibility and rarely due to other minor blood group incompatibility. The authors report two cases of Rh anti c isoimmunization presenting as significant early neonatal jaundice within the 20 h of life. Both the babies were treated with intensive phototherapy. One baby underwent exchange transfusion and the other required packed cell transfusion for anemia.

[Fetomaternal anti-RH3, -4 (anti-E and anti-c) rhesus isoimmunization: a case report]. / Allo-immunisation fœto-maternelle rhésus anti-RH3, 4 (anti-E et anti-c) : à propos d'un cas.

Hemolytic disease of the newborn caused by maternal isoimmunization has been decreasing over the past 10 years because of prophylactic treatment with anti-RH1 (anti-D) immunoglobulin. Nevertheless, there is an increase in the incidence of both relative and absolute numbers of non-RH1 red-cell maternofetal isoimmunizations, essentially anti-RH4 (anti-c), anti-RH3 (anti-E), and anti-Kell. In 8 to 14% of cases, multispecificity antibodies are present, the most common combination being the association of anti-RH3 and -4. Despite absence of specific prophylactic therapy, anti-RH4 isoimmunization could be as severe as anti-RH1 ; as for anti-RH3, it is usually associated with mild to moderate clinical manifestations. Nevertheless, there are few publications on anti-RH3, -4 maternofetal isoimmunization with a bias toward the most severe cases being reported. We report here a case of nonsevere maternofetal anti-RH3, -4 isoimmunization complicated with severe hyperbilirubinemia and delayed profound anemia. Hyperbilirubinemia was controlled using intensive phototherapy. Although anemia was absent at birth, it appeared progressively with a nadir at 7.8 g/dL at 1-month postnatal age. Blood counts were monitored for 3 months but the patient did not require red blood cell transfusion. This report underlines the need for a prolonged and rigorous pediatric follow-up of children born in the context of maternofetal isoimmunization after the acute neonatal period. Furthermore, it stresses the necessity of DAT testing in all pregnant women, even those who are RH1-positive.

Severe hemolytic disease of the newborn from anti-e.

Maternal antibody-mediated fetal red blood cell destruction secondary to non-D Rhesus (Rh) antibodies is a significant cause of hemolytic disease of the newborn (HDN). Here, we report a rare case of severe HDN associated with maternal antibody to Rh e. In addition to severe anemia, the infant developed thrombocytopenia, conjugated hyperbilirubinemia and cholelithiasis. Resolution of the infant's cholelithiasis occurred following treatment with ursodeoxycholic acid.

[Foetomaternal erythrocyte incompatibilities: from immunohaematologic surveillance of pregnant women to haemolytic disease of the newborn]. / Incompatibilités foetomaternelles érythrocytaires (IFME): de la surveillance immunohématologique des femmes enceintes à la maladie hémolytique du nouveau-né (MHNN).

Despite the generalization of prevention measures against foetomaternal alloimmunization with anti-D immunoprophylaxis since 1970s, retrospectively 30 years later, its complications (new-born child's severe haemolytic disease, foetal death by anemia or nuclear icterus by bilirubin encephalopathy) have not disappeared. At the same time, alloimmunizations against antigens other than D increase with no possible prevention. As part of the set up in France of regional files analysing and making an inventory of serious foetomaternal incompatibilities requiring in utero or neonatal transfusion, we felt the need to synthesize current data, biological profiles (early screening of erythrocytic alloimmunization and its follow up during pregnancy, father's immunohaematologic status, evaluation of in utero immune haemolysis and impact of new non invasive techniques of diagnosis-RH1 foetal genotypage from ADN foetal of RH1--mothers' maternal plasma), clinical and paraclinical data (evaluation of foetal haemolysis by echography, recording of foetal movements and foetal cardiac rhythm), therapeutic indicators (in utero foetal transfusions or exsanguinotransfusions, neo and postnatal transfusions or exsanguinotransfusions, induced premature labour, newborn's intensive continue phototherapy and Rhesus immunoprophylaxis) in order to enable medical and paramedical professionals to carry out the specific supervision of pregnancies with foetomaternal incompatibility, the in utero, neo- and postnatal treatment of child and the efficient therapeutic prevention of anti-D alloimmunization, in a cooperative way.

Maternal ABO-mismatched blood for intrauterine transfusion of severe hemolytic disease of the newborn due to anti-Rh17.

BACKGROUND: Clinically significant antibodies to high-incident antigens present a challenge in hemolytic disease of the newborn. Antigen-negative blood may be difficult to obtain for intrauterine transfusion (IUT). In these instances, maternal blood is de facto compatible regardless of an ABO mismatch. CASE REPORT: A group B/D-- woman with a history of hemolytic disease of the newborn due to anti-Rh17 (titer 256) presented to the obstetrical clinic at 12 weeks gestation for management of her third pregnancy. She consented to donate blood for possible IUT. STUDY DESIGN AND METHODS: Washed maternal packed cells were suspended in saline to 75 percent Hct and irradiated before transfusion. The fetus was transfused via the intrahepatic vein. RESULTS: Ultrasound examination at 19 weeks indicated a hydropic fetus. The fetal blood group was O Rh+, direct antiglobulin test 4+, and hemoglobin 22 g per L. A total of 368 mL of maternal blood was transfused during seven procedures. Labor was induced at 38 weeks, and a 2560-g male infant was delivered by Caesarian-section due to fetal distress. The infant grouped as B Rh+, direct antiglobulin test negative. No group O red blood cells were detected. The hemoglobin level was 143 g per L rising to 209 g per L at discharge 3 days later. The indirect bilirubin was 55 micromol/L and remained stable during the hospital stay. Phototherapy was discontinued after 1 day, and the infant was discharged without an exchange or top-up transfusion. CONCLUSIONS: Maternal ABO-mismatched blood is an alternate source for IUT in instances when antigen-compatible allogenic blood is unavailable.

Hydrops fetalis caused by homozygous alpha-thalassemia and Rh antigen alloimmunization: report of a survivor and literature review.

Hematologic causes of hydrops fetalis include homozygous alpha-thalassemia and immune hemolytic anemias. We report the case of a boy with hydrops fetalis who had homozygous alpha-thalassemia and alloimmune hemolytic anemia due to anti-E and anti-C blood group antibodies. He received intrauterine red blood cell transfusions and postnatal chronic transfusion with iron chelation therapy. A non-myeloablative sibling stem cell transplant failed. He is now 5 years and 6 months of age, hypothyroid with short stature, but in overall good health. He is one of the oldest reported homozygous alpha-thalassemia survivors and, to our knowledge, the only survivor with immune- and nonimmune-induced hydrops fetalis.

The prevalence of red cell antibodies in pregnancy correlated to the outcome of the newborn: a 12 year study in central Sweden.

BACKGROUND: All maternal red cell antibodies found during pregnancy in a 12 year period have been compiled. The efficacy of the current antenatal screening and management programme has been ascertained by reviewing the outcome of all newborns to these immunized mothers. METHOD: Patient selection was carried out by computerised searching for all known records of registered antibodies during the study period. Each mother's obstetric record and her baby's hospital file was studied and relevant clinical treatment and laboratory data on both mother and child was recorded and analysed. RESULTS: Eight hundred and twenty-one alloantibodies were detected in 629 immunized pregnant women with 753 fetuses. An overall antibody incidence of 0.57% was observed which included 373 clinically significant antibodies found in 261 mothers (0.24%). Multiple antibodies were present in 8.2% of all samples. Anti-D, by itself or in combination with other Rh-antibodies, caused more severe forms of hemolytic disease of the newborn (HDN) with 46% of all Rh-positive babies having phototherapy and 29% having exchange transfusion. Three of 18 Fya-positive infants required phototherapy and one required exchange transfusion and in the 16 Kell-positive babies, three required phototherapy and one required exchange transfusions. CONCLUSIONS: Few antibodies to blood group antigens other than those in the Rhesus system were found to cause severe HDN. Antibodies that are generally considered non-significant did not cause HDN in this study. All antibodies that induced HDN were detected in time so that adequate measures could be taken to reduce the effects in the newborn. The antenatal screening and management programme currently in use is considered to be reliable.

Flow cytometric analyses of the subclasses of red cell IgG antibodies.

We report on flow cytometric IgG subclass determinations of red cell antibodies using polyclonal FITC-labeled antibodies. The limit of detection of this method was 1 ng anti-D per 1 x 10(7) red cells. The inter- and intra-assay coefficients of variance were 8.2 and 2.3%, respectively. In 8 newborns with a positive direct antiglobulin test (DAT) in the gel centrifugation test (GCT), due to ABO antibodies, IgG1 was detected in all and IgG2 additionally in 4 of these cases. In 5 severe cases of hemolytic disease of the newborn (HDN) due to anti-D, large amounts of IgG1 were found, and in 3 of these 5, IgG3 in combination with IgG1. In 8 mild or moderate HDN cases (4 anti-D, 2 anti-E, 1 anti-Fya, 1 anti-Jka), phototherapy sufficed, and IgG1 was the only antibody. In 7 adult patients with malignant lymphoma and a positive DAT (GCT), only small amounts of IgG1 red cell autoantibodies could be demonstrated by flow cytometry. In 5 further patients with malignant lymphoma, a positive DAT, and severe hemolytic anemia, large amounts of IgG1 autoantibodies were found and IgG3 was also present in 3 of these cases. Flow-cytometric determination of IgG subclasses may be a useful tool in immunohematology, since subclass determinations were possible in all of these cases. This method is suited for clinical routine and offers the possibility of sufficient standardization.

Rh immunization by the partial D antigen of category DVa.

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.

[The activation of the immunosorptive properties of blood during its UV irradiation at therapeutic doses]. / Aktivatsiia immunosorbtsionnykh svoistv krovi pri ee UF-obluchenii v terapevtichekikh dozakh.

UV irradiation of donor rhesus-positive blood in apparatus, applied in Soviet hospitals for autotransfusion of UV-irradiated blood produces a 2-fold increase of the blood capacity to bind antirhesus antibodies in blood or serum from sensibilized women. The above data can be used for increase in therapeutic effect of blood exchange transfusion in children with rhesus-conflict hemolytic disease.