blood components and component therapy22222
TRANSCRIPT
Compiled by: Victor Perlas Jr., RMT, AMT, IMT (ASCP, HAAD)This lecture handout will be utilized only by University of Saint Louis’ Medical Technology students for their Immunohematology class.
BLOOD COMPONENTS AND COMPONENT THERAPY
I. GeneralA. Basic concept of “component therapy”
1. More efficient use of products by giving patient what he needs and avoiding what he doesn’t need.
2. Made possible by advent of plastic bags around 1950.
3. Single unit may be made into numerous components (see figure below representing classical US method).
Figure 1: Basic component processing
B. Anticoagulant/preservative solutions 1. Allows blood to be stored for extended periods
without drastic effects on most metabolic and therapeutic qualities
2. Red cell storage defined by 75% survival of RBCs 24 hours after transfusion with <1% hemolysis (FDA)
3. Historic anticoagulant/preservatives: Acid Citrate Dextrose (ACD):
Used for apheresis platelets Formerly used for RBCs; 21 day
storage Citrate-phosphate-dextrose (CPD) and
citrate-phosphate-dextrose-dextrose (CP2D)
Allow 21 days of RBC/whole blood storage
Citrate-phosphate-dextrose-adenine (CPDA-1)
Very similar to CPD but with 17.3 mg of adenine (no adenine
in CPD) Allows 35 days of RBC/Whole
Blood storage 4. Additive solutions (“Adenine Saline” additives)
Increases shelf life of RBCs to 42 days Most common types
AS-1 (Adsol)
AS-3 (Nutricel) AS-5 (Optisol) AS-7 (SOLX)
Specifics vary, but all add more dextrose and adenine to increase blood shelf life.
AS-1, AS-5, AS-7 contain mannitol in varying quantities for RBC preservation
5. Preparation of additive solution RBCs: RBCs with additive solution process:
Blood collected in CPD or CP2D (NOT CPDA-1), spun, then mixed with 110 mL additive solution for 500 mL collections (100 mL for 450 mL bags)
This gives a product with more volume and less plasma (HCT usually 55-65%)
6. Know storage details for various products
WHOLE BLOODIndication Provide blood volume
expansion and RBC mass in acute blood loss
Storage 1-6oCTransport 1-10oCShelf-life 21 days (CPD/2D)
35 days (CPDA-1)42 days (AS)Open System – 24 hours
PACKED RBCsIndication Increase RBC mass of
symptomatic, normovolemic patients
Storage 1-6oCShelf-life 21 days (CPD/2D)
35 days (CPDA-1)42 days (AS)Open System – 24 hours
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Compiled by: Victor Perlas Jr., RMT, AMT, IMT (ASCP, HAAD)This lecture handout will be utilized only by University of Saint Louis’ Medical Technology students for their Immunohematology class.
“For God did not give us a spirit of timidity, but a spirit of power, of love and of self-discipline.”2 Timothy 1:7
LEUKOCYTE-REDUCED RBCsIndication Increase RBC mass in
patients with severe and/or recurrent febrile transfusion reactions due to leukocyte antibodiesIncrease RBC mass in patients at risk for HLAAlloimmunization to HLA antigens or susceptible to CMV
Storage 1-6oCShelf-life 21 days (CPD/2D)
35 days (CPDA-1)42 days (AS)Open System – 24 hours
WASHED RBCsIndication Increase RBC mass of
symptomatic anemic patients with history of allergic, febrile, urticarial and anaphylactic reactions
Storage 1-6oCShelf-life Open System – 24 hours
FROZEN RBCsIndication Storage of rare and
autologous unitsStorage -65oC
Shelf-life 10 years24 hours @ 1-6oC after thaw
PLATELET CONCENTRATEIndication For bleeding due to
thrombocytopenia or thrombocytopathy
Storage 20-24oC / room temperature (with gentle
agitation)
Shelf-life Closed system – 5 daysOpen system – 4 hours
Nice to know:
CORRECTED COUNT INCREMENT
Absolute platelet increment/uL x body surface area (m 2 ) Number of platelet transfused (1011)
Minimum CCI is 10, 000/uL per m2
“Cast all your anxiety on Him for He cares for you.”1 Peter 5:7
PLATELET, PHERESISIndication For thrombocytopenic
patients alloimmunized to HLA or platelet antigen (donor should be HLA matched)Limit donor exposure in thrombocytopenic patients who acquire long term platelet transfusions
Storage 20-24oC / room temperature (with gentle
agitation)Shelf-life 5 days
FROZEN PLASMA (FFP or FP24)Indication Correct multiple
coagulation factor deficiencyReplace isolated factor deficiencies when specific component is not availableReverse affects of warfarin (Coumadin) anticoagulant drug
Storage -18oC or colderShelf-life 1 year @ –18oC
7 years @ -65oC24 hours at 1-6oC after thaw
FP24 not used within 24 hours after thawing can be relabeled as “Thawed
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Compiled by: Victor Perlas Jr., RMT, AMT, IMT (ASCP, HAAD)This lecture handout will be utilized only by University of Saint Louis’ Medical Technology students for their Immunohematology class.
Plasma” and stored at 1-6oC for 5 days while adequate levels of Factors V and VIII are maintained.
CRYOPRECIPITATEIndication For treatment of fibrinogen
deficiency, haemophilia A, von Willebrand’s disease and factor XIII deficiency
Storage 1 year @ –18oCShelf-life 6 hours @ 20-24oC after
thaw (4 hours if pooled in open system)
GRANULOCYTES, PHERESISIndication Patients with granulocyte
dysfunction or myeloid hypoplasia who are unresponsive to antibiotics
Storage 20-24oC / room temperature (WITHOUT
agitation)Shelf-life 24 hours
C. Quality control of blood products 1. Blood is a controlled product that is tightly
regulated by the FDA (with more regulations from AABB & CAP).
2. Very specific, detailed requirements acceptability
Quality Control for Blood Products (US)Product QC
RBCs HCT < 80% (all);> 50 g HGB in 95% (apheresis RBCs)
RBCs Leukoreduced
≤ 5 x 106 WBCs in 95%, retain 85% of RBCs
Platelet Concentrate (PC)
≥ 5.5 x 1010 and pH ≥ 6.2 in 90%
PC Leukoreduced ≥ 5.5 x 1010 in 75%, pH≥ 6.2 in 90%, AND <8.3 x 105 WBCs in 95%
Apheresis Platelets
≥ 3.0 x 1011 and pH ≥ 6.2 in 90%
Apheresis Platelets Leukoreduced
Above + < 5.0 x 106 residual WBCs in 95%
CRYO Factor VIII ≥ 80 IU (all)
Fibrinogen ≥ 150 mg (all)Granulocyte concentrate ≥ 1.0 x 1010 in 75%
II. Blood and Components
A. Blood Components1. Red blood cells/additive solution red blood cells 2. Platelets
Whole blood-derived platelets (WBD-PLTs)
Apheresis-derived platelets (AD-PLTs) 3. Modified RBCs and Platelets
Leukocyte reduced products Irradiated products Frozen products Washed products
4. Plasma and derivatives Fresh frozen plasma (FFP) FFP alternatives (including PF24) Cryoprecipitate (“antihemophilic
factor”) Factor concentrates
Other plasma derivatives 5. Miscellaneous products
Granulocyte concentrate DDAVP Recombinant activated factor VII
(NovoSeven)
B. Whole Blood1. The original blood product!2. Minimal availability in most blood banks today
3. Potential indications: Massive blood loss (30-40% or more of
blood volume) Trauma/emergency transfusions
most commonly
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Compiled by: Victor Perlas Jr., RMT, AMT, IMT (ASCP, HAAD)This lecture handout will be utilized only by University of Saint Louis’ Medical Technology students for their Immunohematology class.
This is popular in combat transfusions (“fresh whole blood”)
Occasional requests by trauma surgeons
Not commonly available in civilian settings
Use may lead to less exposure by providing coag factors (+/- functional PLTs), as well as volume
Whole blood must be ABO identical due to plasma; tougher to use in emergencies.
Exchange transfusions in neonates (more often “reconstituted” from separate RBCs and FFP)
Autologous transfusions4. Contraindications:
Transfusion Associated Circulatory Overload
5. Storage Time and Conditions Length depends on
anticoagulant/preservative used 1-6oC
C. Red Blood Cells (with and without additives)1. Most commonly used blood component (over
15 million units per year in the US as of 2008)
2. Prepared by centrifugation and removal of most of plasma layer of whole blood, or by apheresis collection.
May be transfused without modification after preparation or may use additive solution
3. Requirements: HCT < 80% for all RBCs (easy with
AS-RBCs)
Apheresis RBCs: 95% must have >50 g HGB or 150 mL of RBCs
4. Indications Oxygen delivery (DO2) insufficient
for oxygen consumption (VO2) Hemoglobin level and cardiac
output (CO) are most important factors in DO2
DO2 = CO x Arterial O2
content Arterial O2 made up of
hemoglobin-bound O2
(vast majority) and dissolved O2 (minority)
Oxygen consumption / demand (VO2)
VO2 is constant across a wide spectrum of DO2, so even with low hemoglobin, oxygen consumption is stable
So, transfusion is unnecessary and unhelpful in mild anemia without cardiac dysfunction despite a decreased DO2
HGB dissociation curve shift to right, incr. cardiac output, decr. blood viscosity, incr. respirations, etc. help compensate
Ischemia happens when DO2 drops so far that it can’t keep up with VO2 (“critical DO2”)
Once this point is reached, transfusion may be helpful, but defining critical DO2 is tough
Some suggestions:-Mixed venous O2 sat (SvO2) <60% -O2 extraction ratio >40-50% -VO2 decreased by >10%
Deciding if RBC transfusion is indicated:
Balance risks of anemia vs. risks of transfusion
HGB alone a very poor indicator for transfusion
All factors should be considered
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Compiled by: Victor Perlas Jr., RMT, AMT, IMT (ASCP, HAAD)This lecture handout will be utilized only by University of Saint Louis’ Medical Technology students for their Immunohematology class.
Acute vs. Chronic loss Evidence of ischemia Comorbidities, age, medications, history
Situations that may require red cell transfusion:
Acute hemorrhage (> 30% acute blood vol loss)
Hemolysis Marrow failure
Thresholds
HGB 10 g/dL/HCT 30% trigger is bad practice
General guidelines from multiple specialties:
If HGB < 6 g/dL, transfusion usually needed
If HGB >10 g/dL, transfusion rarely needed
If HGB is between 6 and 10, clinical judgment, assessment of situation, etc, is required
It is reasonable to assess need for further transfusion after each unit given
AABB recommendations (Annals of IM, Mar 12):
Stable, ICU, hospital pts: 7 g/dL
Post-surgery patients: 8 g/dL or symptoms
Chronic cardiovascular disease: 8 g/dL
Acute coronary syndrome: No recommendation (no studies address this prospectively)
Other indication: Exchange transfusions
Sickle cell patients (esp. stroke or presurgery)
Hemolytic disease of the newborn/fetus (HDFN)
5. Contraindications Acute hemorrhage of < 20% of blood
volume Crystalloids are adequate in
most of these cases Chronic nutritional anemias (folate,
B12, iron)
6. Expected effect (per unit) HCT increases 3%, HGB 1 g/dL
(without acute bleeding or hemolysis) Effect can be measured 15 minutes
after transfusion
7. ABO compatibility
ABO type of transfused RBCs must be compatible with recipient plasma ABO antibodies
8. Storage and shipping Same as for whole blood if CPD, CP2D,
CPDA-1 42 days at 1-6 C if AS used Shipping temperature 1-10 C
9. Compatible fluids Normal saline (0.9%, not 0.45%) ABO-compatible plasma 5% albumin Normosol-R pH 7.4 and Plasma-Lyte
148 and –A Red cells should not contact lactated
Ringer’s (LR), D5W, 0.45% NS, antibiotics/other drugs, or TPN
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Compiled by: Victor Perlas Jr., RMT, AMT, IMT (ASCP, HAAD)This lecture handout will be utilized only by University of Saint Louis’ Medical Technology students for their Immunohematology class.
Hypotonic solutions - red cells swell and burst; hypertonic solutions - red cell shrinkage
LR has enough calcium to counteract the citrate anticoagulant in blood (LR has 3 mEq Ca2+/L)
10. A couple of unusual RBC types Red Blood Cells, Low Volume
Prepared from whole blood collection 66-90% of the target volume (for 500 mL bags, 333-449 mL)
RBCs may still be used, but not plasma
Red Blood Cells, Rejuvenated RBCs may be “rejuvenated” up
to 3 days after expiration in CPD or CPDA-1, or up to the expiration date in AS-1 with “Rejuvesol.”
Restores ATP, 2,3-DPG levels to near-normal levels
Rejuvenated product is frozen (10 years for CPD, CPDA-1 RBCs; 3 years for AS-1) or transfused
Product must be washed, transfused within 24 hrs
D. Platelets1. Whole blood-derived platelets (platelet
concentrate, “random platelets”, WBD-PLTs) Prepared via centrifugation from one
whole blood unit The initial “soft” spin leaves
“platelet-rich plasma” on top, so the method is known as the PRP method
In Europe, order of spins is reversed; the initial “hard” spin creates a buffy coat
May be pre-pooled at blood center, or pooled in transfusion service before transfusion
Traditional dose 1 unit per 10 Kg body weight is
good estimate Commonly given 4-8 bags at a
time (6 most often) 10-15 mL/Kg in neonates
2. Apheresis platelets (“single donor”, “AD-PLTs”)
Made from one donor via apheresis procedure
Roughly 85% of platelets transfused in the US
“Double” or “triple” platelets products can come from 1 donor (each unit > 3.0 x 1011 PLTs)
Recent development: Platelet additive solutions
Dilutes proteins and may decrease allergic reactions and breakdown product accumulation
PAS-C and PAS-F currently approved
“Therefore, humble yourselves under the mighty hand of God, that He may exalt you at the proper time. Casting all your anxiety on Him, because He cares for you.”I Peter 5:6-7
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Compiled by: Victor Perlas Jr., RMT, AMT, IMT (ASCP, HAAD)This lecture handout will be utilized only by University of Saint Louis’ Medical Technology students for their Immunohematology class.
Why choose AD-PLTs over WBD-PLTs?
Limiting exposure For potential decrease
in infectious disease transmission (viruses, parasites, bacteria, etc.)
1 unit for AD-PLTs vs. six for WBD-PLTs mathematically decreases potential exposure
AD-PLTs have less bacterial contamination
Platelet refractoriness Lack of response to
platelet transfusion (immune and nonimmune causes)
May be used as HLA-matched or crossmatched doses for immune refractoriness.
3. Indications for platelet transfusion: Thrombocytopenia
Prophylactic (just in case)/therapeutic (bleeding)
Prophylactic transfusions Data supports
prophylactic threshold of <5,000 (but most use 10K)
20K threshold if patient has risk factor (Fever, sepsis, bleeding, thrombocytopathy)
50K if about to have major surgery
Therapeutic 50K if bleeding 100K reasonable for
patients with intracranial and pulmonary hemorrhage
Controversy in liver biopsy, endoscopy
Many use 50K or 100K prophylactic threshold
Not proven; count not predictive of bleeding
Thrombocytopathy Prophylactic transfusions not
indicated Therapeutic indications:
Congenital defects with bleeding
Drugs (Plavix, ASA most common)
Increased bleeding in emergency surgical patients, especially cardiac surgery
External agents (Cardiac bypass, ECMO)
Metabolic effects (e.g., chronic renal failure)
4. Contraindications to platelet transfusion Thrombotic thrombocytopenic
purpura (TTP) ADAMTS13 enzyme
deficiency most common leading to large vWF multimers and subsequent platelet microthrombi
More platelets could lead to more thrombi
May be overblown fear; many use PLTs in life- threatening situations without problems.
Hemolytic-uremic syndrome (HUS) similar to TTP without neurologic symptoms
Heparin-induced thrombocytopenia, type II
Antibody vs. heparin/platelet factor 4 complex
These patients are at great risk for thrombosis, and platelets should be avoided if possible
Immune/idiopathic thrombocytopenic purpura (relative)
Doesn’t help count, and patients don’t usually bleed
Use only if significant bleeding occurs
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Compiled by: Victor Perlas Jr., RMT, AMT, IMT (ASCP, HAAD)This lecture handout will be utilized only by University of Saint Louis’ Medical Technology students for their Immunohematology class.
Post-transfusion Purpura (PTP) Uncommon antibody vs.
transfused PLTs Most transfused PLTs will be
antigen-positive
5. General comments about platelets Expected effect
Generally, if one hour post-count increases by >20,000-30,000, response is adequate (“eyeball”)
Minor value in assessing response adequacy, even if count doesn’t increase much
One-hour post-transfusion count is standard
10-minute post count has value as a screen
No increase on 10-minute post count strongly suggests alloimmunization
Storage and shipping 5 days at 20-24 C (with
gentle agitation) Shipping range “as close as
possible” to 20-24 C < 24 hours without agitation
during shipping 4 hours after transfusion
service pooling (in “open” system; “pre-pooled” PLTS have normal shelf life)
ABO and RhD PLTs do not require
pretransfusion crossmatches, and ABO-incompatible platelets commonly given
Platelet ABO incompatibilities
Major = platelet ABO antigens incompatible with recipient plasma (like A PLTs to O recip)
Cleared from circulation faster; less effect Some concern about effect of antibodies binding
to transfused soluble antigens Minor = donor AB
antibodies incompatible with recipient RBCs (like O PLTs to A recip)
A concern in children, neonates, and high- titer donors (“reverse” hemolytic reactions)
ABO-identical is best, but not always practical
RhD antigens are NOT present on platelets.
RBCs in PLTs have RhD (esp WBD PLTs)
Risk of making anti-D is low without prophylaxis (3.8% in recent ten-year study)
Consider Rh prophylaxis in premenopausal D-neg women (1 vial RhIG per 2-3 weeks; effective as long as anti-D is detectable)
Platelet sterility AABB Standards requires
centers to both limit and detect bacterial contamination of ALL platelets
Limiting contamination Careful skin
preparation Discarding initial 20-
30 cc of blood (done automatically with diversion pouches) Exclusive use of apheresis platelets
Detecting contamination Culture-based methods
Require 24 hour wait before taking sample BacT/ALERT (bioMerieux, Inc) Enhanced Bacterial Detection System (eBDS)
Pre-issue bacterial detection
Verax PGD (Verax Biomedical); approved for
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Compiled by: Victor Perlas Jr., RMT, AMT, IMT (ASCP, HAAD)This lecture handout will be utilized only by University of Saint Louis’ Medical Technology students for their Immunohematology class.
leukoreduced AD-Platelets and pooled WBD-platelets
BacTx (immunetics); approved for transfusion service-pooled WBD-platelets
Old (no longer accepted) methods
Gram stain, swirling, glucose checks
E. Modifications to red cells and platelets Leukocyte reduction (LR)
Definitions (as of AABB Standards, 27th ed.)
In US: ≤ 5 x 106
residual WBCs In Europe: ≤ 1 x 106
residual WBCs US rules:
≤ 5 x 106 white cells in 95% of tested units defines leukocyte-reduced (RBCs, AD-PLTs, and whole blood)
≤ 8.3 x 105 WBCs in 95% of tested units defines leukocyte-reduced [WBD-PLTs (NOTE: 8.3 x 105 x 6 = 5 x 106)]
Each must also retain at least 85% of original component and meet all other QC standards.
Methods Leukocyte reduction
filters [At least 99.99% of WBCs (“4 log” reduction)]
Apheresis collection devices
“Universal” LR not mandated in the US, but vast majority of cellular components are leukoreduced
Types “Prestorage” leukocyte
reduction Usually < 72 hours after draw (always <5 days).
Inline filters at time of collection or post collection filters for red cells.
Apheresis LR is prestorage by definition “Pretransfusion”
leukocyte reduction Immediately prior to transfusion (“bedside”)
• Least desirable• Lack of available QC, poor training• Many older studies done with this
method (especially CMV studies) Better done in
transfusion service before issuing
Established benefits: Prevention of febrile
nonhemolytic transfusion reactions
Generally benign, but mimic early hemolysis First type: WBCs secrete pyrogenic cytokines in
bag before transfusion: Common with PLTs Second type: Pyrogenic cytokines secreted after
transfusion• Seen more commonly with RBC
transfusions• Recipient antibodies against transfused
WBC antigens or immune complexes (donor WBCs and coating antibodies) binding to recipient macrophages
• Prestorage LR prevents both, pretransfusion only the second type
Prevention of HLA immunization
HLA antibody formation requires HLA class I antigens be presented by transfused lymphocytes
LR works well to prevent this interaction Use for multiple transfusion recipients UV-B treatment also works; not available in US.
Prevention of CMV transmission
Virus carried only in a small minority of donor WBCs (monocytes).
Blood. 1995;86,3598-3603; “The Bowden Study” – landmark LR study
• Filtered products equivalent to CMV
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“For I know the plans I have for you, declares the Lord, plans to prosper you and not to harm you, plan
to give hope and a future.”Jeremiah 29:11
Compiled by: Victor Perlas Jr., RMT, AMT, IMT (ASCP, HAAD)This lecture handout will be utilized only by University of Saint Louis’ Medical Technology students for their Immunohematology class.
seronegative in preventing seroconversion.
Neither method is perfect; very early infection may escape testing and/or leukoreduction
Reduction of reperfusion injury post cardiac bypass
Potential benefits: Prevention of
transfusion-related immunomodulation (TRIM)
Controversial, not universally accepted Transfusion seems to immunosuppress
recipients• Increased post-op infections,cancer
recurrence, mortality in transfused patients
Donor WBCs may be the cause, but studies since LR widespread has not proven effect
Reduction of bacterial/parasitic contamination
Some studies suggest reduction in organisms like Yersinia or Leishmania with leukoreduction.
Probably not reliable enough to depend on! Reduction in the risk of
prion disease One of the reasons for universal LR in Europe Current: Prion known to be in plasma, too Prion-specific filters developed
Contraindications: Prevention of
transfusion-associated GVHD
Irradiation is only proven method (cases of TA-GVHD with leukoreduced blood reported)
Transfusion of granulocyte concentrate
Transfusion of previously frozen products (FFP, cryo, etc); most consider unnecessary
Washing 1-2 L of saline removes
about 99% of plasma Generally takes one to
several hours (automated)
Shelf life: Red cells: 24
hours post-wash Platelets: 4
hours post-wash Why bother?
a. Removal of plasma proteins for hypersensitivity (RBCs and platelets)
Classic example: IgA deficiency
A few IgA deficient patients develop anti-IgA; exposure leads to anaphylaxis.
Requires intense washing (3L or so) IgA-deficient donors are alternative
Haptoglobin deficiency
May be similar to IgA deficiency Especially common in Asians
Removal of unwanted antibodies
ABO antibodies (neonatal transfusions) T-activation (polyagglutination)
b. Neonatal alloimmune thrombocytopenia (NAT, NAIT, FNAIT)
Severe thrombocytopenia in neonate/fetus usually due to maternal anti-HPA-1A(80%); similar to HDFN in concept
Exposure to antigen via pregnancy or transfusion, antibody formed
IgG crosses placenta, attacks baby’s platelets 25% 1st pregnancy (rapid antibody formation) 10-30% get intracranial hemorrhage
Maternal IVIG used before birth (+/-intrauterine platelet transfusion)
Platelet choices: HPA-1A negative platelets given after birth Washed, irradiated maternal platelets may also
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Compiled by: Victor Perlas Jr., RMT, AMT, IMT (ASCP, HAAD)This lecture handout will be utilized only by University of Saint Louis’ Medical Technology students for their Immunohematology class.
be used (lack antigen and antibody)
c. Removal of unwanted electrolytes (RBCs/PLTs)
Especially in neonatal transfusions
Large-volume or irradiated products
Freezing Cryopreservative agents protect
component while freezing and thawing
Most common: Glycerol at 40% concentration
Deglycerolization before transfusion = washing
DMSO for platelets, but recovery is very poor (1/3)
Why bother?a. Storage of rare, autologous, or O-
negative unitsb. Plasma hypersensitivities (as with
washed)c. Repeated febrile reactions (as with
washed) Storage
Before freezing: CPD, CPDA-1, or CP2D: Maximum 6 day shelf
life before glycerolization Additive solutions (AS-1, AS-3, AS-5): Up to
full 42 day shelf life before glycerolization Red Cells
10 years at –65 C (40% glycerol) 24 hours at 1-6 C after thawing/deglycerolizing
Platelets At least two years at -80 C
Irradiation of cellular components Irradiation dose deactivates T-
lymphocytes Prevent transfusion-associated
graft vs. host disease. Radiation dose:
2500 cGy (“rad”) dose required targeted to center of bag, with at least 1500 cGy in all parts of the bag
Indications for irradiation Immunosuppression
1.Congenital T-cell deficiencies (DiGeorge’s, SCID, Wiskott-Aldrich)
2.Stem cell or marrow transplant recipients3.Patients taking chemo agents that attack T-
cells (Fludarabine, other purine analogs)4.Aplastic anemia patients5.Patients with solid tumors getting intensive
chemotherapy/radiation
Intrauterine transfusions, premature neonatal transfusions, and neonatal exchange transfusions
Hematologic malignancies (esp. Hodgkin’s) Granulocyte transfusions Receiving blood from a first-degree relative
donor or receiving HLA-matched units
Patients probably NOT at risk (but often get irradiated products anyway).
Solid organ transplant recipients Term neonates AIDS patients Patients receiving previously frozen blood
products (FFP, CRYO)
Maximum storage: 28 days after irradiation or regular expiration date, whichever comes first
K+ triples and free hemoglobin increases in plasma, indicative of mild RBC membrane damage
F. Plasma Group
Fresh Frozen Plasma (FFP) Widely used but not well-
studied prospectively Whole blood-derived or from
apheresis (AD-FFP can have much higher volume)
Specifics for WBD-FFP:
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Compiled by: Victor Perlas Jr., RMT, AMT, IMT (ASCP, HAAD)This lecture handout will be utilized only by University of Saint Louis’ Medical Technology students for their Immunohematology class.
General notes about coagulation and FFP transfusion:
30-40% of coag factors required for hemostasis. “Adequate” factor levels don’t necessarily give
normal coag tests (mild elevations common) Most FFP transfusions are given for elevated
PT/INR levels (Factor VII most responsible)• Factor VII in-vivo half-life is only about
4 hours• The INR of FFP is roughly 1.2-1.5!
Prophylactic FFP use with mild lab elevations is usually a mistake, even before procedures
• No evidence of bleeding prevention or lab value correction when these patients are transfused
No universal threshold exists, but many use INR of 2.0 as indicator of serious factor deficiency
Indications: Bleeding patients with coagulopathy due to
multiple factor deficiencies• Hepatic Failure• Dilution from massive transfusion• Consumptive processes (DIC)
Bleeding patients requiring urgent reversal of vitamin K deficiency from warfarin effect
• Warfarin affects factors II, VII, IX, X• Vitamin K (even IV) takes hours
(between 6 and 12) to result in replenishment of these factors
• For non-bleeding patients, correct without FFP administration (hold dose and give vitamin K)
• In bleeding patients, Prothrombin Complex Concentrate (PCC, containing II/VII/IX/X) may be better choice than FFP
• In general, need at least 10-20 ml/Kg of FFP to attain hemostasis in these patients (usually more)
• Chest 2008;133:160S-198S; guidelines on correction of warfarin-related coagulopathy
Trauma transfusion• Recent literature suggesting that trauma
patients given plasma in close to 1:1
ratio with RBCs have better survival (first reported in military)
• Many trauma centers have established “trauma/massive transfusion protocols” that attempt to make 1:1 ratio automatic
• Concerns about plasma transfusion complications (TRALI) and AB plasma wastage
Dilutional coagulopathy• Transfusion of multiple coag factor poor
products (RBCs and crystalloids in massive transfusion) dilutes coag factors.
• Usually not apparent until after at least 10-15 or more units of RBCs (with accompanying fluid) in a 24 hour time span
• May be less of an issue with massive transfusion protocols and 1:1 ratios mentioned above
Transfusion or plasma exchange for TTP/HUS
• Acquired or congenital ADAMTS13 deficiency; large vWF multimers lead to platelet thrombi
• FFP has normal amounts of ADAMTS13
• Plasma exchange standard treatment• Treatment until PLT count is at least
100K with near normal LDH Other factor-specific coagulopathies without
an available factor concentrate (V, X, XI in US)
C1-esterase inhibitor deficiency
Contraindications: Volume expansion
• Albumin, crystalloids are safer. Heparin reversal
• Antithrombin, which potentiates heparin!
• Use protamine sulfate or just stop the heparin.
Factor deficiencies with available concentrates Prophylactic or pre-procedure treatment of mild
elevations of PT/PTT “Nutrition,” “Wound healing,” or “well-being”
Preparation/storage Pre-storage
• Separated and placed at -18 C within 8
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Compiled by: Victor Perlas Jr., RMT, AMT, IMT (ASCP, HAAD)This lecture handout will be utilized only by University of Saint Louis’ Medical Technology students for their Immunohematology class.
hours• NOTE: FFP does not have to be
completely frozen at 8 hours, just in -18C environment
Pre-transfusion• Stored at -18C up to 1 year (or -65C for
7 yrs)• Thawed at 30-37C (water bath/approved
device)• Stored after thawing at 1-6 C for 24
hours*** FDA historically allowed 6 hours; now allows 24 hrs as specified in Circular of Info; May extend beyond 24 hours per AABB (see“thawed plasma” below)
Dosage Commonly given two bags at a time in adults 10-20 mL/Kg more appropriate (3-7 bags if 70
Kg) 10-15 mL/Kg appropriate dose in neonates.
Effect Standard dose increases factor levels by about
20-30% in a 70 Kg person. Transient due to short half-lives (FVII) Greatly elevated PT/PTT more affected than
mild Will not help if INR is <1.5-1.6!
ABO and Rh Donor antibodies compatible with recipient
RBCs. Give without regard to Rh.
ABO compatibility for plasma transfusion
Plasma Variants Plasma frozen within 24 hours
of phlebotomy (PF24 or “FP24”)
Not frozen in 8 hours like FFP, but 24 hours
Factor V levels essentially equal to those in FFP, while factor VIII levels decline 20-25% vs. FFP
Stored and managed just like FFP Except for DIC patients, can be used identically
to FFP (low FV and/or FVIII is uncommon) Can’t be used to make CRYO May be from whole blood or from apheresis
plasma collection
Plasma frozen within 24 hours of phlebotomy held at room temperature up to 24 hours after phlebotomy (PF24RT24)
Horribly named product (HAHAHAHA! I’m sorry for this guys!); only from apheresis plasma collections
As per the name, held up to 24 hrs at RT before freezing
As expected, decreased FV, FVIII (also protein S) vs. FFP
Store and use just like FFP/FP24
“Thawed Plasma” FFP/PF24/PF24RT24, once thawed, is only
good for 24 hours Thawed FFP/FP24/PF24RT24 may be relabeled
as “Thawed Plasma” and kept at 1-6 C for up to 5 days
Indications are essentially identical to FFP, despite a decrease in FV and FVIII to ~50% by 5 days
Plasma, cryoprecipitate reduced (“CRYO- reduced plasma”, “cryosupernatant”)
Residual plasma that remains after cryoprecipitate harvested from FFP.
Decreased levels of stuff that is in CRYO (FVIII, fibrinogen, vWF, FXIII)
Sole indication: TTP patients (due to less vWF), used in plasma exchanges if regular FFP doesn’t work (literature shows mixed results on this).
Storage and transfusion just like FFP.
Source plasma Apheresis collection, usually paid donors Used for manufacture, not transfusion Licensed product
Recovered plasma
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Compiled by: Victor Perlas Jr., RMT, AMT, IMT (ASCP, HAAD)This lecture handout will be utilized only by University of Saint Louis’ Medical Technology students for their Immunohematology class.
Plasma from volunteer whole blood donation Unused units of frozen plasma may be relabeled
as recovered and sold for further manufacture (albumin, etc) under short supply agreement
Unlicensed product, blood center revenue source
Liquid plasma/plasma
Plasma separated from whole blood up to 5 days after expiration
Liquid plasma: stored at 1-6 C, not frozen (Can be transfused up to 5 days after whole blood expiration date, but rarely used)
Plasma: stored at -18 C or below; rarely used
Cryoprecipitate Also has seen increased use in
recent years
QC Requirements: > 80 IU FVIII per bag > 150 mg fibrinogen per bag (easy! Most
contain at least 250-300 mg)
Indications Fibrinogen deficiency (congenital or
acquired)• General threshold: 100 mg/dl for
adequate hemostasis post-surgery.• Many use 10-20 bags per dose in adults,
more if fibrinogen is less than 50 mg/dl.• 10 bags deliver about 2500 mg of
fibrinogen in about 150 ml of volume (> 1 liter FFP needed for same amount!)
• Fibrinogen concentrate may decrease future use
Treatment of uremic thrombocytopathy• Acquired adhesion defect (probably)
which may respond to vWF supplementation
• Generally seen with creatinine levels > 3
mg/dL• Second line of defense (after DDAVP,
dialysis)• Also: Conjug. estrogens, inc. HCT to
~30%• Am J Med. 1994;96:168-79 describes
treatment of uremic thrombocytopathy.
Factor XIII deficiency (if concentrate unavailable)
Topical “glue”• Historically mixed with bovine
thrombin and applied directly to raw surfaces
• Currently available fibrin sealants (treated, virus-free) have made this less common.
Treatment of von Willebrand’s disease• Use only if FVIII concentrates are not
available [Some FVIII concentrates (e.g., “Humate- P”) contain vWF]
• Cryo may be used for severe forms. • DDAVP can be used for milder forms
Treatment of hemophilia A• Use only if emergency and no factor
VIII concentrate available.
Manufacture Made from a single unit of FFP (not PF24 or
PF24RT24) Thaw FFP at 1-6 C, spin and remove liquid, re-
freeze slushy precipitate within 24 hours Commonly “pre-pooled” (before storage) under
sterile conditions at blood centers (variants: 4, 5, 8, 10 bags most common)
Storage and preparation for transfusion
-18 C for 1 year After thawing (at 30-37 C, like FFP), store up to
6 hours at 20-24 C (unlike FFP) (Pre-pooled CRYO has a 6 hour shelf life after thawing)
If units are pooled without sterile docking equipment, transfuse within 4 hours.
No compatibility testing required ABO-compatible is preferred by some, but
paucity of anti-A/B makes it really not important Can give without regard to Rh status
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Compiled by: Victor Perlas Jr., RMT, AMT, IMT (ASCP, HAAD)This lecture handout will be utilized only by University of Saint Louis’ Medical Technology students for their Immunohematology class.
Factor concentrates Factor VIII concentrate
Used for moderate to severe hemophilia A Virus inactivated or recombinant May contain vWF and be used in vWD.
Factor IX concentrate Used for hemophilia B Virus inactivated or recombinant NOT the same as Factor IX Complex
Concentrate
Prothrombin Complex Concentrate (PCC)
Or, “Factor IX Complex Concentrate” Approved only for bleeding hemophilia B
patients, but USED in warfarin overdose correction
Not “activated” as in the past; much less thrombosis
All U.S. versions except one lack Factor VII, which limits utility
Albumin and plasma protein fraction
Virus inactivated, expensive volume expanders
Differ only in composition Albumin: 96% albumin, 4% globulins/others PPF: 83% albumin, 17% globulins/others.
G. Granulocyte concentrate Increasing use due to off-label use of
donor stimulation with G-CSF and/or steroids
Effect not definitively proven Indications
Consider in premature neonates with sepsis or infections, transplant patients with infections, patients with chronic granulomatous disease
Aside from above, a clinical situation including:
Fever for 24-48 hours, Proven bacterial or fungal infection No response to antibiotic therapy Neutropenia (<500/uL; <3000/uL in neonates) Reversible bone marrow hypoplasia
Not currently indicated for: Prophylactic use Patients with no hope of marrow
recovery 1.0 x 1010 is minimum yield (required in
75%), but stimulation gives much greater yield; not FDA-approved
Cans and Cant’s! Can (and must) irradiate to
prevent TA-GVHD. (Irradiation deactivates T-lymphs but not PMNs)
Can’t leukoreduce to prevent CMV transmission.
Storage conditions 24 hours from collection at 20-
24 C, without agitation Cautions
Must be ABO, Rh, and crossmatch compatible
Most are transfused before inf. disease testing is done; recently tested apheresis PLT donors commonly used
H. DDAVP (Desmopressin) Synthetic ADH used for treatment of
diabetes insipidus. Causes release of vWF from endothelial
cells; functionally increases FVIII, as well.
Potential indications: Uremic thrombocytopathy
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Cast your cares on the Lord and He will sustain you; He will never let the righteous fall.Psalm 55:22
Compiled by: Victor Perlas Jr., RMT, AMT, IMT (ASCP, HAAD)This lecture handout will be utilized only by University of Saint Louis’ Medical Technology students for their Immunohematology class.
0.3-0.4 g/Kg IV x 1; repeat with caution Should be considered before platelets or CRYO.
Mild hemophilia A (>5% FVIII levels) and von Willebrand’s disease (type I)
0.3 g/Kg IV x over 30 min (30 min before surgery); repeat with caution
Effect decreases with doses >q 48 hrs (“tachyphylaxis”)
I. Recombinant activated factor VII (NovoSeven) Non-human-plasma-derived product that
is currently FDA-approved for use in: Hemophiliacs (A or B) with
inhibitors (bleeding prevention and bleeding treatment)
Patients with congenital factor VII deficiency (bleeding prevention and bleeding treatment)
Widespread “off-label” use has occurred, as NovoSeven gained traction as a “magical” hemostatic agent!
Estimated 1-2% risk of thrombosis is concerning
JAMA. 2006;295:293-298 (O’Connell, et al) article reported that most serious thromboembolic complications from NovoSeven followed off-label use
Thrombotic stroke, acute MI, and pulmonary emboli; NOTE that these were not definitely caused by NovoSeven, just associated with its use.
Off-label use may be considered for: Treat/prevent surgical bleeding
in trauma patients Reversal of anticoagulant
therapy (warfarin and factor Xa inhibitors)
Treat/prevent surgical bleeding in advanced liver failure
patients. Perioperative blood loss
prevention (after failed clotting factor replacement therapy) in cardiac surgery, neurosurgery, OB/GYN surgery, and urologic surgery
Not indicated for routine pre-procedure prophylaxis
Typical doses: 20 to 40 mcg/Kg in non-emergencies, 41 to 90 mcg/Kg otherwise
Roughly 2-hour half-life, repeat dose often
"Don't Quit" From an internet source
When things go wrong, as they sometimes will,when the road you’re retrudging seems all up hill,when the funds are low and the debts are high,and you want to smile, but you have to sigh,when care is pressing you down a bit,rest, if you must-but don’t you quit.
Life is queer with its twists and turns,as every one of us sometimes learns, and many a failure turns abut,when we might have won had we stuck it out,don’t give up, though the pace seems slow-you might succeed with another blow.
Often the goal is nearer than it seems to a faint faltering man,often the struggler has given upwhen he might have captured the victor’s cup,and he learned too late, when the night slipped down, how close he was to the golden crown.
Succeed is failure turned inside out-the silver tint of the clouds of doubt-and you never can tell how close you are,it may be near when it seems afar;
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Compiled by: Victor Perlas Jr., RMT, AMT, IMT (ASCP, HAAD)This lecture handout will be utilized only by University of Saint Louis’ Medical Technology students for their Immunohematology class.
so stick to the fight when you’re hardest hit-it’s when things seem worst that you ’t quit.
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