Successful management of concurrent congenital dyserythropoietic anaemia and autoimmune haemolytic anaemia with splenectomy.

This first known case of concurrent congenital dyserythropoietic anaemia (CDA) and autoimmune haemolytic anaemia (AIHA) which occurred in a hispanic male and spanned 6 years from the age of 2. Light and electron microscopy of bone marrow erythroblasts and immunophenotyping confirmed CDA; serum/eluate warm autoantibodies and positive direct antiglobulin tests (DAT) associated with severe, episodic anaemias established AIHA. Cytogenetic analysis of bone marrow cells and peripheral blood lymphocytes ascertained sex chromosome aneuploidy (48 XY,+ Y,+ Y). Recurrent, life-threatening episodes of transfusion-dependent anaemia refractory to steroids and intravenous immune globulin, were put into stable remission at age 8 years when splenectomy successfully managed both disorders.

Delayed hemolytic transfusion reaction due to anti-Js(a) in an alloimmunized patient with a sickle cell syndrome.

Delayed hemolytic transfusion reactions occur via an anamnestic immune response in patients previously alloimmunized by certain RBC antigens. Conventional pretransfusion antibody screening tests and crossmatches are unable to detect certain antibodies that potentially can cause these reactions because they may be present in low concentrations or have low affinity for their respective antigen or their indicator antigen may be absent from test RBCs. We report the second case of a delayed hemolytic transfusion reaction caused by an undetectable (by routine methods) anti-Js(a) in a patient with a sickle cell syndrome (hemoglobin SC disease) and multiple alloantibodies, in whom retrospective indirect antiglobulin tests enhanced by polyethylene glycol revealed the presence of weakly reactive anti-Js(a).

Antibody-mediated hemolytic anemia following ABO-mismatched organ transplantation: contributory role of HLA matching and polyclonal antilymphocyte globulin.

We report three instances of antibody-mediated hemolytic anemia following ABO-mismatched, but compatible, renal (n = 2) and simultaneous pancreas-kidney (n = 1) transplantation. The two renal allograft recipients had received a 6-antigen matched transplant; one received polyclonal antilymphocyte globulin to treat an early rejection episode. The simultaneous pancreas-kidney transplant received polyclonal antilymphocyte globulin (ALG) as part of a quadruple therapy induction regimen. All three patients developed severe, but self-limited, antibody-mediated hemolytic anemia within two weeks of their transplants. Serologic testing demonstrated the hemolysis to be antibody mediated; furthermore, testing of the ALG lots demonstrated high titers of anti-red blood cell antibodies. The possible contribution of ALG and HLA matching to the hemolysis seen in these patients after ABO mismatched organ transplantation is discussed.

The predictive value of maternal serum testing for detection of fetal anemia in red blood cell alloimmunization.

OBJECTIVE: Current management protocols for pregnancies complicated by red blood cell alloimmunization use the maternal antibody titer to predict the need for invasive testing for detection of fetal anemia. We investigated the use of three maternal serum tests to assess their usefulness in predicting fetal disease: indirect Coombs' titer, Marsh score, and monocyte monolayer assay. STUDY DESIGN: Forty-seven serum samples from pregnant women with red blood cell antibodies associated with fetal anemia were analyzed at cordocentesis. Fetal blood was analyzed for hematocrit (corrected for gestational age) and antigen status. Fetal anemia was defined as a hematocrit value of < 2 SD from the mean value for gestational age. Fetuses were classified into three groups: Antigen positive with anemia (n = 19), antigen positive without anemia (n = 17), antigen negative (n = 11). Statistical methods included Kruskal-Wallis test, Newman-Keuls test, Spearman's rank correlation, and receiver-operator characteristic curves; p < 0.05 was considered significant. RESULTS: The median monocyte monolayer assay (phagocytosis, adherence, and association) did not differ among the three groups. Both maternal titers and Marsh scores were significantly higher in fetuses with anemia compared with the other two groups of fetuses (256 vs 64 vs 64, p < 0.001, and 86 vs 69 vs 64, p = 0.02, respectively). Both titer and Marsh score exhibited significant correlations with corrected fetal hematocrit (r = -0.70, p < 0.001; r = -0.63, p < 0.001, respectively). Comparison of the overall receiver-operator characteristic curves for titer and Marsh score revealed no statistical difference; however, a Marsh score of 57 was noted to have a superior specificity than a titer of 16 (p = 0.02). CONCLUSION: The maternal Marsh score can be performed in conjunction with standard indirect Coombs' titers to enhance the predictability of fetal anemia.

A simple, practical model for reducing alloimmunization in patients with sickle cell disease.

Patients with sickle cell disease (SCD) form immune alloantibodies more frequently than other transfused populations because red cells (RBCs) from white donors (with a higher incidence of certain Rh, Duffy, Kell, and Kidd blood group antigens) are transfused to black patients often lacking these antigens. We propose a model to reduce alloimmunization in patients with SCD by providing them with blood from only black random donors. Rationale is shown by examining calculations based on the phenotype E-, C-, Fy(a-), K-, and Jk(b-). There is a 7% probability that this phenotype belongs to a white donor, while there is a 93% probability that this phenotype belongs to a black donor. The probability of selecting blood from a black donor identical with the above phenotype for black recipients from an all black population and from a typical urban blood inventory population (90% white, 10% black) is 1/4 and 1/33, respectively. Therefore, an 8-fold greater chance of selecting antigen non-identical blood occurs if blood is obtained from a typical urban donor population as compared to a black population. Based on these calculations, alloimmunization can be reduced prospectively in patients with SCD by meeting their transfusion requirements with blood selected from random black blood donors.

The relative utility of the autologous control and the antiglobulin test phase of the crossmatch.

A retrospective study of pretransfusion testing records compared the utility of the antiglobulin test (AGT) phase of the crossmatch and the autologous control (autocontrol) for detecting clinically significant alloimmunization to red cells (RBCs). Of 110,780 consecutive crossmatches, 141 were positive after a negative antibody screening test; only 4 of these were due to alloantibodies of potential clinical significance, for a predictive value of a positive AGT crossmatch, after a negative antibody screen, of 2.8 percent (4/141). The frequency of potentially shortened RBC survival was 1 in 27,685 units crossmatched. During a similar period, 56,090 autocontrols were performed with the antibody screen. The autocontrol was positive on 902 samples in which the antibody screen was negative. Antibody identification performed in 684 cases generally yielded only cold or warm autoagglutinins. In 96 cases, some form of alloantibody was detected, but only 25 had potential clinical significance by our criteria. Eight of these alloantibodies had concurrently caused in vivo sensitization of RBCs and were classified as delayed hemolytic transfusion reactions. The predictive value of the autocontrol, calculated as the number of significant alloantibodies detected in autocontrol-positive, antibody-screen-negative samples, was 3.6 percent (25/684). Inspection of these cases revealed 11 in which shortened RBC survival might have resulted if the serologic abnormality had not been detected. Thus, the autocontrol had a slightly greater yield of clinically significant findings than the AGT crossmatch.(ABSTRACT TRUNCATED AT 250 WORDS)

The prevalence of immunization to Duffy antigens in a population of known racial distribution.

A retrospective study at our hospital determined the race or ethnicity of patients seen in an 8-year period who had formed antibodies to Duffy antigens. During that time, 9876 serologic investigations had been performed as a result of a positive direct or indirect antiglobulin test. Among these samples, sera from 45 previously transfused or pregnant patients contained anti-Fya and two contained anti-Fy3. Twenty-nine of the sera that contained anti-Fya (62%) were from blacks, 12 (25%) were from whites, and 6 (13%) were from Hispanics. Both examples of anti-Fy3 were made by black patients. Red cells (RBCs) from 21 of the black patients were Fy(a-b-), those from 7 were Fy(a-b+), and those from 1 could not be phenotyped. RBCs from 17 of the non-black patients were Fy(a-b+) and those from 1 could not be phenotyped. The population of transfused patients evaluated in this study was 47 percent black, 29 percent white, and 24 percent Hispanic. Calculations based on an expected Fy(a-) frequency of 88 percent in blacks, 33 percent in whites, and 20 percent in Hispanics predict that the racial makeup of the Fy(a-) population at our hospital would be 73 percent black, 18 percent white, and 9 percent Hispanic, which is not significantly different (p = 0.25) from the racial makeup of the patients forming anti-Fya and -Fy3. These data indicate that blacks make antibodies to Duffy antigens as frequently as non-blacks.

Immune hemolytic anemia associated with probenecid.

Upon hospital admission a patient was found to have severe anemia and a strongly positive direct antiglobulin test (DAT). The patient was taking probenecid periodically for gout. An antibody was detected in the patient's serum that only reacted with red blood cells (RBCs) when probenecid was added. Eluates from the patient's RBCs, with and without the presence of drug, were nonreactive. Upon the discontinuation of probenecid, the patient's hemoglobin level improved steadily. We believe this to be the first reported case of immune hemolytic anemia associated with probenecid.

Acute hemolytic anemia associated with a chlorpropamide-induced apparent auto-anti-Jka.

A patient with acute hemolytic anemia and a positive direct antiglobulin test was found to be Jk(a + b +) with anti-Jka in her serum. For 2 weeks prior to admission, the patient had taken chlorpropamide, a hypoglycemic agent. The drug was discontinued upon the diagnosis of hemolytic anemia, and the hemoglobin concentration gradually increased. When chlorpropamide was added to the patient's serum in vitro, it enhanced the reactivity of the anti-Jka, and 40 days posttransfusion, the serum would only react with Jk(a+) red cells when chlorpropamide was present. These findings suggest that a chlorpropamide-dependent antibody with Jka specificity had formed. We do not know why the antibody induced by chlorpropamide reacted preferentially with Jk(a+) red cells.