5.3 Apheresis Products & Fractionation Products

Apheresis as a Collection Platform

Apheresis withdraws whole blood from a donor, anticoagulates it (typically with ACD-A, acid-citrate-dextrose), separates it by centrifugation or, less commonly, membrane filtration, retains the target component, and returns the remaining components to the donor. The same platform collects platelets, transfusable plasma, double red cells, granulocytes, and hematopoietic progenitor cells (HPCs), simply by adjusting the separation interface and collection parameters. Because citrate anticoagulant binds calcium, donors and patients undergoing apheresis are monitored for citrate toxicity - perioral or extremity tingling and, if untreated, hypocalcemia - typically managed with oral calcium supplementation or by slowing the return rate.

Source Plasma, Recovered Plasma, and Transfusable Apheresis Plasma

Three plasma streams feed different purposes, and the SBB exam expects the distinction to be precise:

• Transfusable apheresis plasma (FFP, PF24, etc.) is collected specifically for direct patient transfusion, meets the same infectious disease testing and ABO labeling requirements as whole blood-derived plasma, and follows standard donation intervals.
• Source plasma is collected by apheresis specifically as feedstock for fractionation into plasma derivatives, not for direct transfusion, under 21 CFR 630 and 640. Because manufacturing itself adds dedicated pathogen-reduction and purification steps, FDA rules permit source plasma donors to donate up to twice within 7 days, with at least 2 days between donations, a substantially shorter interval than whole blood or transfusable plasma donation allows.
• Recovered plasma is the plasma byproduct separated from routine whole blood donations that is not needed for direct transfusion and is instead redirected to fractionation, supplementing the dedicated source plasma supply.

Fractionation: From Pooled Plasma to Derivatives

Large pools of source and recovered plasma are fractionated into purified protein products. The classical method, Cohn cold ethanol fractionation, sequentially precipitates plasma proteins by varying ethanol concentration, temperature, pH, and ionic strength:

Modern manufacturing supplements or replaces steps of the Cohn process with chromatography, but the exam expects familiarity with this classical framework because it explains why a given derivative comes from a specific plasma protein class.

Major Plasma Derivatives and Clinical Use

Regulatory and Safety Distinctions from Cellular Components

Unlike red cells, platelets, or plasma intended for direct transfusion, plasma derivatives generally do not require ABO/Rh matching or pretransfusion compatibility testing, because manufacturing pools, purifies, and dilutes donor antibody to levels that are not clinically significant in routine use. The notable exception the exam likes to test: high-dose IVIG, manufactured from thousands of pooled donations, can retain low but occasionally clinically significant titers of anti-A/anti-B; in non-group-O recipients receiving large or repeated doses, this passively transferred antibody can rarely cause hemolysis.

Because derivatives are pooled from thousands of donors, manufacturers apply dedicated viral inactivation or removal steps beyond donor screening and testing alone:

• Solvent/detergent (S/D) treatment disrupts the lipid envelope of enveloped viruses (HIV, hepatitis B, hepatitis C) but has no effect on non-enveloped viruses such as hepatitis A virus or parvovirus B19.
• Pasteurization (heat treatment, e.g., albumin heated near 60C for about 10 hours) inactivates most viruses, including some non-enveloped types, through heat denaturation.
• Nanofiltration physically removes virus particles by size exclusion regardless of envelope status, complementing chemical or heat methods.

Layering multiple methods compensates for the gap each method leaves on its own, which is why a single derivative product often undergoes more than one inactivation step during manufacturing.

Apheresis-Collected Cellular Products

The same apheresis platform used for plasma exchange and plasma collection also collects single-donor cellular products discussed elsewhere in this chapter and guide: apheresis platelets (Section 5.1), granulocyte concentrates, and hematopoietic progenitor cells (Section 5.4). All rely on the identical principle of density-gradient centrifugation to isolate a target cell layer while returning the remainder of the donor's blood.

Worked Example

A manufacturer needs to remove both enveloped and non-enveloped viral contamination risk from a pooled Factor VIII concentrate. Because solvent/detergent treatment alone would leave non-enveloped viruses such as parvovirus B19 unaddressed, the manufacturer adds a nanofiltration step, which removes virus particles by physical size regardless of envelope status, providing a second, independent layer of viral safety.

Common Traps

• Assuming plasma derivatives require the same ABO crossmatch as cellular blood components.
• Forgetting that solvent/detergent treatment does not inactivate non-enveloped viruses.
• Confusing source plasma's shorter donation interval with whole blood or transfusable plasma donation frequency rules.
• Mixing up which Cohn fraction yields albumin versus immunoglobulins.