Erythropoietic protoporphyria

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73642/1/j.1537-2995.2004.04058.x.pd

Nontransfusion hazards of autologous blood donation

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72837/1/j.1537-2995.2001.41010152.x.pd

A case of extravascular hemolysis with Tk‐activation

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/108281/1/ccr380.pd

Persistence of cefotetan on red blood cells

Cefotetan can cause severe immune hemolytic anemia that may persist long after the drug is discontinued. To study the binding of cefotetan to RBCs, patients who received cefotetan were followed and tested for the presence of antibody to cefotetan. STUDY DESIGN AND METHODS:  Patients receiving cefotetan were identified from pharmacy and nursing records. Blood samples obtained for routine hematology tests were analyzed. Cefotetan binding to patients’ RBCs was tested using a previously characterized high-titer anticefotetan serum by gel technique. To determine the minimum amount of drug necessary for binding to occur, RBCs were incubated with serial dilutions of cefotetan at pH 7.4. RESULTS:  Sixty patients receiving 1 to 25 g IV (median, 2 g) of cefotetan were followed for 1 to 123 days (median, 18 days). All were initially positive, for cefotetan on RBCs. Positivity persisted for up to 98 days after the last dose of drug. Fifteen patients became negative during follow-up. The first negative sample occurred at Day 30 to 123. Using the midpoint between the last positive and first negative to estimate of the duration of positivity, we estimate that cefotetan remains RBC-bound for 16.5 to 92 days (median, 67.5 days). During the follow-up period, five patients developed anticefotetan detectable in the serum. Twenty patients receiving other cephalosporin antibiotics showed no specific reactivity of their RBCs with anticefotetan. In vitro studies showed a minimum necessary drug concentration of 1 µmol/L at physiologic pH, which was not significantly altered by RBC pretreatment with ficin, sialydase, or DTT. CONCLUSIONS:  Cefotetan is tightly bound to RBCs after intravenous administration and remains detectable for weeks after the last dose. Antibodies to cefotetan may occur in about 8 percent of patients receiving the drug. The minimum necessary concentration for RBC binding is low compared to an estimated plasma concentration of 240 µmol/L from a single IV dose of 1 g.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72360/1/j.1537-2995.2004.03360.x.pd

Delayed platelet engraftment in group O patients after autologous progenitor cell transplantation

Fucosylated glycans, including H-antigen, play critical roles in hematopoietic progenitor cell homing, adhesion, growth, and differentiation. H-active antigens are strongly expressed on CD34+ progenitor cells and committed megakaryocytic progenitors and may mediate adhesion to marrow stromal fibroblasts. We examined the possible influence of donor ABO type on platelet (PLT) engraftment after autologous peripheral blood progenitor cell transplant (PBPCT). STUDY DESIGN AND METHODS: A retrospective analysis of all patients who underwent a single autologous PBPCT between 1996 and 2000 were reviewed. Neutrophil and PLT engraftment were compared by patient ABO type and CD34+ cell dose by t test, chi-square test, analysis of variance, Kaplan-Meier probability, and log-rank test. RESULTS: Engraftment data was available in 195 patients. PLT engraftment was delayed in all patients, regardless of ABO type, at CD34+ PBPC doses of 2 × 10 6 to 3 × 10 6 per kg (p  50 × 10 9 /L) was significantly delayed in group O patients relative to all non-group O patients (32.4 days vs. 19.6 days, p < 0.001). Approximately 50 percent of group O patients required more than 40 days to achieve late PLT recovery (p < 0.005). CONCLUSIONS: A group O phenotype may be associated with delayed PLT engraftment at lower CD34 doses.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73409/1/j.1537-2995.2005.04346.x.pd

Anti-A and anti-B titers in pooled group O platelets are comparable to apheresis platelets

Although uncommon, acute hemolytic transfusion reactions (AHTRs) have been reported after transfusion of group O single-donor apheresis platelets (SDPs) to group A, B, and AB recipients. Current methods for identifying “high-titer” SDPs include tube and gel methods. The risk of a high-titer unit is considered low with group O, poststorage, pooled platelet concentrates (PPLTs); however, data regarding anti-A and anti-B titers in PPLTs are lacking. STUDY DESIGN AND METHODS: Anti-A and anti-B titers were determined in 185 PPLTs by direct agglutination using manual gel and tube methods. PPLTs tested included 124 group O PPLTs, 25 group A PPLTs, 26 group B PPLTs, and 10 PPLTs containing a mix of either groups O plus A or groups O plus B (mixed PPLTs). The reciprocal of the highest dilution giving macroscopic agglutination was considered the agglutinin titer. RESULTS: Mean anti-A and anti-B titers in group O PPLTs were, respectively, 16 and 8 by tube and 64 and 32 by gel (p < 0.0001). Gel titers were one to two dilutions higher than tube and sensitive to reagent red cell lots. With the use of at least 64 as a critical titer, 60 percent of group O PPLTs tested by gel would be considered high-titer. In mixed PPLTs, the addition of one non-group O PLT significantly decreased or neutralized the corresponding anti-A or anti-B (p < 0.0001). CONCLUSION: Anti-A and anti-B titers in group O PPLTs are comparable to those reported in group O SDPs and significantly lower than titers reported in AHTR. A critical direct agglutinin titer of 64 for identifying high-titer units by gel is too low and should be increased to 128 or higher.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73545/1/j.1537-2995.2008.01814.x.pd

Revisiting the issue: can the reading for serologic reactivity following 37°C incubation be omitted?

Omitting the 37°C reading from screening tests for unexpected antibodies results in failure to detect some Rh, K, and Jk agglutinins of potential significance (wanted positives). However, this measure avoids unwanted positive tests due to cold agglutinins. STUDY DESIGN AND METHODS : Using data from prior publications, actual risk calculations (ARCs) were made to predict the risk of eliminating the 37°C reading, pretransfusion direct antiglobulin test (DAT), and routine indirect antiglobulin crossmatch (IAT-XM). ARCs used the equation: wanted positives missed × 0.34 (or 0.80) × 5 × percent antigen-positive, where 0.34 = percent of patients transfused (ARCs for 37°C reading and DAT); 0.80 = percent of crossmatched patients transfused (ARCs for IAT-XM); 5 = average number of units transfused. Following elimination of the 37°C reading, the impact of this change on patient care was monitored. Antibody detection and identification data and transfusion reaction reports for 6 months after the change were reviewed. Recently transfused patients with new antibodies were evaluated for immune hemolysis by review of clinical and laboratory data. The findings were compared with those from the same dates of the preceding year. RESULTS : The risk of transfusing incompatible blood by eliminating the DAT, IAT-XM, and 37°C reading is approximately 1:13,000, 1:2,000, and 1:2,400 units transfused, respectively. The cumulative risk from eliminating all three tests is approximately. 1:1,000 units. With respect to the 37°C reading, there were no differences between the pre-change and post-change study periods in the incidence of reported transfusion reactions or cases of immune hemolysis associated with newly formed antibodies. However, unwanted positive tests decreased from 162 to 61 following elimination of the 37°C reading. This represents a decrease of 20 percent in the number of samples requiring antibody identification annually. CONCLUSIONS : Eliminating the 37°C reading from pretransfusion antibody screening tests imposes less risk than omitting the routine IAT-XM, and it avoids the time and costs of evaluating unwanted positive tests, thus reducing expenditures and delays in patient care.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74728/1/j.1537-2995.1999.39399219287.x.pd

Efficacy of plasmapheresis on donor‐specific antibody reduction by HLA specificity in post–kidney transplant recipients

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111098/1/trf12923.pd

Packed Red Blood Cells Are an Abundant and Proximate Potential Source of Nitric Oxide Synthase Inhibition

<div><p>Objective</p><p>We determined, for packed red blood cells (PRBC) and fresh frozen plasma, the maximum content, and ability to release the endogenous nitric oxide synthase (NOS) inhibitors asymmetric dimethylarginine (ADMA) and monomethylarginine (LNMMA).</p><p>Background</p><p>ADMA and LNMMA are near equipotent NOS inhibitors forming blood’s total NOS inhibitory content. The balance between removal from, and addition to plasma determines their free concentrations. Removal from plasma is by well-characterized specific hydrolases while formation is restricted to posttranslational protein methylation. When released into plasma they can readily enter endothelial cells and inhibit NOS. Fresh rat and human whole blood contain substantial protein incorporated ADMA however; the maximum content of ADMA and LNMMA in PRBC and fresh frozen plasma has not been determined.</p><p>Methods</p><p>We measured total (free and protein incorporated) ADMA and LNMMA content in PRBCs and fresh frozen plasma, as well as their incubation induced release, using HPLC with fluorescence detection. We tested the hypothesis that PRBC and fresh frozen plasma contain substantial inhibitory methylarginines that can be released chemically by complete <i>in vitro</i> acid hydrolysis or physiologically at 37°C by enzymatic blood proteolysis.</p><p>Results</p><p><i>In vitro</i> strong-acid-hydrolysis revealed a large PRBC reservoir of ADMA (54.5 ± 9.7 µM) and LNMMA (58.9 ± 28.9 μM) that persisted over 42-d at 6° or -80°C. <i>In vitro</i> 5h incubation at 37°C nearly doubled free ADMA and LNMMNA concentration from PRBCs while no change was detected in fresh frozen plasma.</p><p>Conclusion</p><p>The compelling physiological ramifications are that regardless of storage age, 1) PRBCs can rapidly release pathologically relevant quantities of ADMA and LNMMA when incubated and 2) PRBCs have a protein-incorporated inhibitory methylarginines reservoir 100 times that of normal free inhibitory methylarginines in blood and thus could represent a clinically relevant and proximate risk for iatrogenic NOS inhibition upon transfusion.</p></div