• Introduction to Transfusion History: • Plasma Expressors:

• Blood acquisition, storage, and transfusion initially as whole blood. • Types:

• Transition in the 1950s with the introduction of plastic bags and refrigerated • Basic (spring-loaded Plexiglas)
centrifuges, leading to component therapy.
• Automated (e.g., Compomat G5 by Fenwal)
• Component Preparation:
• Features of automated devices:
• Blood donation providing therapy in forms of:
• Barcode scanners, pneumatic pumps, integrated scales, BECS
• Red blood cells (RBCs) interfaces
• Platelets • Justification for cost:
• Fresh-frozen plasma • Consistent product quality, higher plasma yield, better ergonomics,
effective workforce utilization
• Cryoprecipitate
• Comparison shown in Figure 15–1 (place figure here)
• Derivatives of plasma (e.g., immune serum globulin)
• Manufacturing Process:
• Tubing Sealers
• Transformation methods:
• Functionality
• Centrifugation from whole blood
• Utilize targeted radio frequency energy and pressure to seal PVC
• Apheresis at donor’s bedside tubing
• Collection Profiles: • Activated by a trigger when sealing is required
• Apheresis platelets: • Seal includes a thin band for easy separation
• One donation up to 3 adult doses (18 times from whole
• Segmentation Process
blood)
• Seals placed strategically to segment blood components
• Apheresis plasma:
• Each segment includes a serial number for traceability
• One donation up to 1 L (3-4 times from whole blood)
• Starting sealing from the closed end towards the open container to
• Apheresis double-red blood cells:
prevent pressure buildup
• One donation up to 2 units (double from whole blood)
• Sterile Connection Devices (SCDs)
• Combinations (platelets and plasma, platelets and RBCs, plasma
• Connection Mechanism
and RBCs)
• Connects two blood bags via PVC tubing without breaching integrity
• Equipment:
• Utilizes single-use copper wafer heated to a sterile temperature
• Intended for manufacturing, quality control, or storage
• Wafer slices through tubing, which is then realigned and sealed
• Influence of factors like anticoagulant/preservative, additive, satellite
bags, inline leukoreduction filter • Process
• Documentation of Manufacturing Steps: • Clamping of tubing in channel
• Critical steps documentation: • Heating and slicing with copper wafer
• Performer, equipment used • Alignment, sealing, and cooling of tubing
• Date and time for time-sensitive components • Inspection for proper alignment and leaks
• Role of Blood Establishment Computer System (BECS) • Plasma Freezers
• Compliance with FDA and AABB requirements • Freezing Methods
• Retention and protection of manufacturing records • Standard freezer (-18°C or colder) for gradual freezing
• Centrifuges: • Rapid freezing devices for enhanced clotting factor recovery
• Types: • Blast freezers using circulating cooled air
• Large floor units • Immersion baths circulating antifreeze and water mixture
• Large tabletop units • Techniques
• Capacity: • Plasma units placed flat on trays or in protective pockets
• Up to 6 to 12 units of whole blood • Rapid freezing to maximize throughput
• Programmable settings: • Blood Component Storage Devices
• Speed (RPM) and time • Selection and Validation
• Profile influenced by components: • Devices must maintain FDA-regulated storage temperatures
• Red blood cells, plasma, platelets, cryoprecipitate • Continuous temperature monitoring and recording
• AABB-recommended centrifuge conditions provided in Table 15–1 (place • Alert system for unacceptable temperature conditions
table here)
• Types of Devices
• Refrigerators, freezers, and platelet agitators
• Optional environmental chamber for platelet storage at 20° to 24°C
• Blood Product Manufacturing and Quality Control
• Whole Blood Collection
• Ratio of anticoagulant/preservative to blood volume (14 mL per 100
mL)
•
 • Variations in collection volumes and anticoagulant/preservative types
• 450 mL (±10%) with 63 mL anticoagulant-preservative
• 500 mL (±10%) with 70 mL anticoagulant-preservative
• Minimum donor hematocrit of 38%
• Shelf life and storage conditions based on anticoagulant/preservative
used
• ACD-A, CPD, or CP2D: 21 days at 1° to 6°C
• CPDA-1: 35 days at 1° to 6°C
• Quality Control
• Routine quality-control indicators not measured
• Process control measures during blood collection
• Quality control of hemoglobinometers and scales used
• Ensures whole blood component meets required
characteristics
• Figure 15–1 (Comparison of automated Compomat G5 (Fresenius Kabi) to a manual
plasma expressor)

• Red Blood Cell (RBC) Separation Methods:

• Centrifugation
• Apheresis
• Sedimentation
• Quality Control:
• Timing of RBC Preparation:
• RBCs without additive solution: finished hematocrit < 80%
• Typically shortly after donation to allow manufacture of other blood
• Measured by commercial hematology analyzer or manual capillary
components
tube method
• Platelet concentrates, frozen plasma, or cryoprecipitate prepared within 8 to
• RBCs with additive solution: no hematocrit testing required
24 hours after collection
• Addition of 100 mL or more of additive solution results in hematocrit
• Additive Solutions (AS):
of ~55%
• Must be added within 3 days of collection if employed
• AABB Standards for Blood Banks and Transfusion Services (for Apheresis):
• Results in finished product with hematocrit of 55% to 65%
• Mean hemoglobin: at least 60 g or 180 mL of RBC volume
• If not used, plasma volume removed to achieve hematocrit of 65% to 80%
• 95% of units tested: greater than 50 g of hemoglobin or 150 mL of RBC
• RBC Component Characteristics: volume

• Final red cell volume: 160 to 275 mL • Parameters may vary based on FDA-approved instructions for use of
collection device
• Hemoglobin content: 50 to 80 g suspended in residual plasma and/or additive
solution
Platelets
• Storage Conditions:
• Platelet Collection Methods:
• RBCs stored at 1° to 6°C
• Apheresis Platelet Collection:
• Shelf Life:
• Increasing trend observed in the United States.
• Without additive solution: 21 (CPD, CP2D, ACD-A) or 35 (CPDA-1) days
• Platelets from Whole Blood:
• With additive solution: 42 days
• Collection within 8 hours of donation.
• Licensed Anticoagulant-Preservative and Additive Combinations in the US:
• Donors taking platelet-inhibiting drugs (e.g., aspirin) may be
• CPD with AS-1 or AS-5 excluded.
• CP2D with AS-3 • Mechanism for donor exclusion required.
• ACD-A with AS-3

• Platelet Types:
 • Random-donor platelets (RDPs):
• Derived from whole blood.
• Relatively inexpensive.
• Collection bag systems with platelet storage containers.
• Second spin for harvesting additional components.
• Prone to RBC contamination.
• Single-donor platelets (SDPs):
• Derived from apheresis donations.
• Each component contains one adult dose.
• Expensive to collect and process.
• Apheresis equipment, disposable kits, solutions, and staff labor
required.
• Low RBC contamination.
• Manufacturing Methods:
• Platelet-Rich Plasma (PRP) Method (Used in the United States):
• Centrifugation at slower speed and shorter time.
• Platelets remain suspended in plasma.
• Harvesting of PRP followed by centrifugation for platelet separation.
• Buffy Coat Method (Used in other countries):
• Centrifugation at hard-spin profile.
• Harvesting of platelet-rich buffy coat.
• Pooling and addition of synthetic medium.
• Centrifugation at soft-spin setting for platelet harvesting.
• Bacterial Contamination:
• Risk of bacterial growth due to storage conditions.
• Bacterial contamination estimated at 1 in 2,000 to 1 in 3,000 components.
• AABB Standards and FDA regulations for detection and prevention.
• Detection Methods:
• Haemonetics eBDS System:
• Oxygen consumption as surrogate marker.
• Incubation and oxygen content measurement.
• BacT/ALERT 3D System:
• Liquid growth medium with carbon dioxide sensor.
• Incubation and color change detection.
• Pathogen Reduction Technology (PRT):
• FDA-approved technology for certain platelet products.
• Extends platelet dating to 7 days.
• Testing requirements for extended dating.
• Quality Control:
• Platelet Count:
• Whole blood-derived: ≥5.5 × 10^10 platelets.
• Apheresis/single-donor: ≥3 × 10^11 platelets.
• pH Maintenance:
• ≥6.2 throughout storage period.
• FDA Guidance for Apheresis Platelets:
• Statistically sound sample sizes for yield and pH.
• Minimum sample sizes: 11 platelets/month for yield, 60
platelets/month for pH.
• No failures allowed.
• FDA Approvals and Studies:
• PASSPORT Study (2005-2008):
• Extension of platelet product outdate to 7 days.
• Testing with BacT/ALERT 3D system.
• High risk of bacterial contamination led to study termination.
• Verax Platelet PGD Test Approval (2011):
• Safety measure for bacterial contamination detection.
• FDA Clearance for 7-Day Platelet Dating (2015):
• Point-of-issue safety device testing within 24 hours before
transfusion.
• FDA Draft Guidance (March 2016):
• Proposed steps to reduce adverse reactions due to bacterial
contamination.
• Requirement for PGD testing on days 4 and 5 of shelf life.
• PRT-treated platelets must be transfused within 5 days.
• Leukoreduction (Leukocyte Reduction)
• Definition: Removal of white blood cells (WBCs) from blood or blood
components before transfusion.
• FDA Recommendations (1996):
• Leukoreduced blood components to contain less than:
• 5.0 × 10^6 residual WBCs per each whole blood, red blood
cells, or apheresis platelet.
• 8.3 × 10^5 residual WBCs per each platelet derived from
whole blood.
• At least 85% recovery of the original component after leukoreduction.
• Benefits:
• Reduces recurrent febrile nonhemolytic transfusion reactions.
• Reduces alloimmunization to leukocyte antigens.
• Protects against transmission of cytomegalovirus (CMV).
• Methods:
• Pre-storage leukoreduction: performed within 72 hours of collection.
• Bedside filtration: for components not leukoreduced early in shelf life.
• Reports: Over 84% of whole blood/RBCs and over 86% of apheresis
platelets in the US are leukoreduced.
• Policy: 73% of transfusing facilities exclusively transfuse
leukoreduced blood components.
• Leukoreduction Statistics:
• Almost 12 million leukoreduced blood components
transfused in 2011.
• Only 1.1% leukoreduced at bedside; 98.9% leukoreduced
before or during storage.
• Biological Response Modifiers (BRMs)
• Released from leukocytes during storage.
• Promote febrile transfusion reactions.
• Examples:
• Proinflammatory cytokines: interleukin-1, interleukin-6, tumor
necrosis factor.
• Complement fragments: C5a, C3a.
• Impetus for Pre-storage Leukoreduction:
• BRMs released during storage implicated in febrile reactions.
• Bedside Filtration
• Association with Adverse Effects:
• Precipitous hypotension, particularly in patients on ACE inhibitors.
• No association with:
• Pre-storage leukocyte reduction.
• Leukocyte Antibodies and BRMs
• Removing leukocytes before transfusion prevents reactions caused by:
• Leukocyte antibodies in patient's plasma.
• Leukocytes present in transfused blood.
 • Does not prevent reactions caused by:
• BRMs from leukocytes present during storage.
• Preparation of Leukoreduced RBCs and Whole Blood
• Special Filters:
• Achieve at least 99.9% removal of leukocytes.
• Employ multiple layers of polyester or cellulose acetate nonwoven
fibers.
• Filter Attachment:
• Integral attachment by manufacturer or individual attachment post-
manufacture.
• Financial considerations for the collecting facility.
• Filter Types for Pre-storage Leukoreduction
• Method 1:
• Characteristics of FFP, PF24, and LP:
• FFP:
• Contains maximum levels of stable and labile clotting factors (about 1
IU/mL).
• Can be further manufactured into cryoprecipitate and cryo-poor
plasma.
• PF24:
• Contains all stable proteins found in FFP.
• Normal levels of factor V.
• Slightly reduced levels of factor VIII.
• Known to have reduced levels of labile clotting factors, especially
factor VIII, but differences are mostly statistically insignificant or
maintain hemostatic activity well above the minimum required for
safe surgical hemostasis.

• Whole blood passed through leukoreduction filter before • LP:

centrifugation. • Factor levels poorly characterized.
• Platelets may also be trapped in the filter, hindering manufacturing of • Variability depending on manufacturing process.
random-donor platelets.
• Thawing and Storage:
• Method 2:
• Thawing:
• Whole blood centrifuged, plasma removed, packed cells passed
through leukoreduction filter. • FFP and PF24 thawed at 30° to 37°C or in an FDA-approved
microwave device.
• RBC Inventory
• If a water bath is used, product must be protected from water
• Many institutions maintain 100% of RBC inventory as pre-storage contact.
leukoreduced products.
• Storage:
• Historical Methods for RBC Leukoreduction
• Thawed plasma may be stored at 1° to 6°C for up to 24 hours.
• Centrifugation and washing.
• If not transfused within 24 hours, can be stored for up to 5 days but
• Freezing, thawing, and deglycerolizing. labeled as "thawed plasma".
• Apheresis Platelet Collection • Volume and Yield:
• Configured to collect a leukocyte-poor product without filtration. • FFP and PF24 from apheresis:
• Considered pre-storage leukoreduction. • Volume may be up to 800 mL.
• Quality Control Testing • Large apheresis plasma donations may also be divided into smaller
• WBC Count: doses.

• Below level of linearity or detectability for routine hematology • FFP and PF24 from whole blood collection:
analyzers. • Volume varies (200 to 375 mL) depending on factors such as original
• Methods: collection volume, donor’s hematocrit, and processing.

• Manual counting using specialized hemocytometer (Nagoette • Example: If 550 mL collected with 38% hematocrit, plasma yield is
chamber). 310 mL.

• Flow cytometry. • Yield may vary due to factors like hematocrit and processing
methods.
• Quality Control:
• Plasma Components and Storage:
• Neither FDA nor AABB mandate quality control testing for plasma
• Plasma from whole blood donations can be manufactured into various components.
components:
• Importance of accurate labeling and volume measurement:
• Fresh-frozen plasma (FFP): frozen within 8 hours.
• Scales must be calibrated and tested for accuracy.
• Plasma frozen within 24 hours (PF24): frozen within 24 hours.
• Practical checks to avoid mislabeling or miskeyed entries.
• Storage Conditions:
• Manual labeling processes should include steps for accurate labeling
• FFP and PF24: and to avoid errors.
• Stored at –18°C or colder for 1 year or at –65°C or below
for 7 years with FDA approval.
• Cryoprecipitated Antihemophilic Factor (Cryoprecipitate)
• Liquid plasma (LP):
• Definition: Coldprecipitated concentration of factor VIII
• Stored at 1° to 6°C.
• Components:
• LP expires 5 days after the whole blood shelf life from which
it was collected. • Factor VIII (AHF)

• Example: CPD LP has a shelf life of 26 days (CPD whole • Fibrinogen

blood shelf life is 21 days), CPDA-1 LP has a shelf life of 40 • Factor XIII
days (CPDA-1 whole blood shelf life is 35 days).
• von Willebrand factor (vWF)
• Apheresis Plasma:
• Cryoglobulin
• Must be frozen within specified time frames and stored under
conditions specified by the collection device’s labeled indications. • Fibronectin
 • Preparation Process:
• Thawing FFP at 1° to 6°C
• Centrifugation at 4°C
• Harvesting cryoprecipitate within 1 hour
• Unit Preparation:
• 1 unit of FFP yields 1 unit of cryoprecipitate
• Adult dose: 10 units
• Storage:
• Below –18°C for up to 1 year from collection date
• Transfusion: • Quality Control

• Thawed quickly at 30° to 37°C • Cryoprecipitate:

• Must be transfused within 6 hours of thawing • Contains at least 80 units of AHF activity and at least 150 mg of
fibrinogen
• Pooled cryoprecipitate transfused within 4 hours if prepared in open
system • Factor VIII and fibrinogen activity assays performed

• Indications: • Cryopoor Plasma:

• Factor XIII deficiency • No quality control indicated

• Hypofibrinogenemia
• Secondary treatment for hemophilia A and von Willebrand’s disease • Granulocyte Concentrates

• Other Uses: • Definition: A component containing at least 1 × 10^10 granulocytes

• Production of fibrin glue • Measurement: Can be done using an automated hematology analyzer within
linearity limits
• Virally inactivated commercial products for controlling bleeding in
cardiovascular surgeries • Dilutions may be necessary at higher WBC concentrations

• Cryopoor Plasma (CPP) • For detailed information, see leukapheresis in Chapter 18, “Apheresis” (Table
15–2)
• Definition: Plasma after removal of cryoprecipitate
• Components:
• Albumin
• Factors II, V, VII, IX, X, XI
• ADAMTS13
• Preparation Process:
• Thawing FFP at 1° to 6°C
• Centrifugation at 4°C
• Refreezing within 24 hours
• Storage:
• Below –18°C for up to 1 year from collection date
• Transfusion:
• Thawed at 30° to 37°C
• Must be transfused within 24 hours, or up to 5 days if relabeled as
thawed plasma, cryoprecipitate reduced
• Indications:
• Transfusion or plasma exchange in Thrombotic Thrombocytopenia
Purpura (TTP) patients
• Preparation of Cryoprecipitate and Cryopoor Plasma
• Process outlined in Box 15–3
• Thawing FFP at 1° to 6°C
• Centrifugation at 4°C
• Harvesting cryoprecipitate within 1 hour
• Refreezing CPP within 24 hours
• Additional Manufacturing: Irradiation
• Indications: To prevent transfusion-associated graft-versus-host disease (TA-
GVHD)
• Recommended minimum dose: Gamma irradiation of 25 Gy to central portion
of blood unit, with no less than 15 Gy delivered to any part
• Methods: Radioactive source (cesium-137 or cobalt-60) or x-ray
• Confirmation: Radiochromic film label darkening confirms irradiation
• Verification: Semiannual or annual dose delivery verification required
• Expiration Dates:
• RBCs: 28 days from irradiation or original outdate, whichever is
sooner
• Platelets and granulocytes: Expiration not impacted by irradiation
• Storage Conditions for Red Blood Cells (RBCs) and Platelets:
• RBCs stored in a solution containing additive solution, residual plasma, and
anticoagulant for up to 42 days.
• Stored at 1° to 6°C for up to 24 hours after washing.
• Platelets stored in donor plasma and anticoagulant solution with or without
additive.
• Stored at 20° to 24°C and must be transfused within 4 hours.
• Methods of Washing Components:
• Automated washing devices commercially available.
• Manual washing process using a centrifuge:
• Adding wash solution to the component.
• Centrifuging.
• Manually expressing supernatant into a waste bag.
• Indications for Washing Components:
• Allergic Reactions:
• Washing for patients with severe allergic reactions to residual plasma
proteins.
• Reserved for anaphylactic or anaphylactoid reactions unresponsive
to pre-transfusion medication.
• Some IgA-deficient patients may develop anti-IgA reactions.
• Removal of Antibody:
• In cases of hemolytic disease of the fetus and newborn or neonatal
alloimmune thrombocytopenia.
• Washing allows transfusion without additional antibody
exposure to the fetus/newborn.
• Group O RBCs may be washed to remove small amounts of anti-A,
anti-B, and anti-A,B.
• Removal of Other Substances:
• Potassium Removal:
• Washing to avoid hyperkalemic cardiac arrhythmias or
arrest.
• Extracellular potassium levels can reach up to 60 mEq/L
after 32 days of storage.
• Irradiated RBCs may have levels up to 31 mEq/L as early as
2 days post-irradiation.
• Washing after irradiation reduces extracellular potassium
levels.
• Clinical Concerns and Effects of Potassium:
• Effects of High Potassium Levels:
• Potassium levels of 7.5 mEq/L and higher can depress cardiac
muscle electrical signal conduction.
• In large patients or those with normal compensatory functions,
potassium load may be neutralized.
• In small patients with central venous catheters, high potassium can
cause cardiac arrhythmias, arrest, or death.
• Extracellular Potassium Levels in Stored RBCs:
• Levels documented up to 60 mEq/L after 32 days of storage.
• Irradiated RBCs may have levels up to 31 mEq/L as early as 2 days post-
irradiation.
• Effect of Washing on Potassium Levels:
• Washing RBCs after irradiation shown to reduce extracellular potassium
levels.
Aliquots
• Aliquoted Blood Products in Neonatal Transfusions
• Indications for Small-Volume Transfusion:
• Anemia due to various causes such as:
• Spontaneous fetomaternal or fetoplacental hemorrhage
• Twin-twin transfusion
• Obstetric accidents
• Internal hemorrhage
• Iatrogenic Anemia:
• Blood drawn for laboratory testing may lead to transfusion if >10% of
blood volume is lost.
• Frequency: every 2 days for infants requiring close monitoring.
• Transfusion Dosage:
• Typically 10 to 15 mL/kg.
• Preparation of Aliquots:
• Red blood cells (RBCs) or platelets are aliquoted from single-donor
units.
• Plasma aliquots prepared before initial freezing and stored frozen at
–18°C or below for up to 1 year.
• Procedure:
• Zeroing scale with empty container.
• Slowly adding product to final container until target volume
is reached.
• Transfusion Procedure:
• Aspirating desired volume into a syringe through a large-bore needle.
• Labeling with expiration date, patient ID, volume transfused,
preservative, and ABO type.
• RBC Transfusion Impact:
• RBCs with hematocrit level of 80%: Raises hemoglobin by 3 g/dL.
• Use of RBC components in additive solution with lower hematocrit
would raise hemoglobin by smaller increment.
• Closed system maintains original RBC component's outdate.
• CPDA-1 RBC components historically popular, but additive solutions
like AS-3 considered safe.
• Platelet Transfusions:
• Indicated for counts <50,000/mL with bleeding.
• Random or apheresis platelets may be transfused.
• Dose: 5 to 10 mL/kg.
• Increase platelet count by 50,000 to 100,000.
• Storage:
• Quality control testing recommended for pH maintenance.
• Platelet aliquots should not be stored longer than necessary.
• Original component must meet bag manufacturer’s volume
specifications.
• Transfusion-Associated Circulatory Overload (TACO):
• Leading cause of transfusion-related morbidity and mortality.
• Mitigation: slower rate transfusion or dividing blood components.
• Risk factors include various diagnoses and positive fluid balance.
 • Platelet Aliquots for Neonates Procedure (Box 15–4):
• Outlined procedure for preparing platelet aliquots.
• Introduction to Cryopreservation of Red Blood Cells (RBCs)
• Glycerolization of RBCs since the 1950s
• Storage duration: Up to 10 years for rare phenotypes, autologous use, and
military purposes
• Deglycerolized product: Free of leukocytes, platelets, and plasma
• Applications for patients with paroxysmal nocturnal hemoglobinuria and IgA
deficiency
• Cryoprotective Agents
• Penetrating agents: Small molecules (e.g., glycerol)
• Small molecules cross cell membrane into cytoplasm
• Prevent extracellular ice formation
• Nonpenetrating agents: Large molecules (e.g., hydroxyethyl starch,
dimethylsulfoxide)
• Form shell around cells
• Prevent loss of water and dehydration

Pooling
• Pooling Blood Components
• Types of Pooled Components:
• All the same or combination depending on patient's need.
• Traceability and Trackability:
• High-Glycerol Method (40% Weight per Volume)
• Essential for lookbacks or recalls.
• Allows slow, uncontrolled freezing process
• Pooled Cryoprecipitate
• Storage temperature: -65°C or below
• Pooled Types:
• Equipment: Mechanical freezer
• Part of initial manufacturing or pooled after thawing.
• Washing process: Requires larger volume of wash solution
• Prestorage pooled units must be used within 6 hours.
• Timeframe for freezing RBCs: Within 6 days of collection
• Pooled Plasma
• Rejuvenation: Possible up to 3 days after expiration
• Volume Required:
• AABB Standards: Freezer placement within 4 hours of opening
• Depends on factors like patient's height, weight, and hematocrit.
• Thawing process: Approximately 45 minutes in 30° to 37°C water bath
• Multiple liters may be needed.
• Washing solutions: Decreasing osmolarity (e.g., 12% NaCl, 1.6%
• Pooled Platelets
NaCl, 0.9% NaCl with 0.2% dextrose)
• Platelet Count and Dose:
• Exception for sickle trait donors: Use of hypertonic solutions
• Whole blood–derived platelet contains at least 5.5 × 10^10 platelets.
• Storage post-deglycerolization: 24 hours at 1° to 6°C
• Adult dose: 3.0 × 10^11 platelets.
• Low-Glycerol Method (20% Weight per Volume)
• Pooling Procedure:
• Minimal cryoprotection by glycerol
• Six RDPs may be pooled into one bag approved for platelet storage.
• Rapid, controlled freezing procedure required
• Platelets pooled in an open system must be transfused within 4
• Storage temperature: -120°C or below (using liquid nitrogen)
hours.
• Quality Control
• Reconstituted Whole Blood
• Standard procedures for monitoring equipment
• Purpose:
• Objective: At least 80% RBC recovery, <1% residual intracellular glycerol
• Supports neonatal exchange transfusions.
• Example study: Valeri et al. achieved 75% RBC recovery and 1% hemolysis
• Components:
after freezing RBCs for up to 37 years using the high-glycerol method.
• Red blood cells (usually group O) and plasma (usually group AB).
• Preparation:
• Red blood cells may be irradiated, then washed before adding
plasma.
• Target hematocrit: usually 45% to 55%.
• Quality Assurance:
• Testing to ensure finished product is within target range.
 • Provides effective hemostatic control
• Residual porcine vWF enhances hemostasis
• Recombinant Factor VIII
• Synthesized using recombinant DNA technology
• rFVIII-FS (next generation)
• Stabilized with sucrose instead of albumin
• Available in three doses (250, 500, and 1,000 IU)
• Demonstrated predictable clinical hemostatic response
• Inhibitors present in 15% of previously untreated patients
• No transmission of hepatitis or HIV reported
• Factor IX Concentrates
• Available forms:
• Prothrombin complex concentrates (PCCs)
• Factor IX concentrates
• Plasma Derivatives • Recombinant FIX
• Preparation from pooled human source or recovered plasma • Prothrombin Complex Concentrates (PCCs)
• Manufacturing process: Separation, manipulation of pH, alcohol content, • Contains vitamin K–dependent factors II, VII, IX, and X
temperature
• Prepared from large volumes of pooled plasma
• Viral inactivation methods: Heat, solvent-detergent treatment, nanofiltration
• Factors absorbed using barium sulfate or aluminum hydroxide
• Testing for hepatitis A and parvovirus B19
• Lyophilized and virally inactivated (e.g., solvent/detergent)
• Activated Factor VII (Factor VIIa)
• Factor IX (FIX) Concentrate
• Production: Recombinant DNA technology
• Developed by monoclonal antibody purification
• Approved uses: Hemophilia A or B with inhibitors, congenital factor VII
deficiency, Glanzmann thrombasthenia • Less thrombogenic than PCCs

• Off-label uses: Trauma, massive transfusion, liver transplantation • Contains approximately 20% to 30% of FIX

• Notable successes: Controlling intracranial bleeding, uncontrolled nonsurgical • Stored in the refrigerator in lyophilized form
hemorrhages post-VAD implantation
• Recombinant Factor IX (rFIX)
• Risks: Increased risk of thrombosis, thromboemboli
• Produced in Chinese hamster ovary cell line
• Mechanism: Binding to tissue factor, activation of factor IX and X, thrombin
• Not thought to transmit human infectious disease
generation
• Factor XIII Concentrates
• Full thrombin generation: Occurs after addition of up to 150 nm of recombinant
FVIIa • Factor XIII Deficiency
• Severe autosomal-recessive bleeding disorder
• Factor VIII Concentrates (FVIII) • Associated with neonatal hemorrhage and lifelong bleeding diathesis
• Human Source • Commercially Available
• Prepared from pooled human plasma • Human-derived factor XIII concentrate
• Viral contamination eliminated through: • Temporarily replaces missing factor XIII
• Pasteurization • Recombinant factor XIII
• Heating to 60°C for 10 hours • Homodimer composed of two factor XIII A-subunits
• Addition of stabilizers (albumin, sucrose, or • Indicated for routine prevention of bleeding
glycine)
• Immune Serum Globulin
• Stabilizers removed, product lyophilized
• Concentrate of plasma gamma globulins
• Solvent/detergent treatment
• Prepared from pooled plasma by cold ethanol fractionation
• Using ethyl ether, tri(nbutyl) phosphate, sodium
cholate, and Tween 80 • Preparations available in:

• Disrupting viral coat membrane • Intravenous (IV) or intramuscular (IM) solutions

• Solvent and detergent removed, product • Indications

lyophilized • Immunodeficiency diseases
• Monoclonal purification • Severe combined immunodeficiency
• Immunoaffinity chromatography to select vWF/FVIII • Wiskott-Aldrich syndrome
complex
• Passive antibody prophylaxis against:
• Murine monoclonal antibody used
• Hepatitis
• Product in lyophilized form
• Herpes
• Porcine Factor VIII
• Used in:
• Made from porcine plasma
• Idiopathic thrombocytopenic purpura
• Beneficial for patients with inhibitors to human factor VIII
 • Posttransfusion purpura • Predominantly IgG anti-D
• HIV-related thrombocytopenia • Uses
• Neonatal alloimmune thrombocytopenia • Treatment of ITP
• Considerations • Prevention of Rh hemolytic disease of the newborn
• Individuals with: • FDA Approved Doses
• History of IgA deficiency • 120 mg
• Anaphylactic reactions • 300 mg
• IVIg treated with solvent/detergent for viral inactivation • IM and IV preparations
• No documented cases of HIV or hepatitis B transmission • Dosage Scenarios for Prevention of Immunization
• Hepatitis C transmission reported with IVIg preparations • Varying dosages based on gestation stage
• Use in Rh-positive Platelet Transfusions
• Normal Serum Albumin (NSA) • 300 mg dose IM (120 mg IV) protects against D-positive RBCs
• Preparation Process • Synthetic Volume Expanders
• Prepared from salvaged plasma • Crystalloids
• Pooled and fractionated by a cold alcohol process • Ringer’s lactate
• Treated with heat inactivation (60°C for 10 hours) • Composition: sodium, chloride, potassium, calcium, lactate
ions
• Removes risk of hepatitis or HIV infection
• Normal isotonic saline
• Composition
• Composition: sodium, chloride ions
• 96% albumin
• Use in Burn Patients
• 4% globulin
• Colloids
• Available Solutions
• Dextran
• 25%
• 6% and 10% solutions
• 5%
• Half-life: 6 hours
• Indications
• HES (Hydroxyethyl starch)
• Hypovolemic and hypoproteinemic patients
• 6% solution
• Clinical settings for shock and burn patients
• Half-life: >24 hours
• Contraindications
• Use in Hemorrhagic Shock and Burn Patients
• 25% preparation in dehydrated patients without crystalloid infusions
• Transmission Risk
• Storage
• Free from viral transmission
• 5 years at 2° to 10°C
• Transmission Risk
• Not reported for HIV or hepatitis
• Plasma Protein Fraction (PPF)
• Preparation Process
• Similar to NSA with fewer purification steps
• Composition
• 83% albumin
• 17% globulins
• Available Solution
• 5%
• Indications
• Parallel to NSA
• Contraindications
• Infusion during cardiopulmonary bypass procedures • Antithrombin III Concentrates (AT-III)
• Storage • Preparation
• 5 years at 2° to 10°C • Prepared from pooled human plasma
• Transmission Risk • Heat-treated to prevent viral transmission
• Not reported for HIV or hepatitis • Use
• Rho(D) Immune Globulin (RhIg) • Patients with hereditary AT deficiency
• Preparation • Surgical or obstetrical procedures
• Concentrated antiRho(D) from pooled human plasma • Thromboembolism
• Composition • Inhibitory Targets
 • Clotting factors IX, X, XI, XII, and thrombin • Special Labeling Indications:
• Risk Levels • Types of barcodes in use in the United States include CMV seronegative,
negative for Zika virus by investigational nucleic acid test, and RBC
• Patients with plasma levels of AT-III less than 50% of normal are at
phenotypes.
risk of thrombosis
• Verification Process:
• Recombinant AT (rhAT)
• Unique identifier of the unit, ABO/Rh type, expiration date, and component
• Produced using transgenic technology
labels must be checked with a second person.
• Developed as an alternative to pdAT
• Traceability:
• Minimal adverse events reported
• Method required to trace the unit from its origin to its final disposition.

• Blood Component Labeling Regulations:

• FDA recognizes two acceptable languages for blood component labeling: ABC
Codabar and ISBT 128.
• ABC Codabar:
• Recommended in the 1970s by the Committee for
Commonality in Blood Banking Automation.
• Supported by FDA in 1985 through Guideline for Uniform
Labeling of Blood and Blood Components.
• ISBT 128:
• Developed by the International Society for Blood
Transfusion (ISBT) working group.
• Managed by the International Council for Commonality in
Blood Banking Automation (ICCBBA).
• Recognized by FDA in 2000.
• Mandated by AABB starting from the 25th edition of the
Standards in May 2008.
• ISBT 128 Label Structure:
• 4- by 4-inch label with four 2- by 3-inch quadrants.
• Upper Left Quadrant: Donation and collection facility identifiers.
• Upper Right Quadrant: Blood type.
• Lower Left Quadrant: Product description.
• Lower Right Quadrant: Expiration date and special labels.
• Donor Identification Number (DIN):
• 14 characters containing country, center of origin, year of collection,
sequential number, and check character.
• Unique worldwide and nonrepetitive for 100 years.
• Labeling Components Protocol:
• Each blood center or transfusion service should have its own protocol.
• Original unit, its components, or any modifications must be identified clearly.
• Handwritten changes, if necessary, must be legible.
• ABO/Rh Labeling:
• Indicated by a four-digit code.
• First two digits describe ABO and D type.
• Different codes for allogeneic and autologous donations.
• ABO/Rh and DIN labels strategically placed in line with each other due to
donor's influence on blood type.
• Product Code in Lower Left Quadrant:
• Eight characters indicating component type, subtype, donation type, and
aliquots/divisions.
• First character: Type of component (blood, tissue, hematopoietic
progenitor cell).
• Second to fifth characters: Type of component.
• Sixth character: Donation type matching ABO/Rh labeling.
• Last two characters: Indicate aliquots and divisions.
• Expiration Date and Time:
• Strategically placed in line with product code.
• Expiration barcode: 10 characters (year, Julian date, expiration time).