Therapeutic Apheresis

The contract between this chapter and the reader.

1. 1. Explain how therapeutic plasma exchange removes pathogenic plasma factors.
2. 2. Quantify removal in plasma volumes and explain why sessions are repeated.
3. 3. Identify the strong renal and neurological indications.
4. 4. Choose the replacement fluid — albumin or fresh frozen plasma.
5. 5. Anticipate depletion of clotting factors and immunoglobulins.
6. 6. Manage access and citrate anticoagulation, including hypocalcemia.
7. 7. Recognise the complications of apheresis.
8. 8. Distinguish adsorption, hemoperfusion, and immunoadsorption from dialysis.
9. 9. Apply apheresis safely around drugs and procedures.

A sixty-second reading. Each bullet stands alone.

• Therapeutic plasma exchange separates plasma from blood cells, discards the patient's plasma with its pathogenic factors, and replaces it with albumin or fresh frozen plasma.
• It removes large, protein-bound, or antibody-mediated pathogens that dialysis cannot — autoantibodies, immune complexes, paraproteins, and inhibitors.
• One plasma-volume exchange removes about two-thirds of an intravascular substance, so sessions are repeated as the factor re-equilibrates.
• Strong indications include TTP, anti-GBM disease, severe ANCA vasculitis, Guillain-Barré syndrome, myasthenic crisis, and hyperviscosity.
• Albumin is the usual replacement fluid; fresh frozen plasma is used for coagulopathy or when factor replacement is needed — as in TTP, where it supplies ADAMTS13.
• Plasma exchange depletes clotting factors and immunoglobulins, so it is scheduled around surgery and timed with drugs.
• Access is a large-bore central catheter, and citrate anticoagulation is common.
• Citrate chelates calcium, so hypocalcemia is the commonest complication and calcium is supplemented.
• Other complications include coagulopathy, removal of therapeutic drugs, allergic reactions to plasma, and access infection.
• ACE inhibitors are held before albumin-replaced exchange to avoid bradykinin reactions.
• Hemoperfusion passes blood over a sorbent that adsorbs toxins, for selected poisonings and emerging applications.
• Adsorption binds solutes to a surface — distinct from the diffusion and convection of dialysis.

The medical core. An expert should agree therapeutic apheresis and adsorption are fully covered here.

Why it matters at the bedside

Some things that harm the kidney and the patient are too big, too protein-bound, or too antibody-shaped for dialysis to touch. Apheresis reaches them: it throws away the plasma that carries the pathogen and gives clean fluid back. Used for the right disease, at the right moment, it is occasionally life-saving — and used carelessly, it strips clotting factors and calcium along the way.

How plasma exchange works

• Therapeutic plasma exchange separates plasma from the blood cells — by centrifugation or membrane filtration — discards the patient's plasma with whatever pathogenic factor it carries, and returns the cells with a replacement fluid. It is the tool for diseases driven by something in the plasma that dialysis cannot remove: autoantibodies (anti-GBM, ANCA, anti-acetylcholine-receptor), immune complexes, paraproteins, cryoglobulins, and circulating inhibitors such as the ADAMTS13 autoantibody of TTP.

How much it removes

• Removal follows simple kinetics: exchanging one plasma volume removes roughly two-thirds (about 63%) of an intravascular substance, with diminishing returns beyond that — so a session of one to one-and-a-half plasma volumes is typical. Because the factor then re-equilibrates from the extravascular space and continues to be produced, exchanges are repeated over days.

The indications

• The strongest indications span specialties: in nephrology, anti-GBM disease (urgent exchange plus immunosuppression), severe ANCA vasculitis with pulmonary haemorrhage or severe renal failure, recurrent FSGS after transplant, antibody-mediated rejection and desensitization, and cryoglobulinaemia; beyond the kidney, TTP, Guillain-Barré syndrome, myasthenic crisis, and hyperviscosity from paraproteinaemia. Evidence-graded category systems exist to rank these.

Replacement fluid: albumin versus FFP

• Five-percent albumin is the default replacement, but fresh frozen plasma is chosen when the patient is coagulopathic or when factor replacement is the point — most importantly in TTP, where the FFP supplies the deficient ADAMTS13. FFP carries its own costs: citrate load, allergic and anaphylactoid reactions, transfusion-related lung injury, and volume.

What else gets removed

• Plasma exchange is not selective: it removes clotting factors and immunoglobulins along with the pathogen. This is why it is not performed immediately before surgery or an invasive procedure (the patient is transiently coagulopathic), why fresh frozen plasma is used when bleeding risk is high, and why therapeutic drugs and immunoglobulin are given after a session rather than before.

Access and citrate anticoagulation

• Apheresis needs flow, so a large-bore central catheter (or apheresis-capable access) is used, and the circuit is usually anticoagulated with regional citrate. Citrate chelates calcium, so its signature complication is hypocalcemia — perioral and peripheral tingling, and, if severe, tetany or arrhythmia — managed by monitoring and supplementing calcium.

Complications

• Citrate-induced hypocalcemia is the commonest problem; others are coagulopathy from factor depletion, removal of therapeutic drugs, allergic or anaphylactoid reactions (especially with FFP), access complications, and hypotension. A specific and avoidable one is the bradykinin reaction when an ACE inhibitor is combined with albumin replacement, so ACE inhibitors are held beforehand.

Adsorption and hemoperfusion

• Adsorption therapies work on a different principle: blood (hemoperfusion) or separated plasma is passed over a sorbent — activated charcoal or a resin — that binds the target. Hemoperfusion clears certain poisonings, particularly lipophilic or protein-bound toxins that dialysis handles poorly. This is distinct from dialysis, which removes by diffusion and convection rather than by binding.

Immunoadsorption and other apheresis

• Immunoadsorption passes plasma over a column that selectively binds immunoglobulin, removing antibody without discarding plasma or needing replacement fluid. Lipoprotein apheresis removes LDL and Lp(a) in refractory hypercholesterolaemia, and investigational columns aim to adsorb cytokines or endotoxin in sepsis.

Using it safely around drugs and procedures

• Because apheresis removes what is in the plasma, timing matters: give immunoglobulin and removable drugs after a session, avoid exchange immediately before surgery, hold ACE inhibitors before albumin replacement, and coordinate with the transfusion or apheresis service that runs the procedure.

Five fully-built tables.

Table A — Strong indications

Table B — Removal kinetics

Table C — Replacement fluid

Table D — Complications and management

Table E — Apheresis and adsorption modalities

Visualise & Map

Causal chains, each ending in a named action.

Chain 1 — Removing the pathogen

Pathogenic factor circulates in plasma → plasma exchange discards the plasma → the factor is cleared → ACTION: use TPE for antibody- or protein-mediated disease dialysis cannot treat.

Chain 2 — The kinetics of repetition

One plasma volume removes ~63% → diminishing returns, and the factor re-equilibrates and is re-made → ACTION: exchange ~1–1.5 plasma volumes and repeat over days.

Chain 3 — Citrate and calcium

Citrate anticoagulation → chelates ionised calcium → hypocalcemia (tingling, tetany) → ACTION: monitor and supplement calcium.

Chain 4 — Non-selective removal

TPE removes clotting factors and immunoglobulins with the pathogen → transient coagulopathy and immune depletion → ACTION: avoid before surgery; use FFP if bleeding; dose drugs/Ig after the session.

Chain 5 — Adsorption versus dialysis

Some toxins are protein-bound or lipophilic and poorly dialyzed → they bind to a sorbent → hemoperfusion clears them → ACTION: choose adsorption, not dialysis, for charcoal-adsorbable poisons.

Numbered rules. These numbers are the cross-reference handle for the cases and flowcharts.

Clinical Reasoning

Five cases. Each stops you at a decision before it answers it.

Every mechanism from Level 3 earns a bedside consequence and an action.

Exhaustive. Every rule in the chapter is here.

Safety & Evidence

Panel A — Red flags

Panel B — NEVER DO

Anti-patterns clinicians fall into. Each becomes a Level 22 distractor.

The grade reflects strength of evidence, not importance.

Patient Decisions

Outcomes as natural frequencies. Figures are representative; the direction of effect is given where precise numbers are uncertain.

Apply & Test

Copy-paste chart notes that map to the real decisions in this chapter.

Template 1 — Plasma-exchange prescription note

• Indication and removable factor: ___; evidence category (if known): ___.
• Plasma volumes per session: ___; schedule (daily / alternate): ___.
• Replacement fluid: albumin / FFP (FFP if TTP or coagulopathic).
• Access: large-bore central catheter; anticoagulation: citrate / heparin.
• ACE inhibitor held (if albumin): yes/no; disease-directed therapy: ___.

Template 2 — Apheresis monitoring / safety note

• Ionised calcium and symptoms (tingling/tetany): ___; calcium given: ___.
• Coagulation after session (if pre-procedure concern): ___.
• Drugs / immunoglobulin timed after the session: ___.
• Reaction to replacement fluid (FFP): none / ___.
• Response of the target factor / disease; plan for next session: ___.

Pre-rounds compression. Rules only.

Active recall. At least one card per objective.

Micro-teaching for rounds. Two scenarios, five steps each.

Nine items, each anchored in this chapter. At least one per objective.