Therapeutic Apheresis: Novel Indications & Emerging Technologies

Abstract

The guest editors’ introduction to the theme issue. Two forces are expanding therapeutic apheresis beyond its established role in autoimmune, hematologic, and neurologic disease: the growing recognition that circulating mediators — autoantibodies, immune complexes, inflammatory cytokines, atherogenic lipoproteins, and protein-bound toxins — contribute to a widening range of conditions, and a technological shift away from the wholesale removal of plasma toward the selective extraction of specific pathogenic components. Together these mark a transition from apheresis as a rescue intervention toward what may be called precision apheresis.

Abstract

This article examines the expanding role of therapeutic plasma exchange (TPE) in Alzheimer’s disease (AD), alongside recent developments in diagnostic approaches, disease mechanisms, and emerging disease-modifying treatments. Although AD has historically been considered a disorder defined by amyloid and tau pathology, contemporary models increasingly emphasize a multifactorial systems-biology framework that includes immune dysregulation, oxidative stress, vascular injury, impaired protein clearance, and synaptic dysfunction. Within this evolving model, TPE has emerged as a biologically rational, broadly acting therapeutic strategy that contrasts mechanistically with selective anti-amyloid monoclonal antibodies. The article reviews the AMBAR trial and the pilot work that supported it, real-world cohort evidence, the author’s clinical experience, and the evolution of TPE from acute hospital-based therapy to chronic outpatient disease management.

Abstract

Post-infectious syndromes including post-treatment Lyme disease syndrome (PTLDS), long COVID, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and PANS/PANDAS share overlapping clinical phenotypes characterized by fatigue, cognitive dysfunction, sleep disturbance, and neuropsychiatric symptoms. This narrative review synthesizes the literature describing immune abnormalities across these syndromes and evaluates the rationale for immunomodulatory therapies, including IVIG, rituximab, and therapeutic plasma exchange. Notably, the phase III RituxME trial in ME/CFS and a phase II trial of TPE in post-COVID condition both failed to demonstrate efficacy in unselected populations, reinforcing the importance of biomarker-guided patient stratification.

Abstract

Lipoprotein apheresis (LA) achieves acute reductions of 60–80% in LDL cholesterol and lipoprotein(a) through extracorporeal removal of apolipoprotein B-containing particles, and remains the cornerstone of treatment for homozygous familial hypercholesterolemia and severe heterozygous FH refractory to pharmacotherapy. Registry data, including more than 11 years of follow-up from the German Lipoprotein Apheresis Registry, document consistent reductions in major adverse cardiovascular events across all principal indications, though randomized controlled trial evidence is absent. The review examines integration with PCSK9 inhibitors, inclisiran, and emerging RNA-based Lp(a)-lowering agents, and evaluates evidence in peripheral arterial disease and steroid-resistant focal segmental glomerulosclerosis.

Abstract

Therapeutic plasma exchange is well established but intrinsically non-selective: protective immunoglobulins, coagulation factors, and albumin are depleted alongside pathogenic substances, and reliance on donor-derived replacement fluid carries logistical and immunological costs. The MTx.100 column is a selective plasma adsorption device that targets pro-inflammatory cytokines, protein-bound metabolic waste, hydrophobic environmental contaminants, and microparticulates while preserving immunoglobulins, coagulation factors, and electrolytes — the patient’s own plasma is treated and returned, eliminating replacement-fluid dependency. Clinical experience encompasses approximately 1,000 procedures globally, including a prospective multicenter trial in 107 critically ill COVID-19 patients and 114 elective outpatient procedures in which third-party laboratory analyses confirmed measurable reduction of PFAS, microplastics, and persistent organic pollutants.