How are hospitals that use 5% albumin as a replacement fluid for some therapeutic plasma exchange procedures addressing a lack of supply of that solution? Do colleagues consider the use of plasma protein fraction to be a safe alternative?

A transfusion medicine physician in Boston reports that his hospital has been having difficulty procuring 5% albumin solution for use as a replacement fluid in selected therapeutic plasma exchange procedures. The inquiring physician is reluctant to use plasma instead of 5% albumin, nor is he enthused about using colloidal starch. The pharmacy handles the albumin products, and recently, when all the 5% albumin solution is gone, they have been diluting stocks of 25% albumin solution down to 5% to use for pheresis--but the supply of the 25% albumin solution seems to be dwindling as well. He would like to know if anyone has experience using Plasma Protein Fraction (PPF) 5% as a substitute for 5% albumin in plasma exchanges. He is aware that some practitioners have previously used PPF as a replacement fluid when albumin was unavailable. The inquiring colleague has found a few very old references related to using PPF during cardiac bypass, and there are reports of hypotensive reactions. A recent package insert for Plasmanate® (Talecris Biotherapeutics, Inc.) still lists hypotension as a risk.

The following comments have been received.

ADDENDA Nov. 22, 2006

1. Dr. James Faed, Transfusion Medicine Specialist at the New Zealand Blood Service and University of Otago in Dunedin, New Zealand (attribution used with permission) reports that his practice for selecting replacement fluids for TPE over the past 23 years has been to use a mix of Normal Saline, a colloid plasma volume expander (usually a gelatin solution) and Albumin 4%, except in those cases where plasma has been specifically indicated. The solutions are usually used in a 1:1:1 ratio in patients who have normal albumin levels, but with a progressively increased albumin replacement component where serum albumin levels are reduced below 30g/L. The total volume infused is expanded above the volume of plasma removed to allow for some saline redistribution to the extravascular space and this has normally been achieved with an additional 500 mL saline for a 3 liter exchange. The proportion of colloid (either gelatin or albumin) has also been increased in some patients with autonomic instability or other cause for cardiovascular instability. The sequence of fluid infusion has been managed in a 2-phase approach. During the intial phase the replacement fluid comprises 1:1 volumes of Normal Saline and Gelatin colloid, achieved by hanging both solutions beside each other and switching between the two solutions via a 3-way tap connector, every 200-300mL. During the second (final) phase 100% albumin is infused. The Albumin is held until the final stage to minimise the amount removed by the plasma exchange process.
   
   Dr. Faed reports that the aforementioned protocol has been used with good success in terms of clinical outcomes from plasma exchange which are consistent with those published for the various conditions treated and for any adverse effects during the procedure. Occasional issues have arisen from time to time when operators did not follow the 1:1 mix protocol during the first phase of fluid replacement and attempted to give all of the saline followed by all of the gelatin colloid, with resulting hypotension problems in some patients. Dr. Faed cautions that clear briefing and training of staff on this issue is required. He concludes saying "The procedure can be used for daily plasma exchange proceduers without difficulty as the liver has considerable ability to ramp up albumin synthesis and regular monitoring of serum albumin permits pre-emptive adjustment of the amount of albumin infused, if and when needed."

ADDENDA Aug. 21, 2008

2. A pediatric transfusion medicine specialist from a large hospital in the Mid Atlantic region writes: We recently needed to perform plasmpaheresis on a 99 kg patient with recurrent FSGS but were told by the pharmacy that they could not support giving us 4 L of 5% albumin for 6 procedures over a two week period. Is there a nationwide shortage of 5% albumin? What are other's experience using plasmanate instead of 5% albumin as replacement? We are interested as to what others think about the use of this product in plasmapheresis.

ADDENDA Aug. 29, 2008

3. A physician in Florida reports that at his hospital they are currently treating a 8 year old boy with cystic fibrosis and recurrent focal segmental glomerulosclerosis (FSGS) in an allograft with thrice weekly 1.5 plasma volume exchanges using 5% plasma protein fraction because of the albumin shortage. Plasmanate is 88% albumin, but doesn't seem to be affected by the national albumin shortage. He reports that their patient has not experienced any side effects - although he still has not responded. His urine protein/creatinine ratio dropped initially from around 30 into mid teens - where it continues to hover. His plasma creatinine remains in the 1.2-1.5 range off dialysis. The Floridian does not think the failure to respond is related to the choice of replacement fluids. They have not treated a child for recurrent FSGN previously, and some of the reports in the literature describe patients who required 50 - 70 exchanges before going into a sustained remission. Their nephrologists are prepared to do this indefinitely - they are at 33 so far. He asks if anyone has any suggestions for what else might be attempted, or if there are endpoints other than remission or graft failure?
   
   
4. Dr. Ted Eastlund (attribution used with permission) expresses the opinion that Plasma Protein Fraction (PPF) should be freely used for plasma exchange when there is a shortage of albumin. He points out that it is similar to 5% albumin but not purified as well so it contains extra proteins as impurities. One of these was prekallikrein contained in certain lots many decades ago. When used in cardiac bypass there were acute hypotension episodes because of the kallikrein-mediated bradykinin generation and the fact that the lungs that contain important kininase activity were bypassed. Theoretically, if a patient is on ACE inhibitors, which block the major plasma kininase responsible for most bradykinin degradation, the patient may be at increased risk for facial flushing and hypotension. However, since ACE inhibitors are usually discontinued, at least the day of the procedure, this should not be a serious problem.

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