Transfusion Medicine Flashcards
tube testing
Immediate spin:
IgM antibodies and insignificant
37ºC phase
IAT phase:
Detects RBCs coated with IgG +/- complement
Antibodies reacting at IAT are more often significant
Blood Groups
Clinically significant Hemolytic transfusion reaction Hemolytic disease of the newborn/ fetus Most significant antibodies Require previous exposure IgG warm reactive (37˚C) Most insignificant antibodies Naturally occurring IgM Cold reactive (below 37˚C)
ABO Blood systems- Type I chains
Type 1 chains: glycoproteins and glycolipids free-floating in secretions and plasma
ABO Blood systems- Type II chains
Type 2 chains: glycolipid and glycoprotein antigens bound to the red cell membrane
ABO Blood systems- Se gene
Se gene modifies type 1 chains to produce H antigen (substance)
ABO Blood systems- H gene
H gene modifies type 2 chains to produce H antigen (substance)
H antigen is further modified to make
A antigen
B antigen
ABO Blood systems- O gene
O antigen has no further modification of H antigen
ABO blood systems
Most important blood group
Genotype determined by three codominant alleles on the long arm of chromosome 9
Antigens are also carried on platelets, endothelium, kidney, heart, lung, bowel and pancreas
ABO antigens are present on fetal RBC’s by 6 weeks of gestation and reach adult levels by age 4
Bombay (Oh)
Bombay (Oh)
Lack of H, A and B antigens
Due to lack of H and Se genes (hh, sese)
ABO blood system - antibodies
Antibodies are clinically significant and naturally occurring Activates complement Immediate intravascular HTR Appear at 4 months of age and reach adult levels at age 10 Antibodies may disappear with age Three antibodies: Anti-A Anti-B Anti-A,B
ABO blood system - antibodies; Group A blood
Group A blood: anti-B IgM antibodies that react strongly at body temperatures (37ºC)
ABO blood system - antibodies; Group B blood
Group B blood: anti-A IgM antibodies that react strongly at body temperatures
ABO blood system - antibodies; Group O blood
Group O blood:
anti-A and anti-B IgG antibodies that react best at body temperatures
anti-A,B IgG against A or B cells
Mild HDFN (most common)
ABO Blood System - Forward typing
Forward typing
Red cell grouping
Patient’s red cells agglutinated by test anti-A, anti-B antibodies
ABO Blood System - Reverse typing
Serum grouping
Patient’s serum or plasma agglutinated by test A1 and B RBC
Rh System
Second most important blood group
Two genes:
RHD (D/-)
RHCE (C/c, E/e)
Antibodies: D makes most antibodies, then c and E D is very immunogenic; 80% of D-neg make anti-D HTR with extravascular hemolysis Severe HDFN with anti-D and anti-c Mild HDFN with anti-C, anti-D and anti-e
Rh System - Antibodies
Prototypical HDFN
Not first pregnancy unless mom was previously transfused
D-neg mom with D+ baby
Prevention: RhIG (commercially prepared anti-D)
D-neg females at 28 weeks gestation
D-neg females ≤72 hrs. of D+ baby’s birth
D-neg females with pregnancy complications or invasive procedure (amniocentesis, etc..)
Contraindications:
D-neg female who already has anti-D
D+ females
D-neg mom with D-neg baby
RhIG dosing
RhIG Dosage:
One full dose vial (300µg) per 30 ml of D+ whole blood
One full dose vial (300µg) per 15ml D+ RBCs
Determine percentage of fetal-maternal hemorrhage:
Fetal blood screen; qualitative
Kleihauer-Betke; quantitative but poorly reproducible
Flow cytometry; quantitative and more accurate
Rh system
KB% x blood volume = baby blood in mom Blood volume = 70 kg x 70ml/kg = 4900ml (if no weight is given use 5000 ml) 0.02 x 4900 = 98ml D+ baby blood 98/30 =3.2 Give 4 units RhIG
RhIG rules
If number after decimal is <5, round up
If number after decimal is ≥5, round up twice
Lewis System
Similar biochemistry to ABO system
In secretors, Leb mostly formed
In non-secretors, mostly Lea formed
Insignificant, naturally occurring, cold-reacting IgM antibodies
MNS system
Anti-M and anti-N: Insignificant, naturally occurring, cold-reacting IgM
Anti-S, anti-s, anti-U: Significant, exposure requiring, warm-reacting IgG
Anti-M is rarely associated with severe HDFN
I system
Antigens are built on 2 types of chains Simple (i) chains found in neonates Branched I chains found in adults Insignificant, naturally occurring, cold-reacting IgM auto-antibody Auto-anti-I: -Cold agglutinin disease -Mycoplasma pneumonia infections Auto-anti-i: -Infectious mononucleosis
P system
Similar biochemistry to ABO system
P antigen is the parvovirus B19 receptor
Pk antigen is receptor for various bacteria and toxins
Insignificant, naturally occurring, cold-reacting IgM
Auto-anti-P:
-Paroxysmal cold hemoglobinuria
-Biphasic IgG autoantibody (bind cold, hemolyzes warm
Kidd System
Significant, exposure requiring, warm-reacting IgG (with IgM component)
Can fix complement with IgM component
Severe acute HTR possible
Delayed HTR, anamnestic, intravascular and severe
Mild HDFN
Kell System
K antigen low frequency; k antigen high frequency (99.8%)
Anti-K
Most common non-ABO antibody after anti-D
Significant, exposure requiring, warm-reacting IgG1
Most due to transfusion, not pregnancy
Anti-k
Very uncommon due to high frequency antigen
Severe acute or delayed, extravascular HTR
Severe HDFN
McLeod phenotype/ McLeod Syndrome
All Kell antigens decreased
Hemolytic anemias with acanthocytes, myopathy, ataxia, peripheral neuropathy, cardiomyopathy
X-linked chronic granulomatous disease
Duffy
Anti-Fya more common and significant than anti-Fyb
Significant, exposure requiring, warm-reacting IgG
Severe HTR, delayed and extravascular
Mild, but occasionally severe HDFN
Fy(a-b-) most common phenotype in African-Americans
Fy(a-b-) are resistant to Plasmodium vivax and P. knowlesi infection
Blood Donation Permanent Deferrals
High risk behavior for AIDS (IVDA, male-male sex, exposure) Receiving money for sex Serologic positivity for HIV, HBV, HCV, HTLV Viral hepatitis after 11th birthday Use of transfusion clotting concentrates History of babesiosis or Chagas disease Growth hormone from human source Insulin from bovine sources Dura mater graft Lymphoma or leukemia Medication teratogens: Tegison vCJD risk
Blood Donation 3 year deferrals
Recovered from malaria
Immigrants from malaria endemic areas (5 years of living)
Medication teratogens: Soriatane
Blood Donation 1 year deferrals
Needle stick or other contact with blood Sex with person with HIV or hepatitis Sex with IVDA Rape victims Incarcerated >72 hrs. Paying for sex Allogeneic blood transfusion Allogeneic transplant Living with person with active hepatitis Receiving HBIG Tattoos/piercings Travel to malaria endemic area Syphilis or gonorrhea Non-prophylactic rabies vaccines Travel to Iraq
Other Blood Donation Deferrals
Pregnant: 6 wks. postpartum Non-routine dental work: 72 hrs. Immunizations: 2 or 4 week deferrals Drugs: Accutaine, finasteride: 30 days Duasteride: 30 days Aspirin: 48 hrs. Plavix or Ticlid: 2 weeks
Blood Donation Donor Testing
500 ml taken ABO/RH Antibody screen Anti-HTLV I/II West Nile Virus NAT Anti-Trypanosoma cruzi (Chagas) Serologic syphilis RPR/VDRL FTA-ABS Hepatitis B HBsAg Anti-HBc HBV NAT Hepatitis C Anti-HCV HCV NAT HIV Anti-HIV1/2 HIV-1 NAT
Preoperative autologous blood donation
Less screening than allogeneic
AABB standard: not to be crossed over into regular inventory
Infectious disease screening not required unless units shipped to another facility
Type and Screen
Type and screen
Records check: Previous antibodies or compatibility problems
ABO/Rh testing
Antibody screen
Group O phenotyped RBCs
Antigens required by FDA: D, C, c, E, e, Fya, Fyb, Jka, Jkb, K, k, Lea, Leb, M, N, P1, S, s
Type and Cross Match
Major crossmatch: recipient’s serum with donor RBCs
Minor crossmatch: donor serum with recipient’s RBCs
Blood Components - RBCs
expected to raise HCT 3%, HGB 1% g/dL
Can be measured 15 minutes after transfusion
Can be transfused with NS, ABO compatible plasma and 5% albumin
Blood Components - Platelets
Expected to raise count 20,000-30,000 in 1 hour
Do not require crossmatch or ABO compatibility
Leukoreduction
Leukoreduction: reduce the number of WBCs in the blood product
Filters (prestorage) at time of collection
Filters (pretranfusion) at bedside
Washing Blood Components
Washing: remove 99% of plasma
IgA deficiency
Blood Components: Irradiation
Irradiation: deactivates T-lymphocytes
Immunosuppression
Intrauterine transfusions, neonatal transfusions
Hematologic malignancies
Granulocyte transfusion
Receiving blood from first degree relative donor
Receiving HLA-matched units
Acute Transfusion Reactions Presenting With Fevers
Acute Hemolytic
Febrile Non-hemolytic
Transfusion Related Sepsis
TRALI
Acute Transfusion Reactions Presenting Without Fevers
Allergic
Hypotensive
Transfusion-associated dyspnea
TACO
Delayed Transfusion Reactions Presenting With Fevers
Delayed Hemolytic
TA-GVHD
Delayed Transfusion Reactions Presenting Without Fevers
Delayed Serologic
Post-transfusion Purpura
Iron Overload
Acute Transfusion Reaction
Signs and symptoms present within 24 hours of a transfusion
Delayed Transfusion Reaction
Signs and symptoms present after 24 hours of a transfusion
Signs, Symptoms, and Etiology of Immune Transfusion Reactions
Abdominal, chest, flank or back pain Pain at infusion site Feeling of impending doom Hemoglobinemia Hemoglobinuria Renal failure/ Shock DIC
Type II (antibody-mediated IgG /IgM) hypersensitivity reaction
Signs, Symptoms, and Etiology of Non-Immune Transfusion Reactions
Asymptomatic hemoglobinuria
Chemical or mechanical damage to blood product
Acute hemolytic transfusion reaction - Intravascular
Due to ABO incompatibility
ABO antibodies fix complement and leads to rapid lysis
Also seen with other antibodies (Kidd)
Acute hemolytic transfusion reaction - Extravascular
Usually (but not always) less severe due to lack of systemic complement and cytokine activation
Seen with Rh, Kell, Duffy antibodies
Acute hemolytic transfusion reaction - Treatment
Hydration/diuresis
Exchange transfusion
Transfusion Reaction Work Up
- STOP THE TRANSFUSION!
- Clerical check
a. Bedside paperwork/ bag check
b. Blood bank paperwork/ computer check - Draw post-transfusion sample
a. Visible hemoglobinemia
b. Compare to pre-transfusion sample - DAT
a. Demonstrate RBC coating with IgG &/or b. complement in vivo
b. Positive DAT does not prove AHTR
c. Negative DAT does not disprove AHTR - Repeat ABO/Rh testing
Febrile non-hemolytic transfusion reaction
Most frequently reported reaction
Unexplained increase in temperature 1ºC
Etiology: increased pyrogenic substances from WBCs
-Pretransfusion: donor WBCs secrete cytokines in storage bag
-During transfusion: Recipient antibodies attack donor WBCs or vice versa
Treatment
-Antipyretics
-Demerol
Symptoms, Mechanism, Treatment and Prevention of Mild Allergic Reactions
Very common Localized hives Angioedema Mild respiratory symptoms Mild laryngeal edema
Type I (IgE-mediated) hypersensitivity to transfused plasma proteins Mast cell secretion of histamine and other mediators of allergic reactions
Diphenhydramine IV or oral (prevention)
Wash blood products
May restart transfusion after hives clear
Symptoms, Mechanism, Treatment and Prevention of Moderate Allergic Reactions
Stridor Hoarseness Wheezing Chest tightness Dyspnea
Type I (IgE-mediated) hypersensitivity to transfused plasma proteins Mast cell secretion of histamine and other mediators of allergic reactions
Diphenhydramine IV
Epinephrine
Symptoms, Mechanism, Treatment and Prevention of Severe (anaphylactic) Allergic Reactions
Uncommon Anaphylaxis very early Hypotension Lower airway obstruction Abdominal distress Systemic crash Urticaria Puritis
IgA deficient recipient with IgE anti-IgA
Haptoglobin deficiency
Latex drugs or foods in donor can lead to severe reactions in recipients
Washed blood products
IgA deficient blood products
Benadryl with corticosteroids
Epinephrine
Delayed hemolytic transfusion reactions
Extravascular hemolysis at least 24 hours but less than 28 days after transfusion
Etiology
Anamnestic response
-Antibody formed but fades over time
-Anamnestic rapid production of IgG antibody
-Typical for Kidd, Duffy and Kell antibodies
Primary response
-Antibody is quickly formed and attacks still c-irculating transfused red cells
Transfusion associated graft vs. host disease (TA-GVHD)
Attack on recipient cells by viable T-lymphocytes in transfused blood product
Patients present with
- Fever 7-10 days post-transfusion
- Face/trunk rash that spreads to extremities
- Mucositis, nausea/vomiting, watery diarrhea
- Hepatitis
- Pancytopenia
Patients at risk: all those requiring irradiation
Treatment: Irradiate blood products
Transfusion Associated Sepsis
Transfusion associated sepsis
Acute non-immune transfusion reaction
Due to bacteria in contaminated platelets and RBCs
Staph, strep, Yersinia, bacillus, pseudomonas, E. coli
Hypotensive Transfusion Reaction
Similar to severe allergic reaction but no skin symptoms, no GI or respiratory issues
>30mm Hg drop in systolic BP; diastolic ≤80mm Hg
Occurs <10 after stop
Associated with patients taking ACE inhibitors or receiving blood with negatively charged filters
Transfusion related acute lung injury (TRALI)
1 cause of transfusion related fatality in US
New acute lung injury ≤6 hrs. post transfusion
Associated with platelets but also RBC/WB
Two proposed methods
Neutrophils produce toxic free radicals that damage endothelial cells
Donor anti-HLA or anti-neutrophil antibodies bind to recipient antigens and damage endothelial cells
Transfusion
Transfusion associated circulatory overload
Acute onset of congestive heart failure as a direct result of blood transfusion
Post Transfusion Purpura
Rare
Marked thrombocytopenia and increased risk of bleeding 10 days following transfusion
Due to antibody against a common platelet antigen
Anti-HPA-1A
PLA1 has a frequency of 98%
