-
Pediatric Health, Medicine and... 2021Hemolytic disease of the newborn (HDN), also known as , is a hemolytic condition that predominantly affects rhesus-positive fetuses and infants born to rhesus-negative... (Review)
Review
Hemolytic disease of the newborn (HDN), also known as , is a hemolytic condition that predominantly affects rhesus-positive fetuses and infants born to rhesus-negative mothers. The pathophysiology of HDN begins with maternal antibodies attacking fetal red blood cells following alloimmunization due to rhesus or ABO incompatibility between the maternal and fetal blood. Previously, HDN was known to cause fetal death in 1% of all pregnancies, but with the advent of immunoprophylactic therapies, the condition can be currently fairly well managed with fewer complications if diagnosed early. Diagnosis calls for extensive history taking, physical examination, serological studies, and imaging modalities such as pelvic ultrasound scans. To prevent the disease, earlier intravenous immunoglobulin (IVIG) should be given to pregnant Rh- women who have not been sensitized. It is also vital to understand prospective complications such as severe hyperbilirubinemia and develop appropriate remedies. Because of its great incidence and nature, HDN has been thoroughly explored, and more studies are being conducted each year, revealing new insights about the condition. This review covers the disorder's etiology, diagnosis, and management, including the most current findings as of 2021, as well as trends and prospects, to help in future research and evidence-based medical practice.
PubMed: 34675752
DOI: 10.2147/PHMT.S327032 -
The New England Journal of Medicine Jul 2019
Review
Topics: Blood Group Incompatibility; Diagnosis, Differential; Hemolysis; History, 17th Century; History, 20th Century; Humans; Transfusion Reaction
PubMed: 31291517
DOI: 10.1056/NEJMra1802338 -
Hematology. American Society of... Dec 2020Platelets express ABO antigens and are collected in plasma, which contains ABO antibodies as would be consistent with the donor ABO group. Platelet ABO antigens that are... (Review)
Review
Platelets express ABO antigens and are collected in plasma, which contains ABO antibodies as would be consistent with the donor ABO group. Platelet ABO antigens that are incompatible with recipient ABO antibodies may have accelerated clearance from circulation and result in lower count increments. ABO antibodies that are passively transferred from donor plasma may result in hemolysis of recipient red blood cells. Although platelets do not express Rh antigens, they contain small numbers of intact red blood cells or fragments, which can lead to alloimmunization in the recipient. Alloimmunization to the RhD antigen may occur when platelets obtained from RhD-positive donors are transfused to RhD-negative recipients. All of these compatibility considerations must be balanced against the available supply, which may be limited due to the 5- to 7-day shelf life of platelets. This articles describes considerations for platelet ABO and RhD selection for platelet transfusions, including the impact of major ABO incompatibility on count increments, the risks of hemolysis associated with minor ABO incompatibility, and the risk of RhD alloimmunization when RhD-negative patients receive platelets obtained from RhD-positive donors.
Topics: ABO Blood-Group System; Blood Group Incompatibility; Blood Grouping and Crossmatching; Erythrocytes; Female; Humans; Middle Aged; Platelet Transfusion; Rh-Hr Blood-Group System; Transfusion Reaction
PubMed: 33275681
DOI: 10.1182/hematology.2020000135 -
Journal of Perinatology : Official... Feb 2023The diagnosis of ABO hemolytic disease of the newborn (ABO HDN) has been the subject of considerable debate and clinical confusion. Its use as an overarching default... (Review)
Review
The diagnosis of ABO hemolytic disease of the newborn (ABO HDN) has been the subject of considerable debate and clinical confusion. Its use as an overarching default diagnosis for hyperbilirubinemia in all ABO incompatible neonates regardless of serological findings is problematic and lacks diagnostic precision. Data on hemolysis indexed by carbon monoxide (CO) levels in expired air (ETCOc) and blood (COHbc) support an essential role for a positive direct antiglobulin test (DAT) in making a more precise diagnosis of ABO HDN. A working definition that includes ABO incompatibility, significant neonatal hyperbilirubinemia, and a positive DAT is needed to gain clarity and consistency in the diagnosis of ABO HDN. Absent a positive DAT, the diagnosis of ABO HDN is suspect. Instead, a negative DAT in a severely hyperbilirubinemic ABO incompatible neonate should trigger an exhaustive search for an alternative cause, a search that may require the use of targeted gene panels.
Topics: Infant, Newborn; Female; Humans; ABO Blood-Group System; Erythroblastosis, Fetal; Blood Group Incompatibility; Hyperbilirubinemia, Neonatal; Hemolysis; Coombs Test
PubMed: 36344813
DOI: 10.1038/s41372-022-01556-6 -
JAMA Sep 2023While population-level data suggest Rh immunoglobulin is unnecessary before 12 weeks' gestation, clinical evidence is limited. Thus, guidelines vary, creating confusion... (Observational Study)
Observational Study
IMPORTANCE
While population-level data suggest Rh immunoglobulin is unnecessary before 12 weeks' gestation, clinical evidence is limited. Thus, guidelines vary, creating confusion surrounding risks and benefits of Rh testing and treatment. As abortion care in traditional clinical settings becomes harder to access, many people are choosing to self-manage and need to know if ancillary blood type testing is necessary.
OBJECTIVE
To determine how frequently maternal exposure to fetal red blood cells (fRBCs) exceeds the most conservative published threshold for Rh sensitization in induced first-trimester abortion.
DESIGN, SETTING, AND PARTICIPANTS
Multicenter, observational, prospective cohort study using high-throughput flow cytometry to detect circulating fRBCs in paired maternal blood samples before and after induced first-trimester abortion (medication or procedural). Individuals undergoing induced first-trimester abortion before 12 weeks 0 days' gestation were included. Paired blood samples were available from 506 participants who underwent either medical (n = 319 [63.0%]) or procedural (n = 187 [37.0%]) abortion.
EXPOSURE
Induced first-trimester abortion.
MAIN OUTCOMES AND MEASURES
The primary outcome was the proportion of participants with fRBC counts above the sensitization threshold (125 fRBCs/5 million total RBCs) after induced first-trimester abortion.
RESULTS
Among the 506 participants, the mean (SD) age was 27.4 (5.5) years, 313 (61.9%) were Black, and 123 (24.3%) were White. Three of the 506 participants had elevated fRBC counts at baseline; 1 of these patients had an elevated fRBC count following the abortion (0.2% [95% CI, 0%-0.93%]). No other participants had elevated fRBC counts above the sensitization threshold after induced first-trimester abortion. The median change from baseline was 0 fRBCs, with upper 95th and 99th percentiles of 24 and 35.6 fRBCs, respectively. Although there was a strong association between the preabortion and postabortion fRBC counts, no other baseline characteristic was significantly associated with postabortion fRBC count.
CONCLUSIONS AND RELEVANCE
Induced first-trimester abortion is not a risk factor for Rh sensitization, indicating that Rh testing and treatment are unnecessary before 12 weeks' gestation. This evidence may be used to inform international guidelines for Rh immunoglobulin administration following first-trimester induced abortion.
Topics: Adult; Female; Humans; Pregnancy; Abortion, Induced; Immunoglobulins; Prospective Studies; Rh Isoimmunization; Risk; Pregnancy Trimester, First; Erythrocytes; Young Adult; Black or African American; White
PubMed: 37750879
DOI: 10.1001/jama.2023.16953 -
Contraception Oct 2022Historical evidence that fetal red blood cell (RBC) exposure during early spontaneous or induced abortion can cause maternal Rh sensitization is limited. A close reading... (Review)
Review
Historical evidence that fetal red blood cell (RBC) exposure during early spontaneous or induced abortion can cause maternal Rh sensitization is limited. A close reading of these studies indicates that forgoing Rh immunoglobulin administration before 12weeks gestation is highly unlikely to increase risk of Rh (D) antibody development, and recent studies indicate that fetal RBC exposure during aspiration abortion <12 weeks gestation is below the calculated threshold to cause maternal Rh sensitization, and the amount of fetomaternal hemorrhage during dilation and evacuation procedures up to 18weeks gestation is adequately treated with 100mcg of Rh immunoglobulin. We provide updated recommendations for Rh immunoglobulin administration based on this new evidence.
Topics: Consensus; Family Planning Services; Female; Humans; Immunoglobulins; Pregnancy; Rh Isoimmunization; Rho(D) Immune Globulin
PubMed: 35872236
DOI: 10.1016/j.contraception.2022.07.002 -
American Journal of Kidney Diseases :... Jan 2020With implementation of the Kidney Allocation System, the growth of kidney paired donation programs, and advances in desensitization and immunosuppression, the outlook... (Review)
Review
With implementation of the Kidney Allocation System, the growth of kidney paired donation programs, and advances in desensitization and immunosuppression, the outlook for "untransplantable" kidney transplantation candidates has never been more promising. The Kidney Allocation System prioritized compatible matches for candidates with calculated panel-reactive antibody levels of 98%, 99%, or 100% and broadened allocation of non-A1 and non-A1-B subgroup kidneys to blood group type B candidates. Concurrently, the growth of kidney paired donation programs and use of incompatible transplantation as part of kidney paired donation to achieve "more compatible" kidney transplantation has improved options for candidates with an incompatible living donor. Finally, advances in desensitization and immunosuppression have strengthened the ability to manage donor-specific antibodies and antibody-mediated rejection. Although no patient should be labeled "untransplantable" due to blood group type or donor-specific antibody, all candidates should be provided with individualized and realistic counseling regarding their anticipated wait times for deceased donor or kidney paired donation matching, with early referral to expert centers when needed. In this Perspective, we consider blood group type ABO incompatibility, HLA antigen incompatibility, antibody-mediated rejection, kidney paired donation, and recent developments in incompatible transplantation in more depth and recommend an approach to the sensitized candidate.
Topics: ABO Blood-Group System; Blood Group Incompatibility; Desensitization, Immunologic; Directed Tissue Donation; Donor Selection; HLA Antigens; Histocompatibility; Humans; Kidney Transplantation; Living Donors; Tissue and Organ Procurement
PubMed: 31255336
DOI: 10.1053/j.ajkd.2019.04.025 -
Romanian Journal of Morphology and... 2022Next to A and B antigens, agglutinogen D exhibits the highest immunogenicity. Following the transfusion of D-positive red blood cells (RBCs), almost 80% of D-negative... (Review)
Review
Next to A and B antigens, agglutinogen D exhibits the highest immunogenicity. Following the transfusion of D-positive red blood cells (RBCs), almost 80% of D-negative recipients develop anti-D antibodies (Abs). Subsequently, anti-D immunization further promotes the synthesis of Abs towards other blood group antigens in or outside the Rh system. The D antigen is also involved in 95% of cases of hemolytic disease of the newborn. Transfusions, hemotherapy, grafts, and obstetric history (abortions, ectopic pregnancy, births) are all risk factors for Rh isoimmunization. In the case of ABO compatibility between mother and fetus, Rh-positive fetal RBCs that have reached the maternal bloodstream are not destroyed by group agglutinins, and Rh antigenic sites are not hidden by the maternal immune system. But a Rh-negative mother with a homozygous Rh-positive husband will certainly have a Rh-positive fetus. As it has an irreversible evolution, the Rh isoimmunization once installed cannot be influenced in the sense of decreasing the Ab titer, therefore, injectable globulin has no effect. A particular case was that of a newborn with Rh system incompatibility associated with hereditary spherocytosis The clinical balance at birth reflects the severe jaundice of the female newborn of 3140 g, gestational age 38∕39 weeks, extracted by lower-segment transverse Caesarean section, with a double loop nuchal cord, Apgar score 8. Because the jaundice was severe and atypical (face and upper chest), we considered the possibility of coexistence of hemolytic disease of the newborn by Rh blood group incompatibility associated with hereditary spherocytosis, as it turned out to be true and mentioned. Changes in genes encoding proteins in the structure of the RBC membrane have amplified hemolysis induced by maternal-fetal isoimmunization in the Rh system. Massive hemolysis accentuated by congenital spherocytosis, confirmed later, imposed blood transfusion and dynamic monitoring.
Topics: Blood Group Incompatibility; Cesarean Section; Female; Hemolysis; Humans; Infant; Infant, Newborn; Jaundice; Pregnancy; Pregnancy Complications; Rh Isoimmunization
PubMed: 36074689
DOI: 10.47162/RJME.63.1.26 -
PloS One 2020In the mid-20th century, Hemolytic Disease of the Fetus and Newborn, caused by maternal alloimmunization to the Rh(D) blood group antigen expressed by fetal red blood...
In the mid-20th century, Hemolytic Disease of the Fetus and Newborn, caused by maternal alloimmunization to the Rh(D) blood group antigen expressed by fetal red blood cells (i.e., "Rh disease"), was a major cause of fetal and neonatal morbidity and mortality. However, with the regulatory approval, in 1968, of IgG anti-Rh(D) immunoprophylaxis to prevent maternal sensitization, the prospect of eradicating Rh disease was at hand. Indeed, the combination of antenatal and post-partum immunoprophylaxis is ~99% effective at preventing maternal sensitization to Rh(D). To investigate global compliance with this therapeutic intervention, we used an epidemiological approach to estimate the current annual number of pregnancies worldwide involving an Rh(D)-negative mother and an Rh(D)-positive fetus. The annual number of doses of anti-Rh(D) IgG required for successful immunoprophylaxis for these cases was then calculated and compared with an estimate of the annual number of doses of anti-Rh(D) produced and provided worldwide. Our results suggest that ~50% of the women around the world who require this type of immunoprophylaxis do not receive it, presumably due to a lack of awareness, availability, and/or affordability, thereby putting hundreds of thousands of fetuses and neonates at risk for Rh disease each year. The global failure to provide this generally acknowledged standard-of-care to prevent Rh disease, even 50 years after its availability, contributes to an enormous, continuing burden of fetal and neonatal disease and provides a critically important challenge to the international health care system.
Topics: Erythroblastosis, Fetal; Female; Humans; Immunotherapy; Infant, Newborn; Pregnancy; Rh Isoimmunization; Rh-Hr Blood-Group System; Rho(D) Immune Globulin
PubMed: 32687543
DOI: 10.1371/journal.pone.0235807