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

A hemolytic anti‐LKE associated with a rare LKE‐negative, “weak P” red blood cell phenotype: alloanti‐LKE and alloanti‐P recognize galactosylgloboside and monosialogalactosylgloboside (LKE) antigens

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110583/1/trf12772.pd

Case report and literature review: transient Inab phenotype and an agglutinating anti-IFC in a patient with a gastrointestinal problem

The Inab phenotype is a rare deficiency of all Cromer antigens. These antigens are carried on the decay-accelerating factor (DAF, CD55) molecule that is attached to the red blood cell (RBC) membrane by a glycosylphosphatidylinositol (GPI) anchor. Although typically inherited, an acquired and transient form of the Inab phenotype also exists. A patient with the triad of transient Inab phenotype, a direct-agglutinating anti-IFC, and gastrointestinal (GI) abnormalities is reported. CASE REPORT: An 18-month-old boy with gastroesophageal reflux disease requiring a feeding tube, milk and soy intolerance, and severe growth retardation, as well as vision and hearing deficits from cytomegalovirus infection, was identified when pretransfusion testing revealed a potent panagglutinin (titer > 2000 at 4°C). This antibody did not react with Dr(a–) and IFC RBCs, and the autocontrol was negative. The patient’s RBCs lacked CD55 by flow cytometric techniques but had normal levels of CD59 and antigens such as Yt a and Emm, carried on GPI-linked proteins, thus excluding paroxysmal nocturnal hemoglobinuria. Several months after initial detection, the anti-IFC was virtually undetectable and his cells reacted weakly with anti-IFC, anti-Dr a , and anti-CD55. RBCs from the propositus’ parents and brother demonstrated normal CD55 and CD59 expression. CONCLUSION: This is the first example of a direct-agglutinating anti-IFC. The cause of the transient depression in CD55 protein (and thus Cromer system antigens) and appearance of anti-IFC remains unknown, as does the relationship between the patient’s GI system abnormalities and these serologic findings.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71992/1/j.1537-2995.2006.00933.x.pd