4.4 Apheresis Products, Fractionation, and Hematopoietic Progenitors

4.4 Apheresis Products, Fractionation, and Hematopoietic Progenitors

Quick Answer: Apheresis collects platelets, plasma, double red cells, granulocytes, or concurrent combinations and returns the rest of the blood to the donor. Fractionation turns large pathogen-inactivated plasma pools into albumin, IVIG, factor concentrates, and RhIG. HPC products are marrow, apheresis PBSC, and cord blood; they are processed, often frozen in DMSO, dosed by CD34, and regulated as HCT/Ps under 21 CFR 1271, not as 21 CFR 640 blood components. ABO-incompatible HPC grafts can cause immediate residual-red-cell hemolysis and later passenger-lymphocyte hemolysis.

I.D.8, I.D.9, and I.D.14 sit together because students flatten them into “anything collected on a machine.” The exam distinction is the regulatory class and the intended use. Apheresis platelets are still a blood component. Albumin is a plasma derivative. An HPC bag is a cellular-therapy product.

Apheresis products — same donor, different bags

Apheresis withdraws whole blood, separates a target component, and returns the remainder with citrate anticoagulant (usually ACD-A). The donor’s eligibility still follows 21 CFR 630 on the day of the procedure, plus device-specific extracorporeal-volume and red-cell-loss limits (Chapter 2).

Plateletpheresis produces one (or a split pair of) adult platelet doses meeting ≥ 3.0 × 10^11. Interval is commonly no more than twice in 7 days and 24 procedures in 12 months. Aspirin generally defers platelet donation for 48 hours; it does not defer a whole-blood red-cell donation.

Plasmapheresis produces a “jumbo” plasma unit, often 500–800 mL, which can be frozen as FFP or PF24 if freeze-time rules are met, or sent as recovered/source plasma for fractionation. Source Plasma donors have extra 21 CFR 630.15(b) rules (protein, annual physical). Apheresis plasma can be FFP; the freeze clock, not the machine, decides the label.

Double red-cell apheresis (2RBC, “Power Red”) collects two red-cell units and returns plasma and saline. Donor hematocrit/hemoglobin and height/weight gates are stricter than whole blood because two units leave the donor. The interval is 16 weeks (112 days), not 8 weeks. Labeling is two red-cell products, each with its own DIN-linked product code, not one “double” bag issued as a single unit unless the facility’s licensed process says otherwise.

Concurrent collections take more than one component in one sitting — platelets plus plasma is the classic pair; some devices allow platelets plus red cells within red-cell-loss limits. Each bag is labeled and dated as its own component. Granulocyte apheresis was covered in 4.3; it is still an apheresis product, just not a stock inventory item.

Citrate toxicity (perioral tingling, hypocalcemia) is a donor reaction during return, not a recipient transfusion reaction. The extracorporeal circuit does not exempt the products from infectious-disease testing, bacterial-risk control (platelets), or irradiation rules.

Fractionation — pools, inactivation, derivatives

Hospital FFP is one donor, one bag, 21 CFR 640. Plasma derivatives start as large pools of Source Plasma and recovered plasma, then go through industrial fractionation (cold-ethanol/Cohn-Oncley methods, chromatography, or both) plus pathogen inactivation steps such as solvent-detergent treatment, nanofiltration, pasteurization, or low-pH incubation. Pooling without inactivation would be an infectious-disease disaster; the inactivation step is why derivatives are a different safety model from single-unit FFP.

Know the named products at BB level:

• Albumin (5% and 25%) — colloid volume expansion and, in some protocols, replacement during plasma exchange. Not a coagulation-factor product.
• IVIG (and hyperimmune globulins) — replacement or immunomodulation. RhIG is the blood-bank-critical hyperimmune: plasma-derived anti-D used to prevent D alloimmunization, manufactured from large pools, not from one directed donor’s plasma bag.
• Plasma-derived factor concentrates — Factor VIII, Factor IX, prothrombin complex concentrates, antithrombin, fibrinogen concentrate. Many hemophilia patients now receive recombinant factors; plasma-derived products still exist and still come from fractionated pools.
• Other derivatives (alpha-1 antitrypsin, C1 esterase inhibitor) are pharmacy products, not transfusion-service red-cell substitutes.

Do not manufacture “albumin” in the hospital blood bank by concentrating one FFP. Do not treat IVIG or RhIG as cryoprecipitate. Do not list HPC under fractionation. Dating, reconstitution, and viral-safety claims follow each derivative’s license, not the 5-day thawed-plasma rule.

Hematopoietic progenitor cells — not a blood component

HPC products reconstitute marrow. They do not treat anemia or coagulopathy the way Red Blood Cells, platelets, or FFP do. Three collection sources:

• HPC, Marrow — operating-room harvest from posterior iliac crests.
• HPC, Apheresis (peripheral-blood stem cells) — donor or patient mobilized with G-CSF, sometimes plus plerixafor, then collected on an apheresis instrument.
• HPC, Cord Blood — collected from the placenta/umbilical cord after delivery, typically volume-reduced and cryopreserved in a cord-blood bank.

Processing may include volume reduction, RBC depletion (major ABO mismatch), and plasma reduction (minor ABO mismatch). Cryopreservation commonly uses about 10% DMSO, controlled-rate freezing, and vapor-phase liquid-nitrogen storage. CD34+ cell content is the usual potency/dose marker for PBSC (and a key marker for cord blood). Infusion of a freshly thawed DMSO-containing product can cause a characteristic odor, bradycardia, or blood-pressure changes — recipient infusion reactions, not a “bad unit of FFP.”

ABO incompatibility is expected and managed, not ignored.

• Major mismatch — recipient isoagglutinins against donor red cells (for example group A graft into group O recipient). Residual donor RBCs in the HPC product can hemolyze at infusion → RBC deplete the graft.
• Minor mismatch — donor isoagglutinins against recipient red cells (group O graft into group A recipient). Extra plasma in the product can hemolyze recipient RBCs at infusion → plasma reduce. Later, donor B lymphocytes in the graft can produce isoagglutinins against the recipient’s remaining red cells: passenger-lymphocyte syndrome, typically a delayed hemolysis 1–3 weeks after transplant.
• Bidirectional mismatch combines both problems.

Passenger-lymphocyte hemolysis is an HPC/transplant phenomenon. It is not a routine complication of issuing group O red cells to a group A patient from the general inventory.

FDA HCT/P versus blood regulations

Routine blood components (Whole Blood, Red Blood Cells, Platelets, Plasma, Cryoprecipitated AHF, Source Plasma) are licensed biologics manufactured under 21 CFR 606 (CGMP), 610 (tests), 630 (donors), and 640 (component standards). HPC products are human cells, tissues, and cellular and tissue-based products (HCT/Ps) under 21 CFR 1271 and the Public Health Service Act.

At BB-exam altitude:

• Section 361 HCT/Ps are minimally manipulated, intended for homologous use, and not combined with another article. Many autologous or allogeneic marrow and minimally manipulated PBSC collections sit in this lane, overseen for communicable-disease prevention rather than as a fully licensed 640 component.
• Section 351 biologics are more than minimally manipulated, non-homologous, or otherwise outside the 361 criteria. Licensed HPC, Cord Blood from several U.S. banks is a 351 biologic.

A facility may hold both a blood-establishment registration and a 1271 HCT/P registration. FACT and AABB cellular-therapy standards govern HPC processing more than the Circular of Information does. The practical exam point: do not apply platelet bacterial-culture dating, 42-day AS-RBC outdates, or FFP freeze-time rules to an HPC bag, and do not issue HPC as if it were leukoreduced irradiated red cells with a CD34 label stuck on.

Worked scenario. A group O recipient receives a group A HPC, Apheresis graft that was RBC-depleted and DMSO-cryopreserved. Immediate major-mismatch hemolysis risk is reduced by the RBC depletion. Two weeks later the patient hemolyzes with a newly appearing anti-A: that is passenger-lymphocyte syndrome from donor B cells, not a mislabeled FFP transfusion and not a failure to leukoreduce the HPC product.

Exam traps. Double RBC is a 16-week donor interval. Apheresis plasma can still be FFP if frozen in time. Albumin/IVIG/RhIG are pooled, pathogen-inactivated derivatives, not single-unit components. HPC is an HCT/P under 1271, dosed by CD34, frozen with DMSO, and capable of passenger-lymphocyte hemolysis. Do not treat HPC as a sixth blood component on the 640 list.