Lowering the Cost / Improving Access for Therapeutic Plasma Exchange (Plasmapheresis)

What I posted above is misleading. Looked around a little more and found a company that will take plasma donors much older than Grifols and the others will. BioLife Plasma Services will go up to 99 years old.

Donating twice in a week and then when next eligible might have an effect similar to the big dilutions. Maybe it’s only the 70% replacements that work and nothing less does anything, but I don’t think we know that.

2 Likes

Yes you can .

You can do any reasonable amount.j

All can be done by gravity feed{all with one vein punch], no mechanical pumping required.

The entire procedure, removal of blood and infusion of albumin, should take under 1 hour doing 500ml.

Interesting… I have no idea if dialysis machines are the same as plasmapheresis machines. From the sounds of this study, I seems you can use or modify a dialysis machine for use in TPE:

We should try to pull together a list of all the equipment types and vendors that we could use for a project like this.

Plasmapheresis can be accomplished through centrifuge-based platforms such the Cobe Spectra, Fenwal Aurora, and the Fresenius COM.TEC series of devices. Patients require either a double-lumen central venous catheter or two large-bore antecubital peripheral lines.

Plasmapheresis can be performed using a semipermeable membrane–based device in combination with hemodialysis equipment. Central lines, as opposed to peripheral lines, are required for membrane-based plasmapheresis because of their higher flow rates of roughly 100-150 mL/min, as compared with 50-70 mL/min for centrifuge-based equipment

Two types of membrane-based plasmapheresis technologies exist: hollow fiber and parallel plate. Hollow-fiber dialyzers consist of a bundle of capillaries potted (glued) at both ends into a plastic cylindrical shell. Parallel-plate dialyzers contain layers of stacked membranes with ridges and grooves. Both technologies allow for the separation of plasma from the cellular components of blood based on particle size as well as pressure gradients.

The major advantage of hollow-fiber dialyzers is that they are considered more gentle than parallel-plate technology and are therefore more commonly used in pediatrics. Parallel-plate dialyzers, on the other hand, require less blood volume and therefore less anticoagulant, thereby minimizing the side effects associated with citrate or heparin. Asahi Plasma-Flo is an example of hollow-fiber technology, and Cobe TPE is an example of parallel-plate technology.

An advantage of membrane-based plasmapheresis is that multiple cycles of filtration and ultrafiltration can take place, potentially allowing for the return of beneficial plasma elements while discarding the pathogenic components. [[5](javascript:void(0);)]

https://emedicine.medscape.com/article/1895577-periprocedure

Plasmapheresis

Steps in therapeutic plasma exchange

The following is an example of the steps involved in performing therapeutic plasma exchange using centrifugation-based equipment such as the Spectra Auto PBSC:

  • Any heparin that may be present in each of the two lumina of a central venous catheter is removed

  • A waste of 3 mL is then discarded

  • Laboratory studies, including complete blood count (CBC), calcium, and fibrinogen, are ordered and specimens sent from the draw lumen

  • A flush with 10 mL of normal saline is placed in the draw lumen

  • The draw and return lumina are then connected to the tubing, which is previously primed with normal saline; however, if a patient weighs less than 20 kg, then the draw and return tubing are primed with packed red blood cells (RBCs) instead of normal saline

  • Height and weight are then entered into the system to allow estimation of total blood volume (TBV)

  • Plasma volume is then calculated as follows: TBV × (1 – hematocrit)

  • A replacement product is chosen

  • The total volume of the desired replacement product is entered—usually either 1 plasma volume (40 mL/kg) or 1.5 plasma volume (60 mL/kg)

  • A centrifuge speed is determined by the software on the basis of the data entered

  • The device then draws whole blood through the draw lumen to the centrifuge

  • Plasma is separated by the centrifuge and collected for discard

  • RBCs are also separated by the centrifuge, then returned to the patient along with the previously selected colloid of either albumin or fresh frozen plasma (FFP)

  • After the desired amount of plasma is removed, the machine is disconnected from the patient, and heparin is instilled into each catheter lumen to prevent clotting until the lumen is accessed again

  • A post–plasma exchange fibrinogen level is checked if albumin was used as the replacement product (albumin does not contain fibrinogen, as opposed to FFP) to assess whether the patient has become severely hypofibrinogenemic

Replacement products

Options for replacement fluid during plasma exchange include albumin, electrolyte solutions, hydroxyethyl starch, FFP, and purified protein products such as individual clotting factors or antithrombin III. [[18](javascript:void(0);)] Deciding which replacement product to use is based on the underlying condition and the risks and benefits associated with each replacement product. In general, albumin is the most common replacement product because of its low side-effect profile and broad availability. [[18](javascript:void(0);)]

Symptomatic adjustments

If signs of hypocalcemia are present, replacement calcium can be administered either intravenously (IV) or orally. Additionally, the whole blood–to–citrate ratio can be titrated to minimize hypocalcemic symptoms, which are usually related to the amount of citrate being used as an anticoagulant. [[19](javascript:void(0);)]

If signs of hypomagnesemia are present, replacement magnesium can be administered IV.

If signs of general discomfort are present, the return rate can be adjusted downward.

If signs of hypotension are present, normal saline boluses can be administered.

If signs of a transfusion reaction are present, the product infusion is discontinued, and diphenhydramine and hydrocortisone are given. In cases of anaphylaxis or respiratory distress, epinephrine can be administered as well.

The link that you posted prior shows a dialysis machine. To use such equipment at home (frequently), one would need either a port catheter or a fistula. Any vein would fail very quickly after a few times because of pressure. Also, it has to be done in presence of one more trained person, otherwise could be dangerous.

1 Like

As I have stated before equipment is the easiest part.

Where are you going to get your blood products?

So - it seems we have two options; Albumin (which seems like we can get if we can get a prescription), and young blood plasma.

Its interesting… at point of purchase (i.e. what companies are currently paying people for a liter of blood plasma) it seems to be priced in the $100 to $200 range. That same liter (after processing… which I’ve yet to see defined exactly) it sells for $8,000 per liter from companies like the former Ambrosia.

If you want to do a frequent plasmapheresis, which I suspect might be weekly or every two weeks, most people are going to want to target paying at the lower end of the $100 to $8,000 per liter range.

Perhaps we need to start a non-profit organization for young blood donations that targets college athletes around the world, with an offer that gives these people a good income (perhaps paying $500 / liter), and also providing a priority access for the parents of the people doing the donating, for more incentive, and a viral marketing approach to get the word out. Develop a simple and viral phone app that teens and 20-somethings would find helpful, and the potential to tell friends about this income opportunity, so that they can easily get a bonus for signing up their friends.

To keep costs low, the customers (e.g. us ) could be offered subscription plans to get the young blood plasma mailed to you in cold containers every week, two weeks, etc. and you could either do the plasmapheresis process yourself or take the blood to a clinic where they do it for you.

This may also be a “for-profit” opportunity, but there is already lots of competition in companies buying blood plasma, and given the desire to get the price down as low as possible and also appeal to people’s better nature of helping older people (at a price most donor’s parents can afford), it seems like a non-profit or perhaps a public benefit (B- corp) might be a better organizational structure.

Payment for young blood is not allowed in many countries, I see: Blood for money: my journey in the industry buying poor Americans’ plasma | US healthcare | The Guardian

Hunting around more on the refurbished equipment side, @lara is right, it seems there are some much smaller devices that look more like a laser printer. You can put it on your office desk and use it while you are working on your computer :slight_smile:

1987226

https://bimedis.com/a-item/plasmapheresis-machines-haemonetics-pcs2-1987226

1 Like

That is a plasma collection unit, used for the collect plasma from whole blood.

In my view, “Ambrosia” is/was for people with more money than brains

Yes - they used something like this (I think, not sure of the specific names) when I went into Dobri Kiprov’s clinic.

image

How long can you leave these things in your arm? Seems like if you’re active you might run into issues with it getting dislodged, etc. Perhaps a protective covering could be designed. I suspect most of these types of things are designed for sick people who are not out there exercising a ton.

vascular-access-guide2.pdf (608.4 KB)

If you are going to require access that much, you use a PIC/PICC line.

Access with a regular cather is fine.

1 Like

I’m just hunting around and learning more about the plasmapheresis market and technlogies and applications.

This submission to the FDA on the plasmapheresis clinical trial for alzheimers is really interesting and indepth… perhaps others here may be interested:

A MULTICENTER, RANDOMIZED, CONTROLLED STUDY TO EVALUATE THE EFFICACY AND SAFETY OF SHORTTERM PLASMA EXCHANGE FOLLOWED BY LONG-TERM PLASMAPHERESIS WITH INFUSION OF HUMAN ALBUMIN COMBINED WITH INTRAVENOUS IMMUNOGLOBULIN IN PATIENTS WITH MILD-MODERATE ALZHEIMER’S DISEASE

1 Like

And I found this Takeda presentation helpful to understand the market better:

TakedaPlasma20190712-ir-presentation-on-pdt_final_e.pdf (915.3 KB)

FWIW

Generic

2 viles, 500ml of 5% Albumin Human

$286.09 self pay

2 Likes

Love this overall thread.

Capturing the health benefit of donating blood might be a good way to get health conscious young people to want to do it. (Perhaps a simple clinical trial on that could provide great data).

Does anyone know:

  1. what is the impact on ones blood stem cells/bone marrow if they are asked to keep generating new cells after each round of plasmapheresis, could they get depleted at an earlier age (reach exhaustion and even the Hayflick limit earlier)?

  2. what is the impact on one’s immunity? eg say one has good protection again Covid (either by recent vaccine or recent infection of both) and one then does a ton of plasmapheresis, will one lose a lot of those valuable antibodies? What about valuable t-cells and b-cells?

  3. what are the risks of communicable disease or cancer spreading via (young) plasma? via donor albumin?

3 Likes

Btw if one were to do this as chain of centers (perhaps franchised to speed growth) vs the at home route the centers could offer a lot of alternative configurations.

For instance, those wanting to optimize Apo B without or with less pharmacological intervention or just wanted to drive Apo B to child like levels could add on Lipoprotein Apheresis.

Same for those wanting to optimize their Lp(a).

I both cases the procedure involves the physical removal of lipoproteins from the blood:

And for Lp(a)

https://www.ahajournals.org/doi/full/10.1161/ATVBAHA.116.307983

2 Likes

There are facilities that offer “Lipoprotein apheresis”

The cost is why many do not hear/know of this procedure.

Difficult to get insurance to pay.

Self Pay is expensive, $2,500.00 average per treatment.

Review

Also Review;

https://www.ahajournals.org/doi/full/10.1161/ATVBAHA.116.307983

And

Published: 17 February 2021

“LDL Apheresis and Lp (a) Apheresis: A Clinician’s Perspective”

1 Like

It’s wonderful that you had the courage to go through this process, I actually chickened out! It isn’t risk free but Dr Kiprov is an expert in this process so probably as safe as currently possible.

My thoughts on your experience is that, with you not knowing which group you were in, you are probably not experiencing a placebo effect. Given that, and the fact that this is a pretty dramatic intervention, I would expect that you would actually notice some effect if you were in the actual exchange group.

I believe you wrote earlier that you didn’t notice any difference in how you felt. It will be very interesting to learn which group you were in.

1 Like

FWIW

My biggest issue with any blood product is foreign particulate material{not just virus], material that are known {known to science] and unknown.

Example viruses can not be “filtered” out.

Even with testing, particles are there, just not detectable.

The risk potential{unknown] reward is more risk than potential reward.

3 Likes

Thanks for those links @Joseph

Exactly. That is the whole point of this thread - what models, logistics efforts could provide scale and lower cost.

The nice thing is that no new fda approvals are needed, etc.

Just adding that similar to all the longevity benefits @RapAdmin laid our in the first post and the other threads earlier in the week, the same model could also help within the number one killer (cardiovascular disease)

…,and that the ideas of how to scale and lower costs could be applied to both and if the centers/locations offered both they could provide and capture more value - hence making the logistic/business model stronger

1 Like

All the evidence on this points to something in older blood being the issue (I think it is IL-10). On that basis it should be possible to create a replacement plasma without the bad things and with what is needed (albumin etc) and the work on doing this should not be that difficult.

People could then wash away the IL-10 (or whatever it is) from time to time.

Personally, however, I think the solution is to reduce the quantity of senescent cells.

1 Like

Perhaps the model is plasmapheresis to take out the bad/old and the we need manufactured albumin and other potential young blood proteins, so not from a donors blood, but in a similar way to how one can make insulin in pharma factories.

That way there is no risk of being contaminated via donor material.

And the things that are added could be improved upon over time as we learn more and more. Eg in the beginning just albumin. Then GDF11, etc,

Below is a recent review of some of the young blood factors that have been identified and should be able to be manufactured in standard pharma biological manufacturing ways:

  • One of the first reported rejuvenating factors in young blood was growth differentiation factor 11 (GDF11)

  • A second young blood-derived rejuvenating factor, the bone-derived hormone osteocalcin

  • Within human umbilical cord plasma, tissue inhibitor of metalloproteinases 2 (TIMP2) and colony-stimulating factor 2 (CSF2 or granulocyte–macrophage colony-stimulating factor (GM-CSF)) were identified as two factors that decrease by early adulthood

  • This work revealed two factors capable of promoting synaptogenesis and dendrite arborization: the secreted matricellular proteins thrombospondin 4 (THBS4) and SPARC-like protein 1 (SPARCL1)

  • Glycosylphosphatidylinositol (GPI)-specific phospholipase D1 (Gpld1)

https://www.nature.com/articles/s41593-022-01238-8