Therapeutic Apheresis · Review 05
Apheresis biomarkers: what a laboratory change can and cannot tell us
A treatment can change proteins, antibodies or biological clocks without proving that patients live longer, function better or recover from illness.
- PROCEDURE STATUS
- Measurement framework
- INDICATION EVIDENCE
- Established principle: surrogate markers require validation
- REVIEW STATUS
- Clinical review required
- NEXT REVIEW
- January 2027
In short
A post-apheresis change in lipids, antibodies, inflammatory proteins or an aging clock can show that the intervention altered a measured biological signal. It does not by itself prove recovery, prevention of disease or longer life. The marker must be validated for the intended outcome, and patient benefit should be demonstrated independently.
The clinical question
When does a biomarker change after apheresis support a clinical conclusion, and when does it only show that the procedure altered the blood?
Some laboratory changes are expected from the procedure
Apheresis is designed to remove circulating material. Lower fibrinogen, lipids, antibodies or selected proteins immediately after treatment may therefore demonstrate technical performance. The INUSpheresis proteomic and Long COVID studies provide clear examples of this expected biological action.[1][2]
A surrogate becomes useful only when it predicts something that matters
A biomarker is clinically useful when changes in it reliably predict a meaningful outcome for the relevant population. Association with disease, removal by a filter and short-term movement after treatment are separate steps. None automatically proves that changing the marker changes the outcome.[3][4]
Large plasma-proteomic studies can identify signatures associated with age, disease or mortality risk. These signatures are valuable research tools, but their predictive association does not establish that deliberately shifting the signature with apheresis will improve those outcomes.[3][4]
Controlled trials test whether the marker story reaches the patient
The Long COVID randomized trial found no efficacy difference despite the strong biological rationale for removing inflammatory or coagulation-related factors. In longevity research, one 2025 trial reported favorable movement in several aging clocks while another found no significant epigenetic rejuvenation and unfavorable movement in some clocks.[5][6][7]
These results do not make biomarkers useless. They show why AION should track them as part of a clinical question rather than present them as the outcome itself.[5][7]
The three-question test
Was the marker validated for this patient and outcome? Did the treatment improve the outcome compared with a control? Did the benefit last long enough to matter?
What this means for you
Every evidence review here keeps laboratory endpoints and patient outcomes labeled separately, because they are not the same thing. A favorable lab number alone does not justify continuing a treatment if you are not getting a real clinical benefit from it, and a commercial biological-age score is never translated directly into years of life gained, no matter how appealing that math looks.[6][7]
- Record when the sample was taken relative to treatment.
- Distinguish expected removal from a durable biological change.
- Predefine the patient outcome that the marker is meant to support.
- Report null or unfavorable markers alongside favorable ones.
Source register
Every material source used in this review, with the study design and the limitation that matters when interpreting it.
- [1]Yin X, et al. Precision Medicine Approach for Cardiometabolic Risk Factors in Therapeutic Apheresis.
Hormone and Metabolic Research · 2022 · Proteomic filter-comparison study
PMID 35413745 · DOI 10.1055/a-1776-7943
- WHAT IT ADDS
- Demonstrates measurable, filter-dependent removal of circulating proteins.
- LIMITATION
- Technical and biomarker findings do not establish general clinical benefit.
- [2]Achleitner M, et al. Clinical improvement of Long-COVID is associated with reduction in autoantibodies, lipids, and inflammation following therapeutic apheresis.
Molecular Psychiatry · 2023 · Uncontrolled biomarker cohort
PMID 37131073 · DOI 10.1038/s41380-023-02084-1
- WHAT IT ADDS
- Shows substantial immediate changes across several biomarker classes.
- LIMITATION
- No control group and no causal link between marker reduction and improvement.
- [3]Sathyan S, et al. Plasma proteomic biomarker signature of age predicts health and life span.
eLife · 2020 · Large observational proteomic cohort
PMID 33210602 · DOI 10.7554/eLife.61073
- WHAT IT ADDS
- Identifies a plasma-protein signature associated with age, morbidity and mortality.
- LIMITATION
- Prediction and association do not prove that changing the signature changes risk.
- [4]Oh HS, et al. Organ aging signatures in the plasma proteome track health and disease.
Nature · 2023 · Multi-cohort observational proteomic study
PMID 38057571 · DOI 10.1038/s41586-023-06802-1
- WHAT IT ADDS
- Associates organ-specific proteomic aging estimates with disease and prognosis.
- LIMITATION
- Does not test whether apheresis-induced score changes improve clinical outcomes.
- [5]Vidal-Alaball J, et al. Plasma exchange therapy for the post COVID-19 condition: a phase II randomized trial.
Nature Communications · 2025 · Randomized sham-controlled clinical trial
PMID 39994269 · DOI 10.1038/s41467-025-57198-7
- WHAT IT ADDS
- Found no efficacy advantage over sham treatment.
- LIMITATION
- One condition, one protocol and a phase II sample size.
- [6]Kiprov DD, et al. Multi-Omics Analysis Reveals Biomarkers That Contribute to Biological Age Rejuvenation in Response to Therapeutic Plasma Exchange.
Aging Cell · 2025 · Small randomized placebo-controlled biomarker trial
PMID 40424097 · DOI 10.1111/acel.70103
- WHAT IT ADDS
- Reports favorable movement in multiple molecular aging clocks.
- LIMITATION
- Surrogate outcomes, small sample and disclosed commercial involvement.
- [7]Borsky P, et al. Human clinical trial of plasmapheresis effects on biomarkers of aging.
Scientific Reports · 2025 · Randomized cross-over biomarker trial
PMID 40592961 · DOI 10.1038/s41598-025-05396-0
- WHAT IT ADDS
- Reports no significant epigenetic rejuvenation and several unfavorable clock changes.
- LIMITATION
- Healthy-donor protocol and no long-term clinical outcomes.
Research changes the question.
A physician owns the answer.
This review is educational and remains marked for clinical review. It does not determine whether any therapy is appropriate for an individual patient.