A colleague at a blood center in Wisconsin wonders if any blood centers in USA maintain an inventory of low titre anti-T plasma, and if so, how do they screen donors to identify those with low titre anti-T?

The following comments have been received.

ADDENDA Mar. 5, 2004

1. A colleague in Colorado reports that in the last few years they seem to have had an 'outbreak' of patients who have become T- or Tk- activated (and even an acquired B!). They attribute this to a heightened awareness of screening septic patients among their intensive care and neonatal physicians. They utilize washed red cells and platelets for these patients. When the use of fresh frozen plasma cannot be avoided, they attempt to perform minor crossmatching from integral unit segments in the effort to select 'least incompatible' units. The Colorado colleague states that in Applied Blood Group Serology, 4th ed., Issitt references Nancy Heddle as reporting the uneventful transfusion of plasma-containing products to three premature infants with necrotizing enterocolitis (NEC) and T-activated red blood cells. If one makes the effort to screen, some degree of T- or Tk- activation will be found in most infants with NEC. In the Colorado colleague's opinion, observation of a greater degree of severity of T-activation, demonstrating polyagglutination and red cell hemolysis, would be the situation in which one would proceed with extreme caution with the administration of fresh frozen plasma. That is of course problematic because septic children frequently have accompanying coagulopathies.

2. A transfusion medicine physician at an academic center in New Mexico comments that in his opinion, many case reports over the past 50 years have erroneously suggested that T activation CAUSES hemolysis and that plasma used for infants with T activation should be screened for anti-T.

An exhaustive review of this topic is available in the first reference below (Crookston KP et al), along with experimental data supporting the argument that when hemolysis is seen it is not immune-mediated. The New Mexico colleague adds that another study (Boralessa, H et al., Transfusion, 2000) also suggested that there is no need for a low-titer anti-T inventory.

He adds that in his opinion, the best studies ever done on the topic were published in Danish in a PhD dissertation by Poulsen (Poulsen, MPE, 1961. Polyagglutinabilitet og T-omdannelse. Medicine. Copenhagen, Denmark, University of Copenhagen: 186 pages.) This contains over one hundred tables of experimental evidence and also the data from two papers he published in the journal Nature in 1954. This work is also summarized in the first reference below by Crookston et al. but has been otherwise ignored in the English literature. That said, if clinicians are really worried, you can satisfy them by doing a simple minor crossmatch.

The first two of the above-mentioned references are provided here, along with pertinent excerpts from the articles.

Crookston KP, Reiner AP et al. (2000). "RBC T activation and hemolysis: implications for pediatric transfusion management." Transfusion 40(7): 801-12 (no abstract).

"T activation due to decreased sialic acid residues on the RBC membrane is not uncommon and can be detected in about 1 of 180 apparently normal blood donors and at much higher rates in children with NEC or S. pneumoniae-associated HUS. A cause-and-effect relationship between anti-T and hemolysis in patients with RBC T activation has not been clearly substantiated. Most cases of RBC T activation go undetected and are not associated with hemolysis. Data from animal studies suggest that the accelerated clearance of T-activated RBCs is not due to an immune mechanism. When hemolysis occurs in the presence of T activation, it is most likely due to one or more of the following: 1) a shortened RBC survival secondary to decreased sialic acid on the membranes; 2) direct action of hemolytic bacterial enzymes; or 3) microhemangiopathic hemolysis (seen in HUS). Therefore, the administration of blood components containing anti-T should not cause increased hemolysis in patients whose RBCs are T activated; however, it is not known whether these data can be extrapolated to all related types of T activation. In patients with S. pneumoniae-associated HUS and RBC T activation, there is a possible risk that glomerular binding of anti-T present in transfused plasma products may increase the renal damage. Prudence should be used in selecting blood components for transfusion to patients with RBC T activation, to ensure that the actual need for hemostatic components is not neglected because of a perceived potential risk of hemolysis from plasma-containing products."

Boralessa, H, Modi N et al. (2002). "RBC T activation and hemolysis in a neonatal intensive care population: implications for transfusion practice." Transfusion 42(11): 1428-34.

"It was reassuring that hemolysis following the transfusion of standard blood components was not seen in any of the infants in our study. These data suggest that routine screening for T activation of infants with sepsis or NEC is not justified. However, where there is evidence of transfusion-associated hemolysis, screening followed by differentiation of T from T variant activation may be useful in identifying true cases of T activation. We also believe it reasonable to conclude that in neonatal populations, including those neonates with NEC or sepsis, the routine provision of low-titer anti-T components, washed RBCs, or platelets suspended in AS is not warranted and should be considered only in the very small proportion of infants with true T activation and transfusion-associated hemolysis; it is of note that no such babies were identified from over 2000 screened samples in our study."

ADDENDA May 16, 2007

3. Editors' note: The Blood First Edition Paper by Jozsi M, et al. Anti-factor H autoantibodies block C-terminal recognition function of factor H in hemolytic uremic syndrome prepublished online May 10, 2007 may be germane to this discussion.

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