Predisposing factors for anti-D immune response in D- patients with chronic liver disease transfused with D+ platelet concentrates.

BACKGROUND: Recent reports have indicated that the risk of anti-D alloimmunization following D-incompatible platelet (PLT) transfusion is low in hematology and oncology patients. We investigated the rate of anti-D alloimmunization in RhD-negative (D- ) patients with chronic liver disease transfused with D+ platelet concentrates (PCs) and the factors involved, at a liver transplant (LT) center. STUDY DESIGN AND METHODS: We reviewed the blood bank database from January 2003 to October 2016. D- patients who had received D+ PLT transfusions were eligible if they had undergone antibody screening at least 28 days after the first D+ PC transfusion, had no previous or concomitant exposure to D+ blood products, and had not received anti-D immunoglobulins. RESULTS: Six of the 56 eligible patients (10.7%) had anti-D antibodies. All had received whole blood-derived PCs. Four of 20 patients (20%) untransplanted or transfused before LT and only two of 36 patients (5.6%) transfused during or after LT produced anti-D antibodies. These two patients were on maintenance immunosuppression based on low-dose steroids and tacrolimus. The factors identified as significantly associated with anti-D immune response were the presence of red blood cell immune alloantibodies before D+ PLT transfusion (p = 0.003), and D+ PLT transfusion outside the operative and postoperative (5 days) periods for LT (p = 0.023). CONCLUSION: D- patients with chronic liver disease transfused with D+ PLTs before LT are at high risk of developing anti-D antibodies. Preventive measures should be considered for these patients.

Severe hemolysis after plasma transfusion in a neonate with necrotizing enterocolitis, Clostridium perfringens infection, and red blood cell T-polyagglutination.

BACKGROUND: Red blood cell (RBC) Thomsen-Friedenreich antigen exposure (T activation) in infants with necrotizing enterocolitis (NEC) has occasionally been associated with posttransfusional intravascular hemolysis thought to be due to anti-T antibodies in the donor plasma. STUDY DESIGN AND METHODS: We describe an infant with NEC and Clostridium perfringens infection complicated by severe hemolysis after plasma transfusion. After this case, infants with confirmed NEC were prospectively evaluated for T activation. We checked for hemolysis in patients with T activation receiving plasma-containing blood products. RESULTS: The infant had received 80 mL of fresh-frozen plasma (FFP). His RBCs displayed strong T activation, and agglutination was observed with four of six ABO-compatible FFP units. A direct antiglobulin test was negative. IgM-class anti-T antibodies were present in small amounts (titer of 8) in the transfused FFP. Anti-T antibodies from the blood donor were not hemolytic in vitro. In the prospective study, T activation was observed in three of 28 infants with NEC (11%). One infant presented moderate T activation and two infants presented very strong T activation but only moderate decreases in sialic acid expression on the RBC membrane. These three infants presented no signs of hemolysis after transfusion with unwashed blood products or FFP. CONCLUSION: Anti-T antibodies are unlikely to be the etiologic factor for the hemolytic reactions observed in infants with NEC and T activation. Massive RBC desialylation and the direct action of bacterial toxins are more probable causes. Strict avoidance of plasma-containing blood products does not seem justified in these infants.

Red blood cell Thomsen-Friedenreich antigen expression and galectin-3 plasma concentrations in Streptococcus pneumoniae-associated hemolytic uremic syndrome and hemolytic anemia.

BACKGROUND: Pneumococcal hemolytic uremic syndrome (P-HUS) is a rare but severe complication of invasive pneumococcal disease (IPD) in young children. Consensual biologic diagnosis criteria are currently lacking. STUDY DESIGN AND METHODS: A prospective study was conducted on 10 children with culture-confirmed IPD. Five presented with full-blown P-HUS, three had an incomplete form with hemolytic anemia and mild or no uremia (P-HA), and two had neither HUS nor HA. Thomsen-Friedenreich (T), Th, and Tk cryptantigens and sialic acid expression were determined on red blood cells (RBCs) with peanut (PNA), Glycine soja (SBA), Bandeiraea simplicifolia II, and Maackia amurensis lectins. Plasma concentrations of the major endogenous T-antigen-binding protein, galectin-3 (Gal-3), were analyzed. RESULTS: We found that RBCs strongly reacted with PNA and SBA lectins in all P-HUS and P-HA patients. Three P-HUS and three P-HA patients showed also concomitant Tk activation. Direct antiglobulin test (DAT) was positive in three P-HUS (one with anti-C3d and two with anti-IgG) and two P-HA patients (one with anti-C3d and one with anti-IgG). RBCs derived from the two uncomplicated IPD patients reacted with PNA but not with SBA lectin. Gal-3 plasma concentrations were increased in all P-HUS patients. CONCLUSIONS: The results indicate high levels of neuraminidase activity and desialylation in both P-HUS and P-HA patients. T-antigen activation is more sensitive than DAT for P-HUS diagnosis. Combining PNA and SBA lectins is needed to improve the specificity of T-antigen activation. High concentrations of Gal-3 in P-HUS patients suggest that Gal-3 may contribute to the pathogenesis of P-HUS.

Immunohematologic tolerance of chronic transfusion exchanges with erythrocytapheresis in sickle cell disease.

BACKGROUND: Sickle cell disease (SCD) has become a major public health issue. Hydroxyurea and red blood cell (RBC) transfusion are the cornerstone treatments. Erythrocytapheresis (ECP) is an automated method for transfusion exchange. Given that ECP requires more blood than conventional transfusion, there is concern about alloimmunization and hemolytic transfusion reactions. We evaluate the incidence of hemolytic transfusion reactions and alloimmunization rates in patients receiving conventional blood transfusions and in patients participating in long-term blood exchange programs with ECP. STUDY DESIGN AND METHODS: All hemolytic transfusion reactions and alloimmunizations in SCD patients were recorded over the period 2006 to 2011. Conventional transfusions and ECP were compared. RESULTS: The cohort consisted of 188 SCD patients. The median (±SD) age was 23 (±14) years. The ECP and conventional transfusion groups comprised 49 and 139 patients, respectively. The prevalence of alloimmunization was 33% in the ECP group and 22% in the conventional transfusion group (p = 0.1797). The alloimmunization/RBC unit (RBCU) ratio was lower in the ECP group than in the conventional transfusion group (1.6 and 11.6 per 1000, respectively; p < 0.0001). Although patients in the ECP group received more than 10 times more RBCUs than patients in the conventional transfusion group (206 vs. 19 RBCUs per patient, respectively; p < 0.0001), none of the four recorded hemolytic transfusion reactions (n = 4) occurred. CONCLUSION: Regarding alloimmunization, ECP exhibits a good immunohematologic safety profile relative to conventional transfusion in a large SCD mainly adult cohort.

ceRA: an RH allele variant producing a new rare blood.

BACKGROUND: Antibodies against RH antigens are clinically significant. Some rare RH phenotypes, for example, RH:-46 (R(N)), RH:-18 (Hr(s)-), RH:-34 (Hr(b)-), and homozygous partial RH5 (e), are found exclusively in black persons of African descent. Quantitative and qualitative RHCE variants require characterization because the presence of these alleles can lead to difficulties when transfusion is needed. STUDY DESIGN AND METHODS: Here a new RH5 variant (ceRA) in an Indian patient is described and investigated by serology (agglutination and flow cytometry analysis) and molecular and immunoblot analysis. RESULTS: Red blood cells (RBCs), typed as RH:-1,-2, -3,4,w5, expressed a very depressed RH5 antigen, with no expression of the RH19 (h) high-frequency antigen. Molecular analysis revealed a new Rhce allele (homozygous state), hereafter called ceRA. This new allele exhibited a G48C mutation in exon 1 and a G538C mutation in exon 4, predicting, respectively, a Trp16Cys substitution and a Gly180Arg substitution, both in the intramembranous domain of the Rhce polypeptide. Immunoblot analysis showed that this defect results in a dramatic loss of the amount of RHCE polypeptides within the RBC membrane. No reactivity was evidenced with most of anti-RH5, in agglutination as well as in flow cytometry techniques. CONCLUSION: Both serologic results and localization of the Gly180Arg substitution emphasize the risk of anti-RH5 alloimmunization for patients expressing this new allele ceRA at the homozygous state. These results point out the importance of obtaining blood donations for the frozen rare blood bank in case future transfusion is needed.