Rh immune globulin: an interfering substance in compatibility testing.

CONCLUSIONS: Immunoglobulin therapy that interferes with pretransfusion testing may complicate the interpretation of test results and adversely affect patient management. Rh immune globulin (RhIG) should be considered an interfering immunoglobulin therapy when it is detected in an antibody detection test of a sample from a patient who has been treated with RhIG. Frequently, detection occurs in mother's or newborn's plasma. Because an antenatal injection of RhIG is indicated for pregnant Rh-negative women, anti-D is detected frequently by today's highly sensitive antibody screen methods when the mother's plasma is tested subsequently at delivery. Ascertaining the source of anti-D is complicated by the inability of routine clinical laboratory methods to distinguish anti-D due to RhIG from alloimmune anti-D. A combination of qualitative and quantitative test methods, as well as a complete clinical history, is necessary for accurate diagnosis and patient management.

Cellular immunological changes in patients with LADA are a mixture of those seen in patients with type 1 and type 2 diabetes.

There is currently scarce knowledge of the immunological profile of patients with latent autoimmune diabetes mellitus in the adult (LADA) when compared with healthy controls (HC) and patients with classical type 1 diabetes (T1D) and type 2 diabetes (T2D). The objective of this study was to investigate the cellular immunological profile of LADA patients and compare to HC and patients with T1D and T2D. All patients and age-matched HC were recruited from Uppsala County. Peripheral blood mononuclear cells were isolated from freshly collected blood to determine the proportions of immune cells by flow cytometry. Plasma concentrations of the cytokine interleukin (IL)-35 were measured by enzyme-linked immunosorbent assay (ELISA). The proportion of CD11c+ CD123- antigen-presenting cells (APCs) was lower, while the proportions of CD11c+ CD123+ APCs and IL-35+ tolerogenic APCs were higher in LADA patients than in T1D patients. The proportion of CD3- CD56high CD16+ natural killer (NK) cells was higher in LADA patients than in both HC and T2D patients. The frequency of IL-35+ regulatory T cells and plasma IL-35 concentrations in LADA patients were similar to those in T1D and T2D patients, but lower than in HC. The proportion of regulatory B cells in LADA patients was higher than in healthy controls, T1D and T2D patients, and the frequency of IL-35+ regulatory B cells was higher than in T1D patients. LADA presents a mixed cellular immunological pattern with features overlapping with both T1D and T2D.

Nonhemolytic passenger lymphocyte syndrome.

BACKGROUND: An 8-month-old recipient of a liver segment transplant had anti-D detected for the first time in her Day 5 posttransplant plasma and anti-C detected for the first time in her Day 55 posttransplant plasma. The donor's plasma contained anti-C and anti-D. Clinical and laboratory findings established a diagnosis of passenger lymphocyte syndrome (PLS). Hemolysis did not occur, because the recipient's blood group phenotype was, by chance, D- C-. STUDY DESIGN AND METHODS: To evaluate contemporary practice for diagnosing PLS, we conducted a retrospective 10-year literature review. RESULTS: There were 31 studies (63 cases) of PLS of which eight cases (four studies) were hematopoietic stem cell and 55 (27 studies) were organ transplants. All eight (100%) hematopoietic stem cell and 52 (95%) organ transplants were associated with hemolysis. Of the four studies of hematopoietic stem cell PLS, three actively screened for posttransplant blood group antibodies. Of 27 studies of organ PLS, one actively screened for antibodies. Antibody screens detected five cases of hematopoietic stem cell PLS before hemolysis was apparent and two cases of organ PLS with antibodies without hemolysis. CONCLUSION: Focusing on hemolysis, without a comparable effort to detect donor-derived antibodies diverts from the primary pathophysiology of PLS and limits capturing the full scope of the syndrome. Recognition of hemolytic and nonhemolytic subcategories of PLS is recommended. When feasible, an antibody screen performed on the donor's plasma when collecting the hematopoietic stem cells or before an organ harvest could result in an alert that the donor has formed an alloantibody(s) and the recipient is a risk for PLS. Alternatively, a routine antibody screen performed on the recipient's plasma 1 week posttransplant and, if negative, repeated 3 to 5 weeks posttransplant would detect any donor-derived antibodies and improve alignment of clinical practice with the pathophysiology of PLS.

DEL phenotype.

CONCLUSIONS: DEL red blood cells (RBCs) type as D- by routine serologic methods and are transfused routinely, without being identified as expressing a very weak D antigen, to D- recipients. DEL RBCs are detected only by adsorption and elution of anti-D or by molecular methods. Most DEL phenotypes have been reported in population studies conducted in East Asia, although DEL phenotypes have been detected also among Caucasian individuals. Approximately 98 percent of DEL phenotypes in East Asians are associated with the RHD*DEL1 or RHD*01EL.01 allele. The prevalence of DEL phenotypes has been reported among D- Han Chinese (30%), Japanese (28%), and Korean (17%) populations. The prevalence of DEL phenotypes is significantly lower among D- Caucasian populations (0.1%). Among the 3-5 percent of African individuals who are D-, there are no reports of the DEL phenotype. Case reports from East Asia indicate that transfusion of DEL RBCs to D- recipients has been associated with D alloimmunization. East Asian immigrants constitute 2.1 percent of the 318.9 million persons residing in the United States, and an estimated 2.8 percent are blood donors. Using these statistics, we estimate that 68-683 units of DEL RBCs from donors of East Asian ancestry are transfused as D- annually in the United States. Given the reports from East Asia of D alloimmunization attributed to transfusion of DEL RBCs, one would expect an occasional report of D alloimmunization in the United States following transfusion of DEL RBCs to a D- recipient. If such cases do occur, the most likely reason that they are not detected is the absence of active post-transfusion monitoring for formation of anti-D.

A Guide to Terminology for Rh Immunoprophylaxis.

Rh immunoprophylaxis for Rh-negative women requires an understanding of terminology used for Rh blood typing laboratory reports. The pathophysiology of Rh hemolytic disease of the fetus and newborn was elucidated by studies in rhesus monkeys. Subsequent studies revealed that the human blood group antigen responsible for Rh hemolytic disease of the newborn (D antigen) is related to, but different from, the rhesus monkey antigen. Weak expression of the D antigen on red cells, originally termed D, is currently reported by laboratories as a "serologic weak D phenotype," which can be further defined by RHD genotyping to be either a weak D type or a partial D phenotype. Weak D types 1, 2, or 3 are molecularly defined RHD weak D types, which have an adequate number of intact D antigens to be managed safely as Rh-positive. Partial D phenotypes result from mutations causing loss of one or more D epitopes. Most persons with a partial D phenotype have sufficient D antigen to type as Rh-positive. Some women with a partial D phenotype are detected as serologic weak D phenotypes by routine Rh typing. Whether they type as Rh-positive or serologic weak D phenotype, after being exposed to Rh-positive red cells by transfusion or pregnancy, women with partial D phenotype can form anti-D antibodies and, if they do, are at risk for hemolytic disease of the fetus and newborn. A pregnant woman with a laboratory report of a serologic weak D phenotype should be further tested for her RHD genotype to resolve whether her case should be managed as Rh-positive or Rh-negative. For more than five decades, the practice of Rh immunoprophylaxis has remained unchanged in terms of the dose of Rh immune globulin and timing of injections. In contrast, advances in the science of Rh blood typing have resulted in a continuously evolving terminology, obliging obstetricians to update their vocabulary to guide their practice. The following review and glossary provide guidance for current Rh terminology and the rationale for changes.

Bloody Brilliant: A History of Blood Groups and Blood Groupers.

CONCLUSIONS: What a joy and privilege to read and reread this unique and extraordinarily informative history for this review! Pierce and Reid have authored a 633-page, 28-chapter tome, containing 796 illustrations, including photographs of individual contributors to the field of blood group serology, as well as group photographs of landmark meetings and conferences held during the past 100 years. The Index lists the names of 1046 individuals who are acknowledged as contributors to the history of blood group serology, many of whom are the subject of cameo biographies.

Serological weak D phenotypes: a review and guidance for interpreting the RhD blood type using the RHD genotype.

Approximately 0·2-1% of routine RhD blood typings result in a "serological weak D phenotype." For more than 50 years, serological weak D phenotypes have been managed by policies to protect RhD-negative women of child-bearing potential from exposure to weak D antigens. Typically, blood donors with a serological weak D phenotype have been managed as RhD-positive, in contrast to transfusion recipients and pregnant women, who have been managed as RhD-negative. Most serological weak D phenotypes in Caucasians express molecularly defined weak D types 1, 2 or 3 and can be managed safely as RhD-positive, eliminating unnecessary injections of Rh immune globulin and conserving limited supplies of RhD-negative RBCs. If laboratories in the UK, Ireland and other European countries validated the use of potent anti-D reagents to result in weak D types 1, 2 and 3 typing initially as RhD-positive, such laboratory results would not require further testing. When serological weak D phenotypes are detected, laboratories should complete RhD testing by determining RHD genotypes (internally or by referral). Individuals with a serological weak D phenotype should be managed as RhD-positive or RhD-negative, according to their RHD genotype.

A model for integrating molecular-based testing in transfusion services.

BACKGROUND: Molecular-based laboratory tests can predict blood group antigens and supplement serological methods, adding a unique technology to assist in resolving discrepant or incomplete blood group typing or antibody identification. Hospital transfusion services have options for integrating molecular-based methods in their routine operations. We describe here the model of a hospital-reference laboratory partnership. MATERIALS AND METHODS: Blood samples for compatibility testing were obtained from patients in a 609-bed hospital serving an urban multiethnic and multiracial population. When results of blood group phenotyping by serological methods were inconclusive, samples were referred for molecular-based testing. The reference laboratory used several methods for genotyping, including polymerase chain reaction followed by restriction enzyme-linked polymorphism analysis, sequence-specific primer polymerase chain reaction and array-based approaches. Human erythrocyte antigen, RHCE and RHD single nucleotide polymorphism arrays were integrated into the laboratory as they became commercially available. RESULTS: The hospital-reference laboratory model made it possible to integrate blood group genotyping promptly by current technology without the expense of new laboratory equipment or adding personnel with technical expertise. We describe ten cases that illustrate the categories of serological problems that were resolved by molecular methods. DISCUSSION: In-hospital molecular testing for transfusion services has logistical advantages, but is financially impractical for most hospitals. Our model demonstrates the advantages of a hospital-reference laboratory partnership. In conclusion, hospital transfusion services can integrate molecular-based testing in their routine services without delay by establishing a partnership with a molecular blood group reference laboratory. The hospital reference-laboratory model promotes genomic medicine without the expense of new equipment and skilled personnel, while supporting the economy of centralised large-scale laboratory operations.

Rh Immunoprophylaxis for Women With a Serologic Weak D Phenotype.

It is standard practice for pregnant RhD-negative women who have not already formed anti-D to receive antepartum Rh immunoprophylaxis and, if they deliver an RhD-positive neonate, to receive postpartum Rh immunoprophylaxis. An estimated 0.6% to 1.0% of white women have red blood cells that express a serologic weak D phenotype. Of these women, approximately 80% will have a weak D type 1, 2, or 3 that could be managed safely as RhD-positive. Surveys of laboratory practice reveal a lack of standards for interpreting the RhD type for women with a serologic weak D and for determining their need for Rh immunoprophylaxis. RhD genotyping is recommended to determine the molecular basis of serologic weak D phenotypes in pregnant women as a basis for determining their candidacy for Rh immunoprophylaxis.

Financial implications of RHD genotyping of pregnant women with a serologic weak D phenotype.

BACKGROUND: Hemolytic disease of the fetus and newborn, classically caused by maternal-fetal incompatibility of the Rh blood group D antigen, can be prevented by RhIG prophylaxis. While prophylactic practices for pregnant women with serologic weak D phenotypes vary widely, RHD genotyping could provide clear guidance for management. This analysis evaluated the financial implications of using RHD genotyping to guide RhIG prophylaxis among pregnant females. STUDY DESIGN AND METHODS: A Markov-based model was constructed to evaluate the costs of RHD genotyping for pregnant females with serologic weak D phenotypes to inform RhIG prophylaxis. Using a comparison strategy of managing these women conservatively as D-, direct medical costs were assessed over 10- and 20-year periods for a simulated population of US women. One-way and probabilistic sensitivity analyses were used to assess the robustness of conclusions. RESULTS: Using base-case variables, RHD genotyping for pregnant women with serologic weak D phenotypes is expected to marginally reduce overall costs. RHD genotyping these patients, rather than conservatively managing them as D-, would be cost-saving when the cost of genotyping is below $256. Genotyping would decrease net costs among non-Hispanic Caucasian females (-$0.17/pregnancy), but would increase costs among non-Hispanic African Americans (+$0.51/pregnancy), non-Hispanic American Indian/Alaskans (+$0.10/pregnancy), and Hispanics (+$0.37/pregnancy). Incorporating RHD genotyping would not significantly impact costs among Asians and Hawaiians/Pacific Islanders. CONCLUSIONS: Using RHD genotyping to guide RhIG prophylaxis among pregnant women with serologic weak D phenotypes may be clinically beneficial without increasing overall costs.