Quinidine Hemolytic Anemia in the Absence of Thrombocytopenia in a Patient with Hemoglobin D

A patient on quinidine therapy was found to have a positive direct Coombs test and low grade hemolytic anemia without thrombocytopenia. The serum and red cell eluates contained an antibody which reacted by indirect Coombs technic against red cells presensitized with quinidine gluconate. The serum also contained weak anti‐Sd^a. The hemolytic anemia, anti‐Sd^a, and positive direct Coombs test disappeared three months after the drug was discontinued. The serologic findings are described. An incidental finding of hemoglobin D is also noted, and its relationship to the hemolysis is considered.     

Rapid detection of anti-Lub with recombinant Lub protein and the particle gel immunoassay

BACKGROUND: Until now, it was not possible to identify antibodies to red blood cells (RBCs) except with pretyped RBCs. Here, a novel method with particles coated with recombinant Lu^b protein for detection of anti-Lu^b is described.
STUDY DESIGN AND METHODS: Prokaryotic recombinant Lu^b proteins were generated and coupled onto superparamagnetic particles coated with streptavidin. The coated particles were tested in the presence of different serum and plasma samples (13 anti-Lu^b, 6 anti-Lu^a, 20 other antibodies, and 35 serum samples from blood donors) with the particle gel immunoassay (ID-PaGIA).
RESULTS: Lu^b-coated particles reacted with all 13 samples containing anti-Lu^b, but not with any samples lacking anti-Lu^b. In addition, the anti-Lu^b titers were higher with Lu^b-coated particles than with Lu(a–b+) RBCs in almost all cases.
CONCLUSION: Recombinant blood group proteins may be able to dispense with the need for RBCs for identification of certain RBC alloantibodies.     

The Lutheran Blood Groups: A Progress Report with Observations on the Development of the Antigens and Characteristics of the Antibodies

Scoring titrations with anti-Lu^a on 81 members of the families of seven Lu(a+b—) propositi did not produce any evidence for the presence of Lu genes. In the Lu(a+b+) heterozygotes the Lu^a antigen was only weakly expressed at birth increasing progressively during the first 15 years. The red cells of Lu(a+b—) children gave scores comparable to those of adults. The reactions of Lu(a—b+) cord cells were somewhat weaker than those of adults but the red cells of Lu(a+b+) infants reacted very weakly with anti-Lu^a. Four infants born to mothers with anti-Lu^b had no evidence of hemolytic disease due to this antibody. Serologic, immunochemical and ultrafiltration studies suggest that the examples of anti-Lu^b studied are mainly IgA. These observations can explain why no unequivocal examples of hemolytic disease of the newborn due to anti-Lu^b have been encountered.     

Normal Survival of Incompatible Red Cells in the Presence of Anti-Lua

A case is reported in which incompatible Lu(a+) red cells survived normally in the presence of anti-Lu^a as indicated by hemoglobin-hematocrit determinations and by differential agglutination. This fact was later confirmed by Cr⁵¹ tagged cell studies. Sensitization apparently existed prior to transfusion although it was not detected by crossmatching at that time. The direct non-gamma antiglobulin test became positive and a potent antibody was produced which reacted well at 37 C. and in albumin, enzyme, and antiglobulin tests. The findings in this patient are discussed in the light of previously reported cases.     

The Rho Variant-Du

A simplified test for the D^u factor employing a reagent containing 25 per cent serum albumin, the "stick" technic to introduce cells and forceful cen-trifugation has been given an extensive trial in a routine blood bank operation. A routine preliminary test with anti-D gave 5,051 negative reactions among 26,753 bloods tested. The D^u tube test was then performed on the former with an anti-CDE reagent in parallel with the indirect antiglobulin test done with anti-D. All bloods positive by one or both tests were tested further for D antigens by an anti-D elution technic; they were also tested for Rh-Hr factors.
Among the 126 bloods positive by elution for the D^ufactor, 122 and 126 were positive respectively by the antiglobulin and the D^u tube tests. The two tests were in agreement on all eight of the type ccD^uee bloods found in the study. The D^utube test, as done with anti-CDE, gave no false negative reactions. It is, thus, concluded that bloods which are negative with this test will be type ccddee and can be labeled "Rh negative tested for D^u. Serological factors which might account for sensitivity of the D^u tube test's being the equal of the antiglobulin test are considered, as are the probabilities of the existence of D variants so weak that they could not be detected by either test.     

The In Vivo Survival of Coombs Positive Autologous Erythrocytes Produced by Agglomeration

Coombs positive erythrocytes were observed following the preservation of autologous, human erythrocytes using glycerol, slow freezing, and agglomeration. In 22 of 48 autotransfusions, the preserved erythrocytes were Coombs positive when tested with an anti-gamma + non-gamma globulin serum. In ten of these 22 units, the erythrocytes were tested with both an anti-7S gamma globulin serum and an anti-β₁C globulin serum. All of the erythrocytes in these ten units reacted positively with the anti-β₁C globulin serum, and only one unit reacted equivocally with the anti-7S gamma globulin serum.
The reduction in ionic strength during glycerolization allowed for the uptake of the complement fraction β₁C by the erythrocytes. There was a significant correlation between the Coombs test and the per cent of initial ionic strength of the erythrocyte resuspension medium after glycerolization.
There was no significant correlation between the Coombs test and the 24-hour and seven-day chromium survivals.     

Deficiency In Serum Ionized Magnesium But Not Total Magnesium In Patients With Migraines. Possible Role Of Ica2+/IMg2+ Ratio

SYNOPSIS
It has been suggested that magnesium (Mg) may play a role in the pathogenesis of headaches. Serum and intracellular measurements of Mg in headache patients have produced inconsistent results. The recent development of an ion-selective electrode for Mg²⁺ allowed precise measurement of serum ionized magnesium (IMg²⁺) in patients with various headache syndromes. Low serum Img²⁺ and a high ICa²⁺/IMg²⁺ ratio were found in 42% of patients having an attack of migraine, but only in 23% of patients with e severe continuous headache. Total serum Mg was normal in both groups of patients. However, in patients with low serum IMg²⁺ total serum Mg was lower than in patients with normal serum IMg²⁺. These results are compatible with the serotonin and vascular concepts of migraine pathogenesis. Low IMg²⁺ and a high ICa²⁺/Img²⁺ would result in cerebral vasospasm and reduced blood flow in the brain. The activity of serotonin receptors can also be affected by changes in IMg²⁺ levels. The finding of a difference in IMg²⁺ levels in two different headache types suggests a possible novel classification of headaches and that migraine patients with a low serum IMg²⁺ or a high ICa²⁺/IMg²⁺ ratio may benefit from Mg supplementation.     

The Phenotype Rhod: Study of Another Family

A case is described in which an Rh_o-positive Negro woman suffered a transfusion reaction. Her serum was found to contain anti-rh", anti-Fy^a, anti-Jk^b and an antibody resembling anti-Rh_o. A family investigation showed that the propositus and two of her five children belong to the pheno- type Rh_o^d. This evidence gives further support to the theory that the agglutinogen Rh_o^d is determined by a corresponding allelic gene R ^od.     

Delayed Hemolytic Transfusion Reaction Due to Appearance of Multiple Antibodies Following Transfusion of Apparently Compatible Blood

A delayed hemolytic transfusion reaction, appearing seven days after transfusions, characterized by jaundice, hemolysis and hemoglobinuria accompanied by the appearance of multiple antibodies in the patient's serum (anti-hr" (c) anti-rh" (E) and anti-Jk^b) is explained as an anamnestic phenomenon. The original sensitizing antigens and those which precipitated the recall mechanism may be traced to her 20-year-old son and to the single-unit transfusion which she received five years previous to the last admission, and to the transfusions given with the operation from which she recovered.
The important fact is that these latent antibodies failed to be detected by standard crossmatching tests (saline, high protein and Coombs) and by a pool of cells containing most of the antigens. The triple enzyme method was the only test which detected the anti-rh" (E) antibody.
The direct Coombs test became positive at the height of the reaction and persisted for 48 hours. Blood tests after 31/2 and 41/2 months revealed that both the anti-Jk^b and anti-rh" (E) antibodies had vanished and only anti-hr' (c) of low titer was still present.     

The Specificity of Anti-Human Gamma Globulin Reagents

DEAE cellulose chromatography and immuni-electrophoresis demonstrated immunochemical and serological differences between gamma globulin molecules with anti-D and Anti-Fy^a specificity. Partial neutralization of anti-gamma globulin sera with specific subtractions of human gamma globulin showed that anti-Fy^a frequently appears to occur exclusively in the fast migrating components of gamma globulins whereas anti-D occurs in both the "fast" and "slow" components. Other blood group systems were also studied with the same antiglobulin reagents.
The antigenic determinant groups of the fast migrating components of whole gamma globulin and papain split gamma² globulin appear to be identical.
The standardization of anti-gamma globulin (Coombs) reagents is discussed in the light of these findings.     

An IgG Anti-IT Detected in a Caucasian American

An isoantibody was detected in the serum of a Caucasian with Hodgkin's disease. The antibody reacted strongly by the indirect antiglobulin test with all fetal cord cells but was negative or only weakly positive when tested with adult cells, including five examples of the rare adult i cells. Rhesus monkey and rabbit cells also failed to react. No autoagglutination was seen and the direct antiglobulin test was negative. The antibody sensitized cells optimally at 37 C, reacting with anti-IgG but not anti-IgM, anti-IgA or anti-complement antiglobulin reagents. It was not inhibited by human saliva, milk, or 2-mercaptoethanol. The specificity met the criteria set for anti-I^T. It is unique among antibodies of this specificity since it is an IgG isoantibody, reacting optimally at 37 C by the indirect antiglobulin test, showing a marked difference in reaction between cord and adult cells and occurring in a Caucasian. This contrasts with the only other anti-I^T antibodies described in the literature which are all cold autoagglutinins occurring in isolated populations (Melanesians and Yanomama Indians of Venezuela), showing only marginal differences between adult and cord cells.     

The Third Example of Anti-hrS

A third example of anti-hr^S, first described by Shapiro in 1960, was detected in the serum of a Bantu woman whose newborn infant suffered from mild hemolytic disease of the newborn.     

Gu, a Variant of G

G^u, analogous to D^u and E^u, is a weak variant of G appearing in a haplotype lacking C, D, and E but having e^s.
In a preliminary survey, the red blood cells ot three of 186 Negro blood donors found negative when tested for C, D (incuding D^u), and E were shown to be G^u-positive when tested with anti-CD by the antiglobulin technic.
Fourteen additional examples from unrelated persons and five members of a family have been investigated in this study. All G^u-positive individuals tested are VS-positive, but V-negative, and all are Negro. Although G cells show greater antibody uptake when used to absorb anti-CD, G^u cells elute anti-G in substantially greater amounts than do G cells. Comparative studies demonstrate similarity of specificity but a difference of avidity, which could be due to the influence of e^s(VS) in cis position.
G^u-positive bloods have been shown to stimulate the production of anti-G in Rh-negative recipients. The test for G^u can be incorporated in the test for D^u by substituting anti-CD or anti-CDE for anti-D serum.     

Delayed Transfusion Reaction Attributed to Anti-Jkb

A hemolytic transfusion reaction, attributed to anti-Jk^b, occurred in a multiparous woman four days posttransfusion. Anti-Jk^b was not detectable in the patient's serum prior to transfusion, but was readily demonstrable seven days following transfusion. The anti-Jk^b was not accompanied by any other atypical blood group antibody.     

The Rho Variant — Du

In a survey of 18,365 bloods for the incidence of the D^u factor, in a population comprised approximately of 72 per cent Caucasoids, 15 per cent Negroids, 10 per cent Mexicans and 3 per cent Orientals, 78 D^u bloods were found of which seven were type ccD^uee. Of the latter, five came from Negroids and two from Caucasoids; the frequency among the two populations approximates respectively one in 6,000 and one in 500. In the general population of this region it is one in 2,500.
The degree of reactivity of the type ccD^uee found in this study was that of the "low grade" variety. However, from the remaining 71 "low grade" D^u bloods, substantially weaker examples were found among type CcD^uee and ccD^uEe. The indirect antiglobulin and ficinized cell method readily detected type ccD^uee; however, among the weaker variants, the antiglobulin method gave the more consistent results.
It is concluded, therefore, that type ccD^uee does occur in this area with a frequency that is considered significant and that its detection rests on the antiglobulin or other equally sensitive methods.     

The incidence of anti-Wraand Wraantigen in blood donors and hospital patients

Summary. A retrospective study of positive 37°C indirect antiglobulin test IAT) for compatibility following negative antibody screens in a hospital laboratory revealed an unexpectedly high incidence of Wr^a-incompatible units. Over the course of 1 month 1112 routine patients' samples containing no other atypical antibodies were tested for the presence of anti-Wr^a. Anti-Wr^awas found in 88 patients, an incidence of 7.9%. Testing of 5098 healthy blood donor samples found 54 donors positive for anti-Wr^a, an incidence of 1–06%. A survey of 5253 healthy blood donor samples for Wr^aantigen found only two Wr^a-positive samples, suggesting an incidence between 1 in 1000 and < 1 in 10000. The significance of this finding is discussed in relation to the continuing use of an IAT compatibility test.     

Hemolytic Disease of the Newborn Due to Anti-Jsa

A case of hemolytic disease of the newborn caused by Js^a sensitization is reported. The antibody, the sixth example of anti-Js^a, was detected in the serum of the mother of a nine-day-old anemic infant who required supportive transfusion.     

Anti-Lub and Mild Hemolytic Disease of the Newborn: A Case Report

The occurrence of anti-Lu^b is uncommon. A group O, Rh-negative woman developed atypical antibodies during her second pregnancy. The direct antiglobulin reaction on the cord blood was weakly positive and the infant developed mild jaundice. The mother's cells were determined to be Lu^b-negative and the antibody in the serum was identified as anti-Lu^b.     

Hemorrhagic and Hemolytic Transfusion Reaction Due to Anti-Lea

A case is described in which a severe hemolytic and hemorrhagic reaction occurred as the result of incompatibility involving an anti-Le^a antibody of "immune" type. This antibody must have developed before the surgical procedure at which the reaction occurred, but was not detected because patient specimens for crossmatching had not been obtained frequently enough during multiple transfusions. The patient had a stormy postoperative course, mainly as a result of hematoma formation and renal shutdown, but recovered completely. Five months after the reaction, the antibody was detectable only after EDTA treatment of the serum or the addition of complement. This appears to be the first example of a hemorrhagic syndrome due to anti-Le^a.     

Combined Maternal Erythrocyte Autosensitization and Materno-Fetal Jka Incompatibility

A black woman in the second month of her fourth pregnancy was found to have moderately strong autosensitization of her own erythrocytes (RBC) by C3d (α2D); at the same time, anti-Jk^a was detected in her serum. At term she delivered a healthy Jk^a-positive ABO-compatible infant whose RBC were very strongly coated by C3d. Anti-Jk^a was demonstrable in maternal and cord serum at a titer of 1/64, and in an eluate from the newborn infant's washed RBC at a titer of 1/8. Despite very strong RBC C3d sensitization and the persistence of free anti-Jk^a in the infant's circulation for at least six weeks postpartum, no evidence for hemolytic disease of the newborn developed. The infant's benign course is discussed in relation to 16 reports of maternofetal Kidd isosensitization in pregnancy.