Materiały źródłowe

• #1 Rh Incompatibility: Practice Essentials, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/797150-overview

  The Rh factor (ie, Rhesus factor) is a red blood cell surface antigen that was named after the monkeys in which it was first discovered. Rh incompatibility, also known as Rh disease, is a condition that occurs when a woman with Rh-negative blood type is exposed to Rh-positive blood cells, leading to the development of Rh antibodies. […] Rh incompatibility can occur by 2 main mechanisms. The most common type occurs when an Rh-negative pregnant mother is exposed to Rh-positive fetal red blood cells secondary to fetomaternal hemorrhage during the course of pregnancy from spontaneous or induced abortion, trauma, invasive obstetric procedures, or normal delivery. Rh incompatibility can also occur when an Rh-negative female receives an Rh-positive blood transfusion. In part, this is the reason that blood banks prefer using blood type „O negative” or „type O, Rh negative,” as the universal donor type in emergency situations when there is no time to type and crossmatch blood.

• #1 Rh Hemolytic Disease(Archived) – PubMed

  https://pubmed.ncbi.nlm.nih.gov/32809323/

  The Rhesus factor (Rh factor) is a surface antigen of erythrocytes. The Rh blood group system consists of multiple antigens (over 50), but D, C, c, E, and e are the most common antigens identified. D antigen is mainly responsible for Rh disease due to its high immunogenicity. A person can be Rh-positive or Rh-negative based on the presence or absence of D antigen on the surface of red blood cells respectively. […] Rh-hemolytic disease, also known as Rh incompatibility, is a condition that occurs when a woman with Rhesus-negative blood type is exposed to Rhesus-positive blood cells, leading to the development of anti-D antibodies by a process called isoimmunization. After this sensitization, these maternal alloantibodies (IgG immunoglobulins) may persist for life and move freely across the placenta to the fetal circulation during subsequent pregnancies, where they lead to the destruction of fetal erythrocytes after forming antigen-antibody complexes with their surface D antigen. This results in alloimmune hemolytic anemia in the fetus, known as erythroblastosis fetalis. The severity of illness depends greatly on the number of immunoglobulins, the gestational age, and the enzymatic activity of the fetus.

• #2 Rh disease – Wikipedia

  https://en.wikipedia.org/wiki/Rh_disease

  Rh disease (also known as rhesus isoimmunization, Rh (D) disease, or rhesus incompatibility, and blue baby disease) is a type of hemolytic disease of the fetus and newborn (HDFN). […] The disease ranges from mild to severe, and occurs in the second or subsequent pregnancies of Rh-D negative women when the biological father is Rh-D positive. […] During pregnancy, there is normally a barrier between maternal and fetal blood called the placenta, a temporary organ that connects a mothers uterus to the umbilical cord to provide nutrients and oxygen to the fetus. However, in certain circumstances, small amounts of fetal blood cells may enter the mothers circulation. […] Once the fetal Rh-positive red blood cells enter the bloodstream of a Rh-negative mother, they are recognized as foreign. The mothers immune system reacts to the Rh-positive red blood cells the same way that it would respond to something like a virus or bacteria, activating B cells—a type of white blood cell that is key to the triggering of an immune response. These activated B cells then differentiate into plasma cells, which produce anti-D antibodies. After the primary exposure, some of these B cells become memory cells that remember the original exposure, and produce IgG antibodies, which are smaller and can cross the placental barrier. Once they cross this barrier into the fetal bloodstream, they bind to fetal Rh-positive cells, triggering opsonization, which marks the red blood cells for destruction.

• #2 Rh Disease – Stanford Medicine Children’s Health

  https://www.stanfordchildrens.org/en/topic/default?id=rh-disease-90-P02498

  Rh disease occurs during pregnancy. It happens when the Rh factors in the moms and babys blood dont match. […] The Rh factor is a protein on the covering of the red blood cells. If the Rh factor protein is on the cells, the person is Rh positive. If theres no Rh factor protein, the person is Rh negative. […] If the baby’s Rh factor is positive, like his or her father’s, this can be an issue if the baby’s red blood cells cross to the Rh negative mother. When this happens, the mom becomes sensitized to Rh positive blood. […] The Rh negative moms immune system sees the baby’s Rh positive red blood cells as foreign. Your immune system responds by making antibodies to fight and destroy these foreign cells. Your immune system stores these antibodies in case these foreign cells come back again. This can happen in a future pregnancy. You are now Rh sensitized.

• #3 Rh Disease | Children’s Hospital of Philadelphia

  https://www.chop.edu/conditions-diseases/rh-disease

  Rh disease occurs during pregnancy when there is an incompatibility between the blood types of the mother and baby. […] Problems with the Rh factor occur only when the mother’s Rh factor is negative and the baby’s is positive. […] When an Rh negative mother has a baby that is Rh positive, problems can develop if the baby’s red blood cells cross to the Rh negative mother. This usually happens at delivery when the placenta detaches. […] The mother’s immune system sees the baby’s Rh positive red blood cells as foreign. Just as when bacteria invade the body, the immune system responds by developing antibodies to fight and destroy these foreign cells. The mother’s immune system keeps the antibodies in case the foreign cells appear again, even in a future pregnancy. The mother is now Rh sensitized.

• #3 Rh disease – Wikipedia

  https://en.wikipedia.org/wiki/Rh_disease

  During the first pregnancy, the Rh mother’s initial exposure to fetal Rh+ red blood cells (RBCs) is usually not sufficient to activate her Rh-recognizing B cells. However, during delivery, the placenta separates from the uterine wall, causing umbilical cord blood to enter the maternal circulation, which results in the mother’s proliferation of IgM-secreting plasma B cells to eliminate the fetal Rh+ cells from her blood stream. […] However, in subsequent pregnancies with Rh+ fetuses, the IgG memory B cells mount an immune response when re-exposed, and these IgG anti-Rh(D) antibodies do cross the placenta and enter fetal circulation. These antibodies are directed against the Rhesus (Rh) factor, a protein found on the surface of the fetal RBCs. The antibody-coated RBCs are destroyed by IgG antibodies binding and activating complement pathways.

• #3 Rh Incompatibility: Practice Essentials, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/797150-overview

  The most common cause of Rh incompatibility is exposure from an Rh-negative mother by Rh-positive fetal blood during pregnancy or delivery. As a consequence, blood from the fetal circulation may leak into the maternal circulation, and, after a significant exposure, sensitization occurs leading to maternal antibody production against the foreign Rh antigen. […] Once produced, maternal Rh immunoglobulin G (IgG) antibodies persist for life and may cross freely from the placenta to the fetal circulation, where they form antigen-antibody complexes with Rh-positive fetal erythrocytes and eventually are destroyed, resulting in a fetal alloimmune-induced hemolytic anemia. […] The risk and severity of sensitization response increases with each subsequent pregnancy involving a fetus with Rh-positive blood. In women who are prone to Rh incompatibility, the second pregnancy with an Rh-positive fetus often produces a mildly anemic infant, whereas succeeding pregnancies produce more seriously affected infants who ultimately may die in utero from massive antibody-induced hemolytic anemia.

• #4 Volume 3, Chapter 66. Alloimmune Hemolytic Disease of the Fetus and Newborn (Erythroblastosis Fetalis): Diagnosis, Management, and Prevention

  https://www.glowm.com/resources/glowm/cd/pages/v3/v3c066.html

  The fundamental cause of erythroblastosis fetalis is hemolysis of Rh-positive fetal RBCs by maternal anti-D IgG antibody. Hemolysis causes fetal anemia, which stimulates the production of erythropoietin. Erythropoiesis increases. Fetal marrow RBC production cannot keep up with the RBC destruction, and extramedullary erythropoiesis (spleen, liver, kidneys, adrenals) recurs. Hepatosplenomegaly is a hallmark of erythroblastosis fetalis. […] When anti-D attaches to the D antigen in the RBC membrane, the attraction of macrophages for the coated RBCs (chemotaxis) is increased. The coated RBCs adhere to the macrophages, forming rosettes, particularly in the spleen, where the circulation slows and the hematocrit increases, bringing RBCs and macrophages into close apposition. Electron microscopy reveals macrophage pseudopods attaching to the RBC membrane, puckering and invaginating it. A portion of the membrane breaks off, and the defect seals. Loss of membrane substance causes sphering of the RBC, with greater rigidity and loss of deformability. Even if the RBC escapes the macrophage, it is damaged, with greater osmotic fragility and likelihood of lysis. Rh-antibody-mediated RBC destruction follows the chain of events outlined: rosette formation around macrophages in the spleen, loss of RBC membrane with sphering and rigidity, and osmotic fragility with lysis and phagocytosis of RBC fragments.

• #5 Hemolytic Disease of the Newborn: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/974349-overview

  A French midwife was the first to report hemolytic disease of the newborn (HDN) in a set of twins in 1609. […] In 1953, Chown subsequently confirmed the pathogenesis of Rh alloimmunization to be the result of passage of Rh-positive fetal RBCs after transplacental hemorrhage into maternal circulation that lacked this antigen. […] The exposure of the Rh-negative mother to Rh-positive red cells occurs as a result of asymptomatic fetomaternal hemorrhage during pregnancy. […] After sensitization, maternal anti-D antibodies cross the placenta into fetal circulation and attach to Rh antigen on fetal RBCs, which form rosettes on macrophages in the reticuloendothelial system, especially in the spleen. […] These antibody-coated RBCs are lysed by lysosomal enzymes released by macrophages and natural killer lymphocytes and are independent of the activation of the complement system.

• #6 Hemolytic Disease of the Newborn: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/974349-overview

  Prolonged hemolysis leads to severe anemia, which stimulates fetal erythropoiesis in the liver, spleen, bone marrow, and extramedullary sites, such as the skin and placenta. […] Destruction of RBCs releases heme that is converted to unconjugated bilirubin. […] HDN due to Kell sensitization results in hemolysis and suppression of erythropoiesis because the Kell antigen is expressed on the surface of erythroid progenitors. […] Hemolysis associated with ABO incompatibility exclusively occurs in type-O mothers with fetuses who have type A or type B blood. […] Hemolysis due to anti-A is more common than hemolysis due to anti-B, and affected neonates usually have positive direct Coombs test results. […] In addition, fetal RBCs appear to have less surface expression of A or B antigen, resulting in few reactive sites; hence the low incidence of significant hemolysis in affected neonates.

• #7 Elucidation of the molecular bases of the Rh system and its contribution to transfusion and obstetric medicine—historical and current perspective: a review – Cotorruelo – Annals of Blood

  https://aob.amegroups.org/article/view/8450/html

  The Rh system, the most polymorphic of the human blood groups, is of major clinical interest in transfusion and obstetric medicine due to the participation of Rh antibodies in phenomena of immune mediated red blood cell destruction. Rh antigens are highly immunogenic and are often involved in haemolytic transfusion reactions and in the Haemolytic Disease of the Newborn (HDN). […] The five principal Rh antigens D, C, c, E, and e are highly immunogenic and play a central role in the pathogenesis of the Haemolytic Disease of the Newborn (HDN), haemolytic transfusion reactions and some cases of autoimmune haemolytic anaemia. […] The RH locus is composed of two adjacent homologous structural genes denoted RHD and RHCE. […] The RHD gene encodes the RhD protein that expresses the epitopes of the D antigen.

• #8 Elucidation of the molecular bases of the Rh system and its contribution to transfusion and obstetric medicine—historical and current perspective: a review – Cotorruelo – Annals of Blood

  https://aob.amegroups.org/article/view/8450/html

  The RHCE gene has 4 most common allelic forms: RHCE*ce, RHCE*Ce, RHCE*cE and RHCE*CE and each allele determines the expression of two antigens in ce, Ce, cE or CE combination carried by the RhCE protein (RHCE is the collective name of the 4 alleles). […] The RH locus consists of two highly homologous genes denoted RHD and RHCE. Both genes have 10 exons encompassing approximately 58 kb of DNA each and reside in tandem in opposite orientation. […] The analysis of the hybrid Rhesus box (a marker for RHD deletion) may be a predictor of the RHD zygosity. […] The RHD*01 allele is the reference sequence for the RHD gene and is responsible for the normal D-positive phenotype. […] RHD alleles have been classified according to the encoded phenotype in silent, partial D, weak D and DEL alleles.

• #9 The RH system – NHS Blood Donation

  https://www.blood.co.uk/why-give-blood/demand-for-different-blood-types/the-rh-system/

  The D antigen is the most immunogenic, meaning it provokes an immune response that makes it most likely to cause a transfusion reaction in the recipient. […] Alloantibody produced by transfusion of Rh D positive blood to Rh D negative women, or as a result of specific events during pregnancy, can cause Haemolytic Disease of the Fetus and Newborn (HDFN). […] HDFN occurs when, either during a previous transfusion or a previous pregnancy, alloantibody in the mothers blood crosses the placenta, binding to the fetal red cells. This breaks down the fetal red blood cells causing anaemia, referred to as haemolytic anaemia. […] Alloimmunisation is exacerbated by differences in blood group distribution between patients with sickle cell disease (SCD) and the predominantly White European blood donor population.

• #10 Elucidation of the molecular bases of the Rh system and its contribution to transfusion and obstetric medicine—historical and current perspective: a review – Cotorruelo – Annals of Blood

  https://aob.amegroups.org/article/view/8450/html

  Partial D alleles encode RhD proteins with amino acid substitutions predicted to be located in exofacial loops that cause the loss of one or more D specific epitopes. […] The presence or absence of the D antigen in the RBC membrane allows individuals to be classified as D-positive or D-negative, respectively. […] Molecular methods can be applied to achieve a deeper analysis of the Rh system and overcome the limitations of serology.

• #11

  https://www.nationwidechildrens.org/conditions/health-library/rh-disease

  Rh sensitization normally isn’t a problem with a first pregnancy. Most issues occur in future pregnancies with another Rh positive baby. During that pregnancy, your antibodies cross the placenta to fight the Rh positive cells in your baby’s body. As the antibodies destroy the cells, your baby gets sick. Your baby could have jaundice, heart failure, and enlarged organs. […] If the Rh negative birth parent has been sensitized to Rh positive blood, her immune system will make antibodies to attack her baby. […] When the antibodies enter your baby’s bloodstream, they will attack the red blood cells, causing them to break down. This can lead to problems. […] This condition can be prevented. People who are Rh negative and haven’t been sensitized can receive medicine. This medicine can stop your antibodies from reacting to your baby’s Rh positive cells.

• #12

  https://myhealth.alberta.ca/Health/pages/conditions.aspx?hwid=tn10329&lang=en-ca

  Rh disease is the result of Rh sensitization, which causes the Rh-negative mother to make antibodies that attack the fetus’s Rh-positive red blood cells. […] The more red blood cells are destroyed, the worse the effect on the fetus. […] In severe cases, the baby may die before or after birth. […] Rh sensitization usually happens during childbirth, so a fetus in a first pregnancy may not have Rh disease. […] But each future Rh-positive fetus will be at risk, and Rh disease tends to be worse with each Rh-positive pregnancy. […] A blood test can show if a woman has Rh sensitization and whether her baby is at risk.

• #13 Rh Incompatibility: Practice Essentials, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/797150-overview

  The incidence of Rh incompatibility in the Rh-negative mother who is also ABO incompatible is reduced dramatically to 1-2% and is believed to occur because the mother’s serum contains antibodies against the ABO blood group of the fetus. The few fetal red blood cells that are mixed with the maternal circulation are destroyed before Rh sensitization can proceed to a significant extent. […] Rh incompatibility is only of medical concern for females who are pregnant or plan to have children in the future. Rh-positive antibodies circulating in the bloodstream of an Rh-negative woman otherwise have no adverse effects.

• #14 Hemolytic disease of the fetus and newborn – Knowledge @ AMBOSS

  https://www.amboss.com/us/knowledge/hemolytic-disease-of-the-fetus-and-newborn/

  In a subsequent pregnancy with an Rh-positive fetus: rapid production of maternal IgG anti-D antibodies to fetal RhD antigens Rh-IgG agglutination of fetal RBCs with hemolytic anemia risk of HDFN with possible hydrops fetalis. […] Rh-incompatibility in combination with ABO incompatibility: reduction of Rh(D)-isoimmunization in Rh-negative mothers. […] Maternal exposure to Kell antigen in previous pregnancy through the placenta or through blood transfusions sensitization and production of maternal anti-Kell antibodies antibodies enter circulation of Kell-positive fetus through placenta destruction of fetal RBC precursors and mature RBCs production of RBCs and hemolysis severe fetal anemia.

• #15 Rh disease pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Rh_disease_pathophysiology

  During any pregnancy a small amount of the baby’s blood can enter the mother’s circulation. If the mother is Rh negative and the baby is Rh positive, the mother produces antibodies (including IgG) against the Rhesus D antigens on her baby’s red blood cells. During this and subsequent pregnancies the IgG is able to pass through the placenta into the fetus and if the level of it is sufficient it will cause a Rhesus D positive fetus to develop Rh disease. The mechanism is maternal anti-D IgG passing through the placenta to the fetus causing destruction of fetal red blood cells. Generally Rhesus disease becomes worse with each additional Rhesus incompatible pregnancy. […] The main and most frequent sensitizing event is child birth (about 86% of sensitized cases), but fetal blood may pass into the maternal circulation earlier during the pregnancy (about 14% of sensitized cases). […] Rh disease sensitization is about 10 times more likely to occur if the fetus is ABO compatible with the mother than if the mother and fetus are ABO incompatible.

• #16 Hemolytic disease of the fetus and newborn – Knowledge @ AMBOSS

  https://www.amboss.com/us/knowledge/hemolytic-disease-of-the-fetus-and-newborn/

  Hemolytic disease of the fetus and newborn (HDFN) is a condition characterized by the destruction of fetal red blood cells (RBC) and subsequent anemia. […] In Rh incompatibility, maternal IgG antibodies form after maternal exposure to fetal Rh-positive blood during birth or potentially sensitizing antepartum events. […] Maternal antibodies (anti-A and/or anti-B) against nonself antigens of the ABO system are present even if sensitization has not occurred; so fetal hemolysis may occur during the first pregnancy. […] Production of maternal IgM antibodies against the Rh antigen occurs after exposure of fetal blood cells to the maternal circulation (fetomaternal hemorrhage) during delivery or an antepartum Rh sensitizing event. […] Over time, maternal IgM antibodies seroconvert to Rh-IgG (antibodies are able to cross the placenta).

• #17

  https://step2.medbullets.com/obstetrics/120372/rh-disease

  Rh hemolytic disease of the newborn is caused by Rh incompatibility […] maternal anti-Rh IgG antibodies cross the placenta and destroy fetal Rh-positive red blood cells […] Rh factor is a red blood cell antigen […] when a Rh-negative mother is pregnant with a Rh-positive fetus, the mother is exposed to Rh-positive red blood cells and leads to maternal antibody production (IgG) against the foreign Rh antigen […] as IgG can cross the placenta, subsequent pregnancy with Rh-positive fetus will result in fetal alloimmune induced hemolytic anemia […] development of antibody depends on volume of transplacental crossover of red blood cells, concurrent presence of ABO incompatibility, and extent of maternal immune response […] breakdown of red blood cells causes elevation of bilirubin.

• #18 Hemolytic Disease of the Fetus and Newborn – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK557423/

  HDFN is caused by the destruction of the fetus or neonate’s red blood cells (RBCs) by maternal immunoglobulin G (IgG) antibodies due to maternal-fetal blood group incompatibility. These maternal antibodies are produced (by a process termed alloimmunization) when a foreign RBC antigen from an exogenous source (eg, growing fetus or transfusion) enters the maternal circulation and becomes exposed to her immune system, resulting in sensitization. As little as 0.1 mL of fetal blood entering maternal circulation is sufficient to cause alloimmunization. In fact, 15% to 50% of gestations have sufficient fetomaternal hemorrhage to cause alloimmunization, and only 1% to 2% of all Rh alloimmunization is caused by antepartum hemorrhage. The primary mechanisms by which sensitization occurs involve the Rh and ABO systems.

• #19 Hemolytic Disease of the Fetus and Newborn | 5-Minute Pediatric Consult

  https://peds.unboundmedicine.com/pedscentral/view/5-Minute-Pediatric-Consult/617597/all/Hemolytic_Disease_of_the_Fetus_and_Newborn

  Hemolytic disease of a fetus or newborn (HDFN) occurs due to the destruction of fetal and newborn red blood cells (RBCs) by maternal antibodies passively transferred across the placenta. […] Passage of fetal RBCs into maternal circulation occurs as a result of asymptomatic transplacental hemorrhage. Initial sensitization of mother from fetomaternal hemorrhage can occur with placental abruption, abortion, ectopic pregnancy, or procedures (chorionic villus sampling, amniocentesis, or cordocentesis). Exposure triggers maternal immune response (anti-D antibodies). Maternal IgG antibodies cross the placenta and bind to fetal RBCs. Coated RBCs are then destroyed in the reticuloendothelial system, primarily the spleen. Isoimmunization may lead to hyperbilirubinemia, severe anemia, and potentially hydrops.

• #20 Rh disease – Wikipedia

  https://en.wikipedia.org/wiki/Rh_disease

  The destruction of RBCs leads to elevated bilirubin levels (hyperbilirubinemia) as a byproduct. […] However, once the infant is delivered, the immature system is not able to handle this amount of bilirubin alone and jaundice or kernicterus (bilirubin deposition in the brain) can develop which may lead to brain damage or death.

• #21 Rh Disease | Children’s Hospital of Philadelphia

  https://www.chop.edu/conditions-diseases/rh-disease

  During that pregnancy, the mother’s antibodies cross the placenta to fight the Rh positive cells in the baby’s body. As the antibodies destroy the red blood cells, the baby can become anemic. The anemia can lead to other complications including jaundice, heart failure, and organ enlargement. […] Rh disease is also called erythroblastosis fetalis during pregnancy. In the newborn, the resulting condition is called hemolytic disease of the newborn (HDN). […] Some of the more common complications of Rh disease for the fetus and newborn baby include the following: Anemia (in some cases, the anemia is severe with enlargement of the liver and spleen), Jaundice. This is a yellowing of the skin, eyes, and mucous membranes, Severe anemia with enlargement of the liver and spleen, Hydrops fetalis. This occurs as the fetal organs are unable to handle the anemia.

• #22 Hemolytic Disease of the Fetus and Newborn – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK557423/

  Hydrops fetalis, which can be a severe complication of HDFN, results when an underlying etiology increases the fluid transudation rate from the vascular compartment or delays lymphatic return to circulation. Hypoxia may occur secondary to immune hydrops fetalis, increasing catecholamines and decreasing hepatic and renal blood flow because of the redistribution of blood to the brain, heart, adrenals, and ductus venosus. Subsequently, the renin-angiotensin system is activated, leading to an increase in antidiuretic hormone and a decrease in albumin. As a result, central venous pressure is elevated, and lymphatic flow into the systemic circulation is decreased, in turn causing the loss of intravascular volume and severe and progressive fetal edema.

• #23 Rh Disease | Children’s Hospital of Philadelphia

  https://www.chop.edu/conditions-diseases/rh-disease

  After birth, the red blood cell destruction may continue. Problems may include the following: Severe jaundice. The baby’s liver is unable to handle the large amount of a substance called bilirubin that results from red blood cell breakdown. […] RhIg destroys any anti-Rh antibodies that enter in the mother’s circulation before her immune system becomes sensitized. This helps protect a future Rh positive baby.

• #24 Blood Type Incompatibility, Rh Incompatibility, Jaundice | Cerebral Palsy Guidance

  https://www.cerebralpalsyguidance.com/cerebral-palsy/risk-factors/blood-type-incompatibility/

  When triggered by Rh proteins, this disease can be life-threatening for the baby. […] A baby can be born with severe jaundice, characterized by a buildup of a substance called bilirubin. […] The consequences can be serious and include a type of brain damage called kernicterus. […] HDN and the other complications of Rh incompatibility, including cerebral palsy, are highly preventable.

• #25 What is the mechanism of Rh immunoglobulin-VF?

  https://synapse.patsnap.com/article/what-is-the-mechanism-of-rh-immunoglobulin-vf

  Rh immunoglobulin-VF, also known as anti-D immunoglobulin, is a preparation used to prevent Rh sensitization in Rh-negative individuals, particularly during pregnancy. The mechanism behind this preventive measure is a fascinating interplay of immunological principles aimed at safeguarding the health of both mother and fetus. At the core of Rh immunoglobulin-VF’s functionality is its role in preventing the immune system of an Rh-negative individual from mounting a response against Rh-positive red blood cells. This is particularly crucial in scenarios where an Rh-negative mother carries an Rh-positive fetus. If fetal red blood cells, which contain the Rh antigen (D antigen), enter the maternal circulation, the mother’s immune system might recognize these cells as foreign and produce antibodies against them. This immune response can be detrimental, particularly in subsequent pregnancies, where maternal anti-D antibodies can cross the placenta and attack the red blood cells of an Rh-positive fetus, leading to hemolytic disease of the newborn (HDN).

• #26 Rhesus (Rh) Factor: Incompatibility, Complications & Pregnancy

  https://my.clevelandclinic.org/health/diseases/21053-rh-factor

  Rh immune globulin (RhIg or RhoGAM) is a medication that stops your body from making Rh antibodies. Its only helpful if your body hasnt already made Rh antibodies. You receive it as a shot (injection). Rh immunoglobulin shots are usually very successful in treating Rh-incompatibility during pregnancy. Detecting Rh incompatibility early in pregnancy is the best way to prevent serious complications. […] Rh incompatibility can cause hemolytic anemia. Hemolytic anemia destroys the fetuss red blood cells faster than it can replace them. […] Since the development of Rh immune globulin injections, Rh disease occurs infrequently.

• #27 What is the mechanism of Rh immunoglobulin-VF?

  https://synapse.patsnap.com/article/what-is-the-mechanism-of-rh-immunoglobulin-vf

  Rh immunoglobulin-VF works by introducing a sufficient amount of anti-D antibodies into the maternal circulation. These exogenous antibodies bind to any Rh-positive fetal red blood cells that may have entered the mothers bloodstream. This binding effectively masks the Rh antigen on these cells, making them invisible to the maternal immune system. As a result, the mother’s immune response is not activated, and she does not produce her own anti-D antibodies. […] In summary, the mechanism of Rh immunoglobulin-VF involves the passive administration of anti-D antibodies to Rh-negative individuals, which prevents the immune system from recognizing and attacking Rh-positive red blood cells. This strategy effectively prevents Rh sensitization, safeguarding both current and future pregnancies from the potentially severe consequences of Rh incompatibility.

• #28 Rhesus Incompatibility – Zero To Finals

  https://zerotofinals.com/obgyn/antenatal/rhesus/

  The anti-D medication works by attaching itself to the rhesus-D antigens on the fetal red blood cells in the mothers circulation, causing them to be destroyed. This prevents the mother’s immune system recognising the antigen and creating it’s own antibodies to the antigen. It acts as a prevention for the mother becoming sensitised to the rhesus-D antigen.

• #29 Rh disease | HealthLink BC

  https://www.healthlinkbc.ca/healthwise/rh-disease

  In some cases, a fetus in a first pregnancy does have Rh disease. This can happen if the mother was Rh sensitized during a miscarriage, abortion, or ectopic pregnancy or because of a test that causes bleeding in the uterus during pregnancy, such as an amniocentesis or chorionic villus sampling. A blood test can show if a woman has Rh sensitization and whether her baby is at risk. […] Treatment for Rh disease depends on how severe the disease is, which can be checked with regular testing throughout the pregnancy. A fetus with mild Rh disease may not need any special treatment. One who is more severely affected may need to have a blood transfusion while still in the uterus and to be delivered early.

• #30 Rh incompatibility: MedlinePlus Medical EncyclopediaLock

  https://medlineplus.gov/ency/article/001600.htm

  Infants with mild Rh incompatibility may be treated with phototherapy using bilirubin lights. IV immune globulin may also be used. For infants severely affected, an exchange transfusion of blood may be needed. This is to decrease the levels of bilirubin in the blood. […] Special immune globulins, called RhoGAM, are now used to prevent RH incompatibility in mothers who are Rh-negative. […] These injections prevent the development of antibodies against Rh-positive blood.

• #31 Medical Management of Rhesus Disease | Article | GLOWM

  https://www.glowm.com/article/heading/vol-16–the-prevention-and-management-of-rh-disease–medical-management-of-rhesus-disease/id/418123

  The main mechanism of action of IVIg is competitive inhibition, blocking the transplacental transfer of alloimmune IgG. […] M281 is a next-generation Fc receptor (FcRn) blocking agent, which binds with high affinity and specificity to the IgG binding site of FcRn. […] The blockade of FcRn-IgG binding is expected to decrease IgG half-life and serum concentrations including those of pathogenic IgG. […] FcRn antagonism is a promising mechanism of action, with translational research confirming proof of concept, tolerability, and clinical utility.

• #32 Medical Management of Rhesus Disease | Article | GLOWM

  https://www.glowm.com/article/heading/vol-16–the-prevention-and-management-of-rh-disease–medical-management-of-rhesus-disease/id/418123

  Fetal red cell destruction by maternal antibodies remains an important cause of fetal and neonatal morbidity and mortality. […] In order to understand the mechanism of action of contemporary medical treatments, it is important to appreciate the underlying pathophysiology of HDFN. The fetal/neonatal Fc receptor (FcRn) is a heterodimer, first identified in the neonatal rodent intestine transporting IgG in breast milk. […] The movement of IgG across the placenta by FcRn is dependent on several factors, including the amount of antibody in the maternal circulation, the gestational age and placental „integrity”. […] In human disease, this mechanism is potentially harmful, such as in HDFN when alloantibodies enter the fetal circulation to target RBCs for destruction. […] There are four potential mechanisms of action for medical management of red cell alloimmunization. Firstly, a drug might reduce the amount of circulating maternal IgG antibody by preventing its production. Secondly, a molecule might eliminate IgG from the maternal or fetal circulation. A third mechanism would be to prevent IgG against red cell antigen from crossing the placenta (via FcRn) into the fetal circulation. Finally, a therapy could target the antibody-antigen complex and alter the interaction between the antibody and target fetal antigen.

• #33 Rh incompatibility Information | Mount Sinai – New York

  https://www.mountsinai.org/health-library/diseases-conditions/rh-incompatibility

  Rh incompatibility is a condition that develops when a pregnant woman has Rh-negative blood and the baby in her womb has Rh-positive blood. […] If the mother is Rh-negative, her immune system treats Rh-positive fetal cells as if they were a foreign substance. The mother’s body makes antibodies against the fetal blood cells. These antibodies may cross back through the placenta into the developing baby. They destroy the baby’s circulating red blood cells. […] Rh incompatibility develops only when the mother is Rh-negative and the infant is Rh-positive. This problem has become less common in places that provide good prenatal care. This is because special immune globulins called RhoGAM are routinely used. […] Rh incompatibility can be prevented with the use of RhoGAM. Therefore, prevention remains the best treatment. Treatment of an infant who is already affected depends on the severity of the condition. […] Special immune globulins, called RhoGAM, are now used to prevent RH incompatibility in mothers who are Rh-negative.

• #34 Hemolytic Disease | Boston Children’s Hospital

  https://www.childrenshospital.org/conditions/hemolytic-disease

  Hemolytic disease of the newborn (HDN) also called erythroblastosis fetalis is a blood disorder that occurs when the blood types of a mother and baby are incompatible. […] HDN due to Rh incompatibility occurs more frequently and is often called Rh disease; it is about three times more likely in Caucasian babies than in African-American babies. […] HDN occurs when the blood types of a mother and baby are incompatible. If the babys incompatible red blood cells cross over to their mother, through the placenta during pregnancy or at delivery, the immune system sees them as foreign and responds by developing proteins called antibodies to attack and break them down. This can lead to several complications that range from mild to very severe. […] The mothers immune system also keeps these antibodies in case the incompatible red blood cells appear again, making them sensitized. Because of this, HDN is more likely to occur during a second or subsequent pregnancy, or following a miscarriage or abortion.

• #35 Rh-incompatible hemolytic disease of the newborn in Hefei

  https://www.wjgnet.com/2307-8960/full/v7/i20/3202.htm

  The most common etiology of blood group isoimmunization is ABO-isoimmunization while Rh-isoimmunization is the second most common etiology. […] The D gene (D or d) is located on short arm (p) of chromosome 1 with 94% population as RhD (+) and 6% RhD (-) globally. […] The potency of antigenicity studied show D E C c e d which explains the severity of neonatal jaundice caused by the corresponding antibody. […] As compare to ABO-HDN, the Rh-HDN has more aggressive hemolysis as reflected by more of the patients require BET. […] Our results only represent our regional experience. An extensive collaboration between pediatrician, obstetricians, and transfusion experts is required for a better understanding of Rh-HDN that can help us to establish a proper guideline in management.

• #36 Rhesus Factor – Signs & Treatment – Huggies AU

  https://www.huggies.com.au/pregnancy/pregnancy-health-care/rhesus-factor

  People are either Rh-positive or Rh-negative. In 85% of the population, the D antigens are present which means that the majority of the population have a positive blood group. In the remaining 15%, they are absent, which means these individuals have a negative blood group. Problems arise when a mother has a negative blood group though her baby is positive. Rhesus Disease, otherwise known as haemolytic disease of the newborn, is a complication which can occur when a mother produces antibodies which attack her Rh-positive baby’s red blood cells. […] When a mother who is Rh-negative comes into contact with her baby’s Rh-positive blood, she can potentially have an immune reaction. It’s not only during labour when this can happen. Though in a healthy and normal pregnancy, there is no blood to blood contact between a mother and her baby until delivery. […] The mother’s body sends out antibodies, called anti-D antibodies, to attack the baby’s Rh-positive cells which have spilled over into her system. If, at a future pregnancy her baby is Rh-positive then these anti-D antibodies cross the placenta and attack the baby’s red blood cells.

• #37 Rh-incompatible hemolytic disease of the newborn in Hefei

  https://www.wjgnet.com/2307-8960/full/v7/i20/3202.htm

  Anti-D antibody is not the common cause of Rh-isoimmunization in Chinese neonatal jaundice. […] In our region, anti-E (11/18, 61%) is the most common cause of Rh-HDN. […] Hemolytic disease of the newborn (HDN), or erythroblastosis fetalis, is due to blood type incompatibility between the mother and the fetus. This incompatibility causes the mothers immune system to generate IgG antibody against the blood type of the fetus. The IgG antibody binds to fetal red blood cells transplacentally to cause hemolysis. […] Our clinical experience tells us that Rh-isoimmunization is the second most common cause of HDN in Chinese newborns. […] Severe Rh-HDN can also lead to fetal demise, miscarriage, or premature birth. […] The introduction of postpartum Rhogam injection has successfully reduce the Rh (D) sensitization from 14% down to 1%-2% and the addition of antepartum Rhogam injection further reduces the sensitization down to 0.5%.

• #38 Consortium for Universal Rh disease Elimination (CURhE) | Division of Neonatal and Developmental Medicine | Stanford Medicine

  https://med.stanford.edu/content/sm/neonatology/Research/POTR/consortium-for-universal-rh-disease-elimination–curhe-.html

  Rh disease is caused by a calamitous mismatch of blood types. When a woman with Rh Negative blood becomes pregnant by a man who is Rh Positive, the fetus might also be Rh Positive. This can stimulate the mothers immune system to produce defenses against what it takes to be invaders, the babys Rh+ red blood cells. The first such pregnancy usually has no complications since the mothers immune responses take some time to develop, but subsequent pregnancies are very likely to end with severe consequences: stillbirth, newborn death, severe jaundice, brain damage. […] Rh disease has been virtually eliminated in wealthier nations, thanks to a simple and inexpensive prophylactic immunization developed almost fifty years ago.

• #39 Hemolytic disease of the fetus and newborn due to Rh(D) incompatibility: A preventable disease that still produces significant morbidity and mortality in children | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0235807

  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. […] Most severe cases of HDFN were attributed to Rh(D) incompatibility between an Rh(D)-negative woman and her Rh(D)-positive fetus, with Rh(D) alloimmunization having occurred during a previous pregnancy. […] In the 1960s, studies in the United States and in Great Britain determined that passive immunization of Rh(D)-negative mothers with IgG anti-Rh(D), soon after parturition, could protect women from sensitization against Rh(D)-positive red blood cells. […] However, in 1977 it was demonstrated that, despite adequate post-natal prophylaxis, ~10% of Rh(D)-negative women continued to develop anti-Rh(D) antibodies, presumably due to small, transplacental, fetal-maternal hemorrhages during pregnancy.

• #40 Globally, Only Half of Women Get Treatment for Rh Disease | Columbia University Irving Medical Center

  https://www.cuimc.columbia.edu/news/globally-only-half-women-get-treatment-preventable-killer-newborns

  In the 1960s, physicians at VPS developed an immunoprophylaxis therapy, Rh(D) immunoglobulin, that prevents the mother from becoming sensitized to her childs blood cells. […] This treatment is the standard of care for preventing Rh disease, but we recognize that there remain significant obstacles to expanding access to this lifesaving therapy around the world, says Spitalnik, who has been working with an international team of physicians to increase access to therapy with Rh(D) immunoglobulin around the world. […] The study found an annual worldwide gap of more than 2.5 million doses below the minimum recommended threshold for preventing Rh disease. […] A variety of factors, including lack of awareness of Rh incompatibility, limited availability of the therapy, and other health care priorities, play a role in hindering access to this life-saving therapy around the world, Spitalnik says.

• #41 Hemolytic disease of the fetus and newborn due to Rh(D) incompatibility: A preventable disease that still produces significant morbidity and mortality in children | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0235807

  The findings of the current study are tragically surprising and disappointing. They show that (1) worldwide efforts to prevent Rh(D)-negative sensitization are below the minimum threshold and far from the optimum goal, (2) the gap between IgG anti-Rh(D) supply and demand is large in low income countries, and (3) in high income countries, immunoprophylaxis for maternal Rh(D) sensitization also falls below the optimum threshold required to guarantee complete prevention. […] The enormous lack of prevention identified in the current study should be regarded as a global emergency due to a lack of maternal accessibility to IgG anti-Rh(D).

• #42 Globally, Only Half of Women Get Treatment for Rh Disease | Columbia University Irving Medical Center

  https://www.cuimc.columbia.edu/news/globally-only-half-women-get-treatment-preventable-killer-newborns

  A treatment developed over 50 years ago to prevent Rh diseasean often-fatal condition in fetuses and newbornsonly reaches half of the women in the world who need it, according to a study led by researchers at Vagelos College of Physicians and Surgeons (VPS) at Columbia University Irving Medical Center. […] When such women become pregnant, red blood cells from an Rh-positive fetus can make their way into the mothers circulation during pregnancy or at delivery. This incompatibility prompts the mothers immune system to make antibodies and become sensitized to the fetuss red blood cells. During subsequent pregnancies, the mothers sensitized immune system is more likely to launch an attack against her fetus, leading to Rh disease. […] More than half of fetuses or newborns with Rh disease die; those with severe disease who survive may have significant brain damage.

Zobacz więcej