fetomaternal red cell alloimmunization

PURPOSE: To assess the spectrum of underlying diseases in cases of fetal anemia in which the cause was unknown at the time of first and second transfusion or thereafter. MATERIALS AND METHODS: All patients who underwent intrauterine transfusion were identified in the perinatal databases of two tertiary referral centers for prenatal medicine and treatment between 2002 and June 2010. RESULTS: 82 fetuses received intrauterine transfusion in the study period...

During pregnancy, women are tolerant of their semi-allogeneic fetus whilst not being immunosuppressed and indeed readily form alloantibodies. This 'Immunological Paradox of Pregnancy' may be explained by an understanding of placental anatomy and immunology. Trophoblast cells form the interface between the fetus and maternal tissues and blood and escape allorecognition because they lack classical human leucocyte antigen (HLA) class I and II molecules. Local immunoregulation, or tolerance, in the decidua is mediated partly by HLA-G(+) extravillous trophoblasts (EVT) that invade the tissue and prevent killing by maternal natural killer cells, cytotoxic T cells and macrophages...

The long-term neurodevelopmental outcome of children born after intrauterine blood transfusion (IUT) for red cell alloimmunization is considered favorable. Severe hydrops has been identified as a strong predictor for neurodevelopmental impairment. However, the long-term outcome of survivors of IUT for congenital Parvovirus B19 infection and fetomaternal hemorrhage is not well known. Limitations of the follow-up studies to date are small sample size, lack of controls, unclear criteria for impairment and lack of standardized developmental tests...

Feto-maternal red cell alloimmunization is defined by the presence in a pregnant woman of alloantibodies directed against blood group antigens present on the red blood cells of the fetus and inherited from the father. It arises from the immune response to a first contact to these same antigens during a prior transfusion, transplant or pregnancy. The placental transfer and the fixation of the antibodies on the fetal red cells antigenic targets lead to a haemolysis in the fetus and the newborn. The resulting haemolytic disease can show different clinical forms, from a mild anaemia with neonatal hyperbilirubinemia to a major fetal damage with stillbirth caused by hydrops fetalis...

Hemolytic disease of the newborn (HDN) can occur when there are fetomaternal incompatibilities within any number of different erythrocyte antigen systems, including the RhD, Cc, Ee, Kidd and Duffy, and Kell antigen systems. In these disorders, maternal antibodies are developed by alloimmunization of the mother to fetal red blood cells during pregnancy when the fetal cells carry an alloantigen inherited from the father. The maternal antibodies result in the destruction of fetal erythrocytes leading to severe hemolytic anemia and hyperbilirubinemia...

Stillbirth is a major obstetric complication, with 3.2 million stillbirths worldwide and 26,000 stillbirths in the United States every year. The Eunice Kennedy Shriver National Institute of Child Health and Human Development held a workshop from October 22-24, 2007, to review the pathophysiology of conditions underlying stillbirth to define causes of death. The optimal classification system would identify the pathophysiologic entity initiating the chain of events that irreversibly led to death. Because the integrity of the classification is based on available pathologic, clinical, and diagnostic data, experts emphasized that a complete stillbirth workup should be performed...

CONTEXT: Rh(D)-negative women with a large fetomaternal hemorrhage (FMH) from an Rh(D)-positive fetus are at risk for anti-D alloimmunization if they do not receive adequate Rh immune globulin (RhIG). Determination of the adequate RhIG dose for these women is a critical laboratory procedure for protecting their future Rh(D)-positive children. OBJECTIVE: To determine how often laboratories recommended an inaccurate dose of RhIG for excess FMH. DESIGN: Nearly 1600 laboratories using the College of American Pathologists' proficiency testing for fetal red blood cell detection were surveyed to determine (1) their calculation method and (2) the number of RhIG doses recommended for a survey specimen, based on their measured percentage of fetal red blood cells...

The use of Doppler ultrasound evaluation to measure the peak systolic velocity of the fetal middle cerebral artery (MCA) has been a major breakthrough in the noninvasive detection of fetal anemia. An elevated peak MCA velocity of >1.5 multiples of the median is useful in the timing of the initial intrauterine transfusion (IUT) in the red cell-alloimmunized pregnancies. Data reported to date suggest that a threshold of 1.32 multiples of the median can be used to time the second IUT; the MCA Doppler evaluation does not appear sensitive for the timing of subsequent IUTs in these pregnancies...

In red cell immunology, it has long been known that no one technique will detect all clinically significant antibodies. The same appears to be true for platelet immunology, and we highlight this fact by showing four examples of anti-human platelet antigen-1a that were not detected by the monoclonal antibody-specific immobilization of platelet antigen test, the most commonly used technique. Each antibody was found in a case of fetomaternal alloimmune thrombocytopenia in which the fetus or neonate was severely affected...

OBJECTIVE: To assess the peak systolic velocity in the middle cerebral artery (PSV-MCA) in the prediction of fetal anemia in case of severe red-cell alloimmunization. METHODS: A prospective study, from January 2003 to April 2006, of 47 consecutive pregnancies with severe alloimmunization. Fetal surveillance was based on titration and dosage of antibodies, ultrasound scans, and doppler for PSV-MCA measurement up to twice a week. A fetal blood sampling and in utero transfusion was performed in case of increase in PSV-MCA above 1...

A sensitive test for the presence of D-positive fetal red blood cells (RBCs) in the maternal circulation of D-negative women has been developed. It was used to investigate the possibility that the occasional failure in preventing alloimmunization might be due to the administration of inadequate amounts of prophylactic anti-D Rh immune globulin. The standard dose in Australia contains 125 microg of antibody, and can suppress immunization by an estimated 6 mL of packed D-positive RBCs. A fetomaternal hemorrhage (FMH) of this volume is detectable in the maternal circulation as approximately 0...

Several methods for quantitating fetomaternal hemorrhages (FMHs) have been described; these include the Kleihauer-Betke and red cell rosetting tests, and flow cytometry that uses an indirect antiglobulin technique, employing either FITC-conjugated IgG/unlabeled anti-D or streptavidin conjugates with biotinylated anti-D to enumerate D+ red cells in maternal blood. We have used a recently described directly conjugated FITC anti-D for direct flow cytometric (direct FC) quantitation of FMH in a patient who presented with a large fetal bleed (approx...

OBJECTIVES: To determine the perinatal outcome in severe red-cell fetomaternal alloimmunization. METHODS: Retrospective series of 32 affected fetuses treated with intravenous fetal exchange transfusion (IFET) before 22 weeks of gestation. The main outcome measures were the degree of fetal anemia, fetal transfusions and perinatal outcome. RESULTS: The first IFET was performed at 19.8 +/- 1.8 weeks of gestation. All fetuses were severely anemic and hemoglobin levels were not different between 20 hydropic and 12 nonhydropic fetuses (4...

OBJECTIVE: To provide guidelines on use of anti-D prophylaxis to optimize prevention of rhesus (Rh) alloimmunization in Canadian women. OUTCOMES: Decreased incidence of Rh alloimmunization and minimized practice variation with regards to immunoprophylaxis strategies. EVIDENCE: The Cochrane Library and MEDLINE were searched for English-language articles from 1968 to 2001, relating to the prevention of Rh alloimmunization. Search terms included: Rho(D) immune globulin, Rh iso- or allo-immunization, anti-D, anti-Rh, WinRho, Rhogam, and pregnancy...

The Kleihauer technique, based on acid elution of maternal red cells, is the mostly widely used technique in the UK to screen for, and estimate the volume of, foetomaternal haemorrhage (FMH) and for determining the need for additional doses of anti-D immunoglobulin to prevent maternal alloimmunization. However, technicians often report difficulties in identifying and accurately counting maternal red cells in the blood film, leading to imprecision in the calculated FMH. In this report, we describe a simple modification of the standard Kleihauer technique, based on performing acid elution of only half of the film...

Severe fetomaternal alloimmune thrombocytopenia requires urgent treatment with compatible platelet concentrates. As prompt treatment is sometimes delayed owing to the unavailability of compatible platelets, we established an accredited platelet donor panel to provide effective and timely transfusion support for fetal and neonatal therapy. After a mass screening programme of over 60,000 blood donations, 45 HPA-1a-negative donors with no antibodies to HPA, HLA, red cell antigens and granulocytes/lymphocytes, and with low titre anti-A and/or -B were accredited...

PURPOSE: Although neonatal alloimmune thrombocytopenia (NAIT) due to maternal sensitization to human platelet antigens is well described, the role of maternal anti-human lymphocyte antigen (HLA) antibodies in NAIT is not yet firmly established. PATIENT: A 31-week-old girl born prematurely to a G2POA1 mother was noted to have thrombocytopenia which lasted 18 days without any evidence of infection. MATERIALS AND METHODS: Platelet-associated IgG, anti-platelet antibody, and platelet PL(A1) antigen typing were determined using a commercial solid-phase red cell adherent test...

Pregnant women who attended antenatal clinics at King George V Hospital, the Birth Centre or were referred by obstetricians from February 19 July, 1996 were screened for the platelet antigen HPA-1a by flow cytometry. Forty out of 2,300 (1.7%) were found to be negative for this antigen. Of the 28 women followed throughout their pregnancy, none developed antibody to HPA-1a. Platelet counts performed on samples from 17 babies born to 17 of these mothers were all normal. This study proves the simplicity and rapidity of flow cytometry for platelet antigen screening...

Having direct access to the fetoplacental circulation by ultrasound-directed needle puncture has led to therapeutic interventions for fetal anemia and thrombocytopenia. Most cases of red cell alloimmunization associated with fetal anemia are caused by the antibody to the D red cell antigen. The intravascular transfusion of red cells to a hydropic fetus in such cases has notably improved survival. Nonimmune hydrops fetalis due to maternal parvovirus infection has also been treated successfully with the intravascular transfusion of red cells, whereas fetomaternal hemorrhage has not proved amenable to such therapy...

OBJECTIVE: To determine the prevalence of fetomaternal transplacental hemorrhage after funipuncture and its effect on maternal red-cell alloantibody levels. METHODS: The prevalence and size of transplacental hemorrhages at the Health Sciences Centre were studied in two groups of patients: 174 women who were not alloimmunized or were carrying fetuses whose red cells were negative for the antigen to which they were immunized, and 122 women who were alloimmunized and carrying fetuses whose red cells were positive for the antigen to which they were immunized...