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

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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.

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3
Q

A

A

A

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4
Q

What REGULATORY AGENCIES oversee transfusion medicine?

A

FDA, CMS

(all others are professional orgs, eg AABB or JCo)

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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.

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6
Q

Juran’s Quality Trilogy

A

Planning
Control
Improvement

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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

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8
Q

What must be reported in the validation of an LDT?

A

Sensitivity, specificity
Accuracy, precision
Range, reference intervals

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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.

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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

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11
Q

Change control

A

Preventing unplanned changes to processes

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12
Q

Who assumes all responsibility for contracted work?

A

The contracting facility (NOT the contractor, or manufacturer)

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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.

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14
Q

How frequently must customer feedback be collected in contract agreements?

A

Not defined by regulation, but often is good.

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15
Q

How many crossmatch PTs can you fail before being shut down?

A

Shutdown after second unsuccessful PT (unsatisfactory).

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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.

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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.

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18
Q

Pareto chart

A

Bar graph used as a cause analysis tool.

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19
Q

Ishikawa diagram

A

AKA fishbone diagram, used to identify causes of error or manufacturing defects.

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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.

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21
Q

Who can evaluate competency assessment?

A

No special person is required, but one cannot audit their own work.

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22
Q

SQUIPP

A

Safety
Quality
Identity
Potency
Purity

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23
Q

Distinguish between remedial action and corrective action

A

Remedial action alleviates symptoms of nonconformance
Corrective action addresses the cause of nonconformance

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24
Q

In what settings is licensure required for a blood center?

A

When engaging in interstate commerce

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25
Q

In what setting can a blood service be exempt from FDA registration?

A

No collection or major product manipulation.

OK: Irradiation, pooling, leukoreduction.

Must still be CLIA-certified!

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26
Q

What are the required components of a facility safety program (standard hazard model)?

A

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

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27
Q

What regulates facility fire prevention? What are the required components?

A

NFPA Life Safety code
Annual fire safety training
Fire storage cabinets
Extinguishers
Detection / alarm systems
Fire escape paths

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28
Q

Biosafety levels

A

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.

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29
Q

Biosafety cabinets

A

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…

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30
Q

What is the annual dose limit of radiation?

A

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

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31
Q

Food, Drug, and Cosmetic act

A

21 USC 301-399d

Regulates drugs, devices, and blood products. Establishes cGMP regulations.

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32
Q

Public Health Service act

A

Section 351 defines blood as a biologic, requiring licensing for interstate commerce.

Section 361 gives DHHS authority to minimize disease transmission.

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33
Q

Medical device classes

A

Class I - Lowest risk, general controls OK
Class II - Must be approved through 510k pathway
Class III - Most complex

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34
Q

FDA inspections

A

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.

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35
Q

What are the requirements for HCT/Ps to be regulated as a 361 product?

A

Must be minimally manipulated
For homologous use
Must not be mixed

Otherwise, more stringently regulated as a 351 (drug or device)

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36
Q

Deming cycle for continuous quality improvement

A

Plan, Do, Check, Act

System for process improvement. Plan changes, enact them, observe/report, and act on the outcome.

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37
Q

What national hemovigilance programs exist?

A

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

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38
Q

What tools exist for blood donor safety and reactions?

A

A blood donor working group does exist; published Donor Hemovigilance Analysis and Reporting Tool (HART).

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39
Q

What are the most common donor reactions?

A
  1. Vasovagal
  2. Local injuries (incl. nerve, artery)
  3. Apheresis reactions
  4. Allergy
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40
Q

Donor vitals

A

180-90 / 100-50
100-50
<37.5 C / 99.5 F
At least 16yo (depending on state)
110lb (50 kg)

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41
Q

Post-draw donor info permittance

A

24 hours to get full info

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42
Q

Hemoglobin minimum for donation

A

Men: 13g/dL
Women: 12.5g/dL
*May 2015 ruling permits collection of women with 12-12.5g/dL with special procedures.

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43
Q

POC Hemoglobin determination

A

POC Spectrophotometry preferred, not copper sulfate (quantative). Earlobe samples not permitted.

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44
Q

Post-delivery deferral

A

6 weeks

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45
Q

Malaria deferrals:
- Travel to endemic area
- Personal history of infection
- Residing in endemic area

A

Travel - 1yr
Personal Hx - 3yr
Residing - 3yr

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46
Q

When should blood donors be informed of their positive IDM tests?

A

8 weeks

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47
Q

Deferrals: Cancer

A

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.

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48
Q

Deferrals: Teratogenic drugs

A

Etretinate - Forever
Soriatane - 3 years
Dutasteride - 6 months
Finasteride - 1 month
Accutane - 1 month

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49
Q

Hep B vaccine impact on IDM testing

A

Can cause a falsely positive surface antigen (HBsAg) up to 18 days from vaccination.

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50
Q

Donation intervals

A

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

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51
Q

What is the usual hemoglobin content of a pRBC unit?

A

60g per unit

(95% are required to be 50g or above)

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52
Q

Deferrals: CJD

A

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

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53
Q

What is the most common cause for blood donor deferral?

A

Anemia

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54
Q

Abbreviated DHQ

A

Streamlined donor questionnaire that can be used for patients who have completed the full DHQ twice, and have donated in the past 6 months.

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55
Q

Directed donation requirements

A

Same as general allogeneic requirements; irradiate the unit.

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56
Q

Requirements for autologous blood collection

A

Order from MD
Minimum Hgb 11g/dL
72+ hr gap before surgery
No bacteremias
No severe cardiac disease?

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57
Q

Deferral: Vaccines

A

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)

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58
Q

IDM testing in directed donation

A

Only required every 30d, rather than with every donation.

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59
Q

Maximum plasma and RBC losses permitted in platelet donation

A

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.

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60
Q

Requirements & exemptions for source plasma donation

A

Must have total protein >9g/dL. Must be medically assessed. Quantitative Ig q4wk?

Exemption: Malaria deferrals do not apply.

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61
Q

WBD donation duration

A

Usually finish in 10min, must finish by 20min (else fear of coag abnormality).

Can phleb twice to achieve goal!

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62
Q

Low volume collections

A

Less than 90% of target goal (405, 450mL). Can use pRBCs, but must junk plasma products.

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63
Q

Diseases treatable with therapeutic phlebotomy

A

Polycythemia
Hemochromatosis
Porphyria cutanea tarda

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64
Q

Under what settings can therapeutic phlebotomy products be used for allo transfusion?

A

Follow same eligibility criteria
Need a medical order
Cannot charge donor for service

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65
Q

Arterial donor stick

A

Pain, rapid donation (sensitive)
Bright red blood (fairly sensitive)
Pulsatile needle (insensitive)

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66
Q

Nerve donor injury

A

Usually affects young women

Most are transient, nearly all resolve within 1yr.

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67
Q

ANH

A

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.

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68
Q

Cellsaver

A

Uses a filter, gentle (<150 torr) vacuum.

Can transfuse unprocessed (4hr RT) or after washing (4hr RT, 24hr cold)

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69
Q

How should veins be selected and prepared for phlebotomy

A

Prefer antecubitals. Avoid scarring and folds.

Clean thoroughly, and divert first 5-10mL of blood.

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70
Q

What is the weight-based maximum donation volume?

A

10.5 mL / kg

So, 70kg adult can donate up to 735mL

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71
Q

What testing must be performed on all donated blood products?

A

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

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72
Q

Maximum apheresis RBC donation collections

A

RBC, plus any one of:

Second RBC
Platelets
Plasma
Platelets AND plasma

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73
Q

Number of segments per unit

A

13-15

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74
Q

FFP, PF24 expiration?

A

1yr at -18C, or 7yr at -80C.

Once thawed, 24hrs at 1-6C, after which it becomes thawed plasma (4d at 1-6C)

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75
Q

What is still present in cryo-reduced plasma?
What is still present in PF24?

A

Cryo-reduced plasma: Actually, still a lot of everything, including fibrinogen (~200mg/dL)
PF24: 100% of factor 5 activity, 70% of factor 8 activity

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76
Q

How much fibrinogen is in a unit of cryoprecipitate?

A

According to standards, 250mg. Minimum 150mg.

Actually: 388mg per unit.

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77
Q

How quickly does factor 8 degrade at room temperature?

What patient factors affect factor 8 content?

A

10% per 2 hours
Group O patients have much less factor 8 than A/B/AB.

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78
Q

Max unagitated platelet storage time

A

24 hours

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79
Q

How can granulocyte yields be boosted from donors?

A

HES
Steroids
G-CSF

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80
Q

Leukoreduction: Requirements, validation, and causes of failure

A

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.

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81
Q

Who regulates nuclear materials? Which?

A

US Nuclear regulatory commission regulates labs that use Cesium (137) or cobalt (60) to irradiate products.

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82
Q

Irradiation: Consequences

A

Shortdate to 28d
Double potassium supernatant levels within 2 days (may want to volume reduce in peds)

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83
Q

What can be done while a unit is quarantined pending IDM testing?

A

Can still be processed into components.

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84
Q

Required labeling of blood products

A

Barcode, facility ID, donor lot, product code
ABO/Rh of donor
Additional labels for special processing
Tie tags for directed/autologous units

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85
Q

Transcription-Mediated Amplification (TMA)

A

Isothermal amplification method

Relies on reverse transcriptase to generate cDNA which is then acted on by DNA polymerase to make dsDNA.

Faster than PCR

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86
Q

How is the signal of nucleic acid amplification transmitted/detected?

A

Ethidium bromide (old)
TaqMan (fluorochrome and quencher)
FRET
SYBR (like ethidium; only works on dsDNA)

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87
Q

Antibody affinity vs avidity

A

Affinity: Binding strength at one epitope
Avidity: Combined binding strength of all binding sites on an antibody

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88
Q

IgG subclasses

A

IgG1 - Good at binding complement
IgG2 - Poor at binding complement
IgG3 - Good at binding complement
IgG4 - Does NOT bind complement

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89
Q

What blood group antigens are expressed on the X chromosome?

A

Xg (XG on X chr, CD99 on both X and Y chr)

Kx (women can have two populations!)

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90
Q

Capellini effect

A

Phenomenon wherein a C allele in trans to D reduces expression of D.

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91
Q

Kpa, Jsa

A

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.

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92
Q

In(Lu)

A

Dominant suppressor of lutheran blood group (KLF1). Also reduces expression of Indian antigens.

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93
Q

Rh-null

A

Mutation of RhAG on chr 6.

Hemolytic anemia with stomatocytes

Also loses LW antigens, most glycophorin B.

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94
Q

In a recently transfused patient, how should material be obtained for genetic testing?

A

Can obtain from peripheral blood (requires microcentrifugation to harvest reticulocytes)

Better to obtain buccal swab or buffy coat.

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95
Q

Where are most sugartransferases located in the cell?

A

Golgi complex

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96
Q

4 types of carbohydrate chains

A

Type 1 - Free-floating
Type 2 - Fixed to cell membranes
Type 3 - “Repetitive chain”
Type 4 - “Globoside”

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97
Q

When are ABO antigens detectable?
When are isohemagglutinins detectable?

A

Antigens: 5-6wks in utero
Antibodies: 3-6mo into infancy

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98
Q

A2 subgroup - Molecular features

A

About 200k molecules per RBC (compared to 1M in A1)

More reactive to Ulex Europeaeus lectin

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99
Q

B(A) phenomenon

A

B-sugartransferase with weak A-sugartransferase activity.

Note that A(B) exists too.

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100
Q

cisAB

A

Sugartransferase that can equally transfer A and B sugars.

If coinherited with a group O allele, results in “weak A, weak B” phenotype

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101
Q

How can solid tumors cause ABO discrepancies?

A

May secrete large volumes of soluble A/B/H, neutralizing reagent on forward type.

> > Ovarian, hepatobiliary, gastric…

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102
Q

Decreasing H antigen expression

A

O > A2 > B > A2B > A1 > A1B

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103
Q

Para-bombay

A

H-deficient secretor.

May make H, A/B soluble antigens, but should type as O and produce a weak anti-H.

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104
Q

i-adult

A

Seen in asian patients, resulting from autosomal recessive GCNT2 mutation.

Associated with congenital cataracts, HEMPAS

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105
Q

P phenotypes

A

P1 (expresses P, P1, Pk)
P2 (does not express P1; seen mainly in asians)
Pk1, Pk2 (no P, but Pk)
p (null, rare)

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106
Q

What are the biological features of anti-P1?

What can neutralize their reactivity?

A

IgM, rarely causes hemolysis

Neutralizable with hydatid cyst fluid, pigeon egg white

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107
Q

Anti-P/P1/Pk

A

AKA “anti-Tj(a)”

Causes abortions, enriched in Amish populations

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108
Q

FORS

A

Forssman antigen, a low-prevalence antigen attached to P that looks like A.

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109
Q

Relationship between RHD and RHCE

A

Probably arose from duplication event.

Note 97% homology and INVERTED orientation from one another

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110
Q

Cause of partial D

A

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.

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111
Q

Variant RHCE antigens

A

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.

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112
Q

Compound RH antigens

A

G (D+C)
f (c+e)

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113
Q

RHCE antibody most associated with HDFN?

A

> c tends to cause severe HDFN, while C/E/e do not.

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114
Q

Binding receptors for plasmodium falciparum

A

Glycophorins A/B
Glycophorins C/D (Gerbich)
Cromer
Knops

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115
Q

Mi(a)

A

Located on Gp.Mur, a defect glycophorin B.

Presence in some asians creates concern for HDFN, analogously to RhD.

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116
Q

Lutheran antibodies

A

Lu(a) not significant
Lu(b) can cause some HTRs, HDFN

Causes mixed-field agglutination

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117
Q

CD235
CD238

A

CD235 - MNS
CD238 - Kell

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118
Q

Kell null

A

Ko; Kx is preserved. May form anti-Ku which reacts to all Kell antigens.

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119
Q

Function:

Kell
Duffy
Kidd
Rh
MNS

A

Kell - Zinc endopeptidase
Duffy - Chemokine scavenger
Kidd - Urea transporter
Rh - Ammonia transporter, major cytoskeletal element
MNS - Bears sialic acid, links to Rh

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120
Q

Kidd-null phenotypes

A

Jk(a-b-) in some polynesians and finnish (>Jk3)

In(Jk) in Japanese from dominant inhibitor

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121
Q

Kidd antibodies

A

Usually IgG1/3. About half bind complement. Often evanesce.

Rarely cause HDFN

Implicated in acute renal transplant rejection

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122
Q

Diego antigens

A

Di(a) - Low frequency, seen in some asians.
Di(b) - High frequency.

Antibodies can cause HDFN.

Wr(a), Wr(b) part of system…ignore

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123
Q

Cartwright

A

Yt(a) - HIGH prevalence
Yt(b) - Low prevalence

AChE, bound to GPI anchor.

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124
Q

Xg(a)

A

Expressed in 90% of women, 66% of men

Antibodies are insignificant.

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125
Q

Dombrock

A

CD297 (ART4)

Do(a) < Do(b).
Others: Gy(a), Hy

Significant!

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126
Q

Colton

A

Aquaporin-1

Co(a) - HIGH frequency
Co(b) - LOW frequency

Significant!

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127
Q

Landsteiner-Wiener

A

ICAM-4

Bound to Rh, expressed more if Rh(+)

Strongly expressed on cord blood cells?

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128
Q

Gerbich

A

Glycophorin C/D

P. Falciparum receptor, bears sialic acid

Antibodies variably significant

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129
Q

Cromer

A

DAF/CD55 - GPI anchored

P. Falciparum binding receptor

Insignificant!

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130
Q

John Milton Hagen

A

HTLA group that is lost with age.

Prone to autoreactivity

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131
Q

VEL

A

High-prevalence antigen

Antibodies cause severe hemolysis! Need rare antigen-neg units.

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132
Q

Bg

A

Not an actual blood group – HLA Class I antigens

Bg(a) - B7
Bg(b) - B17
Bg(c) - A28

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133
Q

PEG

A

Enhancement media that excludes water. Enhances warm autoantibodies!

CANNOT centrifuge, else causes nonspecific agglutination. WASH.

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134
Q

RESt

A

Rabbit Erythrocyte Stroma

Removes cold autoantibodies (>I, >IH, but also D, E, Vel…)

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135
Q

How can sickle cells be separated from donor cells in vitro?

A

Use hypotonic saline – sickle cells are resistant to lysis

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136
Q

How can coated IgMs be removed from patient cells?

A

Use 0.01M DTT (denatures J-anchor)

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137
Q

ZZAP
Glycine/EDTA
Chloroquine

A

ZZAP - DTT + Proteolytic enzyme
Glycine/EDTA - Strips Bg, Kell
Chloroquine - Strips Bg, Rh

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138
Q

In vitro tests to assess antibody significance

A

Monocyte monolayer
ADCC
Thermal amplitude studies
Chemiluminescence?

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139
Q

DAT testing - Gel vs tube

A

Tube - Wash step required.
Gel - No wash step, more sensitive?

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140
Q

Elution

A

Concentrates coated antibodies.

Usually acid kits > solvent > heat or freeze/thaw

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141
Q

Lui Freeze-Thaw

A

Technique for eluting specifically ABO antibodies in neonatal DAT samples.

Uses very little blood&raquo_space; coat tube interior, freeze, thaw, then use the hemolysate supernatant.

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142
Q

PCH - Testing results

A

Presents with intravascular hemolysis with associated labs

DAT: C3+ (during crisis), IgG+ (generally)
Eluates negative.

Diagnose with Donath-Landsteiner test

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143
Q

Drug-related AIHA - 4 types

A

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

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144
Q

Requirements for re-issue of returned pRBCs

A

Seal intact
At least one segment attached
Between 1-10 degrees
Passed visual inspection

(no time limit)

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145
Q

Glycerol freezing

A

Can freeze slow with 40% glycerol (-80C)
Can freeze fast with 20% glycerol (-180C)

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146
Q

How and why should glycerol be removed in a thawed unit?

A

Causes in vivo or in vitro hemolysis (remains within the RBCs)

Need progressive wash cycles.

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147
Q

When should red cells be frozen?

A

Within 6 days of collection

Or, +3 days after expiration provided they are rejuvenated

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148
Q

Platelet pH limit

A

No lower than 6.2

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149
Q

Platelet storage lesion

A

Decreased pH
Activation from discoid to spherical shape
Shimmering/swirling in bag
Decrease in GP1b expression

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150
Q

Therapeutic plasma dose

A

10-15mL/kg

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151
Q

Cryo contents and recovery

A

Fibrinogen
Factor 8
Factor 13 (only 25% of FFP content)
vwF (only 50% of FFP content)
Fibronectin

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152
Q

Granulocyte unit contents

A

> 1 x 10^10 (10 Bil) granulocytes in 75% of tested units
3 x 10^11 platelets!
20-50mL RBC volume

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153
Q

HES side effects

A

Anaphylaxis
Pruritus
Decrease in vWF, factor 8 – Increased aPTT
Decrease in fibrinogen

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154
Q

What is pathogen reduction ineffective against?

A

Unenveloped viruses

Prions

Sporulated bacteria

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155
Q

Volume reduced platelets - Indications, expiry

A

For TACO, reverse compatibility in children

Expires within 4hrs (opened, RT)

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156
Q

Options for peds aliquoting

A

Aliquot to transfer bag – No change in expiry, if done sterile

Syringes - Generally considered an open method&raquo_space; 4hr vs 24hr expiry

*Aliquot from same primary container to reduce wastage

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157
Q

ABO prevalences across ethnic groups

A

All are O > A > B > AB

Asians have lowest rate of O overall
Native americans have highest rate of O overall

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158
Q

Causes of mixed field reactivity

A

Recent transfusion
Chimerism

ABO subgroups
Sd(a), Lu(a) antibodies

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159
Q

FUT genes transfer __-fucosyltransferase and are located on chr __.

A

L

Chr 19

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160
Q

Anti-H

A

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)

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161
Q

> I vs >IH

A

> 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?)

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162
Q

Griffonia simplificolia
Phaseolus lunatus

A

Both are B lectins

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163
Q

Saline replacement technique

A

For subtracting excess reverse reactivity due to rouleaux.

Incubate reagent cells, then wash and replace with saline to read.

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164
Q

P group pathogenic binding targets

A

P - Parvovirus
Pk - Shiga toxin, strep suis, HIV
PP, P1, PK, LKE - Uropathogenic E.Coli

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165
Q

When does P1 mature?

When is >P reactivity seen?

A

Matures at age 7

May be seen in P2 individuals, maybe in PCH, maybe in parasite infections.

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166
Q

Chido/Rodgers

A

HTLA

On C4 – Neutralized by plasma, but not serum

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167
Q

Sd(a)

A

Antibodies cause orange refractile agglutinates

Neutralizable with guinea pig urine

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168
Q

Causes of in vitro hemolysis

A

I
Lewis
Kidd
PP1Pk
Vel

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169
Q

Lewis phenotypes and antibodies

A

Le(a-b+) - Do not really make Le(a)
Le(a+b-) - Can make Le(b)
Le(a-b-) - Can make both

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170
Q

Brendemoen phenomenon

A

Forming >Le during pregnancy due to dilutional effect

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171
Q

Lewis - Pathogen binding

A

Leb - H. Pylori, norovirus

Note: Le(a-b-) have higher rate of candida infection?

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172
Q

Racial wiener haplotypes

A

White: R1 > r > R2 > R0
Black: R0 > r > R1 > R2

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173
Q

McLeod phenotype

A

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

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174
Q

HTLA groups

A

Chido, Rodgers
Knops
McCoy
York
Cost Sterling
John Milton Hagen (prone to autoreactivity)

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175
Q

Pre-transfusion sample labeling requirements

A

2+ identifiers
Identification of phlebotomist (doesn’t have to be initials)
Date of draw

Must be labeled at bedside.

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176
Q

Segment and T&S retention times

A

1 weeks minimum

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177
Q

Naturally occurring antibodies

A

ABH
I
P
Lewis
M and N

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178
Q

Causes of false positive DAT

A

In vitro coating, T-activation, use of colloidal silica

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179
Q

When can IDM testing be waived?

A

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
Q

Polyagglutinable antigens

A

Acquired: T, Tn, Tk, Tx
Inherited: Cad, Hb-Hyde Park, HEMPAS, NOR

181
Q

Arachis hypogaea
Salvia horminum

A

Arachis hypogaea (Peanut) - T, Th, Tk
Salvia horminum - Tn, Cad

182
Q

Joint Commission transfusion metrics

A

Rate of consent
Appropriate indication
Proper documentation
Pre-op anemia screening
Pre-op T&S testing

183
Q

Evans syndrome

A

ITP + AIHA

Smear may show giant platelets and spherocytes, but generally not schistocytes

Don’t transfuse if patient is stable

184
Q

Cryoprecipitate indications

A

Repletion of fibrinogen, factor XIII, factor VIII (if better options not available)

Uremia refractory to DDAVP

Topical fibrin sealant

185
Q

Granulocyte ANC requirements

A

Adult: <500
Pediatrics: <3000

186
Q

How long can a pre-op T&S hold last?

A

Up to 45d per standards

187
Q

How long and frequently do antibodies evanesce?

A

30% drop in 1yr
50% drop in 10yrs

188
Q

RBC storage lesion, viability requirements

A

Membrane changes
Decreased pH, decreased ATP
Decreased 2,3-DPG
Increased potassium, free hemoglobin

Need <1% lysis at expiration, also 75% 1d recovery

189
Q

What re-typing must be done upon receipt of blood products from a supplier?

A

Confirm ABO for any unit containing >2mL pRBC

Confirm Rh for any status labeled as RhD-neg

190
Q

C:T ratio

A

Units crossmatched versus actually transfused. Keep this at or below 2

Set MSBOS based on this per-op!

191
Q

Max blood warmer temperature

A

42C

Above&raquo_space; Hemolysis

192
Q

IV gauge for transfusion

A

14-22ga for adults
22-25ga for pediatrics (GO SLOW)

193
Q

What conditions must be met for a unit of blood to be issued?

A

Unit is available
Patient consented
Vascular access available
Transfusionist immediately available
Order is OK
Patient is pre-medicated

194
Q

Macroaggregate filters

A

Standard, 170-260um filter. Prime with saline!

195
Q

pRBC transfusion rate

A

Start at 2mL/min

Ok to increase to 2-4mL/min, but ideally target 2-4hr completion

TACO? Try 1mL/kg/hr.

196
Q

TRICC trial

A

Hgb threshold 7 vs 10 does not affect mortality

197
Q

TITRe2 trial

A

Cardiac patients do not benefit from Hgb 9 vs 7.5

*Controversial…

198
Q

Treatment of thalassemia major

A

Transfuse early in childhood to reduce EMH and facilitate growth.

Transfuse q2-4wks with a target Hgb of 9.

199
Q

Indications for SCD RCX

A

Severe ACS
Stroke
Hepatic sequestration
Maybe: TCD > 200, Cholestasis, MODS

No: Splenic or aplastic crisis

200
Q

STOP, STOP2

A

STOP: Chronic transfusion reduces stroke in SCD patients with elevated TCD velocity.
STOP2: Stopping transfusion restores that risk…

201
Q

Storage lesion trials

A

ARIPI - Neonates
ABLE - ICU
RECESS - Cards Surg
TOTAL - Children
INFORM - Adult inpt

202
Q

WENDT study

A

No prophylactic plt transfusion causes more CNS bleeding.

203
Q

TOPPS study

A

Prophylactic plt transfusion confer more benefits to chemo/AML than Auto HSCT

204
Q

PLADO

A

Smaller ppx plt transfusion also improve outcomes, but have to be dosed more frequently

205
Q

Immune vs non-immune platelet refractoriness (features, not examples)

A

Immune: Counts drop faster. 20% of cases

Non-immune: Counts decrement on order of 1-24hrs. 80% of cases.

206
Q

HLA platelet matches

A

A - Identical
B1U - 1 antigen unknown or blank
B1X - 1 cross-reactive group
C - 1 mismatch
D - 2+ mismatches

207
Q

PROMMT, PROPPR

A

Adult traumas have better outcomes with 1:1 pRBC:FFP than >1

208
Q

Fibrinogen levels in pregnancy

A

6g/dL

209
Q

What are the main tools of PBM programs?

A

Identifying and managing anemia
Using blood-sparing techniques
Blood utilization feedback
Clinician education

210
Q

How can pre-operative anemias be treated?

A

Oral or IV iron.

Do not use EPO agonists, due to thrombotic events.

211
Q

For whom is autologous donation recommended?

A

Patients with rare blood, Jehovah’s witnesses

Not favored in general–resulting anemia increases likeliness of transfusion, alternately many units are junked.

212
Q

Post-op blood recovery

A

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
Q

Methods to influence physician ordering behavior

A
  1. Education
  2. Implementing evidence-based guidelines
  3. Reminder at POE (CPOE, CDS)
  4. Audits–prospective or retrospective (compare to peers)
214
Q

Forms of blood auditing

A

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
Q

How can hemolysis trigger DIC?

A

Red cell membrane fragments are thrombogenic

Antigen-antibody complexes may trigger factor XII/kinins

Complement/TNFa/IL-1 increase TF expression

216
Q

Why should blood centers be notified of suspected septic transfusion reactions?

A

To quarantine other donor units

217
Q

Treatment for FNHTR

A

Stop transfusion
Tylenol
Meperidine/Demerol if rigors

218
Q

Causes of anaphylactic transfusion reactions

A

IgA
Haptoglobin
C4

(transient donor antigens, eg. Peanut)

219
Q

Vitals and lab findings in TRALI

A

Severe hypoxemia (<90% on RA, PaO2/FiO2 <300)
May have mild fever
May be hypotensive

Transient neutropenia (due to accumulation in lungs)

220
Q

Hypotensive transfusion reactions

A

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
Q

TA-GVHD: Timing

A

Onset in 3-30d
Death in 1-3wks from onset

222
Q

Treatment of PTP

A

IVIG first-line
Steroids, PLEX second line

223
Q

HDFN caused by >Kell

A

Fewer reticulocytes / precursors
Less bilirubin

224
Q

What causes hydrops fetalis?

A

Impaired oxygen delivery suppresses production of albumin, leading to high volume heart failure.

225
Q

What critical level on fetal MCA doppler sonography indicates fetal anemia?

A

At least 1.5x the MoM

226
Q

What is the quantitative limit of the Rosette test?

A

Detects fetomaternal hemorrhage IN EXCESS OF 10mL

227
Q

Antibodies in FNAIT

A

HPA-1a (» -1b)
HPA-5b
HPA-4b (asians)

228
Q

Management of ITP in pregnancy

A

Supportive for mother, can consider IVIG, PLEX, etc.

No treatment needed for fetus (thrombocytopenic, but rarely bleed)

229
Q

VLBW, ELBW

A

VLBW - 1500g at birth
ELBW - 1000g at birth

230
Q

What drives the nadir of hemoglobin seen in newborns and especially pre-emies?

A

Depression of liver EPO after birth

231
Q

What can be waived in neonatal pre-transfusion testing?

A

Second ABO/Rh and antibody screen is waived before 4mo of age?

232
Q

Neonatal RBC indications

A

<20% crit
<30% if requiring oxygen, or tachycardic, or low weight
<40% if on ECMO or with congenital heart disease

233
Q

Infant blood exchanges: Technique, replacement fluid, removal performance?

A

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
Q

Neonatal polycythemia

A

Seen in babies of diabetic mothers. Crit may exceed 65%!

Causes CHR, flow abnormalities&raquo_space; treat with blood exchange at lower crit.

235
Q

Platelet major antigens

A

HPA-1a/b (GpIIIa)
HPA-2a/b (Gp1ba)
HPA-3a/b (GpIIb)
HPA-12 (Gp1bb)

Note: A > B, always

236
Q

Where are A and B substance carried on platelets?

A

On GpIIb and PECAM-1 (CD31)

237
Q

In what setting can HPA-2a/b or HPA-12 antibodies be seen?

A

In Bernard-Soulier (these make up Gp1b)

238
Q

Treatment for FNAIT

A

IVIG

Antigen-compatible transfusion (consider washed maternal antibodies)

239
Q

How are the antibodies in ITP identified?

A

Most testing looks at reactivity of washings/eluates from patient platelets

240
Q

Major granulocyte antigens

A

HNA-1a/b (FcyRIIIb) - Most implicated in NAN
HNA-3a/b (CTL2) - Most implicated in TRALI

Note: Neutrophils do not express ABO/Rh.

241
Q

Neonatal alloimmune neutropenia

A

Usually arises from maternal antibodies against HNA-1a/b.

Can result in life-threatening infections

Treat with IVIG, G-CSF, PLEX. Treat infections…

242
Q

Class I MHC

A

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
Q

Class II MHC

A

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
Q

Soluble HLA

A

Expressed in inflamed states
Reduced in malignancies

Presence in transfused units may promote TRIM; correlates with WBC load and unit age.

245
Q

“W” HLA nomenclature

A

Formerly “workshop”, now used to identify public antigens Bw4 and Bw6, and to distinguish HLA-C from complement

246
Q

HLA nomenclature

A

Serologic : Allele : Silent mutations : Non-exonic mutations (with modifiers)

Modifiers: N (null), L (low), S (secreted), Q (questionable), C (cytoplasmic)

247
Q

MHC “Class III” region

A

Region on chr 6 that contains:

Complement genes
21-hydroxylase
TNF

248
Q

Class Ib “nonclassical” genes

A

HLA-E (role in NK cell surveillance)
HLA-F
HLA-G (trophoblasts)
HLA-H (misnomer for HFE? pseudogene)

249
Q

What is the chance of a patient having an HLA-identical sibling given # of siblings n?

A

1 - (3/4)^n

250
Q

Low-res vs High-res HLA PCR

A

Low-res only distinguishes serologic equivalents
Hi-res distinguishes alleles

251
Q

What 10 sites must be matched in all HSCT?

A

HLA-A, B, B
HLA-DRB1
HLA-DQB1
(DQ is optional, some centers match)

252
Q

For what solid organ transplants must ABO compatibility be respected?

A

Absolutely must match compatibility for heart, lung, liver.

Major mismatch is permissible in kidney other than A to O/B.

253
Q

HLA allele disease associations

A

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
Q

Plasma EXCHANGE vs plasmaPHERESIS?

A

Exchange is higher volume (>1L)
Pheresis is lower volume (<1L)

255
Q

Rheopheresis

A

Double-filtration plasma exchange that removes large proteins to reduce plasma viscosity…in AMD.

256
Q

Apheresis - Vascular access

A

Need at least 17ga access, 18ga return

257
Q

In what settings is heparin preferred to ACD for apheresis anticoagulation?

A

Children
Metabolic alkalosis
Renal failure

In LDL apheresis using heparin precipitation method.

258
Q

Plasma viscosity

A

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
Q

How does IDM testing of HSC units differ from blood products?

A

Must test same IDMs (including CMV if allo)

Positive test does not invalidate collection or use

260
Q

What are the most important HLA loci to match? Why?

A

HLA-A, HLA-B, HLA-DRB

HLA-C, HLA-DQ

HLA-DP (optional)

Each mismatched allele increases mortality by 10%.

261
Q

Maximal HPC-M donation

A

20ml/kg

Consider collecting an autologous red cell unit first…

262
Q

HSC processing methods

A

Volume reduction (for minor mismatch)
Red cell reduction (for major mismatch)

Elutriation
Cell selection
Expansion

263
Q

HPC cryopreservation

A

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
Q

HPC viability assays

A

CD34+ - Most convenient and common
CFU - Takes weeks to result
Dye exclusion - Trypan, acridine, 7-AAD

265
Q

DMSO reaction

A

Nausea, vomiting
Cough
Headache
Hypertension OR hypotension

266
Q

Major incompatible HPC transplant

A

Associated with acute hemolysis, delayed red cell engraftment
(note: >40d without engraftment is pure red cell aplasia)

267
Q

Minor-incompatible HPC transplant

A

Low risk of reverse hemolysis
Passenger lymphocyte syndrome: 5-16d later, can be severe

268
Q

What tissue grafts are regulated under 21 CFR 1271?

A

Allografted non-vascular tissues: Bone, tendon, cornea, etc.

No autografts (unluess they are treated/modified)

Xenografts/xenotransplants

269
Q

What are the responsibilities born by hospital tissue services?

A

Must handle, trace, detect, and report adverse events

Ensure bidirectional traceability

Inspect, ensure documentation (consents, records…)

270
Q

What is the most common autograft tissue?

A

Craniotomy / skull cap

271
Q

Male vs female sex mismatched HPC transplant

A

Female to male: More GVHD, less relapse
Male to female: More graft failure

272
Q

Incidence of GVHD

A

Both acute and chronic GVHD have 10-50% incidence

Best predictor of chronic GVHD is acute GVHD…

273
Q

HPC-A versus HPC-M

A

HPC-A: Faster engraftment, more GVHD
HPC-M: Slower engraftment, more red cell contamination

274
Q

Best predictors of successful harvest

A

Young age
No history of chemo, radiation
Use of combined mobilization regimen

275
Q

Transfusion support in HSCT

A

In general: Avoid red cell types that will lyse, and avoid plasma types that will attack the graft.

Bidirectional mismatch: Give O/AB

276
Q

HPC infusion

A

Thaw at bedside at 37C

Infuse as rapidly as tolerated; unit must be infused within 1hr of thaw

277
Q

Cord blood characteristics

A

80-100mL, contains 2-4 x 10^6 CD34+ cells.
OK for use in patients up to 45kg.

278
Q

Reduced intensity conditioning

A

Less myeloablative regimen approved for use in patients who cannot tolerate full ablation due to medical comorbidity.

279
Q

Donor Lymphocyte Infusions

A

Post-transplant lymphocytes, given in cases of relapse to re-induce remission.

Indications: CML > AML > ALL > Lymphoid malignancies

280
Q

Mechanisms of RhD loss

A
281
Q

When does ABH expression fully mature?

A

2-4yo ; this is generally true for all carbohydrate antigens

282
Q

How to distinguish RhIg from native anti-D?

A

Best: Allotyping (not widely available)

Lucky: Identify >D at IS (IgM component)

Worse: Titers (NOT reaction strength!)

283
Q

Factors worsening kernicterus

A

Acidosis
Prematurity
Hypoxemia
Hypoalbuminemia

284
Q

Bilirubin, hemoglobin absorption wavelengths

A

Bilirubin: 410nm
Hemoglobin: 450nm, but has overlap at 410nm (must correct)

285
Q

HLA association in PTP/FNAIT

A

Patients with HLA-DRB3*0101 are more likely to form anti-HPA-1a

286
Q

Treatment for FNAIT

A
287
Q

Serologic IDMs

A

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
Q

NAT testing

A

Any positive result kills a unit and defers a donor.

Tested in minipools of 16-24 (exception: WNV is individual)

289
Q

CMV transmission rates

A

CMV-safe (LR): 2-3% transmission
Seronegative: 1-2% transmission

290
Q

When should autologous blood products undergo IDM testing?

A

If the product is to be shipped between facilities

291
Q

HIV screen

A

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
Q

HIV confirmatory testing

A

Western blot

2 bands of: gp41, p24, gp120/160

293
Q

HBV screen

A

HBsAg
Total HBcAb (IgM, IgG)
HBV DNA NAT

~28d window period

294
Q

HCV screen, confirm

A

HCV RNA
Serology (IgG only)

8 day window period

Confirm: RIBA

295
Q

HTLV screen & confirm

A

Screen: Serology-only (cannot distinguish types)
Confirm: Western blot

296
Q

Hepatitis E

A

No screening test currently employed in US.

Note only genotype 3 has been described as a TTI

297
Q

Syphilis screening

A

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
Q

WNV testing

A

Screen: ID NAT, only in areas where activity is high?

299
Q

Chagas screening

A

EIA - One-time test per donor

300
Q

Babesia testing

A

None approved by FDA. IF and NAT tests do exist.

Only defense is history/questionnaire…

301
Q

Parvovirus as a TTI

A

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
Q

Red cell INTERCEPT

A

Uses amustaline and glutathione, rather than methoxypsoralen

303
Q

Most common causes of transfusion mortality

A
  1. TRALI
  2. TACO
  3. AHTR
304
Q

How to distinguish AHTR from septic transfusion reaction?

A

No good clinical features besides hemolysis; rely on lab workup.

Consider the transfused product type–any red cell volume?

305
Q

TRALI is ___ compared to other lung injuries
Implicated products in TRALI include ___
SD treatment ___ risk of TRALI

A

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
Q

Treatment of TACO

A

Stop transfusion
Set patient UPRIGHT
Support ventilation
Diuretics
Consider MICU transfer?

307
Q

Main symptoms in AHTR

A

Fever is most reproducible
Hypotension #2

308
Q

Causes of DHTR

A

Usually Kidd antibodies

Next: Kell, Rh, Duffy

309
Q

Iron content of pRBC unit

A

250mg

310
Q

Acute pain transfusion reaction

A

Affects trunk, proximal extremities

Associated with leukoreduced units

No clear relationship to HbSS?

311
Q

In what setting does air embolism most commonly occur?

A

Operative settings, especially with rapid infusers and intra-op blood recovery (cellsaver)

312
Q

Why does Yersinia persist in pRBC transfusions?

A

Psychrophilic
Prefers low calcium, high iron environments

313
Q

Leukocyte-transmitted TTIs
Plasma-transmitted TTIs

A

Leukocyte: CMV, EBV, HHV8, HTLV
Plasma: HAV, HBV, HCV, parvovirus, syphilis

314
Q

Deferral periods for…
1. Malaria
2. Zika
3. Ebola
4. Chagas
5. Babesia
6. WNV

A
  1. Malaria - 3yr
  2. Zika - 4wk
  3. Ebola - Indefinite
  4. Chagas - Indefinite
  5. Babesia - Indefinite
  6. WNV - 120d
315
Q

Viral transmission risks

A

HBV - 1:500k
HCV - 1:2M
HIV - 1:2M
HTLV - 1:3M
WNV - 1:7M

316
Q

HIV re-entry

A

Most common: RR+, but negative confirmatory and NAT&raquo_space; re-test at 8 weeks. If all negative, then re-entry OK

317
Q

HTLV, HCV long term sequelae

A

HTLV: 2-5% develop ATLL. <1% develop TSP/HAM (HTLV-1 only)

HCV: 80% develop chronic hepatitis!

318
Q

TT-Syphilis

A

Not seen in many decades

Presents as a fulminant second-phase infection

319
Q

Malaria chronicity

A

P. Malariae - May persist asymptomatically for life
P. Vivax - 7 years
P. Ovale - 5 years
P. Falciparum - 5 years (really?)

320
Q

vCJD vs CJD

A

CJD - Older age of onset. Transmission never proven via blood products

vCJD - Younger age, less classic EEG findings. Transmission has been confirmed.

321
Q

Chagas - Features, diagnosis

A

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
Q

WNV - Characteristics, syndrome

A

Birds are reservoir, humans are dead-end host

80% of infected are asymptomatic
20% develop fever and viral prodrome
<1% develop meningo/encephalitis

323
Q

For what infection must the next of kin be notified from a positive donation?

A

HIV

324
Q

Strongest platelet agonist

A

Thrombin

325
Q

TT vs reptilase

A

Both are sensitive to hypo/dysfibrinogenemia, fibrin degradation products

TT is sensitive to heparin, whereas reptilase directly cleaves fibrinogen.

326
Q

Hemophilia A/B in women

A

Usually seen in Turner syndrome or in extreme lyonization

327
Q

Type IIb VWD

A

Mutation in GP1b binding site (INCREASED activity)

Loss of HWM multimers

Sine qua non: Low dose RIPA+

DDAVP is contraindicated&raquo_space; thrombocytopenia

328
Q

Factor VIII inhibitors

A

Usually IgG4

Manifest in older patients, can cause severe bleeding

Treat with steroids, PLEX. Overwhelm weak inhibitors, bypass strong inhibitors.

329
Q

Warfarin-induced skin necrosis

A

Due to short-term protein C deficiency; can treat with protein C concentrates.

330
Q

Platelet aggregation patterns

A

Glanzmann - Responds ONLY to ristocetin
Bernard - Does not respond to ristocetin

331
Q

Factor V leiden

A

Mutation in factor V (usually R506L) that prevents APC from cleaving

332
Q

Wiskott aldrich
Chediak higashi

A

Wiskott: XLD, thrombocytopenia + eczema + immunodeficiency
Chediak: AutRec, albinism + neutropenia + inclusions

333
Q

Natural anticoagulants in DIC

A

C, S, AT-3 all fall in DIC.

Low levels of AT-3 are associated with worsened mortality

334
Q

Type 2N VWD

A

Mutation in fVIII binding site. Presents like hemophilia A with no evidence of inhibitor, yet responses to factor 8 repletion are unsatisfactory.

335
Q

Factor half-lives

A

Factor 7: 4-6hrs
Factor 8: 12hrs
Factor 13: 1 week

336
Q

Platelet GpIIa/IIIb inhibitors

A

Abciximab, tirofiban, eptifibatide

Reversible with platelet transfusion

337
Q

MG antibodies

A

Usually directed at acetylcholine RECEPTOR (not esterase!)

Other antibodies: Anti-MuSK (muscle specific kinase)

338
Q

Treatment of GBS

A

IVIG, PLEX

Steroids not helpful…

339
Q

PLEX for CIDP

A

One treatment results in 10-14d response. Slows demyelination of PERIPHERAL (not central) nerves

340
Q

PLEX for anti-GBM disease

A

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
Q

PLEX in FH

A

Does confer some benefit, though LDL pheresis is likely ebtter?

342
Q

How does hypomagnesemia worsen hypocalcemia?

A

Low magnesium levels inhibit PTH release

343
Q

ECP ASFA categories

A

CTCL: Cat I
GVHD: Cat II
Transplant rejxn: Cat II

344
Q

Metabolic effects of citrate

A

Hypocalcemia
Hypomagnesemia
Metabolic alkalosis
» hypokalemia

345
Q

HLA parentheses

A

Indicates split of a parent antigen

eg. HLA-B44(12) indicates a split of parent antigen 12

346
Q

European vs american leukoreduction

A

European is more stringent (1 x 10^6 max per unit)

347
Q

Reverse TRALI

A

Recipient antibodies reacting with donor WBCs. Very rare.

348
Q

Tissue vendor qualification needs

A

FDA registration
Accreditation
QA resources
Inspection findings
Adequate supply

Contractor should verify qualification annually.

349
Q

Tissue donor assessment

A

Medical evaluation: Records, interview
Labs
Reports: Autopsy, police
Physical assessment

350
Q

When can allogeneic HPC donors be tested for IDMs?

A

Up to 30d before donation, and up to 7d after donation

351
Q

Banked tissue storage and expiry

A

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
Q

Bone grafts

A

Cortical: needs protection. Slower
Cancellous: induces more inflammation

Freezing does not affect mechanical properties

353
Q

Tissue sterilization

A

Ethylene oxide, irradiation

354
Q

What is a “lot” of donated product?

A

Product arising from one donor, in one donation setting

355
Q

Ambient vs room temperature?

A

Room temperature specifically refers to 20-24C.

Ambient just means any routine temperature is tolerated.

356
Q

Tissue allograft record retention period

A

10 years

357
Q

ABO confirmation of organ donors

A

Need 2x, same as blood

358
Q

HIV window period

A

22d (serologic, non-p24)
10d (NAT, p24 antigen)

359
Q

How much time is allowed for notification of recipients in lookbacks?

A

120 days to notify recipient / ordering physician
(conflict: 12 weeks for HIV/HCV? inform next of kin if HIV)

360
Q

Do market recalls or market withdrawals constitute BPD / FDA reportables?

A

Both

361
Q

In what settings is a patient ineligible for EXM?

A

Only one type on record
Any ABO discrepancy
Any significant antibodies

362
Q

Who can receive RhIg for treatment of ITP?

A

Only non-splenectomized, RhD+ patients.

Rationale: RhIg causes red cell coating which competes with coated platelets for removal in RES.

363
Q

RhIg dose in ITP

A

If Hgb > 10: 50-75 ug/kg
If Hgb < 10: 25-40 ug/kg

364
Q

FNAIT incidence (current, subsequent pregnancies)

A

1:2000 (!)

Occurs in first pregnancy, tends to recur as bad or worse.

365
Q

HLA-DRB3*0101

A

HLA allele associated with higher rate of anti-HPA antibody formation (eg FNAIT)

366
Q

Kleihauer-Betke test

A

Acidify smear with citric acid to denature/elute HbA.

Count 2000 cells

Problems: Difficult to interpret (maternal F cells stain equivocally).

367
Q

Rosette test

A

Only valid in RhD- mother with RhD+ baby

Uses R2R2 ficin-treated indicator cells.

Detects down to 10mL FMH.

368
Q

Del

A

Rare RhD+ phenotype in asians, with as few as 22 copies of RhD per RBC. Need elution to detect.

Does not need RhIg.

369
Q

HDFN incidence

A

1:10,000

370
Q

Hydrops fetalis

A

Caused by fetal portal hypertension (generally due to erythroblastosis) suppressing fetal hepatic synthesis of albumin&raquo_space; high output heart failure.

371
Q

Effect of ABO incompatibility on HDFN

A

Protective–fetal cells are cleared more quickly and less likely to trigger immunization

372
Q

Transfusion threshold for IUT

A

Fetal Hct < 30%

(determined by PUBS, have product available on-hand to immediately reflex to IUT)

373
Q

Octaplas

A

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
Q

INTERCEPT

A

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
Q

THERAFLEX

A

THERAFLEX-MB: Methylene Blue treatment. Doesn’t penetrate WBC&raquo_space; needs leukoreduction.
THERAFLEX-UV: UV-C only, no additive. Proteins are unaffected.

376
Q

MIRASOL

A

Riboflavin + UV illumination.

Only used in EU, para-site rich endemic regions in studies.

377
Q

CCI formula

A

(Platelet increment x BSA) / #plts transfused

378
Q

PTP - Incidence, symptoms, treatment

A

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
Q

Filtration pore sizes

A

Platelets - 3um
RBCs - 7um
Lymphs - 10um
Grans - 13um

380
Q

TTP treatment target, adjunctive therapies

A

Exchange until plt > 150k/uL x 2 days, normalized LDH and mental exam.

Adjuncts: Steroids, vincristine, splenectomy. Rituximab (reduces relapses)

381
Q

Weakness of apheresis platelets over WBD platelets

A

Higher incidence of minor-incompatible hemolysis (single donor, rather than averaged pool)

382
Q

Weaknesses of PCR

A

Misses large rearrangements

Relies on sequence primers, so can miss novel mutations.

383
Q

In what settings can prozone effect cause false negative antibody screen results?

A

Hyperviscosity (paraprotein)
Cryptococcus, plasmodium, syphilis infections

384
Q

HDFN due to Anti-G

A

Uncommon; titers rarely get high enough.

Anti-D worse than Anti-C worse than Anti-G.

385
Q

Main cause of death in HbSS

A

Acute Chest Syndrome

386
Q

Splenic sequestration

A

HbSS complication of CHILDHOOD.

Life threatening, treat with transfusion and splenectomy.

387
Q

DIIHA - Incidence, types

A

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
Q

Passenger lymphocyte syndrome

A

Occurs +2 weeks from transplantation of lymphocytes.

Self-limiting, will decrease in titer and severity over time

389
Q

Causes of donor cell pseudo-hemolysis

A

Heat/cold damage - <3C, >50C
Osmotic damage (wrong carrier fluid)
Extracorporeal damage, mechanical damage
Bacterial contamination

G6PD donor (mild transient lysis upon infusion)

390
Q

Anti-E

A

Can cause HTR, or rarely HDFN.

Can have an IgM component detectable at IS (so too can anti-C).

391
Q

Anti-c

A

Can cause severe HTR or HDFN.

392
Q

Anti-e

A

Most common autoantibody specificity.

393
Q

Platelet transfusion lifespan

A

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
Q

ABO determination for organ transplant

A

UNOS requires 2 types for both donors and recipients.

395
Q

Clotting factor concentrate deferrals

A

None–no deferrals for fractionated products anymore

396
Q

Open vs automated deglyc process

A

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
Q

NovoSeven

A

Short-lived, requires dosing every few hours.

Not actually associated with thrombosis?

398
Q

HPA-1a vs 1b

A

1a (98%)
1b (2%)

399
Q

Polycythemia TP goals

A

Target a goal of <45% Hct in white men (?!), <42% in everyone else.

400
Q

Idaricizumab

A

Dabigatran reversal agent

401
Q

Andexanet alfa

A

Direct Xa inhibitor reversal agent (for apixaban, rivaroxaban)

402
Q

Emicizumab

A

Bypass agent in factor 8 inhibitors. Forms the “tenase”, approximating fX and fIX, thereby replacing the role of fVIII.

403
Q
A
  1. Type 2B
  2. Type 2M
  3. Type 2B
404
Q

Hemochromatosis TP targets

A

Initiate for serum ferritin >300/200 for men/women, target goal of 50?

405
Q

Mobilization regimens

A

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
Q

Liquid plasma: When to separate, when expires?

A

Can be separated from WB at any time, but it expires 5 days after that of the whole blood.

407
Q

Neonatal/pediatric blood dosing

A

RBC: 10-15mL/kg&raquo_space; +2-3g/dL
FFP: 10-15mL/kg&raquo_space; +15% factor activity
PLT: 5-10mL/kg&raquo_space; +50k
CRYO: 1u/10kg&raquo_space; +50mg/dL

408
Q

Topical bovine thrombin

A

Associated with formation of factor V inhibitors.

Supplanted by topical fibrin sealants.

409
Q

BARC

A

A neoantigen formed in the most common form of partial D (D-VI)

410
Q

RHD loss mechanisms by race

A

Whites: RHD deletion
Blacks: Point mutation, partial deletion, or recombination event
Asians: Pseudogene (but probably actually DEL)

411
Q

GPA

A

cANCA

PR3

412
Q

Factor 8 dosing

A

kg x delta-activity / 2

May need to dose twice in 24hrs

413
Q

Factor 9 dosing

A

kg x delta-activity

414
Q

vWF dosing

A

kg x delta-activity

415
Q

Anticoagulant deferrals

A

Piroxicam - 2d
Oral anticoagulants - 2d
Prasugrel, ticagrelor - 7d
Warfarin - 7d
Heparin, Fondaparinux - 7d

416
Q

Teriflunomide

A

2yr deferral

417
Q

Maximum radiation dose

A

50 Gy

418
Q

Apheresis collection has a higher/lower reaction rate than WB collection

A

Lower

419
Q

Platelet volume reduction

A

Need at least 85% recovery

420
Q

pRBC, plt content requirements

A

pRBC: >60g in at least 95% of units
Plt: >3 x 10^11 in at least 90% of units

421
Q

Double-red donation requirements

A

At least 130lb (male) or 150lb (female). Crit at least 40%

Most donation must be at least 30% crit

422
Q

Confirmatory IDMs

A

HBsAg has confirmatory
Anti-HIV has confirmatory
Anti-HCV has confirmatory (RIBA no longer available)

423
Q

Deferral re-entry time (HIV, HCV)

A

HIV: 8 weeks
HCV: 6 months

424
Q

IDM testing in leukocyte-rich, reproductive tissues

A

Leukocyte-rich: CMV, HTLV
Reproductive: Gon/Chla

425
Q

NASBA

A

TMA, except that it uses RNAse H to degrade RNA template, while TMA uses RT.

426
Q

IgG subclass ability to bind phagocyte FCR

A

1 = 3 > 4 > 2

427
Q

DAT sensitivity

A

500 IgG per red cell
1000 C4d per red cell

428
Q

A2 platelets

A

Actually do not express any A substance.

429
Q

FOCUS

A

8 vs 10 noninferior in hip frx

430
Q

RhIg in thrombocytopenia

A

Give for ITP, RhD incompatible in young women. Give IV, not IM (hematoma)

431
Q

3- vs 4- factor PCC

A

3: 2, 9, 10
4: 2, 7, 9, 10 (eg. Kcentra)

432
Q

Cryopreserved HPC shpiping

A

Shippers should hold <150C for 2 weeks. Do not X-ray. Use weight to assess remaining LN2.

433
Q

UCB IDM

A

Test mother

434
Q

Allografted tissues requiring ABO/HLA matching

A

Vessels, those containing red cells or marrow, RhD- mom recipients

435
Q

Fridge temperature control

A

Continuous monitoring, recording q4hrs

436
Q

Max platelet collection

A

Max 6x10^11 in 7 days?
Max 2 sessions in 7d, 24 in 1yr

437
Q

Plt LR

A

<8.3 x 10^5 WBC in at least 95% of units

438
Q

RBC Deglyc recovery

A

At least 80%

439
Q

Antigen negative unit confirmation

A

Not necessary; no need to re-test

440
Q

MTP definition

A

Patient blood volume in 24hrs

441
Q

Frozen rejuvenated expiry

A

10yrs (CPD, CPDA-1)
3yrs (AS-1)

442
Q

Cryo single unit expiry after thawing

A

6hrs
(4hrs is for open pools)

443
Q

COVID Vx deferral

A

If live-attenuated, 14 days. If uncertain, 14 days.

444
Q

Deferral: Sex with HBV/HCV positive

A

1yr (has not been reduced to 3mo, like HIV has)

445
Q

Document review interval

A

2 years