Blood System Portfolio: ABO Group

The ABO blood group system was first discovered in 1901 by Karl Landsteiner. In 1902 Sturli and Von Decastello discovered the AB group. The ABH antigens do not develop until about 6 weeks of fetal life and the concentration of antigens increases until 3-4 years of age and level out. Antibodies to the ABO blood group are naturally occurring, meaning that the body will develop immunity without previous exposure to the other blood type antigens. They are high titer antibodies and will bind an activate complement in vivo. Antibodies are not able to be detected in serum until 3-6 months of age and titers decrease markedly after the age of 65.

When classifying an individuals blood type is it typically referred to by the forward and reverse groupings. For example, if someone is blood type A, they will have naturally occurring antibodies to type B. That is why it is very important when selecting blood products for a patient that every precaution is taken to match the blood types as best as possible. The ABO antibodies are clinically significant and the hemolytic reactions are immediate and hemolytic.

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The ABH genes that encode for the ABO blood group system encode for a glycosyl transferase enzyme that adds a specific monosaccharide to a precursor substance which results in a distinguishable antigenic structure. The B gene encodes for a-3-D-galactosyltransferase which adds the D-galactose sugar resulting in the B antigen on the RBC surface. The A gene encodes for a-3-N-acetylgalactosaminyltransferase which adds the N-acetyl-D-galactosamine sugar resulting in the A antigen. The H gene encodes for the a-2-L-fucosyltransferase which adds the L-fucose sugar resulting in the H antigen.

The ABH antigens are membrane bound glycolipids. All ABH antigens have type 2 precursors that are chains linked by a 1,4 linkage. To have an A antigen, the H antigen MUST be present. Same with the B antigen, but absence of the A and B antigens with the H antigen present is considered type “O”. The ABO genes are located on chromosome #9 and there are 4 major alleles; A1, A2, B and O. A1 is codominant with B. A2 is recessive to A1, but also codominant with B. O is recessive to all other alleles. The H gene is located on chromosome #19 and there are 2 alleles that can be expressed. H encodes for fucosyltransferase, and “h” is an amorph. Individuals that have the phenotype “hh” are considered to have the bombay phenotype and are extremely rare. These individuals will not produce the H antigen, therefore there are no A or B antigens as well. It doesn’t matter if the genes for the A and B antigens are present, without the H antigen, there can be no A or B antigen production.

ABO antibodies are primarily IgM that react at room temperature and sometimes at 37 degrees celsius. The antibodies follow Landsteiners law which states an individual possesses antibodies to ABO antigens that are absent from their own cells. As mentioned above, the forward and reverse grouping should agree. If there is a discrepancy there is further testing that can be done to distinguish the problem. Discrepancies can be found in a previous article written titled “ABO discrepancies”. One such test is called the anti-A1 lectin test. 1-8% of A2 individuals will develop anti-A1, although not clinically significant, it can cause discrepancies. Lectin is a plant seed extract that agglutinates specific human cells. It agglutinates to A1 cells, but not A2 cells. Its possible to use this test to help resolve discrepancies.

Stay tuned for the next blood group system discussed.

-Caleb

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Transfusion Reactions

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The blood bank of any laboratory deals with a huge responsibility. They play a role in the initial compatibility testing of blood donor products and the recipient or patient serum. The patients serum contains naturally occurring antibodies or in certain circumstances where the patient has had a previous transfusion, the serum can contain alloantibodies that have been synthesized from previous donor blood products. Research has progressed suggesting that whole blood donor products are not as effective at replacing volume as individual components are. When a donor comes in and donates a pint of blood there are techniques that are used to separate the plasma from the blood products. Platelets are collected via an apheresis machine. When the plasma is separated out it must be frozen at >-20 degrees C within 8 hours of collection. When a patient needs plasma, it takes about 18-20 minutes to thaw and release. Fresh frozen plasma (FFP) has an expiration off 12 months.  Red blood cells are usually stored in a refrigerator at 1-6 degrees C. RBC products have an expiration of 42 days once collected. They can be frozen for 10 years if needed.

For transfusion purposes compatibility needs to be done correctly and cautiously. Platelets do not need to be ABO or Rh compatible, but if ample supply is available, its best to ABO match donors with the patient. Red blood cells absolutely need to be ABO and Rh compatible. If a compatible unit is not available then the hospital should use an O negative unit. O negative units are used as the universal donor. Plasma should be ABO compatible. Contrary to RBCs units, an AB plasma donor is considered the universal donor where in RBC products an O negative donor is the universal donor as mentioned previously. Plasma products contain the donors antibodies. When the donor is AB, they do not have anti-A, or anti-B. It is because of this principle that AB plasma is considered as the universal donor.

Even when every precaution is taken to ensure proper testing took place and compatibility testing was as objectively accurate as possible transfusion reactions can still take place. There is no way to 100% prevent them. Acute hemolytic reactions are typically the most severe and occur when ABO-incompatible blood is given. With acute hemolytic reactions fever and chills develop quickly, back and flank/pain (Renal failure) can occur with hemoglobinuria/hemoglobinemia. Bleeding and DIC can commonly be seen. Treatment is to stop transfusion immediately and volume replacement. Diuretics may be given, most commonly furosemide. Febrile non-hemolytic reactions are typically caused by transfusion of leukocytes that attack the recipient. A fever that is characterized as greater than 1 degree Celsius increase. The infusion of the leukocytes cause cytokine release such as IL-6, and TNF. Transfusion of HLA antibodies can occur as well. Antipyretics can be given to resolve. It is also recommended to infuse leukocyte reduced units in the future.

Bacterial contamination can occur which can cause sepsis. Typically there will be a rapid high fever with symptoms of rigor, shock and gastro symptoms. Bacterial contamination usually is able to be cultured from the donor bag along with the collection site. Antibiotics should be administered with support as necessary. A way to get around this is to leukoreduce donor units.

Transfusion-related Acute Lung Injury (TRALI) is an acute lung injury <6 hours after transfusion that presents with hypoxemia and lung infiltrates. The anti-HLA antibodies activate the PMNs in the lung endothelial which causes physiological stress. TRALI is 20% fatal, but treatment should be aggressive supportive care with fluids.

Acute afebrile reactions include allergic, anaphylactic, and transfusion associated circulatory overload (TACO) reactions. A typical urticarial or allergic reaction presents with localized hives/redness which is caused by a IgE hypersensitivity. Typical treatment includes antihistamines. Anaphylactic reactions are caused by anti-IgA antibodies in the recipient. Usually signifying that the recipient is also IgA deficient. Presents with hypotension, GI symptoms and fever with anti-IgA. Treatment is immediate epinephrine or transfusion with washed RBCs or platelets. TACO usually occurs with a history of cardiopulmonary disease with too rapid of blood infusion. High risk groups include the elderly and adolescents. TACO presents with dyspnea, and hypoxia during and after transfusion. Elevated BNP, JVD and BP. Treatment is to slow the rate of infusion and diuretics.

Delayed febrile reactions typically present greater than one week post transfusion. There is a positive DAT along with hyperbilirubinemia and evidence of a new alloantibody. Delayed febrile reactions are caused by a anamnestic response to re-exposure to red cell antigens. Treatment is support therapy. Graft-vs-host-disease (GVHD) is caused by cellular immune response by transfused T-lymphocytes versus the host or recipient. Presentation includes fever, diarrhea, skin rash. Treatment includes immunosuppressive therapy with supportive care. GVHD can be 90% fatal.

Delayed afebrile reactions include post transfusion purpura and iron overload. PTP is caused by a recipient antibody versus the absent platelet antigen (HPA-1a). There is a decrease in platelets, and increased bleeding. Treatment includes IVIG and plasma exchange. Its important to avoid platelet transfusion. Iron overload typically occurs when >100 units have been transfused. Liver, pancreas, and cardiac dysfunction occurs. Iron chelation is standard treatment.

All reactions are serious and should be treated as such. Its important to check for clerical error in pre-transfusion compatibility testing as that is the number one cause of transfusion related reactions.