Anomaly of the des-Arg9-bradykinin metabolism associated with severe hypotensive reactions during blood transfusions: a preliminary study.

BACKGROUND: Severe hypotensive reactions have been described after the transfusion of platelets or red cells through negatively-charged bedside white cell-reduction filters. The possibility of a role for bradykinin (BK) in the genesis of these reactions has been raised. STUDY DESIGN AND METHODS: To understand if an anomaly of BK metabolism is associated with these reactions, the metabolism of BK and des-Arg9-BK was studied in the sera of four patients who presented with a severe hypotensive transfusion reaction. Tests were performed in the absence and the presence of complete in vitro inhibition of angiotensin-converting enzyme (ACE) activity by enalaprilat. RESULTS: In the presence of ACE inhibition (enalaprilat), the half-life (t1/2) of BK measured in the sera of patients who presented with a severe hypotensive transfusion reaction (361 +/- 90 sec) was not significantly different from that measured in the sera of normal controls (249 +/- 16 sec). In the presence of ACE inhibition (enalaprilat), the t1/2 of des-Arg9-BK was significantly greater in patients who presented with a severe hypotensive transfusion reaction (1549 +/- 319 sec) than in normal controls (661 +/- 38 sec) (p < 0.001). CONCLUSION: A metabolic anomaly mainly affecting the degradation of des-Arg9-BK could be responsible for its accumulation in vivo. Des-Arg9-BK could be responsible, at least in part, for severe hypotensive transfusion reactions.

Transfusion associated graft-versus-host disease, cytomegalovirus infection and HLA alloimmunization in neonatal and pediatric patients.

Modern transfusion support of pediatric patients requires attention to the necessity to provide specialized or modified blood components to these patients who are often immunocompromised and/or affected by very complex medical and surgical illnesses. In this review we will address three potential complications of transfusion that may require specialized components for their prevention in selected patients namely transfusion-associated graft-versus-host disease, transfusion-transmitted cytomegalovirus infection and HLA alloimmunization, with particular reference to the indications for prevention of these transfusion complications in neonatal and pediatric patients.

Hypotensive reactions: a previously uncharacterized complication of platelet transfusion?

BACKGROUND: In 1993, the American Association of Blood Banks (AABB) received reports of severe hypotensive reactions associated with platelet transfusions. The question arose as to whether these reports were indicative of a previously uncharacterized platelet transfusion reaction. STUDY DESIGN AND METHODS: To further characterize these reactions, the AABB Transfusion Practices Committee developed a series of three questionnaires. The initial questionnaire was sent to all AABB institutional members; the two subsequent questionnaires were sent to those institutions reporting severe and/or unusual platelet transfusion reactions. This report focuses on the 24 responses to the third and most detailed questionnaire, which specifically addressed reactions that were characterized by hypotension and/or unexplained respiratory failure. RESULTS: Of the 24 detailed responses received, 4 were not considered to represent unusual reactions to platelet transfusion, 3 described reactions consistent with a (presumably unrecognized) diagnosis of transfusion-related acute lung injury, and 17 described reactions that were primarily characterized by hypotension. The majority of the hypotensive reactions occurred within 1 hour of the beginning of the transfusion (88%), were associated with respiratory distress (82%), and resolved rapidly after cessation of the transfusion (82%). Eighty-eight percent of implicated components had been white cell reduced by filtration. CONCLUSION: The hypotensive platelet transfusion reactions that were described appear to represent a previously uncharacterized complication of platelet transfusion. However, the nature of the questionnaires used in this investigation does not allow the drawing of firm conclusions as to the frequency or the cause of these reactions.

Guidelines for auditing pediatric blood transfusion practices.

Although transfusion of blood products is an essential and potentially life-saving measure, not all blood transfusions are beneficial to patients. The associated risks, particularly transfusion-transmitted viral illnesses, such as hepatitis and acquired immunodeficiency syndrome, require that careful consideration be given before a decision is made to transfuse any blood product. Many institutions have established a local committee to monitor transfusion practices and audit such practices regularly. To assist in this task, the Pediatric Hemotherapy Committee of the American Association of Blood Banks has developed guidelines for the conduct of pediatric blood transfusion audits. These guidelines, summarized herein, cover transfusion of red blood cells, platelets, white blood cells, fresh-frozen plasma, albumin, and clotting concentrates. The use of cytomegalovirus low-risk and irradiated blood products is also discussed. Throughout the report, special attention is given to the transfusion needs of newborn infants.

Commentary on the safety of red cells preserved in extended-storage media for neonatal transfusions.

Red cells preserved in extended-storage media are the standard product dispensed by many regional blood centers. When the red cells are intended for neonatal transfusion, concern exists about the safety of the relatively high quantities of additives present in these media. Definitive studies to address these concerns are not available. Therefore, to estimate the effects of additives and to delineate circumstances in which they might be harmful, the quantities transfused in defined clinical settings were calculated, and the following recommendations are offered for transfusing infants less than 4 months of age. First, red cells preserved in extended-storage media should present no substantive risks when used for small-volume (approximately 10 mL/kg) transfusions of premature infants and can be used without additional processing. Second, the risks of the most premature neonatal patients or those with severe renal and/or hepatic insufficiency cannot be defined clearly, and, because data are not available to ensure safety for these infants, removal of the additive medium and resuspension of the red cells in saline or albumin solution immediately before transfusion are recommended. Third, following a similar rationale, it seems prudent to avoid using entire units of red cells preserved in extended-storage media in massive transfusion settings (e.g., exchange transfusion, cardiac surgery, and extracorporeal membrane oxygenation). In these settings, the preservative medium should be removed and the red cells resuspended in the fluid that is most appropriate for the procedure that is planned. It must be emphasized that these recommendations are based on calculations and hypothetical settings, not actual data. Accordingly, they are tentative and should be altered as definitive information becomes available.

Hemoglobin Montreal: a new variant with an extended beta chain due to a deletion of Asp, Gly, Leu at positions 73, 74, and 75, and an insertion of Ala, Arg, Cys, Gln at the same location.

The unstable hemoglobin Montreal with a deletion of three amino acid residues (Asp, Gly, Leu) at positions 73, 74, and 75 of the beta chain and an insertion of four residues (Ala, Arg, Cys, Gln) at the same location was observed in a 7-year-old Canadian boy suffering from a moderate hemolytic anemia. The introduction of an extra amino acid residue and of other changes in the crevice where the heme group is located is the likely cause of the instability of this hemoglobin variant. The above listed changes were detected through analyses of tryptic peptides of the beta-Montreal chain, sequencing of amplified DNA, and hybridization of amplified DNA with appropriate, 32P-labeled, oligonucleotide probes. It is suggested that a mispairing involving the AGTG sequences at codons 66 and 67 and at codons 72 and 73 of the normal beta gene caused a repetition of a 16-bp segment, while a deletion of 10 nucleotides due to recombination or slippage followed by a second short deletion during DNA repair resulted in the modified sequence of the beta-Montreal gene.

Evaluation of pediatric transfusion practice using criteria maps.

Pediatric blood transfusion practice in a tertiary-care pediatric hospital was evaluated retrospectively by using the technique of criteria mapping. A total of 630 transfusion episodes involving red cell concentrates, frozen plasma (plasma frozen within 24 hours of collection), platelet concentrates, and albumin were reviewed: 243 (86.2%) were reviewed only by a technical assistant, and 87 (13.8%) required additional physician review. Of these, 138 were red cell concentrate transfusions: 79.7 percent of that group were considered appropriate, 11.6 percent of unknown benefit/risk ratio, 5.8 percent inappropriate, and 2.9 percent impossible to evaluate. Some 246 frozen plasma transfusions were reviewed: 42.3 percent were considered appropriate, 32.5 percent of unknown benefit/risk ratio, 17.5 percent inappropriate, and 7.7 percent impossible to evaluate. A total of 139 platelet concentrate transfusions were reviewed: 64.7 percent were considered appropriate, 16.5 percent of unknown benefit/risk ratio, 10.1 percent inappropriate, and 8.6 percent impossible to evaluate. Some 107 albumin transfusions were reviewed: 90.6 percent were considered appropriate, 1.9 percent inappropriate, and 7.5 percent impossible to evaluate. The criteria maps developed for this study were easy for the technical assistant to use, and areas of appropriate and inappropriate pediatric transfusion practice were clearly identified.

Blood component therapy during the neonatal period: a national survey of red cell transfusion practice, 1985.

A questionnaire to determine patterns of neonatal red cell transfusion practice during 1985 was mailed to 2200 blood banks of American Association of Blood Banks (AABB) institutional members and children's hospitals. There were 915 responses (41.6%); 785 responses (86%) contained sufficient data for analysis. The majority (70.6%) of 785 responding hospitals were community/urban institutions. However, more highly specialized, pediatric hospitals were also represented by 92 university/tertiary-care hospitals (11.7% of respondents) and 29 children's hospitals (3.7% of respondents). Two-thirds of hospitals performed a major antiglobulin crossmatch (rather than an abbreviated one) before all neonatal red cell transfusions. The red cell preparation most frequently selected for small-volume transfusions was ABO and Rh group-specific red cell concentrates. When performing only large-volume exchange transfusions, 19.2 percent of hospitals used whole blood; all others prepared reconstituted units of red cells plus fresh-frozen plasma, a practice that frequently causes exposure to two donors per unit. Another practice likely leading to multiple donor exposure is the use of fresh-frozen plasma to adjust the hematocrit of red cell preparations to a predetermined value prior to a small-volume transfusion. Over one-half of hospitals adjusting hematocrits used plasma, presumably from one donor, to dilute packed red cells from another donor, a practice that has no apparent medical benefit. Most hospitals (63.4%) provided red cells with a reduced risk of transmitting cytomegalovirus; blood from seronegative donors was selected by 65 percent of hospitals. The majority of hospitals, including most of the community/urban hospitals, did not irradiate blood products before transfusion.(ABSTRACT TRUNCATED AT 250 WORDS)