Transfusion Reactions - Immune

• The greatest risk of morbidity and mortality from transfusion is from teh non-infectious complications
• transfusion reactions can be categorized as immune or non-immune and delayed or immediate; risks cannot be accurately predicted or completely avoided
• immediate hemolytic transfusion reactions (IHTR) is intravascular and immune mediate
• IHTR is also known as acute hemolytic transfusion reaction (AHTR)
• IHTR is based on the interaction of preformed antibodies with red cell antigens
• as little as 10 mL of blood can produce IHTR symptoms
• We can see IHTR signs and symptoms within minutes, or 1-2 hours

  • immediate intravascular destruction of transfused red cells
• the four most common antibodies involved in IHTR are anti-A, anti-Kell, anti-Jka, and anti-Fya
• immune IHTR may activate 4 major biological systems: complement, anaphylatoxins, coagulation, and kinin
• complement leads to holes in RBCs and intravascular lysis
• Anaphylatoxins: see the release of mast cell granules (which release histamines and serotonin) which leads to fever, chills, and a drop in blood pressure (hypotension) and shock
• Coagulation: clot formation due to DIC which leads to uncontrolled bleeding
• Kinin: neuroendocrine response causes vasoconstriction and a decreased blood supply to major organs including the kidneys, lungs, viscera, and skin, leading to organ failure
• Intravascular hemolysis

  • damaged red cells release hemoglobin directly into the plasma
  • hemoglobin splits into 2 halves (dimers)
• • hemoglobin dimers are bound to the plasma protein haptoglobin
• haptoglobin-hemoglobin complexes travel to the liver where it is processed similarly to extravascular hemolysis
• when haptoglobin is used up, we see free hemoglobin in the plasma and urine
• the kidney can also filter hemoglobin as hemosiderin
• IHTR (immune) symptoms - hemoglobinuria, elevated plasma hemoglobin, increased bilirubin, haptoglobin decreases
• In immune IHTRs, see increased bilirubin level peaks around 4-6 hours and disappears in 24 hours if bilirubin excretion is normal
• in immune IHTR, haptoglobin levels decrease because it binds to free hemoglobin in an effort to remove it
• DIC - results from the stroma of teh red cells
• DIC is characterized by the use and decrease of platelets; the consumption of factors V and VIII and fibrinogen
• DIC is also characterized by increased fibrin thrombi deposits in small blood vessel; this results in excessive bleeding from any open wound; can lead to hypotension and shock
• other signs and symptoms of immune IHTRs:

  • burning or pain at the infusion site
  • pain in the chest, flank, or back
  • restlessness
  • dyspnea
  • a feeling of impending doom
• severity of symptoms of immune IHTR is related to the amount of blood transfused, the antigen density, and antibody characteristics
• treatment of immune IHTRs

  • stop transfusion
  • provide diuretics to increase urine flow
  • treat for shock
  • fluid therapy
  • may need to inhibit complement cascade
• extravascular hemolysis

  • this happens when complement is not activated completely
  • it is characterized by antigen-antibody complex formation on RBCs with incomplete activation of complement
• Extravascular hemolysis - RBC lysis does not occur in the blood vessels, therefore, there is no release of free hemoglobin, RBC enzymes, or RBC stroma in the circulation
• extravascular hemolysis

  • macrophages engulf RBCs coated in Ab
  • globin chains are broken down into amino acids and returned to the plasma protein pool
  • iron is recycled
  • the heme portion is converted to porphyrin and carried to the liver with albumin as unconjugated bilirubin
• extravascular hemolysis - the next step

  • once the unconjugated bilirubin is carried to the liver and combined with glucuronic acid, it is now known as conjugated bilirubin
  • most of it is excreted by the bile ducts into the small intestine
  • In the intestine bilirubin is further altered by bacteria yielding stercobilinogen
  • Stercobilinogen is then excreted in the stool
  • In the intestines a small amount of bilirubin is reabsorbed into the bloodstream, this is later filtered by the kidney as urine urobilinogen
• extravascular immune HTR

  • the signs and symptoms are milder and not life threatening
  • symptoms - fever, chills, unexpected anemia
• DHTR reactions may occur 3-7 days or even a few weeks following transfusion
• DHTR is most often a secondary (anamnestic)response in which the patient has been sensitized by transfusion or pregnancy
• DHTRs wont detect an antibody on screening
• DHTR can also have a primary response with no history
• the development of an alloantibody following transfusion can result in asymptomatic DHTR sometimes
• Patients usually experience extravascular hemolysis and a decrease in hemoglobin and hematocrit levels
• the antibodies commonly implicated in DHTRs are anti-Jka, anti-E, anti-D, anti-C, anti-K, anti-Fya, and anti-M
• extravascular hemolysis is the mechanism of RBC destruction in DHTR