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BLOOD GROUPS. First Blood Transfusions. Harvey Discovered Circulation of Blood. 1628. Wilkins & Lower Transfusions from dog to dog. 1665-’66. 1667. Jean-Baptiste Denis Performed first recorded blood transfusions from animals to humans. 19th Century Transfusions. 1818.
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First Blood Transfusions Harvey Discovered Circulation of Blood 1628 Wilkins & Lower Transfusions from dog to dog 1665-’66 1667 Jean-Baptiste Denis Performed first recorded blood transfusions from animals to humans
19th Century Transfusions 1818 James Blundell, Obstetrician First transfusion of human to human
20th Century Transfusions 1901 Karl Landsteiner Discovers A, B, O Blood Groups Nobel in 1930
20th Century Transfusions 1902 AB Group discovered Importance of crossmatching blood between donor & recipient 1907 Sodium Citrate proposed as anticoagulant 1914 1936 First Blood Bank: Barcelona, Spanish Civil War Levine & Landsteiner, Rhesus blood Group System 1940
Human Blood Groups • RBC membranes have glycoprotein antigens on their external surfaces • These antigens are: • Unique to the individual • Recognized as foreign if transfused into another individual • Promoters of agglutination and are referred to as agglutinogens • Presence or absence of these antigens is used to classify blood groups
Blood Groups • Humans have 30 varieties of naturally occurring RBC antigens • The antigens of the ABO and Rh blood groups cause vigorous transfusion reactions when they are improperly transfused • Other blood groups (M, N, Dufy, Kell, and Lewis) are mainly used for legalities
Blood Grouping • Determined by antigens (agglutinogens) on surface of RBCs • Antibodies (agglutinins) can bind to RBC antigens, resulting in agglutination (clumping) or hemolysis (rupture) of RBCs • Groups • ABO and Rh
ABO Blood Groups • The ABO blood groups consists of: • Two antigens (A and B) on the surface of the RBCs • Two antibodies in the plasma (anti-A and anti-B) • An individual with ABO blood may have various types of antigens and spontaneously preformed antibodies • Agglutinogens and their corresponding antibodies cannot be mixed without serious hemolytic reactions
Genetic Determination of the Agglutinogens • Two genes, one on each of two paired chromosomes, determine the O-A-B blood type. • These genes can be any one of three types but only one type on each of the two chromosomes: type O, type A, or type B. • The type O gene is either functionless or almost functionless, so that it causes no significant type O agglutinogen on the cells. • Conversely, the type A and type B genes do cause strong agglutinogens on the cells.
Agglutinins • Group A - anti-B agglutinin, • Group B – agglutinin • Group O – both anti-B and anti-A agglutinins • AB Group – no agglutinin
Origin of Agglutinins in the Plasma • The agglutinins are gamma globulins, as are almost all antibodies • Most of them are IgM and IgG immunoglobulin molecules. • But why are these agglutinins produced in people who do not have the respective agglutinogens in their red blood cells? • Small amounts of type A and B antigens enter the body in food, in bacteria, and in other ways, and these substances initiate the development of the anti-A and anti-B agglutinins
Figure.Average titers of anti-A and anti-B agglutinins in the plasma of people with different blood types.
Rh antigen Rh+RBC Rh- RBC Rhesus Grouping • The other major blood group system is determined by the presence of the Rhesus protein antigen on RBC. • Blood with the Rhesus antigen on RBC’s is termed rhesus positive (Rh+) while the absence of the rhesus antigen makes the blood rhesus negative (Rh-).
Rh Factor • Agglutinins do not occur naturally, they are produced after being exposed to the antigen • CcDdEe genes determine the antigen type • The most important and common antigen is D • Its antibodies are called anti-D
Rh Blood Groups • There are six different Rh agglutinogens, three of which (C, D, and E) are common • Presence of the Rh agglutinogens on RBCs is indicated as Rh+ • Anti-Rh antibodies are not spontaneously formed in Rh– individuals • However, if an Rh– individual receives Rh+ blood, anti-Rh antibodies form • A second exposure to Rh+ blood will result in a typical transfusion reaction
Rh Blood Group • First studied in rhesus monkeys • Types • Rh positive: Have these antigens present on surface of RBCs • Rh negative: Do not have these antigens present • Hemolytic disease of the newborn (HDN) • Mother produces anti-Rh antibodies that cross placenta and cause agglutination and hemolysis of fetal RBCs
Rh Mismatch & Reaction Father Rh (+) Mother Rh (-) Newborn Rh (+) • Hemolytic disease of the newborn(eritroblastosis fetalis) • Kernicterus
Hemolytic Disease of the Newborn • Hemolytic disease of the newborn – Rh+ antibodies of a sensitized Rh– mother cross the placenta and attack and destroy the RBCs of an Rh+ baby • Rh– mother becomes sensitized when Rh+ blood (from a previous pregnancy of an Rh+ baby or a Rh+ transfusion) causes her body to synthesis Rh+ antibodies • The drug RhoGAM can prevent the Rh– mother from becoming sensitized • The new born is anemic and hypoxic • Treatment of hemolytic disease of the newborn involves pre-birth transfusions and exchange transfusions after birth
It is a solution of IgG anti-D (anti-Rh) • It binds and destroys fetal Rh D positive erythrocytes that have passed through the placenta from the fetus to the maternal circulation. • This prevents maternal B-cell activation and memory cell formation. • With the widespread use Rho(D) Immune Globulin Rh disease of the fetus and newborn has almost disappeared.
Blood Transfusions Transfusion of wrong blood type can cause 2 problems e.g. transfuse type A blood into type B recipient: 1) Donor B antibodies attack recipients RBC’s which have B antigen (in practice diluted to such an extent - negligible) 2) Recipients A antibodies attack donor RBC’s which have A antigen Type AB - no antibodies therefore universal recipients Type O - no antigens therefore universal donors
Blood Transfusions • Whole blood transfusions are used: • When blood loss is substantial • In treating thrombocytopenia • Packed red cells (cells with plasma removed) are used to treat anemia
DID YOU KNOW? • When someone donates a pint of blood, that blood is separated into red cells, plasma and platelets.
Transfusion Reactions • Transfusion reactions occur when mismatched blood is infused • Donor’s cells are attacked by the recipient’s plasma agglutinins causing: • Diminished oxygen-carrying capacity • Clumped cells that impede blood flow • Ruptured RBCs that release free hemoglobin into the bloodstream • Circulating hemoglobin precipitates in the kidneys and causes renal failure
Plasma Volume Expanders • When shock is imminent from low blood volume, volume must be replaced • Plasma or plasma expanders can be administered
Plasma Volume Expanders • Plasma expanders • Have osmotic properties that directly increase fluid volume • Are used when plasma is not available • Examples: purified human serum albumin, plasminate, and dextran • Isotonic saline can also be used to replace lost blood volume
Transplantation of Tissues and Organs • Autografts • Isografts • Allografts • Xsenografts
Tissue Typing – The HLA Complex of Antigens • HLA antigen complex • There are about 150 different antigens to choose from • Six of these antigens are present on the tissue cell membranes of each person • The HLA antigens occur on the white blood cells as well as on the tissue cells.
Suppression of immune system • Importance of T lymphocytes • Glucocorticoid hormones • Drugs with toxic effects on the lymphoid tissue (such as Azathioprine) • Cyclosporine has a specific inhibitory effect on T-helper cells (T-cell mediated rejection)