EBO2 (EBOO) vs Plasmapheresis: What Each Procedure Does to Blood

EBO2 (also called EBOO) and plasmapheresis both draw blood into a machine and return it through a vein, which is why the two get compared. They do different things to that blood. In therapeutic plasma exchange, in the words of a patient fact sheet published by the American Society for Apheresis, “a machine separates and removes the patient’s plasma, replacing it with another fluid,” most often “5% human albumin” [1]. In EBOO, whole blood flows past a membrane carrying a gas “composed of medical oxygen and ozone (about 99 and 1%, respectively),” and the blood goes back to the patient [10][11]. This guide sets the two side by side from FDA records, the Society’s guidelines, its patient fact sheet, and the EBOO papers, so a reader can see what each procedure does, how each is run, and how each is regulated. It makes no claim that either is better for anything. Ozone therapy is not FDA-approved for any condition, and federal regulation calls ozone “a toxic gas with no known useful medical application in specific, adjunctive, or preventive therapy” [15].

What plasma exchange does

Plasma, in the patient fact sheet, is the “liquid” part of blood, which “contains proteins, electrolytes, vitamins, hormones, etc.” but not the blood cells or platelets [1]. Plasma exchange “is used when it is necessary to remove disease-causing proteins, called antibodies,” and because “it is often not possible to remove only the protein that is causing the disease,” the plasma itself is removed [1]. Most machines “use a centrifuge to separate the blood into its different parts,” and “a solution containing citrate” keeps blood from clotting [1]. Blood can be drawn from one arm and returned to the other, or through a central venous catheter in people with small or fragile veins [1]. An average procedure “lasts about 2 hours,” and the number of procedures “depends on the disease that is being treated” [1].

One ASFA registry gives a sense of the amount. In 26 patients with recurrent focal segmental glomerulosclerosis after kidney transplant, treated at seven US centers, most procedures used albumin and citrate and exchanged 1 to 1.5 plasma volumes [4]. The fact sheet also warns that plasma exchange “can remove large amounts of some medications” and advises patients to talk to their physicians about medication changes before the procedure [1].

What EBOO does

EBOO adds something to blood rather than taking a component out. The Siena group that developed it described treating up to 4,800 ml of heparinized blood with an oxygen-ozone mixture “(0.5-1 microg/ml oxygen)” in one hour, and a standard course of 14 one-hour sessions over 7 weeks [8]. Its gas exchanger used ozone-resistant polypropylene fibers, with blood on the outside and gas flowing inside [10]. A later Siena paper describes blood drawn from and returned to “two contralateral veins” and says about 5 L of blood can be treated in an hour [12]. A 2023 US series ran blood through a dialysis chamber at 30 to 40 mL/min for “exactly 1 hour,” with ozone at 10 to 60 μg/mL and heparin given as a slow drip [11].

What the papers measured is the change in the blood, not removal from it. After a session, the developers reported thiobarbituric acid reactants rising four- to fivefold and plasma protein thiols falling “without any appreciable erythrocyte haemolysis” [8]. The 2023 series measured an average ozone uptake of 37% of the generator’s output [11]. No EBOO paper we found reports a plasma component, antibody, or other substance removed and measured. Our guide to what the filter removes goes through what has and has not been measured.

Side by side

Figures are in each source’s own units.

How each is regulated

FDA’s product classification database lists therapeutic plasma separators under two product codes. “Separator, automated, blood cell and plasma, therapeutic” is unclassified with the reason “Pre-Amendment” and reaches the market through a 510(k) submission [5]. “Separator for therapeutic purposes, membrane automated blood cell/plasma” is a Class 3 device that needs premarket approval, and FDA recognizes a consensus standard for it, ISO 8637-3 on plasmafilters [6]. Both are reviewed by FDA’s renal, gastrointestinal, obesity and transplant devices team [5][6].

One regulation often cited for plasmapheresis machines covers something else. 21 CFR 864.9245 identifies an automated blood cell separator that draws whole blood “from a donor” and is “intended for routine collection of blood and blood components for transfusion or further manufacturing use”; it is Class II with special controls [7]. That is donor collection, not therapeutic plasma exchange. An earlier version of this guide cited it for plasma exchange devices, and we have corrected it.

We found no product code for EBOO equipment. A device-name search for “ozone” in FDA’s classification database returned “No records were found” on October 2, 2026 [14]. In July 2025, FDA told a Michigan maker of EBOO equipment that its devices were adulterated because no premarket approval application was in effect and misbranded because it had not filed a 510(k) notification [13]. The same letter records that the maker’s EBOO kits included purchased “High Flux Polyethersulfone Disposable Haemodialysers” from a supplier it had not evaluated [13]. As of October 4, 2026, 148 of the 174 clinics whose EBO2 page we could read do not say there whether EBO2 or its equipment is FDA-approved; the “From our data” section below shows how the rest word it.

Apheresis as a family has other members with FDA-approved uses. An American Heart Association statement says lipoprotein apheresis, which lowers LDL cholesterol and lipoprotein(a), is used in the United States for only “a fraction of its Food and Drug Administration-approved indications” [20].

How the evidence is organized

The American Society for Apheresis grades therapeutic apheresis disease by disease. Since its fourth edition in 2007, its writing committee has used systematic review and evidence-based approaches to grade the evidence and categorize each indication in a fact sheet [3]. The eighth edition, in 2019, held 84 fact sheets with 157 graded and categorized indications [3]. The ninth, in 2023, held 91 fact sheets and 166 graded and categorized indications, including seven new fact sheets and eight changes of category [2]. The tenth, in 2026, holds 93 fact sheets and 183 graded and categorized indications, including two new fact sheets [22]. The patient fact sheet names Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, myasthenia gravis, hyperviscosity, and thrombotic thrombocytopenic purpura among conditions “commonly treated with plasma exchange” [1].

EBOO has no such framework. Its controlled evidence is one randomized trial of 28 patients with peripheral artery disease, comparing EBOO with intravenous prostacyclin at the developers’ hospital [9]. On October 2, 2026, ClinicalTrials.gov listed no registered study under “extracorporeal blood oxygenation and ozonation,” “EBOO,” or “EBO2” [19]. The fuller list of what has been studied is in our guide to whether EBO2 works.

Why the two get compared

Some clinic language invites the comparison. One clinic’s EBOO page describes the procedure as “EBOO (Apheresis)” [17]. Another clinic that offers EBOO draws the line the other way: “The closest medical intervention we have to true ‘filtering’ the blood is called therapeutic plasma exchange (TPE) or plasmapheresis,” which it says can “remove up to 3 liters of your plasma and replace it with new proteins and colloid solution” [16]. The same page says no validated US research shows what an EBOO collection canister contains [16]. The two have also been combined. A 2011 study in the journal Vestnik Oftalmologii described plasmapheresis with ozonation of the cell mass in 179 patients (209 eyes) with uveitis and reported an advantage for the method; its abstract gives no figures and does not say what the comparison groups received [21]. The comparison with kidney dialysis, the other machine EBOO is likened to, is in our EBOO vs dialysis guide.

Risks as each source describes them

The patient fact sheet lists common side effects of plasma exchange as “fatigue, nausea, dizziness, feeling cold and tingling in the fingers and around the mouth, allergic reaction, and lowered blood pressure,” and says serious complications such as “abnormal heart beat, seizures, electrolyte abnormalities, and unexplained bleeding are extremely rare” [1].

For EBOO, the safety record is the developers’ and practitioners’ own reports. The 2005 trial recorded “no side effects or complications” in 210 EBOO treatments [9]; the 2023 US series reports “at least 400 sessions of ozone dialysis with no untoward effects observed” at the authors’ clinic [11]. Neither is a systematic adverse-event study. Other ozone routes have case reports of harm, including a woman with chronic kidney disease who developed high potassium and sinus arrest after ozone autohemotherapy [18]. Our ozone therapy adverse events guide and side effects and safety guide cover the wider record.

Questions to ask if EBOO is offered in place of plasma exchange

These follow from the table and can be put to the clinic and to the physician treating the condition.

1. What does the procedure take out of the blood, how much, and has anyone measured it? For plasma exchange the answer is plasma, by the volume prescribed [1][4]. For EBOO no study we found gives one.
2. What does the fact sheet for this diagnosis in the American Society for Apheresis’s guidelines say about plasma exchange [2]?
3. Which device is used, and what is its FDA status for this use [5][6][13][14]?
4. Which anticoagulant is used, and how much? Plasma exchange usually uses citrate [1]; the EBOO papers describe heparin [8][11].
5. Who manages a reaction during the session, and where is the nearest hospital if one is needed? The patient fact sheet says urgent plasma exchange is done in the hospital [1].
6. What happens to current medicines? Plasma exchange can remove large amounts of some of them [1].

What we could not verify

• The patient fact sheet carries a disclaimer: its publication “does not constitute an endorsement by ASFA,” ASFA “has not reviewed these materials,” and its views “represent the opinion of the authors” [1]. It prints no date; we date it 2021 from its file.
• The definitions of the Society’s categories and grades, and which category each condition holds. We could read only the abstracts of the ninth and tenth editions; the full text of the ninth sat behind the publisher [2][22].
• Typical plasma volumes exchanged across all indications. The one figure we cite comes from a registry of a single condition [4].
• Whether any EBOO circuit in use removes plasma, antibodies, or other proteins in measurable amounts. We found no study that tested it.
• The clinic statement that plasma exchange can remove “up to 3 liters” of plasma [16], which we could not match to a primary source.
• How many US clinics use a dialyzer, a purpose-built gas exchanger, or another cartridge for EBOO.

How this guide was made

This guide rests on 22 sources: a patient fact sheet published by the American Society for Apheresis, three editions of its guidelines, and one of its registry reports; three FDA database records, two federal regulations, and an FDA warning letter; eight other papers listed on PubMed; a ClinicalTrials.gov search; and two clinic pages, which are cited only for what those clinics state. The FDA-wording and course figures in the “From our data” section come from our dataset of clinic pages, as of October 4, 2026. Drafting used AI tools. A human editor has not yet checked this guide claim by claim against its sources. No clinical reviewer has signed off on this guide yet.