VII. Side Notes
A. Questions asked during the break about hypersensitivity:
Lupus (not everything is type III)
Post strep (not everything is type III, either) – can cause type II if its post strep. rheumatic fever, however, if it is post strep glomerulonephritis, that is type III
Thrombocytopenia and Hemolytic anemia = type II PCN rash = type I
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PCN hemolytic anemia = type II (IgG Ab’s against the PCN group attached to the RBC membrane)
Example: most common Ab in the USA is Anti-CMV (everyone has been exposed).
You are safest from getting HIV from blood transfusion than from all the other infections (1/625,000 per unit of blood chance of getting HIV– therefore uncommon get to get HIV from blood). This is due to all the screening tests that they perform. They do the Elisa test – which looks for anti-gp120 Ab’s (remember, it’s the gp-120 Ag that attaches to helper T cell (CD4) molecule). On western blot, looking for more (3 or 4) Ab’s, making it more specific, so if you get this “+” on 3 or more, you are a true positive.
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What is the MC infection transmitted by blood transfusion? CMV, which is the MC overall infection. That is why this antibody is the most common.
What is MCC post transfusion hepatitis? Hep C (1/3000)
In newborn, want to prevent graft vs. host dz and CMV b/c no immune defenses, therefore, need to irradiate the blood. The irradiation kills off the lymphocytes and since the CMV lives in lymphocytes, we kill off the CMV virus also. This why we radiate blood before giving to newborns.
Accidental needle stick from a pt you know nothing about – what is the MC infection you can get? Hep B.
Accidental needle stick from HIV “+” pt; what is the chance of getting HIV+? 1/300. What do you do about it? You go on therapy as if you are HIV+. Go on to triple therapy (2 RTI’s – AZT and a protease inhibitor) for six months and get constant checks – do PCR test looking for RNA in the virus (most sensitive), do Elisa test. In fact, the MC mechanism of a healthcare worker getting HIV = accidental needle stick
Do not transfuse anything into a person unless they are symptomatic in what they are deficient in. Example: If you have 10 grams of Hb, and have no symptoms in the pt, do not transfuse.
You should transfuse the pt if they have COPD and are starting to have angina related to the 10 grams. Example: 50,000 platelet ct – no epistaxis = do not treat them; if they do have
epistaxis, treat the pt.
Every blood product is dangerous b/c you can get infections from it.
B. Fresh frozen plasma – should never be used to expand a pts plasma volume to raise BP – use normal saline (it is too expensive and you run the risk of transmitting dz). Use fresh frozen plasma for multiple coagulation factor deficiencies – ie would be legitimate to give frozen plasma to replace consumed factors, as in DIC.
Example: pt with warfarin is over anticoagulation and bleeding to death – not to give IM vit K will take to long to work (takes 6-8 hrs to work), so the treatment of choice is fresh frozen plasma to immediately replace it. So, fresh frozen plasma is limited to use of multiple factor deficiencies (ie cirrhosis of the liver and you are bleeding – since most of the factors are made in the liver, they are deficient in all proteins).
DOC for heparin overdose is to give protamine sulfate.
C. Know the diff transfusion rxn’s
1. MC transfusion rxn = allergic rxn (itching, hives, anaphylaxis) - this is an example of a type I HPY rxn – ie have unit of blood, and in their plasma you are allergic to something (ie PCN); Rx = benadryl, antihistamines
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2. 2nd transfusion rxn = febrile rxn; it is due to HLA Ab’s; pt has HLA Ab’s against leukocytes of donor Ag. So, when the unit of blood is transfused into me, and there are some leukocytes with HLA Ab on them, my Ab will react against it, destroy the cell and release the pyogenes from neutrophil, leading to fever.
If I’ve never been transfused, should I have HLA Ab’s against anything? No! Continuing question: Who is most at risk for having a febrile rxn with transfusion? Woman – b/c she is has been pregnant – every woman that has had a baby has had a fetal maternal bleed, so some of the babies leukocytes got into the bloodstream, and the woman developed an anti HLA Ab (the HLA’s are from the husband, that have been passed on to the woman). So, the more pregnancies a woman has had, the more anti HLA Ab’s she will develop b/c of her previous pregnancies. This is also true for spontaneous abortions – you can still get HLA Ab’s. So, women are more likely to have transfusion induced febrile rxns b/c they are more likely to have anti-HLA Ab’s (we should not have human being’s HLA’s in our blood stream b/c we haven’t been exposed to human’s blood).
Example: Who has the greatest risk in developing febrile rxn? The answer choices for this question would be a newborn, 12 y/o without transfusion, woman with one pregnancy, woman with spontaneous abortion, and man. The answer is woman with spontaneous abortion b/c that is a pregnancy and there is a potential for HLA ab’s to leak out of the fetus into the mother.
Febrile rxn is a type II HPY rxn against the HLA Ab (allergic rxn is type I)
3. Hemolytic transfusion rxns are very rare. Example: If you are blood group A, and given group B by stupidity b/c the pt has anti-B IgM (remember that IgM is the most potent complement activator and that cell will not last only about 1 msec) This is b/c the IgM will attack it, C1-C9: MAC, anaphylatoxins are released, and shock will ensue – very serious – aka clerical error).
Example: pt has Ab against Ag on RBC’s in the unit – you would think that this shouldn’t happen b/c the crossmatch said it is compatible; and did an Ab screen that was negative (Indirect Coombs). However, some Ab’s are not present, and you have memory B cells.
Suppose if I got blood transfusion 30 years ago, there are no Ab titers now b/c they
would’ve gone away – however, there are memory B cells; these ab’s will be way below the sensitivity of an Ab screen, come out compatible from a crossmatch, and will have neg indirect coomb; however, after transfusion, memory B cells would detect the foreign Ag.
After the B cell detects the Ag, it will start dividing in the germinal follicle and start dividing and become a plasma cell, which would make anti-calla Ab. This can occur in a few hrs or may occur in a week – depending on the Ab. That’s the one they like on the boards – delayed hemolytic transfusion rxn.
Example: woman postpartum, difficult delivery (abruptio placenta) was transfused 3 units of blood. When she left the hospital, she had an Hb of ten. One week later, she is jaundice and week, and has an unconjugated hyperbilirubinemia and has an Hb of 8. What is the dx? Hb was less than what she left the hospital, and they will not mention the coombs test) – What is most likely cause? Halothane (no b/c that takes over a week to develop), hepatitis (no, which takes 6-8 weeks to develop). Answer: delayed hemolytic transfusion rxn – so, they might ask what test would you get? Indirect coombs test to prove it b/c you will see the Ab Coating the RBC. Moral of the story? Transfused with certain level of Hb, 1 week later have jaundice and less Hb = delayed hemolytic transfusion rxn = type II HPY VIII. ABO/Rh incompatibility
A. ABO incompatibility:
If blood group O woman have a baby, the mom will have a problem with ABO
incompatibility b/c mom already have an Ab that can cross the placenta (blood group O
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people have anti A IgM, anti B IgM and anti AB IgG, normally). Normally, there is an anti AB IgG Ab which can cross the placenta, and attack an A or B RBC. So, there could be a problem in the very first pregnancy.
Example: mom is blood group O negative and baby is blood group A negative. Is there an incompatibility of blood groups? Yes. Is there an incompatibility in Rh groups? No. Just the blood groups, since the mom is O while baby is A. The mom is O, she has anti AB IgG, which will cross the placenta; the A part of the Ab will attach to the A part of the A cells of the baby’s. The baby’s macrophages of the spleen will destroy it, which is Type II HPY, mild anemia, and unconjugated bilirubin which is handled by the mom’s liver; no
kernicterus, no probs with jaundice in the baby b/c in utero, the mom’s liver will take care of it. When the baby is born the baby, it will have a mild anemia and jaundice. MCC jaundice in the first 24 hrs for a newborn = ABO incompatibility (not physiologic jaundice of the newborn – that starts on day 3). Why did the baby develop jaundice? B/c the baby’s liver cannot conjugate bilirubin yet and must handle unconjugated bilirubin on its own now, so it builds up. This is an exchange transfusion rxn for ABO incompatibility – most of the time is b9, and put under UV B light. How does UV B light work? It converts the bilirubin in the skin into di-pyrol, which is water soluble and they pee it out (Rx for jaundice in newborn).
Anemia is mild b/c it is not a strong Ag and doesn’t holster a brisk hemolytic anemia. If you do a coomb’s test, it will be positive b/c IgG’s on the RBC’s on the baby. So always an O mom with a blood group A or AB baby. This can occur from the first pregnancy (not like Rh sensitization where the first pregnancy is not a problem). In any pregnancy, if mom is blood group O, and she has a baby with blood group A or B, there will be a problem (blood group O = no problem).
B. Rh incompatibility
Mom is Rh negative and baby is Rh positive. Example: mom is O negative and baby is O positive (not ABO incompatible, but Rh incompatible). In the first pregnancy: deliver baby without going to a Dr, and there is a fetal maternal bleed, some of the babies O positive Ab’s got into my bloodstream, which is not good. So, mom will develop an anti B Ab against it. So, mom is sensitized which means that there is an Ab against that D Ag and now mom is anti D. 1 year later, mom is pregnant again, and still O negative, and have anti D and the baby again is O positive. This is a problem b/c it is an IgG Ab, which will cross the
placenta, attach to the babies D Ag positive cells (of all the Ags, the D Ag hosts the worst hemolytic anemia). So, the baby will be severely anemic with Rh than will ABO
incompatibility. The same thing happens though – baby’s macrophages phagocytose and mom’s liver will work harder. When the baby is born, the bilirubin levels are very high, a severe anemia occurs, and there is an excellent chance that an exchange transfusion will be necessary (99% chance), so take all the blood out (gets rid of all the bilirubin and sensitized RBC’s and transfuse b/c baby is anemic). So, they will usually always have a exchange transfusion.
Therefore, for the first pregnancy, the baby is not affected, and this is when the mother gets sensitized. In future pregnancies, the baby will a lot worse.
How do we prevent? Mom will do an Ab screen test and she is Rh negative. Around the 28th week, give her Rh Ig, which is prophylactic. This is anti D, which comes from woman; it has been sensitized and heat treated and cannot cross the placenta. Why do they give at 28 weeks? Pt may get fetal maternal bleeds before the pregnancy or a car accident or fall can cause babies blood to get into mom’s circulation. So, mom has anti D Ab’s to sit on the D positive cells and destroy them, so mom won’t get sensitized. Then, mom gives birth to baby (lets say it is Rh pos). Do a Plyhowabenti test and takes mom’s blood to ID (if any ) fetal RBC’s in the circulation and count them; they can say how much is in there.
Depending on that, that will determine how many viles of allergen Ig you give the mom to protect her further (anti D only last three months, and need to give more at birth, especially if the baby is Rh positive).
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Example: Mom: O negative; Baby: A positive 2 problems: ABO incompatible and Rh incompatible. But, there is not going to be a prob with sensitization. No Why? After delivery of baby, some of the babies cells (which are A cells) get into the mom’s blood (which mom has anti A IgM) ; those cells will be destroyed so fast, that in most cases the mom cannot generate Ab against those cells b/c they have been destroyed. So, ABO incompatibility protects against Rh sensitization. You still would give Rh Immunoglobulin. So if you are ABO and Rh incompatible, Rh sensitization will be protected against.
Kid with erythroblastosis fetalis will have Rh incompatibility – what do they die of? Heart failure – severe anemias will decrease viscosity of blood, so they get a high output failure:
LHF, then RHF, huge livers b/c extramedullary hematopoesis b/c they are so severe anemic.
112. Child with Rh hemolytic disease of the newborn: Why is the fetus edematous?
The child has hydrops fetalis.
Example: cross section of brainstem from kid – what is the cause of color change? Its yellowish – due to kernicterus – prob from a baby that had Rh incompatibility. Remember, it’s an unconjugated hyperbilirubinemia b/c it’s a hemolytic anemia and lipid soluble; liver cannot syn it; goes to brain and is very toxic leading to severe debilitating dz or death.
113. Brain of the above fetus. What is causing the yellowish discoloration?
The yellow pigment is unconjugated, lipid soluble bilirubin derived from
macrophage destruction of the Rh-sensitized fetal RBCs. The condition is called kernicterus.