All Topics Flashcards
1
Q
What sections of 21 CFR pertain to blood products?
A
Sections 600, 606, 610, and 640 relate to blood/biologics
Sections 1270, 1271 relate to tissues and stem cells
2
Q
What is the difference between QA and QC?
A
QC focuses on evaluation of processes IN PROGRESS.
QA is not directly tied to a process’s performance. Broad.
3
Q
A
A
A
4
Q
What REGULATORY AGENCIES oversee transfusion medicine?
A
FDA, CMS
(all others are professional orgs, eg AABB or JCo)
5
Q
Sentinel events & reporting
A
Sentinel events include patient deaths and near misses.
They are not required to be reported to JCo, but it is a good idea, and if JCo becomes aware of one, a root cause analysis must be undertaken within 45d of the sentinel event.
6
Q
Juran’s Quality Trilogy
A
Planning
Control
Improvement
7
Q
3 forms of validation qualification
A
Installation qualification - Environmental needs
Operational qualification - Device function, alerts, etc
Performance qualifications - Verifying capabilities for intended use
8
Q
What must be reported in the validation of an LDT?
A
Sensitivity, specificity
Accuracy, precision
Range, reference intervals
9
Q
How can competency assessment be performed? How often must it be done?
A
Direct observation
Recording & reporting
QC/PT
Upon initial hire, at 6mo, then annually therafter.
10
Q
What are the roles and reporting for an independent quality unit?
A
Must have the means to address and correct deviations
Must report directly to leadership
11
Q
Change control
A
Preventing unplanned changes to processes
12
Q
Who assumes all responsibility for contracted work?
A
The contracting facility (NOT the contractor, or manufacturer)
13
Q
How are biologic product deviations reported, and when?
A
Report to FDA using form 3486.
Must report within 45d of the cGMP deviation occurring. Product must leave control of manufacturer.
14
Q
How frequently must customer feedback be collected in contract agreements?
A
Not defined by regulation, but often is good.
15
Q
How many crossmatch PTs can you fail before being shut down?
A
Shutdown after second unsuccessful PT (unsatisfactory).
16
Q
How often should devices or reagents be QC’d?
A
Depends on how critical they are, but most things are QC’d daily.
Larger and more complex equipment may be QC’d less frequently.
17
Q
When and how should transfusion (and donor) deaths be reported?
A
Initial report to CBER within 1 day.
Full written report within 7 days.
18
Q
Pareto chart
A
Bar graph used as a cause analysis tool.
19
Q
Ishikawa diagram
A
AKA fishbone diagram, used to identify causes of error or manufacturing defects.
20
Q
Distinguish between market recalls and withdrawals.
A
Recalls: More severe–violation of FDA manufacture laws. Ranges from class I (most severe) to III (most common).
Withdrawals: Not actually subject to legislation. Usually post-donation, done at blood supplier discretion.
21
Q
Who can evaluate competency assessment?
A
No special person is required, but one cannot audit their own work.
22
Q
SQUIPP
A
Safety
Quality
Identity
Potency
Purity
23
Q
Distinguish between remedial action and corrective action
A
Remedial action alleviates symptoms of nonconformance
Corrective action addresses the cause of nonconformance
24
Q
In what settings is licensure required for a blood center?
A
When engaging in interstate commerce
25
In what setting can a blood service be exempt from FDA registration?
No collection or major product manipulation.
OK: Irradiation, pooling, leukoreduction.
Must still be CLIA-certified!
26
What are the required components of a facility safety program (standard hazard model)?
Must define safe work practices
Must identify and communicate hazards
Must train personnel in recognition and handling
Requires engineering controls and PPE
May employe a safety officer
An emergency response plan is required if >10 employees
27
What regulates facility fire prevention? What are the required components?
NFPA Life Safety code
Annual fire safety training
Fire storage cabinets
Extinguishers
Detection / alarm systems
Fire escape paths
28
Biosafety levels
BSL 1 - Minimal potential hazards. Open surfaces, no containment
BSL 2 - Moderate infectious potential (**Most typical of TM)
BSL 3 - Hazardous materials, require measures to minimize aerosols
BSL 4 - Specialized, highly dangerous infectious risks.
29
Biosafety cabinets
Class I - Just for personnel and environmental protection, not product contamination protection. Outside-in air.
Class II - Offers product contamination protection. Laminar airflow, may exit building (type B) or recirculate after filtering (type A)
Class III - Strictest, with negative pressure and gloves-only contact. Mostly seen in BSL-4...
30
What is the annual dose limit of radiation?
Usually 5 rem per year. A rem is a measure of biological damage from radiation.
Usually, rem = rad* x QF (conversion factor)
*100 Rad = 1 Gy
31
Food, Drug, and Cosmetic act
21 USC 301-399d
Regulates drugs, devices, and blood products. Establishes cGMP regulations.
32
Public Health Service act
Section 351 defines blood as a biologic, requiring licensing for interstate commerce.
Section 361 gives DHHS authority to minimize disease transmission.
33
Medical device classes
Class I - Lowest risk, general controls OK
Class II - Must be approved through 510k pathway
Class III - Most complex
34
FDA inspections
May be routine, "For-cause", or pre-approval.
May be Level 1 (thorough), or Level 2 (streamlined, offered after 2x favorable Level 1s)
Findings are summarized in an EIR. Faults are reported using form 483.
35
What are the requirements for HCT/Ps to be regulated as a 361 product?
Must be minimally manipulated
For homologous use
Must not be mixed
Otherwise, more stringently regulated as a 351 (drug or device)
36
Deming cycle for continuous quality improvement
Plan, Do, Check, Act
System for process improvement. Plan changes, enact them, observe/report, and act on the outcome.
37
What national hemovigilance programs exist?
UK: SHOT
Japan: First ever system
US: NHSN Hemovigilance *
*nearly all hospitals use NHSN for nursing safety, but only a minority use the hemovigilance module
38
What tools exist for blood donor safety and reactions?
A blood donor working group does exist; published Donor Hemovigilance Analysis and Reporting Tool (HART).
39
What are the most common donor reactions?
1. Vasovagal
2. Local injuries (incl. nerve, artery)
3. Apheresis reactions
4. Allergy
40
Donor vitals
180-90 / 100-50
100-50
<37.5 C / 99.5 F
At least 16yo (depending on state)
110lb (50 kg)
41
Post-draw donor info permittance
24 hours to get full info
42
Hemoglobin minimum for donation
Men: 13g/dL
Women: 12.5g/dL
*May 2015 ruling permits collection of women with 12-12.5g/dL with special procedures.
43
POC Hemoglobin determination
POC Spectrophotometry preferred, not copper sulfate (quantative). Earlobe samples not permitted.
44
Post-delivery deferral
6 weeks
45
Malaria deferrals:
- Travel to endemic area
- Personal history of infection
- Residing in endemic area
Travel - 1yr
Personal Hx - 3yr
Residing - 3yr
46
When should blood donors be informed of their positive IDM tests?
8 weeks
47
Deferrals: Cancer
Actually not required by FDA, done at discretion of med director.
Most would defer hematolymphoid malignancies permanently.
Most would defer invasive carcinomas 1-5yrs post-cure.
48
Deferrals: Teratogenic drugs
Etretinate - Forever
Soriatane - 3 years
Dutasteride - 6 months
Finasteride - 1 month
Accutane - 1 month
49
Hep B vaccine impact on IDM testing
Can cause a falsely positive surface antigen (HBsAg) up to 18 days from vaccination.
50
Donation intervals
WB: 8 weeks
Double-red: 16 weeks
Platelets: 2 days, with 1 week between pairs
Frequent plasma: As platelets
Infrequent plasma: 4 weeks
WBCs: 2 days?
**These can be bypassed with blood center physician approval
51
What is the usual hemoglobin content of a pRBC unit?
60g per unit
(95% are required to be 50g or above)
52
Deferrals: CJD
Indefinite for:
- From '80 to '96: 3 months in UK, or US military presence
- From '80 onwards: 5 years in EU, or transfusion
- Dura mater graft
53
What is the most common cause for blood donor deferral?
Anemia
54
Abbreviated DHQ
Streamlined donor questionnaire that can be used for patients who have completed the full DHQ twice, and have donated in the past 6 months.
55
Directed donation requirements
Same as general allogeneic requirements; irradiate the unit.
56
Requirements for autologous blood collection
Order from MD
Minimum Hgb 11g/dL
72+ hr gap before surgery
No bacteremias
No severe cardiac disease?
57
Deferral: Vaccines
Experimental, HBIg - 1 year
Rubella, VZV - 4 weeks
All other live-attenuated - 2 weeks
Smallpox - 21d after scab falls off (or 2mo if it was removed early)
58
IDM testing in directed donation
Only required every 30d, rather than with every donation.
59
Maximum plasma and RBC losses permitted in platelet donation
Total volume must not exceed 500mL (600mL if >175lb bodyweight).
RBC losses must be under 200mL, else defer 8 weeks. If >300mL, including across two donations, defer 16 weeks.
60
Requirements & exemptions for source plasma donation
Must have total protein >9g/dL. Must be medically assessed. Quantitative Ig q4wk?
Exemption: Malaria deferrals do not apply.
61
WBD donation duration
Usually finish in 10min, must finish by 20min (else fear of coag abnormality).
Can phleb twice to achieve goal!
62
Low volume collections
Less than 90% of target goal (405, 450mL). Can use pRBCs, but must junk plasma products.
63
Diseases treatable with therapeutic phlebotomy
Polycythemia
Hemochromatosis
Porphyria cutanea tarda
64
Under what settings can therapeutic phlebotomy products be used for allo transfusion?
Follow same eligibility criteria
Need a medical order
Cannot charge donor for service
65
Arterial donor stick
Pain, rapid donation (sensitive)
Bright red blood (fairly sensitive)
Pulsatile needle (insensitive)
66
Nerve donor injury
Usually affects young women
Most are transient, nearly all resolve within 1yr.
67
ANH
Pre-op phlebotomy. Collected blood must be reinfused in reverse order. Full label.
Storage: 8hr (RT), 24hr (cold)
Swap with 3:1 crystalloid, 1:1 colloid fluids.
Best for patients with high crit and low risk of transfusion.
68
Cellsaver
Uses a filter, gentle (<150 torr) vacuum.
Can transfuse unprocessed (4hr RT) or after washing (4hr RT, 24hr cold)
69
How should veins be selected and prepared for phlebotomy
Prefer antecubitals. Avoid scarring and folds.
Clean thoroughly, and divert first 5-10mL of blood.
70
What is the weight-based maximum donation volume?
10.5 mL / kg
So, 70kg adult can donate up to 735mL
71
What testing must be performed on all donated blood products?
ABO/Rh
Antibody screen
TTIs* (HIV 2x, HCV 2x, HBV 2-3x, Syphilis serology, HTLV serology, chagas/WNV variably)
*Unless directed donation with negative testing in last 30d
72
Maximum apheresis RBC donation collections
RBC, plus any one of:
Second RBC
Platelets
Plasma
Platelets AND plasma
73
Number of segments per unit
13-15
74
FFP, PF24 expiration?
1yr at -18C, or 7yr at -80C.
Once thawed, 24hrs at 1-6C, after which it becomes thawed plasma (4d at 1-6C)
75
What is still present in cryo-reduced plasma?
What is still present in PF24?
Cryo-reduced plasma: Actually, still a lot of everything, including fibrinogen (~200mg/dL)
PF24: 100% of factor 5 activity, 70% of factor 8 activity
76
How much fibrinogen is in a unit of cryoprecipitate?
According to standards, 250mg. Minimum 150mg.
Actually: 388mg per unit.
77
How quickly does factor 8 degrade at room temperature?
What patient factors affect factor 8 content?
10% per 2 hours
Group O patients have much less factor 8 than A/B/AB.
78
Max unagitated platelet storage time
24 hours
79
How can granulocyte yields be boosted from donors?
HES
Steroids
G-CSF
80
Leukoreduction: Requirements, validation, and causes of failure
Must cause 3-log-fold reduction of WBCs, with 5 x 10^6 in unit. Confirm with flow or Nageotte hemocytometry
Unit should retain 85% of initial RBC content.
Failure usually due to sickle cell trait.
81
Who regulates nuclear materials? Which?
US Nuclear regulatory commission regulates labs that use Cesium (137) or cobalt (60) to irradiate products.
82
Irradiation: Consequences
Shortdate to 28d
Double potassium supernatant levels within 2 days (may want to volume reduce in peds)
83
What can be done while a unit is quarantined pending IDM testing?
Can still be processed into components.
84
Required labeling of blood products
Barcode, facility ID, donor lot, product code
ABO/Rh of donor
Additional labels for special processing
Tie tags for directed/autologous units
85
Transcription-Mediated Amplification (TMA)
Isothermal amplification method
Relies on reverse transcriptase to generate cDNA which is then acted on by DNA polymerase to make dsDNA.
Faster than PCR
86
How is the signal of nucleic acid amplification transmitted/detected?
Ethidium bromide (old)
TaqMan (fluorochrome and quencher)
FRET
SYBR (like ethidium; only works on dsDNA)
87
Antibody affinity vs avidity
Affinity: Binding strength at one epitope
Avidity: Combined binding strength of all binding sites on an antibody
88
IgG subclasses
IgG1 - Good at binding complement
IgG2 - Poor at binding complement
IgG3 - Good at binding complement
IgG4 - Does NOT bind complement
89
What blood group antigens are expressed on the X chromosome?
Xg (XG on X chr, CD99 on both X and Y chr)
Kx (women can have two populations!)
90
Capellini effect
Phenomenon wherein a C allele in trans to D reduces expression of D.
91
Kpa, Jsa
Kpa - Low frequency antigen expressed in a small number of whites.
*Presence suppresses other Kell antigen expression!
Jsa - Low frequency antigen expressed in a small number of blacks.
92
In(Lu)
Dominant suppressor of lutheran blood group (KLF1). Also reduces expression of Indian antigens.
93
Rh-null
Mutation of RhAG on chr 6.
Hemolytic anemia with stomatocytes
Also loses LW antigens, most glycophorin B.
94
In a recently transfused patient, how should material be obtained for genetic testing?
Can obtain from peripheral blood (requires microcentrifugation to harvest reticulocytes)
Better to obtain buccal swab or buffy coat.
95
Where are most sugartransferases located in the cell?
Golgi complex
96
4 types of carbohydrate chains
Type 1 - Free-floating
Type 2 - Fixed to cell membranes
Type 3 - "Repetitive chain"
Type 4 - "Globoside"
97
When are ABO antigens detectable?
When are isohemagglutinins detectable?
Antigens: 5-6wks in utero
Antibodies: 3-6mo into infancy
98
A2 subgroup - Molecular features
About 200k molecules per RBC (compared to 1M in A1)
More reactive to Ulex Europeaeus lectin
99
B(A) phenomenon
B-sugartransferase with weak A-sugartransferase activity.
Note that A(B) exists too.
100
cisAB
Sugartransferase that can equally transfer A and B sugars.
If coinherited with a group O allele, results in "weak A, weak B" phenotype
101
How can solid tumors cause ABO discrepancies?
May secrete large volumes of soluble A/B/H, neutralizing reagent on forward type.
>>Ovarian, hepatobiliary, gastric...
102
Decreasing H antigen expression
O > A2 > B > A2B > A1 > A1B
103
Para-bombay
H-deficient secretor.
May make H, A/B soluble antigens, but should type as O and produce a weak anti-H.
104
i-adult
Seen in asian patients, resulting from autosomal recessive GCNT2 mutation.
Associated with congenital cataracts, HEMPAS
105
P phenotypes
P1 (expresses P, P1, Pk)
P2 (does not express P1; seen mainly in asians)
Pk1, Pk2 (no P, but Pk)
p (null, rare)
106
What are the biological features of anti-P1?
What can neutralize their reactivity?
IgM, rarely causes hemolysis
Neutralizable with hydatid cyst fluid, pigeon egg white
107
Anti-P/P1/Pk
AKA "anti-Tj(a)"
Causes abortions, enriched in Amish populations
108
FORS
Forssman antigen, a low-prevalence antigen attached to P that looks like A.
109
Relationship between RHD and RHCE
Probably arose from duplication event.
Note 97% homology and INVERTED orientation from one another
110
Cause of partial D
Actually usually due to partial replacement of RHD with RHCE.
Note presence of neoepitopes (eg, BARC on D-IV)
Note that reverse can occur with partial replacement of RHCE with RHD.
111
Variant RHCE antigens
Cw - Altered C, low frequency, whites
Partial e - *ce alleles of AfAm patients. Associated with loss of high-prevalence "hr" antigens and also with partial D.
112
Compound RH antigens
G (D+C)
f (c+e)
113
RHCE antibody most associated with HDFN?
>c tends to cause severe HDFN, while C/E/e do not.
114
Binding receptors for plasmodium falciparum
Glycophorins A/B
Glycophorins C/D (Gerbich)
Cromer
Knops
115
Mi(a)
Located on Gp.Mur, a defect glycophorin B.
Presence in some asians creates concern for HDFN, analogously to RhD.
116
Lutheran antibodies
Lu(a) not significant
Lu(b) can cause some HTRs, HDFN
Causes mixed-field agglutination
117
CD235
CD238
CD235 - MNS
CD238 - Kell
118
Kell null
Ko; Kx is preserved. May form anti-Ku which reacts to all Kell antigens.
119
Function:
Kell
Duffy
Kidd
Rh
MNS
Kell - Zinc endopeptidase
Duffy - Chemokine scavenger
Kidd - Urea transporter
Rh - Ammonia transporter, major cytoskeletal element
MNS - Bears sialic acid, links to Rh
120
Kidd-null phenotypes
Jk(a-b-) in some polynesians and finnish (>Jk3)
In(Jk) in Japanese from dominant inhibitor
121
Kidd antibodies
Usually IgG1/3. About half bind complement. Often evanesce.
Rarely cause HDFN
Implicated in acute renal transplant rejection
122
Diego antigens
Di(a) - Low frequency, seen in some asians.
Di(b) - High frequency.
Antibodies can cause HDFN.
Wr(a), Wr(b) part of system...ignore
123
Cartwright
Yt(a) - HIGH prevalence
Yt(b) - Low prevalence
AChE, bound to GPI anchor.
124
Xg(a)
Expressed in 90% of women, 66% of men
Antibodies are insignificant.
125
Dombrock
CD297 (ART4)
Do(a) < Do(b).
Others: Gy(a), Hy
Significant!
126
Colton
Aquaporin-1
Co(a) - HIGH frequency
Co(b) - LOW frequency
Significant!
127
Landsteiner-Wiener
ICAM-4
Bound to Rh, expressed more if Rh(+)
Strongly expressed on cord blood cells?
128
Gerbich
Glycophorin C/D
P. Falciparum receptor, bears sialic acid
Antibodies variably significant
129
Cromer
DAF/CD55 - GPI anchored
P. Falciparum binding receptor
Insignificant!
130
John Milton Hagen
HTLA group that is lost with age.
Prone to autoreactivity
131
VEL
High-prevalence antigen
Antibodies cause severe hemolysis! Need rare antigen-neg units.
132
Bg
Not an actual blood group -- HLA Class I antigens
Bg(a) - B7
Bg(b) - B17
Bg(c) - A28
133
PEG
Enhancement media that excludes water. Enhances warm autoantibodies!
CANNOT centrifuge, else causes nonspecific agglutination. WASH.
134
RESt
Rabbit Erythrocyte Stroma
Removes cold autoantibodies (>I, >IH, but also D, E, Vel...)
135
How can sickle cells be separated from donor cells in vitro?
Use hypotonic saline -- sickle cells are resistant to lysis
136
How can coated IgMs be removed from patient cells?
Use 0.01M DTT (denatures J-anchor)
137
ZZAP
Glycine/EDTA
Chloroquine
ZZAP - DTT + Proteolytic enzyme
Glycine/EDTA - Strips Bg, Kell
Chloroquine - Strips Bg, Rh
138
In vitro tests to assess antibody significance
Monocyte monolayer
ADCC
Thermal amplitude studies
Chemiluminescence?
139
DAT testing - Gel vs tube
Tube - Wash step required.
Gel - No wash step, more sensitive?
140
Elution
Concentrates coated antibodies.
Usually acid kits > solvent > heat or freeze/thaw
141
Lui Freeze-Thaw
Technique for eluting specifically ABO antibodies in neonatal DAT samples.
Uses very little blood >> coat tube interior, freeze, thaw, then use the hemolysate supernatant.
142
PCH - Testing results
Presents with intravascular hemolysis with associated labs
DAT: C3+ (during crisis), IgG+ (generally)
Eluates negative.
Diagnose with Donath-Landsteiner test
143
Drug-related AIHA - 4 types
Drug-dependent TREATED: Covalently bound, gradual hemolysis
Drug-dependent UNTREATED: Brisk hemolysis
Drug-independent induction: Basically just WAIHA (eg, methyldopa)
Drug-independent adsorption: Nonimmunologic, insignificant
144
Requirements for re-issue of returned pRBCs
Seal intact
At least one segment attached
Between 1-10 degrees
Passed visual inspection
(no time limit)
145
Glycerol freezing
Can freeze slow with 40% glycerol (-80C)
Can freeze fast with 20% glycerol (-180C)
146
How and why should glycerol be removed in a thawed unit?
Causes in vivo or in vitro hemolysis (remains within the RBCs)
Need progressive wash cycles.
147
When should red cells be frozen?
Within 6 days of collection
Or, +3 days after expiration provided they are rejuvenated
148
Platelet pH limit
No lower than 6.2
149
Platelet storage lesion
Decreased pH
Activation from discoid to spherical shape
Shimmering/swirling in bag
Decrease in GP1b expression
150
Therapeutic plasma dose
10-15mL/kg
151
Cryo contents and recovery
Fibrinogen
Factor 8
Factor 13 (only 25% of FFP content)
vwF (only 50% of FFP content)
Fibronectin
152
Granulocyte unit contents
>1 x 10^10 (10 Bil) granulocytes in 75% of tested units
3 x 10^11 platelets!
20-50mL RBC volume
153
HES side effects
Anaphylaxis
Pruritus
Decrease in vWF, factor 8 -- Increased aPTT
Decrease in fibrinogen
154
What is pathogen reduction ineffective against?
Unenveloped viruses
Prions
Sporulated bacteria
155
Volume reduced platelets - Indications, expiry
For TACO, reverse compatibility in children
Expires within 4hrs (opened, RT)
156
Options for peds aliquoting
Aliquot to transfer bag -- No change in expiry, if done sterile
Syringes - Generally considered an open method >> 4hr vs 24hr expiry
*Aliquot from same primary container to reduce wastage
157
ABO prevalences across ethnic groups
All are O > A > B > AB
Asians have lowest rate of O overall
Native americans have highest rate of O overall
158
Causes of mixed field reactivity
Recent transfusion
Chimerism
ABO subgroups
Sd(a), Lu(a) antibodies
159
FUT genes transfer __-fucosyltransferase and are located on chr __.
L
Chr 19
160
Anti-H
Expressed usually in Bombay, less so in para-bombay, and sometimes randomly as an autoantibody
Generally IgM, can cause significant hemolysis (usually just in Bombay)
May not react with low H groups (A, AB)
161
>I vs >IH
>I will react with all cells other than pediatric and i-adult.
>IH needs presence of H, so won't react with Bombay cells. Insignificant?
(Bombay actually has MORE I because of absent H?)
162
Griffonia simplificolia
Phaseolus lunatus
Both are B lectins
163
Saline replacement technique
For subtracting excess reverse reactivity due to rouleaux.
Incubate reagent cells, then wash and replace with saline to read.
164
P group pathogenic binding targets
P - Parvovirus
Pk - Shiga toxin, strep suis, HIV
PP, P1, PK, LKE - Uropathogenic E.Coli
165
When does P1 mature?
When is >P reactivity seen?
Matures at age 7
May be seen in P2 individuals, maybe in PCH, maybe in parasite infections.
166
Chido/Rodgers
HTLA
On C4 -- Neutralized by plasma, but not serum
167
Sd(a)
Antibodies cause orange refractile agglutinates
Neutralizable with guinea pig urine
168
Causes of in vitro hemolysis
I
Lewis
Kidd
PP1Pk
Vel
169
Lewis phenotypes and antibodies
Le(a-b+) - Do not really make Le(a)
Le(a+b-) - Can make Le(b)
Le(a-b-) - Can make both
170
Brendemoen phenomenon
Forming >Le during pregnancy due to dilutional effect
171
Lewis - Pathogen binding
Leb - H. Pylori, norovirus
Note: Le(a-b-) have higher rate of candida infection?
172
Racial wiener haplotypes
White: R1 > r > R2 > R0
Black: R0 > r > R1 > R2
173
McLeod phenotype
Driven by KX loss on Chr X. Loss of all Kell antigens, gain >Kx, >Km.
Acanthocytes, hemolytic anemia, decreased water permeability
Associated with CGD, DMD, and Retinitis Pigmentosa
174
HTLA groups
Chido, Rodgers
Knops
McCoy
York
Cost Sterling
John Milton Hagen (prone to autoreactivity)
175
Pre-transfusion sample labeling requirements
2+ identifiers
Identification of phlebotomist (doesn't have to be initials)
Date of draw
Must be labeled at bedside.
176
Segment and T&S retention times
1 weeks minimum
177
Naturally occurring antibodies
ABH
I
P
Lewis
M and N
178
Causes of false positive DAT
In vitro coating, T-activation, use of colloidal silica
179
When can IDM testing be waived?
In directed donation, if the donor underwent IDM testing within 30 days
When the unit is to be transfused within the collecting facility (ie, Autologous?)
180
Polyagglutinable antigens
Acquired: T, Tn, Tk, Tx
Inherited: Cad, Hb-Hyde Park, HEMPAS, NOR
181
Arachis hypogaea
Salvia horminum
Arachis hypogaea (Peanut) - T, Th, Tk
Salvia horminum - Tn, Cad
182
Joint Commission transfusion metrics
Rate of consent
Appropriate indication
Proper documentation
Pre-op anemia screening
Pre-op T&S testing
183
Evans syndrome
ITP + AIHA
Smear may show giant platelets and spherocytes, but generally not schistocytes
Don't transfuse if patient is stable
184
Cryoprecipitate indications
Repletion of fibrinogen, factor XIII, factor VIII (if better options not available)
Uremia refractory to DDAVP
Topical fibrin sealant
185
Granulocyte ANC requirements
Adult: <500
Pediatrics: <3000
186
How long can a pre-op T&S hold last?
Up to 45d per standards
187
How long and frequently do antibodies evanesce?
30% drop in 1yr
50% drop in 10yrs
188
RBC storage lesion, viability requirements
Membrane changes
Decreased pH, decreased ATP
Decreased 2,3-DPG
Increased potassium, free hemoglobin
Need <1% lysis at expiration, also 75% 1d recovery
189
What re-typing must be done upon receipt of blood products from a supplier?
Confirm ABO for any unit containing >2mL pRBC
Confirm Rh for any status labeled as RhD-neg
190
C:T ratio
Units crossmatched versus actually transfused. Keep this at or below 2
Set MSBOS based on this per-op!
191
Max blood warmer temperature
42C
Above >> Hemolysis
192
IV gauge for transfusion
14-22ga for adults
22-25ga for pediatrics (GO SLOW)
193
What conditions must be met for a unit of blood to be issued?
Unit is available
Patient consented
Vascular access available
Transfusionist immediately available
Order is OK
Patient is pre-medicated
194
Macroaggregate filters
Standard, 170-260um filter. Prime with saline!
195
pRBC transfusion rate
Start at 2mL/min
Ok to increase to 2-4mL/min, but ideally target 2-4hr completion
TACO? Try 1mL/kg/hr.
196
TRICC trial
Hgb threshold 7 vs 10 does not affect mortality
197
TITRe2 trial
Cardiac patients do not benefit from Hgb 9 vs 7.5
*Controversial...
198
Treatment of thalassemia major
Transfuse early in childhood to reduce EMH and facilitate growth.
Transfuse q2-4wks with a target Hgb of 9.
199
Indications for SCD RCX
Severe ACS
Stroke
Hepatic sequestration
Maybe: TCD > 200, Cholestasis, MODS
No: Splenic or aplastic crisis
200
STOP, STOP2
STOP: Chronic transfusion reduces stroke in SCD patients with elevated TCD velocity.
STOP2: Stopping transfusion restores that risk...
201
Storage lesion trials
ARIPI - Neonates
ABLE - ICU
RECESS - Cards Surg
TOTAL - Children
INFORM - Adult inpt
202
WENDT study
No prophylactic plt transfusion causes more CNS bleeding.
203
TOPPS study
Prophylactic plt transfusion confer more benefits to chemo/AML than Auto HSCT
204
PLADO
Smaller ppx plt transfusion also improve outcomes, but have to be dosed more frequently
205
Immune vs non-immune platelet refractoriness (features, not examples)
Immune: Counts drop faster. 20% of cases
Non-immune: Counts decrement on order of 1-24hrs. 80% of cases.
206
HLA platelet matches
A - Identical
B1U - 1 antigen unknown or blank
B1X - 1 cross-reactive group
C - 1 mismatch
D - 2+ mismatches
207
PROMMT, PROPPR
Adult traumas have better outcomes with 1:1 pRBC:FFP than >1
208
Fibrinogen levels in pregnancy
6g/dL
209
What are the main tools of PBM programs?
Identifying and managing anemia
Using blood-sparing techniques
Blood utilization feedback
Clinician education
210
How can pre-operative anemias be treated?
Oral or IV iron.
Do not use EPO agonists, due to thrombotic events.
211
For whom is autologous donation recommended?
Patients with rare blood, Jehovah's witnesses
Not favored in general--resulting anemia increases likeliness of transfusion, alternately many units are junked.
212
Post-op blood recovery
Can collect from drains and wounds, but only for major operations and with washing.
Resulting blood has low crit (20-30%) and has activated factors and junk.
213
Methods to influence physician ordering behavior
1. Education
2. Implementing evidence-based guidelines
3. Reminder at POE (CPOE, CDS)
4. Audits--prospective or retrospective (compare to peers)
214
Forms of blood auditing
Prospective: Usually for housestaff. Good outcomes, but toilsome.
Concurrent: Consultative, usually actually retrospective within 12-24hrs.
Retrospective: Larger scale, should tie to specific ordering providers?
215
How can hemolysis trigger DIC?
Red cell membrane fragments are thrombogenic
Antigen-antibody complexes may trigger factor XII/kinins
Complement/TNFa/IL-1 increase TF expression
216
Why should blood centers be notified of suspected septic transfusion reactions?
To quarantine other donor units
217
Treatment for FNHTR
Stop transfusion
Tylenol
Meperidine/Demerol if rigors
218
Causes of anaphylactic transfusion reactions
IgA
Haptoglobin
C4
(transient donor antigens, eg. Peanut)
219
Vitals and lab findings in TRALI
Severe hypoxemia (<90% on RA, PaO2/FiO2 <300)
May have mild fever
May be hypotensive
Transient neutropenia (due to accumulation in lungs)
220
Hypotensive transfusion reactions
Defined as drop of systolic BP -30mmHg or <80. In children, may define as 25% drop.
Kinin effect caused by ACEi, bypass circuits, and recent prostatectomy
221
TA-GVHD: Timing
Onset in 3-30d
Death in 1-3wks from onset
222
Treatment of PTP
IVIG first-line
Steroids, PLEX second line
223
HDFN caused by >Kell
Fewer reticulocytes / precursors
Less bilirubin
224
What causes hydrops fetalis?
Impaired oxygen delivery suppresses production of albumin, leading to high volume heart failure.
225
What critical level on fetal MCA doppler sonography indicates fetal anemia?
At least 1.5x the MoM
226
What is the quantitative limit of the Rosette test?
Detects fetomaternal hemorrhage IN EXCESS OF 10mL
227
Antibodies in FNAIT
HPA-1a (>> -1b)
HPA-5b
HPA-4b (asians)
228
Management of ITP in pregnancy
Supportive for mother, can consider IVIG, PLEX, etc.
No treatment needed for fetus (thrombocytopenic, but rarely bleed)
229
VLBW, ELBW
VLBW - 1500g at birth
ELBW - 1000g at birth
230
What drives the nadir of hemoglobin seen in newborns and especially pre-emies?
Depression of liver EPO after birth
231
What can be waived in neonatal pre-transfusion testing?
Second ABO/Rh and antibody screen is waived before 4mo of age?
232
Neonatal RBC indications
<20% crit
<30% if requiring oxygen, or tachycardic, or low weight
<40% if on ECMO or with congenital heart disease
233
Infant blood exchanges: Technique, replacement fluid, removal performance?
Can be done with one access (push-pull) or two (simultaneous)
Reconstitute major compatible RBCs with minor compatible FFP. CMV-neg, HgbS-neg.
Standard 2x TBV removes 80% of native RBCs and 50% of bilirubin
234
Neonatal polycythemia
Seen in babies of diabetic mothers. Crit may exceed 65%!
Causes CHR, flow abnormalities >> treat with blood exchange at lower crit.
235
Platelet major antigens
HPA-1a/b (GpIIIa)
HPA-2a/b (Gp1ba)
HPA-3a/b (GpIIb)
HPA-12 (Gp1bb)
Note: A > B, always
236
Where are A and B substance carried on platelets?
On GpIIb and PECAM-1 (CD31)
237
In what setting can HPA-2a/b or HPA-12 antibodies be seen?
In Bernard-Soulier (these make up Gp1b)
238
Treatment for FNAIT
IVIG
Antigen-compatible transfusion (consider washed maternal antibodies)
239
How are the antibodies in ITP identified?
Most testing looks at reactivity of washings/eluates from patient platelets
240
Major granulocyte antigens
HNA-1a/b (FcyRIIIb) - Most implicated in NAN
HNA-3a/b (CTL2) - Most implicated in TRALI
Note: Neutrophils do not express ABO/Rh.
241
Neonatal alloimmune neutropenia
Usually arises from maternal antibodies against HNA-1a/b.
Can result in life-threatening infections
Treat with IVIG, G-CSF, PLEX. Treat infections...
242
Class I MHC
Composed of 3 alpha chains (chr 6) and an extracellular beta-2-microglobulin domain (chr 15).
Ubiquitous, except on most mature RBCs.
Presents antigens digested by LMP (in rER) and transported by TAP.
243
Class II MHC
Heterodimer of two alpha and two beta domains (all chr 6).
Restricted to antigen-producing cells.
Presents antigens when invariant chain "Ii" is replaced by endocytosed/extracellular peptides
244
Soluble HLA
Expressed in inflamed states
Reduced in malignancies
Presence in transfused units may promote TRIM; correlates with WBC load and unit age.
245
"W" HLA nomenclature
Formerly "workshop", now used to identify public antigens Bw4 and Bw6, and to distinguish HLA-C from complement
246
HLA nomenclature
Serologic : Allele : Silent mutations : Non-exonic mutations (with modifiers)
Modifiers: N (null), L (low), S (secreted), Q (questionable), C (cytoplasmic)
247
MHC "Class III" region
Region on chr 6 that contains:
Complement genes
21-hydroxylase
TNF
248
Class Ib "nonclassical" genes
HLA-E (role in NK cell surveillance)
HLA-F
HLA-G (trophoblasts)
HLA-H (misnomer for HFE? pseudogene)
249
What is the chance of a patient having an HLA-identical sibling given # of siblings n?
1 - (3/4)^n
250
Low-res vs High-res HLA PCR
Low-res only distinguishes serologic equivalents
Hi-res distinguishes alleles
251
What 10 sites must be matched in all HSCT?
HLA-A, B, B
HLA-DRB1
HLA-DQB1
(DQ is optional, some centers match)
252
For what solid organ transplants must ABO compatibility be respected?
Absolutely must match compatibility for heart, lung, liver.
Major mismatch is permissible in kidney other than A to O/B.
253
HLA allele disease associations
HLA-DQ2 - Celiac
HLA-DQ6 - Narcolepsy
HLA-DQ8 - T2DM
HLA-B27 - Ankylosing Spondylitis
HLA-B35 - De Quervain Thyroiditis
HLA-DR4 - Rheumatoid arthritis
HLA-DR8 - Juvenile RA
254
Plasma EXCHANGE vs plasmaPHERESIS?
Exchange is higher volume (>1L)
Pheresis is lower volume (<1L)
255
Rheopheresis
Double-filtration plasma exchange that removes large proteins to reduce plasma viscosity...in AMD.
256
Apheresis - Vascular access
Need at least 17ga access, 18ga return
257
In what settings is heparin preferred to ACD for apheresis anticoagulation?
Children
Metabolic alkalosis
Renal failure
In LDL apheresis using heparin precipitation method.
258
Plasma viscosity
Normall 1.4 - 1.8 centipoise, patients tend to become symptomatic above 4.0
IgM causes at 3g/dL
IgG causes at 4g/dL
IgA causes at 6g/dL
259
How does IDM testing of HSC units differ from blood products?
Must test same IDMs (including CMV if allo)
Positive test does not invalidate collection or use
260
What are the most important HLA loci to match? Why?
HLA-A, HLA-B, HLA-DRB
HLA-C, HLA-DQ
HLA-DP (optional)
Each mismatched allele increases mortality by 10%.
261
Maximal HPC-M donation
20ml/kg
Consider collecting an autologous red cell unit first...
262
HSC processing methods
Volume reduction (for minor mismatch)
Red cell reduction (for major mismatch)
Elutriation
Cell selection
Expansion
263
HPC cryopreservation
Preserve in 10% DMSO or 5% DMSO with 6% HES
Freeze at a controlled rate (-1C/min) until ~-20, then supercool to storage temp of -150C.
264
HPC viability assays
CD34+ - Most convenient and common
CFU - Takes weeks to result
Dye exclusion - Trypan, acridine, 7-AAD
265
DMSO reaction
Nausea, vomiting
Cough
Headache
Hypertension OR hypotension
266
Major incompatible HPC transplant
Associated with acute hemolysis, delayed red cell engraftment
(note: >40d without engraftment is pure red cell aplasia)
267
Minor-incompatible HPC transplant
Low risk of reverse hemolysis
Passenger lymphocyte syndrome: 5-16d later, can be severe
268
What tissue grafts are regulated under 21 CFR 1271?
Allografted non-vascular tissues: Bone, tendon, cornea, etc.
No autografts (unluess they are treated/modified)
Xenografts/xenotransplants
269
What are the responsibilities born by hospital tissue services?
Must handle, trace, detect, and report adverse events
Ensure bidirectional traceability
Inspect, ensure documentation (consents, records...)
270
What is the most common autograft tissue?
Craniotomy / skull cap
271
Male vs female sex mismatched HPC transplant
Female to male: More GVHD, less relapse
Male to female: More graft failure
272
Incidence of GVHD
Both acute and chronic GVHD have 10-50% incidence
Best predictor of chronic GVHD is acute GVHD...
273
HPC-A versus HPC-M
HPC-A: Faster engraftment, more GVHD
HPC-M: Slower engraftment, more red cell contamination
274
Best predictors of successful harvest
Young age
No history of chemo, radiation
Use of combined mobilization regimen
275
Transfusion support in HSCT
In general: Avoid red cell types that will lyse, and avoid plasma types that will attack the graft.
Bidirectional mismatch: Give O/AB
276
HPC infusion
Thaw at bedside at 37C
Infuse as rapidly as tolerated; unit must be infused within 1hr of thaw
277
Cord blood characteristics
80-100mL, contains 2-4 x 10^6 CD34+ cells.
OK for use in patients up to 45kg.
278
Reduced intensity conditioning
Less myeloablative regimen approved for use in patients who cannot tolerate full ablation due to medical comorbidity.
279
Donor Lymphocyte Infusions
Post-transplant lymphocytes, given in cases of relapse to re-induce remission.
Indications: CML > AML > ALL > Lymphoid malignancies
280
Mechanisms of RhD loss
281
When does ABH expression fully mature?
2-4yo ; this is generally true for all carbohydrate antigens
282
How to distinguish RhIg from native anti-D?
Best: Allotyping (not widely available)
Lucky: Identify >D at IS (IgM component)
Worse: Titers (NOT reaction strength!)
283
Factors worsening kernicterus
Acidosis
Prematurity
Hypoxemia
Hypoalbuminemia
284
Bilirubin, hemoglobin absorption wavelengths
Bilirubin: 410nm
Hemoglobin: 450nm, but has overlap at 410nm (must correct)
285
HLA association in PTP/FNAIT
Patients with HLA-DRB3*0101 are more likely to form anti-HPA-1a
286
Treatment for FNAIT
287
Serologic IDMs
Test individually. If positive, repeat in DUPLICATE. 2 of 3 is "RR".
If RR, junk unit. Donor may be deferred depending on confirmatory test results
288
NAT testing
Any positive result kills a unit and defers a donor.
Tested in minipools of 16-24 (exception: WNV is individual)
289
CMV transmission rates
CMV-safe (LR): 2-3% transmission
Seronegative: 1-2% transmission
290
When should autologous blood products undergo IDM testing?
If the product is to be shipped between facilities
291
HIV screen
Usually serology + NAT. p24 antigen testing can be done, but confers no benefits over NAT.
9-day window period (25d prior to implemention of NAT or p24)
292
HIV confirmatory testing
Western blot
2 bands of: gp41, p24, gp120/160
293
HBV screen
HBsAg
Total HBcAb (IgM, IgG)
HBV DNA NAT
~28d window period
294
HCV screen, confirm
HCV RNA
Serology (IgG only)
8 day window period
Confirm: RIBA
295
HTLV screen & confirm
Screen: Serology-only (cannot distinguish types)
Confirm: Western blot
296
Hepatitis E
No screening test currently employed in US.
Note only genotype 3 has been described as a TTI
297
Syphilis screening
Start with nontreponemal (sensitive, not specific). If positive, may not have to junk unit.
Continue with treponemal (FTA, ABS etc). If positive, junk unit and defer for 12mo and require treatment
298
WNV testing
Screen: ID NAT, only in areas where activity is high?
299
Chagas screening
EIA - One-time test per donor
300
Babesia testing
None approved by FDA. IF and NAT tests do exist.
Only defense is history/questionnaire...
301
Parvovirus as a TTI
Famously resistant to inactivation methods. Can be found in virtually all lots of pooled plasma derivatives.
However, rarely causes infections. Titers below 10^4 IU/mL are acceptable and don't cause infection.
302
Red cell INTERCEPT
Uses amustaline and glutathione, rather than methoxypsoralen
303
Most common causes of transfusion mortality
1. TRALI
2. TACO
3. AHTR
304
How to distinguish AHTR from septic transfusion reaction?
No good clinical features besides hemolysis; rely on lab workup.
Consider the transfused product type--any red cell volume?
305
TRALI is ___ compared to other lung injuries
Implicated products in TRALI include ___
SD treatment ___ risk of TRALI
Less fatal than other lung injuries
All plasma products (really all blood products) have been implicated
S/D treatment somehow confers less risk of TRALI
306
Treatment of TACO
Stop transfusion
Set patient UPRIGHT
Support ventilation
Diuretics
Consider MICU transfer?
307
Main symptoms in AHTR
Fever is most reproducible
Hypotension #2
308
Causes of DHTR
Usually Kidd antibodies
Next: Kell, Rh, Duffy
309
Iron content of pRBC unit
250mg
310
Acute pain transfusion reaction
Affects trunk, proximal extremities
Associated with leukoreduced units
No clear relationship to HbSS?
311
In what setting does air embolism most commonly occur?
Operative settings, especially with rapid infusers and intra-op blood recovery (cellsaver)
312
Why does Yersinia persist in pRBC transfusions?
Psychrophilic
Prefers low calcium, high iron environments
313
Leukocyte-transmitted TTIs
Plasma-transmitted TTIs
Leukocyte: CMV, EBV, HHV8, HTLV
Plasma: HAV, HBV, HCV, parvovirus, syphilis
314
Deferral periods for...
1. Malaria
2. Zika
3. Ebola
4. Chagas
5. Babesia
6. WNV
1. Malaria - 3yr
2. Zika - 4wk
3. Ebola - Indefinite
4. Chagas - Indefinite
5. Babesia - Indefinite
6. WNV - 120d
315
Viral transmission risks
HBV - 1:500k
HCV - 1:2M
HIV - 1:2M
HTLV - 1:3M
WNV - 1:7M
316
HIV re-entry
Most common: RR+, but negative confirmatory and NAT >> re-test at 8 weeks. If all negative, then re-entry OK
317
HTLV, HCV long term sequelae
HTLV: 2-5% develop ATLL. <1% develop TSP/HAM (HTLV-1 only)
HCV: 80% develop chronic hepatitis!
318
TT-Syphilis
Not seen in many decades
Presents as a fulminant second-phase infection
319
Malaria chronicity
P. Malariae - May persist asymptomatically for life
P. Vivax - 7 years
P. Ovale - 5 years
P. Falciparum - 5 years (really?)
320
vCJD vs CJD
CJD - Older age of onset. Transmission never proven via blood products
vCJD - Younger age, less classic EEG findings. Transmission has been confirmed.
321
Chagas - Features, diagnosis
Can be transmitted between humans vertically or via transfusion (platelets).
Increasing in prevalence in US due to migration trends.
Survives freezing in DMSO!
Diagnosed with EIA
322
WNV - Characteristics, syndrome
Birds are reservoir, humans are dead-end host
80% of infected are asymptomatic
20% develop fever and viral prodrome
<1% develop meningo/encephalitis
323
For what infection must the next of kin be notified from a positive donation?
HIV
324
Strongest platelet agonist
Thrombin
325
TT vs reptilase
Both are sensitive to hypo/dysfibrinogenemia, fibrin degradation products
TT is sensitive to heparin, whereas reptilase directly cleaves fibrinogen.
326
Hemophilia A/B in women
Usually seen in Turner syndrome or in extreme lyonization
327
Type IIb VWD
Mutation in GP1b binding site (INCREASED activity)
Loss of HWM multimers
Sine qua non: Low dose RIPA+
DDAVP is contraindicated >> thrombocytopenia
328
Factor VIII inhibitors
Usually IgG4
Manifest in older patients, can cause severe bleeding
Treat with steroids, PLEX. Overwhelm weak inhibitors, bypass strong inhibitors.
329
Warfarin-induced skin necrosis
Due to short-term protein C deficiency; can treat with protein C concentrates.
330
Platelet aggregation patterns
Glanzmann - Responds ONLY to ristocetin
Bernard - Does not respond to ristocetin
331
Factor V leiden
Mutation in factor V (usually R506L) that prevents APC from cleaving
332
Wiskott aldrich
Chediak higashi
Wiskott: XLD, thrombocytopenia + eczema + immunodeficiency
Chediak: AutRec, albinism + neutropenia + inclusions
333
Natural anticoagulants in DIC
C, S, AT-3 all fall in DIC.
Low levels of AT-3 are associated with worsened mortality
334
Type 2N VWD
Mutation in fVIII binding site. Presents like hemophilia A with no evidence of inhibitor, yet responses to factor 8 repletion are unsatisfactory.
335
Factor half-lives
Factor 7: 4-6hrs
Factor 8: 12hrs
Factor 13: 1 week
336
Platelet GpIIa/IIIb inhibitors
Abciximab, tirofiban, eptifibatide
Reversible with platelet transfusion
337
MG antibodies
Usually directed at acetylcholine RECEPTOR (not esterase!)
Other antibodies: Anti-MuSK (muscle specific kinase)
338
Treatment of GBS
IVIG, PLEX
Steroids not helpful...
339
PLEX for CIDP
One treatment results in 10-14d response. Slows demyelination of PERIPHERAL (not central) nerves
340
PLEX for anti-GBM disease
Note: Goodpasture's refers to anti-GBM with both renal and pulmonary involvement
Start PLEX early to preserve renal function. If ESRD, only do PLEX for pulmonarry hemorrhage.
341
PLEX in FH
Does confer some benefit, though LDL pheresis is likely ebtter?
342
How does hypomagnesemia worsen hypocalcemia?
Low magnesium levels inhibit PTH release
343
ECP ASFA categories
CTCL: Cat I
GVHD: Cat II
Transplant rejxn: Cat II
344
Metabolic effects of citrate
Hypocalcemia
Hypomagnesemia
Metabolic alkalosis
>> hypokalemia
345
HLA parentheses
Indicates split of a parent antigen
eg. HLA-B44(12) indicates a split of parent antigen 12
346
European vs american leukoreduction
European is more stringent (1 x 10^6 max per unit)
347
Reverse TRALI
Recipient antibodies reacting with donor WBCs. Very rare.
348
Tissue vendor qualification needs
FDA registration
Accreditation
QA resources
Inspection findings
Adequate supply
Contractor should verify qualification annually.
349
Tissue donor assessment
Medical evaluation: Records, interview
Labs
Reports: Autopsy, police
Physical assessment
350
When can allogeneic HPC donors be tested for IDMs?
Up to 30d before donation, and up to 7d after donation
351
Banked tissue storage and expiry
Most tissues last for 5 years if either stored at -40C or lyophilized and kept at RT.
Most tissues last 5 days at fridge temperature (1-10C)
Exception: Corneas and skin last 14 days.
352
Bone grafts
Cortical: needs protection. Slower
Cancellous: induces more inflammation
Freezing does not affect mechanical properties
353
Tissue sterilization
Ethylene oxide, irradiation
354
What is a "lot" of donated product?
Product arising from one donor, in one donation setting
355
Ambient vs room temperature?
Room temperature specifically refers to 20-24C.
Ambient just means any routine temperature is tolerated.
356
Tissue allograft record retention period
10 years
357
ABO confirmation of organ donors
Need 2x, same as blood
358
HIV window period
22d (serologic, non-p24)
10d (NAT, p24 antigen)
359
How much time is allowed for notification of recipients in lookbacks?
120 days to notify recipient / ordering physician
(conflict: 12 weeks for HIV/HCV? inform next of kin if HIV)
360
Do market recalls or market withdrawals constitute BPD / FDA reportables?
Both
361
In what settings is a patient ineligible for EXM?
Only one type on record
Any ABO discrepancy
Any significant antibodies
362
Who can receive RhIg for treatment of ITP?
Only non-splenectomized, RhD+ patients.
Rationale: RhIg causes red cell coating which competes with coated platelets for removal in RES.
363
RhIg dose in ITP
If Hgb > 10: 50-75 ug/kg
If Hgb < 10: 25-40 ug/kg
364
FNAIT incidence (current, subsequent pregnancies)
1:2000 (!)
Occurs in first pregnancy, tends to recur as bad or worse.
365
HLA-DRB3*0101
HLA allele associated with higher rate of anti-HPA antibody formation (eg FNAIT)
366
Kleihauer-Betke test
Acidify smear with citric acid to denature/elute HbA.
Count 2000 cells
Problems: Difficult to interpret (maternal F cells stain equivocally).
367
Rosette test
Only valid in RhD- mother with RhD+ baby
Uses R2R2 ficin-treated indicator cells.
Detects down to 10mL FMH.
368
Del
Rare RhD+ phenotype in asians, with as few as 22 copies of RhD per RBC. Need elution to detect.
Does not need RhIg.
369
HDFN incidence
1:10,000
370
Hydrops fetalis
Caused by fetal portal hypertension (generally due to erythroblastosis) suppressing fetal hepatic synthesis of albumin >> high output heart failure.
371
Effect of ABO incompatibility on HDFN
Protective--fetal cells are cleared more quickly and less likely to trigger immunization
372
Transfusion threshold for IUT
Fetal Hct < 30%
(determined by PUBS, have product available on-hand to immediately reflex to IUT)
373
Octaplas
Pooled S/D-treated plasma. Reduces most pathogens, even includes a prion removal step.
Decrease in protein S and alpha-2-antiplasmin (still >40% activity).
Somehow has no detectable HLA antibodies.
Once thawed, lasts 24hrs at 1-6C (as FFP) or 8hrs at RT!
374
INTERCEPT
Platelets, plasma: Psoralen + UV-A (320-400nm), with adsorption step. Full plasma factor recovery, some platelet losses. Contraindicated in psoralen sensitivity, phototherapy.
RBCs: Amustaline (alkylator) and glutathione (rescue). In trials in US...
375
THERAFLEX
THERAFLEX-MB: Methylene Blue treatment. Doesn't penetrate WBC >> needs leukoreduction.
THERAFLEX-UV: UV-C only, no additive. Proteins are unaffected.
376
MIRASOL
Riboflavin + UV illumination.
Only used in EU, para-site rich endemic regions in studies.
377
CCI formula
(Platelet increment x BSA) / #plts transfused
378
PTP - Incidence, symptoms, treatment
1:100,000, mainly affects women (HPA-1a).
Severe thrombocytopenia, may also present with inflammation/bronchospasm. Bystander plt loss.
Tx: IVIG, steroids. Resolves in 2-3 weeks, but has 20% mortality.
379
Filtration pore sizes
Platelets - 3um
RBCs - 7um
Lymphs - 10um
Grans - 13um
380
TTP treatment target, adjunctive therapies
Exchange until plt > 150k/uL x 2 days, normalized LDH and mental exam.
Adjuncts: Steroids, vincristine, splenectomy. Rituximab (reduces relapses)
381
Weakness of apheresis platelets over WBD platelets
Higher incidence of minor-incompatible hemolysis (single donor, rather than averaged pool)
382
Weaknesses of PCR
Misses large rearrangements
Relies on sequence primers, so can miss novel mutations.
383
In what settings can prozone effect cause false negative antibody screen results?
Hyperviscosity (paraprotein)
Cryptococcus, plasmodium, syphilis infections
384
HDFN due to Anti-G
Uncommon; titers rarely get high enough.
Anti-D worse than Anti-C worse than Anti-G.
385
Main cause of death in HbSS
Acute Chest Syndrome
386
Splenic sequestration
HbSS complication of CHILDHOOD.
Life threatening, treat with transfusion and splenectomy.
387
DIIHA - Incidence, types
1:100,000
Haptens: Needs pre-treatment. Slow hemolysis
Immune Complex: No pre-treatment. Fast hemolysis
Autoantibody induction: Like warm auto
Non-immunologic protein adsorption: Insignificant
388
Passenger lymphocyte syndrome
Occurs +2 weeks from transplantation of lymphocytes.
Self-limiting, will decrease in titer and severity over time
389
Causes of donor cell pseudo-hemolysis
Heat/cold damage - <3C, >50C
Osmotic damage (wrong carrier fluid)
Extracorporeal damage, mechanical damage
Bacterial contamination
G6PD donor (mild transient lysis upon infusion)
390
Anti-E
Can cause HTR, or rarely HDFN.
Can have an IgM component detectable at IS (so too can anti-C).
391
Anti-c
Can cause severe HTR or HDFN.
392
Anti-e
Most common autoantibody specificity.
393
Platelet transfusion lifespan
Not more than a few days in best case, but abnormally short in thrombocytopenic patients due to -7.1k/d fixed losses (maintenance of vascular endothelium)
394
ABO determination for organ transplant
UNOS requires 2 types for both donors and recipients.
395
Clotting factor concentrate deferrals
None--no deferrals for fractionated products anymore
396
Open vs automated deglyc process
Open: Final product should be in 0.9% NaCl and 0.2% dextrose. Not sterile, outdates in 4/24hrs.
Automated: End product is suspended in AS-3 and is good for 14d fridge-temp.
397
NovoSeven
Short-lived, requires dosing every few hours.
Not actually associated with thrombosis?
398
HPA-1a vs 1b
1a (98%)
1b (2%)
399
Polycythemia TP goals
Target a goal of <45% Hct in white men (?!), <42% in everyone else.
400
Idaricizumab
Dabigatran reversal agent
401
Andexanet alfa
Direct Xa inhibitor reversal agent (for apixaban, rivaroxaban)
402
Emicizumab
Bypass agent in factor 8 inhibitors. Forms the "tenase", approximating fX and fIX, thereby replacing the role of fVIII.
403
1. Type 2B
2. Type 2M
3. Type 2B
404
Hemochromatosis TP targets
Initiate for serum ferritin >300/200 for men/women, target goal of 50?
405
Mobilization regimens
G-CSF: 2-day dose starting 5 days out.
GM-CSF: Don't use (inferior to G-CSF, side effects)
Plerixafor: 12hr peak
Chemo: 14d peak?
406
Liquid plasma: When to separate, when expires?
Can be separated from WB at any time, but it expires 5 days after that of the whole blood.
407
Neonatal/pediatric blood dosing
RBC: 10-15mL/kg >> +2-3g/dL
FFP: 10-15mL/kg >> +15% factor activity
PLT: 5-10mL/kg >> +50k
CRYO: 1u/10kg >> +50mg/dL
408
Topical bovine thrombin
Associated with formation of factor V inhibitors.
Supplanted by topical fibrin sealants.
409
BARC
A neoantigen formed in the most common form of partial D (D-VI)
410
RHD loss mechanisms by race
Whites: RHD deletion
Blacks: Point mutation, partial deletion, or recombination event
Asians: Pseudogene (but probably actually DEL)
411
GPA
cANCA
PR3
412
Factor 8 dosing
kg x delta-activity / 2
May need to dose twice in 24hrs
413
Factor 9 dosing
kg x delta-activity
414
vWF dosing
kg x delta-activity
415
Anticoagulant deferrals
Piroxicam - 2d
Oral anticoagulants - 2d
Prasugrel, ticagrelor - 7d
Warfarin - 7d
Heparin, Fondaparinux - 7d
416
Teriflunomide
2yr deferral
417
Maximum radiation dose
50 Gy
418
Apheresis collection has a higher/lower reaction rate than WB collection
Lower
419
Platelet volume reduction
Need at least 85% recovery
420
pRBC, plt content requirements
pRBC: >60g in at least 95% of units
Plt: >3 x 10^11 in at least 90% of units
421
Double-red donation requirements
At least 130lb (male) or 150lb (female). Crit at least 40%
Most donation must be at least 30% crit
422
Confirmatory IDMs
HBsAg has confirmatory
Anti-HIV has confirmatory
Anti-HCV has confirmatory (RIBA no longer available)
423
Deferral re-entry time (HIV, HCV)
HIV: 8 weeks
HCV: 6 months
424
IDM testing in leukocyte-rich, reproductive tissues
Leukocyte-rich: CMV, HTLV
Reproductive: Gon/Chla
425
NASBA
TMA, except that it uses RNAse H to degrade RNA template, while TMA uses RT.
426
IgG subclass ability to bind phagocyte FCR
1 = 3 > 4 > 2
427
DAT sensitivity
500 IgG per red cell
1000 C4d per red cell
428
A2 platelets
Actually do not express any A substance.
429
FOCUS
8 vs 10 noninferior in hip frx
430
RhIg in thrombocytopenia
Give for ITP, RhD incompatible in young women. Give IV, not IM (hematoma)
431
3- vs 4- factor PCC
3: 2, 9, 10
4: 2, 7, 9, 10 (eg. Kcentra)
432
Cryopreserved HPC shpiping
Shippers should hold <150C for 2 weeks. Do not X-ray. Use weight to assess remaining LN2.
433
UCB IDM
Test mother
434
Allografted tissues requiring ABO/HLA matching
Vessels, those containing red cells or marrow, RhD- mom recipients
435
Fridge temperature control
Continuous monitoring, recording q4hrs
436
Max platelet collection
Max 6x10^11 in 7 days?
Max 2 sessions in 7d, 24 in 1yr
437
Plt LR
<8.3 x 10^5 WBC in at least 95% of units
438
RBC Deglyc recovery
At least 80%
439
Antigen negative unit confirmation
Not necessary; no need to re-test
440
MTP definition
Patient blood volume in 24hrs
441
Frozen rejuvenated expiry
10yrs (CPD, CPDA-1)
3yrs (AS-1)
442
Cryo single unit expiry after thawing
6hrs
(4hrs is for open pools)
443
COVID Vx deferral
If live-attenuated, 14 days. If uncertain, 14 days.
444
Deferral: Sex with HBV/HCV positive
1yr (has not been reduced to 3mo, like HIV has)
445
Document review interval
2 years
