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3.13 Transfusion reaction and HDFN
by Dr. Barbeau
97
Pathology
Professional
03/13/2012

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Term
What is a transfusion reaction?
Definition
adverse event that occurs as a result of infusing blood components
Term
What are the different types of transfusion reactions?
Definition
hemolytic (acute and delayed) and nonhemolytic= immune but not against red cell antigens (allergic, TRALI, anaphylactic, TA-GVHD), bacterial ("septic") and other (fluid overload, iron overload)
Term
What percent of transfusion fatalities are due to ABO incompatibility?
Definition
40%
Term
What are the classic signs/symptoms of acute hemolytic transfusion reaction?
Definition
burning sensation at infusion site, pain in lumbar region, fever/chills, hypotension, vomiting/diarrhea, feeling of doom
Term
Half of the time the only symptom of a hemolytic transfusion reaction is ______.
Definition
fever, with or without chills
Term
What are the complications of intravascular (acute) hemolytic transfusion reactions?
Definition
acute renal failure, shock, DIC, complement mediated cardiovascular collapse, death
Term
How do you treat acute, intravascular hemolytic transfusion reactions?
Definition
keep urine output >100 mL/hr with fluids/diuretics, analgesics, pressors for hypotension, hemostatic components for bleeding, renal consult
Term
What are the early changes in lab values after an intravascular hemolytic transfusion reaction?
Definition
decreased haptoglobin, hemoglobinemia, hemoglobinuria, increased LDH, positive DAT
soon after= increased serum bilirubin
Term
How do you tell if a red urine sample is red because of bleeding or because of hemoglobin?
Definition
centrifuge; if there is a red pellet at the bottom with clear fluid it was bleeding
Term
How long does it take for a "delayed" hemolytic transfusion reaction to manifest?
Definition
3-14 days after transfusion
Term
WHat can you ask the patient to determine whether they are at risk of delayed hemolytic transfusion reaction?
Definition
history of transfusion or pregnancy
Term
What are the symptoms of delayed hemolytic transfusion reaction?
Definition
low grade fever,anemia, mild jaundice, can be asymptomatic to a severe immunologic response
Term
Which labs are affected by delayed hemolytic transfusion reaction?
Definition
DAT positive, positive antibody screen, hyperbilirubinemia
Term
What are the immune, nonhemolytic transfusion reactions?
Definition
febrile non-hemolytic transfusion reaction (FNHTR), transfusion related acute lung injury (TRALI), allergic, post-transfusion purpura, neonatal alloimmune thrombocytopenia (NAIT)
Term
What is the definition of FNHTR?
Definition
temperature rise of more than 1 degree celsius or 2 degrees farenheit during or shortly after transfusion
Term
What causes FNHTR?
Definition
recpient antibodies against donor white blood cells; may also involve accumulated cytokines from WBCs in the stored blood products (ex. 4 day old platelets)
Term
What are the symptoms of FNHTR?
Definition
fever, chills (seldom involve hypotension or respiratory distress)
Term
What is the treatment of FNHTR?
Definition
symptomatic (i.e. antipyretics)
Term
How do you prevent FNHTR?
Definition
leukoreduced blood products
Term
TRALI is usually associated with what blood products?
Definition
FFP
Term
What causes TRALI?
Definition
donor antibodies against recipient's PMN's. This reaction occurs in the lung, activating pulmonary macrophages and increasing pulmonary vascular permeability
Term
Why are multiparous females' plasma often thrown away?
Definition
because they have been exposed to many foreign WBCs who have antibodies against recipients PMNs causing TRALI
Term
What are the signs/symptoms of TRALI?
Definition
acute onset (4-6 hours) of dyspnea, hypotension, fever, bilateral pulmonary infiltrates
Term
What is the treatment for TRALI?
Definition
supportive (intubation), resolves spontaneously if patient survives
Term
What are the two types of allergic transfusion reactions?
Definition
urticarial and anaphylactic
Term
What are the symptoms of urticarial transfusion reaction?
Definition
urticaria, pruritis, flushing
Term
What are the symptoms of anaphylactic transfusion reactions?
Definition
hypotension, urticaria, bronchospasm
Term
What causes allergic and anaphylactic transfusion reactions?
Definition
substances (usually proteins) in donor blood to which recipient is alelrgic
Term
What is a classical cause of allergic transfusion reaction?
Definition
anti-IgA in patients with congenital IgA deficiency
Term
How do you prevent transfusion allergic reactions in patients with anti IgA?
Definition
wash the RBCs
Term
How do you treat a patient with urticaria after begining transfusion?
Definition
pretreatment with benadryl can help minimize allergic reactions. Restart transfusion after symptoms subside
Term
What is the only type of transfusion reaction in which you can re-start the transfusion after sx subside?
Definition
urticaria
Term
How do manage anaphylaxis after transfusion?
Definition
oxygen, fluids, epinephrine, antihistamines/corticosteroids/beta2 agonists
Term
What is the presentation of post transfusion purpura?
Definition
acute thrombocytopenia 1-2 weeks after transfusions of RBCs (usually) or platelets (RBCs contain some platelets)
Term
What causes post-transfusion purpura?
Definition
in patients that are HPA-1a negative, they will form an antibody to HPA-1a antigen on donor platelets. This anti-platelet antibody destroys donor platelets and also cross reacts with the recipients own platelets. This causes the recipient's platelet count to drop dramatically
Term
What percent of the population is HPA-1a negative?
Definition
1%
Term
What is the treatment for post-transfusion purpura?
Definition
HPA-1a negative platelets; perhaps plasma pheresis (to remove the antibody)
Term
What causes NAIT?
Definition
HPA-1a negative mother reacts to foreign HPA-1a on the child
Term
T/F In Neonatal alloimmune thrombocytopenia, both the mother and the fetus are thrombocytopenic.
Definition
false; only baby is thrombocytopenic
Term
T/F Neonatal Alloimmune Thrombocytopenia can occur in the first pregnancy.
Definition
true!!
Term
What is the treatment for newborns with NAIT?
Definition
platelet replacement with HPA-1A negative platelets from Mom!
Term
What type of patients get TA-GVHD?
Definition
severely immunocompromised (hematopoietic stem cell transplants, chemotherapy for hematologic malignancies)
Term
What causes TA-GVHD?
Definition
donor T cells mount an immune attack against the recipient
Term
What are the symptoms of TA-GVHD?
Definition
fever, rash, diarrhea, liver dysfunction, pancytopenia. Most die within 3 weeks
Term
How do you prevent TA-GVHD?
Definition
irradiation of cellular blood products (platelets, RBCs) cross-links the DNA in the donor lymphocytes, preventing them from replicating; Also need a directed donation from a relative
Term
What type of radiation is used to pretreat blood products given to immunocompromised hosts?
Definition
gamma (25 Gy)
Term
What are non-immunologic and non-septic transfusion reactions?
Definition
volume overload, iron overload, hypothermia, hypocalcemia (because anticoagulant chelates calcium), potassium toxicity (in infants), clotting factor deficiency (dilutional coagulopathy due to massive transfusion)
Term
How can you minimize alloimmunization against platelet antigens?
Definition
use apheresis (single donor) platelets; may even need HLA-matched platelets once immunized although 20-35% of patients who receive HLA-matched platelet transfusion are not benefitted
Term
What methods are used to reduce transfusion transmitted infectious diseases?
Definition
educational materials (donor self-assessment), donor health history questionnaire (risk factors), focused physical exam ("track marks"), infectious disease testing of the blood, donor deferral registry
Term
How long are you deferred from donating blood if you have had a blood transfusion or organ, skin and bone transplant?
Definition
1 year
Term
Name the reasons for permanent deferral for donating blood.
Definition
viral hepatitis after 11 yoa, IVDU, MSM since 1977, HBV, HCV, HIV, HTLV, transfusion of clotting factors, recieving $ or drugs for sex
Term
What diseases are tested for on blood donations?
Definition
anti-HBV (surface antigen), anti-HCV (NAAT), HIV antibodies and NAAT, anti HTLV-1 and 2, serology for syphilis, west nile virus (seasonal), chagas disease
Term
How many transfusions result in HIV transission?
Definition
1/ 2 million
Term
How many transfusions result in HCV transmission?
Definition
1/2 million
Term
How many transfusions result in HBV transmission?
Definition
1/200,000-400,000
Term
How many transfusions result in bacteria?
Definition
1/75,000
Term
How long after being thawed is FFP good for?
Definition
24 hours at 1-6 degrees celcius; 4 hours if pooled
Term
What are the different flora that can contaminate blood products?
Definition
transient flora= adherent to keratin layer
superficial flora= in inner epidermal layer
deep resident flora= in hair follicles, sweat and sebaceous glands
Term
How do you prevent bacteria from skin from getting into donated blood?
Definition
contemporary needle design to minimize skin plug, diversion pouch for the first few mL of blood
Term
What are the common gram negative bacteria in PRBCs?
Definition
yersinia enterocolitica, serratia liquifaciens or serratia marcescens, other enterobacteriaceae, psuedomonas
Term
Gram negative bacteria are common in which blood products?
Definition
PRBCs because they can grow well at 1-6 degrees C (also can be in platelets)
Term
Gram positive bacteria are common in which blood products?
Definition
platelets because at 20-24 C
Term
What are the common gram positive bacteria that contimate platelets?
Definition
staph (S. aureus and coag negative staph), strep, gram negative bacilli
Term
How frequently are platelets contaminated?
Definition
1/3,000
Term
How many contaminated platelets cause a severe septic transfusion reaction?
Definition
1/6
Term
Platelet products MUST be tested for _____
Definition
bacterial contamination
Term
How are people infected with Yersinia enterocolitica?
Definition
infection caused by ingestion of contminated food (such as pork) or water
Term
What are the symptoms of RBC contamination by yersinia?
Definition
mild; perhaps diarrhea 1-2 weeks prior to donation but transient infection may be followed by a prolonged bacteremia
Term
T/F Yersinia grows well at 4 degrees celcius.
Definition
true
Term
What are the symptoms of gram negative septic transfusion reaction?
Definition
fever, rigors, hypotension (rigors, abdominal pain, N/V, shock)
Term
What are the symptoms of gram positive septic transfusion reaction?
Definition
signs and symptoms can be very mild; must havehigh index of suspicion to catch gram negative septic transfusion reaction
Term
What should you send to the blood bank if you suspect a transfusion reaction?
Definition
send post transfusion blood specimen, urine specimen, and remainder of blood product to blood bank
Term
What does the blood bank do when you have reported a transfusion reaction?
Definition
check for clerical errors, repeat ABO testing, DAT/antibody screen, visual check for hemoglobinemia
Term
T/F HDFN can not occur in a first pregnancy.
Definition
false, it can occur in a first pregnancy if mother has been sensitized by a prior transfusion
Term
What kind of Ig is responsible for HDFN?
Definition
IgG
Term
What are three historically distinct diseases that are all caused by HDFN?
Definition
erythroblastosis fetalis, hydrops fetalis, icterus neonatorum gravidum
Term
What is erythroblastosis fetalis?
Definition
destruction of fetal red cells causes increased extramedullary erythropoeisis in the liver and spleen; increased immature erythrocvytes (erythroblasts) in the circulation
Term
Describe the breakdown process of heme?
Definition
heme to biliverdin via heme oxygenase; biliverdin to unconjugated bilirubin via biliverdin reductase; unconjugated bilirubin to conjugated bilirubin by UDP glucuronyl transferase
Term
Why is the fetal liver unable to conjugate bilirubin?
Definition
does not produce enough UDP glucuronyl transferase
Term
When is hemolysis of Hemolytic disease of the newborn at maximum?
Definition
at birth
Term
What are the blood groups that cause HDN in order of importance?
Definition
1) anti-Rh (anti-D)=severe 2) anti A and/or anti B= mild 3) anti-Kell and anti-Duffy= severe
Term
Whta is the most common cause of HDN?
Definition
anti-A or anti-B now that Rhogam is in widespread use
Term
What percent of the population is Rh negative?
Definition
15%
Term
What percent of births are Rh negative mothers with Rh positive fetuses?
Definition
10%
Term
Why doesn't every Rh- mother with an Rh+ fetus develop HDFN?
Definition
quantity of fetal blood cells reaching maternal circulation can be insufficient for sensitization, insufficient anti-Rh reaching fetal circulation, ABO incombatibility can be protective (RBCs destroyed by maternal IgM before mother can become sensitized to Rh antigen), Rh negative individual just isn't sensitive to Rh antigen, first pregnancy is not affected
Term
Mothers with what blood type have the greatest tendency to have HDFN due to ABO incompatibility?
Definition
group O have the greatest tendency to make high titer IgG ABO antibodies
Term
What percent of babies/mothers are ABO incompatible?
Definition
20%
Term
Why is ABO HDFN less severe?
Definition
fetal antigens are poorly developed
Term
How do you treat ABO HDFN?
Definition
usually jsut need phototherapy
Term
What should you do for a mother who isABO incompatible with her fetus?
Definition
nothing; she has already made IgM antibodies, just follow titer levels of antibody
Term
What prenatal screening is performed to protect against HDFN?
Definition
ABO and Rh (D) typing and antibody screen
Term
If a mother's antibody screen is positive, you should...
Definition
identify and titer the antibody then follow the titer during pregnancy to see whether it increases
Term
How do you treat a pregnant women who is Rh negative and has not formed anti-D?
Definition
give 1 dose of Rhogam IM at 28 weeks GA then another dose within 72 hours of delivery
Term
What test is performed if feto-maternal hemorrhage is suspected?
Definition
Kleihauer-Betke test to quantify the amount of fetal RBCs in mother's ciruclation. Tells you the amount of RhIg needed to cover the volume of hemorrhage
Term
What do you do for a pregnant women who has already formed anti D?
Definition
monitor antibody titer throughout pregnancy; if Ab titer >1:16 by 24th week of gestation, amniocentesis is indicated to assess severity of HDN by bilirubin concentrations
Term
How do you treat HDFN prenatally?
Definition
intrauterine transfusion premature induction of labor or plasmapheresis
Term
How do you treat HDFN in the neonate?
Definition
phototherapy to conjugate bilirubin or exchange transfusion
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