The Other Half of the Exchange: Choosing the Right Replacement Fluid

The Overlooked Half of the Exchange

When we talk about plasma exchange, most of the conversation centers on what we’re removing — antibodies, paraproteins, cytokines. But replacement fluid is the other half of the equation. It must maintain intravascular volume and oncotic pressure, and sometimes also return essential plasma proteins like clotting factors.

Choosing the right replacement fluid is one of the most important clinical judgments in apheresis. It affects safety, hemostasis, and the overall trajectory of a patient’s recovery far more than most order sets acknowledge.

The Options Menu

Fluid	What It Brings	When It Shines	Notes
5% Albumin	Volume and oncotic pressure	Stable autoimmune or neurologic diseases	May worsen bleeding risk if used early post-op or in coagulopathic patients; lacks clotting factors and immunoglobulins.
Fresh Frozen Plasma (FFP)	Coagulation factors, fibrinogen, and volume	TTP, pre- and early post-transplant desensitization, active bleeding or bleeding diathesis, coagulopathy	Risk of allergic reactions, TRALI, volume overload; slower thaw-to-infusion logistics.
Cryo-poor Plasma	Volume replacement with reduced fibrinogen	Refractory TTP	Rarely used; availability limited.
Saline (adjunct)	Volume expander	Used with albumin for partial replacement	Can dilute plasma proteins if overused; typically limited to ≤20–25 % of total replacement volume.

Combination strategies: A 50 : 50 replacement can balance safety and practicality. Always run the fluid you want to “stick around" at the end of the procedure.

• For saline : albumin, run albumin last.

• For albumin : FFP, run FFP last.

  
  

Clinical Scenarios — Matching the Fluid to the Patient

TTP:100 % FFP. You’re replacing the very factors the patient lacks, especially ADAMTS13 and other coag proteins essential for recovery.

Transplant-related Apheresis:

• Desensitization: Use FFP before transplant and generally for 1–2 weeks post-transplant, depending on stability and laboratory values (fibrinogen, platelets, INR).

• Antibody-Mediated Rejection (AMR) Post-Transplant: Replacement choice depends on time since surgery and concurrent risks. In early rejection with bleeding risk, use FFP; later or stable cases can transition to albumin or a mix.

  
  

Other Antibody-Mediated Diseases (e.g., MG, CREST, etc.):Albumin is typically adequate. However, for syndromes with vasculopathy or active bleeding (such as diffuse alveolar hemorrhage), use FFP until bleeding risk resolves.

Liver Failure or DIC: Therapeutic plasma exchange in these settings is uncommon and typically limited to specialized protocols (for example, acute liver failure with hyperammonemia or toxin removal). When performed, FFP is used to replace lost function and mitigate coagulopathy.

Myths & Misconceptions

• “Albumin is always safer.” Not when coagulation support is needed — context determines risk.

• “FFP is only for TTP.” It’s also indicated when hemostatic balance is fragile, such as peri-transplant or with bleeding vasculopathies.

• “Replacement fluid choice doesn’t matter.” It quietly dictates post-procedure stability, especially in surgical and critically ill patients.

  
  

The Quiet Art of Replacement

Replacement fluid selection looks mundane on paper, but it’s where clinical judgment lives. It’s the difference between doing an exchange and doing it wisely.

Protocols provide the framework; experience fills in the nuance — knowing when to mix, when to taper, and when to pivot from albumin to plasma because the numbers (or the drain output) tell you to.

In apheresis, the machines may be automated, but judgment isn’t. The fluid you choose — and the order you run it — still depends on the most analog tool we have: your brain.