16.1 Therapeutic Apheresis

16.1 Therapeutic Apheresis

ASCP content outline domain V.D moves beyond the routine hemapheresis basics tested on the generalist MLS/MLT exams into the specialist-level decision-making an SBB is expected to own: which diseases genuinely need apheresis, which replacement fluid a given disease requires, and how to recognize and manage citrate toxicity. This section builds that specialist layer.

Apheresis Mechanics: Centrifugation vs. Filtration

Therapeutic apheresis separates whole blood into components and removes a target component while returning the remainder, plus a replacement fluid, to the patient. Most U.S. instruments use continuous-flow centrifugation: blood spins in a disposable channel so components stratify by density (plasma on top, then platelets, the white cell/buffy-coat layer, and red cells at the bottom), allowing continuous separation while blood cycles between the patient and the machine. Membrane (filtration) plasmapheresis passes plasma through a porous membrane under a pressure gradient instead of spinning it; it is used less often in the U.S. but underlies double filtration plasmapheresis, a secondary filtration step that selectively removes large pathologic proteins (LDL, IgM) while sparing albumin.

Two Broad Categories: Plasma Exchange and Cytapheresis

• Therapeutic Plasma Exchange (TPE) removes plasma, and with it the pathologic substances dissolved in it - autoantibodies, immune complexes, paraproteins, toxins, lipoproteins - and replaces the removed volume with a substitute fluid.
• Cytapheresis removes a cellular component instead of plasma:
  • Leukapheresis removes white cells; therapeutic use targets extreme hyperleukocytosis with leukostasis (blast crisis), while the same technology also collects peripheral blood stem cells or granulocytes for transfusion.
  • Plateletpheresis (thrombocytapheresis) removes platelets; therapeutic use is rare, reserved for extreme thrombocytosis causing thrombotic or hemorrhagic symptoms (essential thrombocythemia crisis).
  • Erythrocytapheresis (RBC exchange) removes and replaces red cells; its main therapeutic use is sickle cell disease (acute stroke, acute chest syndrome, pre-operative prophylaxis), lowering %HbS while avoiding the iron overload and viscosity problems of simple transfusion.
  • Extracorporeal photopheresis (ECP) collects a mononuclear cell fraction, exposes it ex vivo to a photoactive drug (8-methoxypsoralen) and UVA light, then reinfuses the treated cells; it is used for cutaneous T-cell lymphoma, graft-versus-host disease, and solid-organ transplant rejection.

Exchange Volume and Kinetics

Continuous-flow TPE follows first-order (exponential) removal kinetics: removing one plasma volume (1 PV) clears about 63% of an intravascular substance, 1.5 PV clears about 78-80%, and 2 PV clears about 86%. Because the return per additional volume shrinks quickly past 1.5 PV, most protocols exchange 1-1.5 PV per session, typically daily or every other day depending on disease severity. Patient plasma volume is estimated as total blood volume (roughly 70 mL/kg in adults) multiplied by (1 minus hematocrit).

ASFA Categories: Grading the Evidence

The American Society for Apheresis (ASFA) publishes a periodically updated set of disease fact sheets that grade conditions by how strongly the evidence supports apheresis. Conceptually, the four categories are:

Each disease fact sheet also carries a recommendation grade (1A-2C), mirroring GRADE methodology, that separately scores the strength of the recommendation and the quality of the supporting evidence. On the SBB exam, the numbered category (I-IV) is tested far more often than the letter/number grade, because it answers the practical question a blood bank physician or SBB has to answer: is apheresis standard of care for this patient, or is it experimental?

Replacement Fluids

Because TPE removes plasma, something must replace the lost intravascular volume and oncotic pressure. The choice of replacement fluid is disease-driven, not a fixed default:

• 5% albumin is the default replacement for most Category I/II indications. It carries no infectious risk from pooled donor plasma and no risk of a plasma-protein anaphylactoid reaction, but it replaces no coagulation factors. Repeated albumin-only exchanges progressively dilute fibrinogen and other factors and can produce an iatrogenic coagulopathy after several consecutive sessions.
• Fresh frozen plasma (FFP) is required whenever the disease itself depends on restoring a plasma factor. The most classic example is TTP, where FFP supplies ADAMTS13, the von Willebrand factor-cleaving protease that is severely deficient or inhibited in that disease - albumin alone will not treat TTP no matter how much plasma volume is exchanged. FFP is also preferred when the patient is actively bleeding, already coagulopathic, about to undergo an invasive procedure, or is a small-volume pediatric patient where the exchanged volume is a large fraction of total plasma volume.
• Crystalloid (normal saline) can supplement part of the fluid balance but is never used as the sole replacement fluid, because it carries no oncotic pressure and would cause severe third-spacing.
• Combination protocols (predominantly albumin/saline with periodic FFP) are common when both oncotic replacement and modest factor support are needed.

Citrate Anticoagulation and Toxicity

Apheresis instruments prevent clotting inside the extracorporeal circuit using acid-citrate-dextrose solution A (ACD-A), which works by binding ionized calcium. Because a large volume of citrated blood cycles through the patient during a single session, systemic citrate toxicity - functional hypocalcemia - is the most frequent apheresis-specific adverse reaction. Early signs are perioral and digital paresthesias and a metallic taste; progression produces muscle cramps and tetany, and severe cases show a prolonged QT interval and cardiac arrhythmia. Risk rises with faster citrate infusion rates, larger exchange volumes, hepatic impairment (the liver normally metabolizes citrate to bicarbonate), and renal impairment. Management is oral or IV calcium supplementation during the procedure, ionized-calcium monitoring, and slowing the blood return rate; FFP replacement - itself citrated - adds further citrate load compared with albumin, so FFP-heavy exchanges need closer calcium monitoring.

Other Complications and Clinical Correlation

• Vasovagal reactions and hypotension from rapid extracorporeal volume shifts, especially in small or hypovolemic patients.
• Allergic/anaphylactoid reactions to plasma or albumin, including anti-IgA reactions to FFP in IgA-deficient patients.
• Mechanical hemolysis from shear stress in the centrifuge channel or tubing.
• Vascular access complications from the large-bore central catheters TPE requires - pneumothorax, catheter-related infection, and line thrombosis.
• Drug removal: TPE can strip highly protein-bound or low-volume-of-distribution drugs from plasma, so critical medication doses (some antibiotics, immunosuppressants) are often re-dosed after, not before, a session.

Recognizing which replacement fluid a disease requires, why citrate causes hypocalcemia, and where a diagnosis sits on the ASFA I-IV scale are the highest-yield SBB testing points for this section.