High-dose plasma infusion versus plasma exchange as early treatment of thrombotic thrombocytopenic purpura/hemolytic-uremic syndrome

A colleague in Ohio suggests that the e-network forum might be interested in the following article from France by Coppo et al: High-Dose Plasma Infusion versus Plasma Exchange as Early Treatment of Thrombotic Thrombocytopenic Purpura/Hemolytic-Uremic Syndrome, in Medicine 2003;82:27-38.

The Ohio colleague would be most interested in learning if, based on this article people would consider, rather than an initial urgent plasmapheresis being set up at 3am, beginning with plasma infusion and then switching to plasmapheresis later? How do others handle requests for emergency therapeutic plasmapheresis that come in the middle-of-the-night?

The Editor suggests that the e-Network Forum review the following related discussions from the ENF:

• How long should you wait after administering a dose of the platelet inhibitor Plavix (clopidogrel) before a patient may be transfused with platelets?
• Management of thrombocytopenia associated with therapeutic plasma exchange (TPE), when the thrombocytopenia is believed to be heparin-induced
• Maintaining patency of intravenous lines between repeated therapeutic hemapheresis procedures

The following responses have been received.

1. A transfusion medicine physician in Los Angeles reports that in his practice he always recommends starting treatment of TTP with plasma infusion, until therapeutic plasma exchange (TPE) can be initiated. The plasma infusion consists of using cryoprecipitate-depleted plasma (also known as CryoPoor plasma, or Cryosupernatant). This approach can 'buy time' in the middle of the night until the TPE can begin.
   
   
2. A colleague from Irvine, California asked the Ohio colleague who submitted the question to clarify what "High-Dose of Plasma" means. He also asked the following question, "Are they using Cryo-poor or regular FFP? How much? For us an emergency apheresis will take no less than 4 hours to set up, so personally I do not see the advantages of 3 hours of "High Dose Plasma" (especially if it is not Cryo-poor), vis a vis the potential complication of fluid overload."
   
   
3. The Ohio colleague replied to the Irvine colleague as follows (verbatim) "The best answer to these questions is to go directly to the article itself for the definitive information. Having said that I want to add that my sharing this with the CBBS readership should in no way suggest that I endorse the approach reported in the article - I want to see if there is any consensus regarding this as an acceptable approach should one be unable to offer plasmapheresis on a STAT basis. Now, from the article itself, I recollect that FFP is being used (not cryo-poor plasma although I am not sure this would have made a difference). The article states that high dose is on average 25-30 ml/kg/day - although there was some variation in this. The commentor indicates, very astutely, that the time involved in administering this much plasma is no less (and likely more) that the time it would take to accomplish the plasmapheresis; in addition, with the high-dose plasma infusion there is the very real risk (certainly a complication in about half the patients reported in the article) of fluid overload. What then, the commentor asks, is the advantage of high-dose plasma infusion? The only advantage that I see, which nonetheless is significant, is as a temporizing measure if staff are not available around the clock to perform apheresis. In such a case, plasma infusion, it would appear, should be started without delay rather than waiting to begin the apheresis which could take many hours to orchestrate. In essence, treatment might actually begin sooner when starting with plasma infusion possibly resulting, paradoxically, in improved patient care!"

ADDENDA Mar. 7, 2003

4. Ronald E. Domen, MD, Medical Director, Blood Bank and Transfusion Medicine at the Milton S. Hershey Medical Center at Penn State University College of Medicine (attribution used with permission) reports that rarely he will advocate the use of plasma infusion in TTP, primarily in the setting of "buying" time until the patient can be admitted, central lines placed, etc. However, plasma exchange has remained, in his mind, the "gold-standard" of therapy for TTP so his service initiates it as soon as possible after the patient presents. If this means the middle of the night, then they come in and do it. For example, they report that a few months ago having had two TTP patients who presented in one night. It was a very long night, but until the data proves otherwise, he is of the opinion that the patients are best served by starting plasma exchange as quickly as possible. Finally, in his opinion, the data presented in the article from France by Coppo et al (see above for link) is interesting, and should be studied further, but it will not cause him to change his current approach.
   
   
5. A colleague in Sacramento reports that her center provides emergency plasma exchange on a 24/7 basis. However, they have found that the limitation to beginning the first procedure is often how quickly the requesting physician can find a surgeon to place a central venous catheter. This situation often occurs in some of the smaller hospitals where they provide therapeutic apheresis service. If it looks like it may take more than a couple of hours to place a line, they give the requesting physician the option of administering FFP while arrangements are being made for line placement. They suggest that the rate of administration of FFP should be based upon the patients ability to handle a fluid load. They also recommend that FFP be given in place of other maintenance fluids (eg - cancel the order for 100 mL of saline/hr). In this situation, they feel that it is better to get some plasma into the patient than to do nothing while waiting for line placement. If they can get a line placed in less than 4 hours, they will go out in the middle of the night and perform the first plasma exchange.
   
   
6. A transfusion medicine colleague in Minnesota is of the opinion that if plasma exchange therapy is going to be initiated in just a few hours, he DOES NOT recommend plasma infusion. However if the request initiating plasma exchange comes during the evening prior to midnight and if obtaining venous access and performing the procedure will not take place until the following AM or even later because nursing staff is not available, venous access is not established, apheresis physicians are not willing to come in at night, or arrangements for the treatment involve an outside service and there will be a significant delay, then he recommends plasma infusion until the plasma exchange can be initiated.

ADDENDA Mar. 10, 2003

7. A colleague in Dallas, Texas recommends plasma infusion when plasma exchange is going to be delayed for some reason. In his experience, the delay is usually related to line placement. He states that since many patients have a low titer inhibitor to the the metalloproteinase ADAMTS13, it makes some clinical sense to infuse plasma with ADAMTS13 enzyme that can prevent ongoing platelet-VWF clumping, until proper exchange can be initiated. They give 2-3 units of plasma ASAP depending upon the size of the patient and severity of presentation. Since they keep four units of group A and group O thawed plasma on hand at all times in their blood bank, providing plasma is usually very easy to accomplish." (Editor's NOTE: Colleagues can become familiar with ADAMTS13 in this recent review by Tsai, HM.)

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Ira A. Shulman, MD
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W. Tait Stevens, MD
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Elizabeth M. St. Lezin, MD
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