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.

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.

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.

Immunosuppressive protocols for transplantation and certain hematologic malignancies can prevent the primary immune response to the D blood group antigen.

A review of the published literature on Rh alloimmunization reveals that its incidence varies with the volume of infused D+ red blood cells (RBCs), the probable Rh genotype of the RBCs, and the immune competency of the D- recipient. Among the reports of Rh alloimmunization on different clinical circumstances, we identified five studies in which a combined total of 62 D- recipients of hematopoetic stem cell or solid -organ transplants were transfised with D+ RBCs and none (0%) formed anti-D. The observation that immunosuppressive protocols developed to prevent rejection of tissue and organ transplants also prevented alloimmunization to the D blood group antigen raises the possibility of practical applications in blood transfusion practice.

Laboratory methods for Rh immunoprophylaxis: a review.

The recommended dose of Rh immune globulin for postpartum Rh immunoprophylaxis is based on an estimation of the volume of the fetomaternal hemorrhage, if any, measured as the percent of fetal RBCs in a sample of the D­ mother's blood. Laboratory methods for distinguishing fetal from maternal RBCs have been based on their different blood types (D+ versus D­) or predominant hemoglobin content (hemoglobin F versus hemoglobin A). We conducted a review of the medical literature describing laboratory methods for detecting and quantifying fetal RBCs in maternal blood samples. We also used data collected for the College of American Pathologists Fetal RBC Detection Surveys to determine which laboratory methods are used currently in hospitals in the United States. The rosette screen is used widely for identifying D­ mothers who may require additional doses of Rh immune globulin for postpartum immunoprophylaxis. As the rosette screen targets the D antigen, it is not suitable for detecting a fetomaternal hemorrhage in D+ mothers or when the D type of the fetus or newborn is D­ or unknown. The acid-elution (Kleihauer- Betke) assay is a sensitive laboratory method for quantifying a fetomaternal hemorrhage, but it is tedious, often inaccurate, and difficult to reproduce. Flow cytometry, using anti-D or anti-hemoglobin F reagents, offers a more precise quantification of fetal RBCs in maternal blood. However, flow cytometry services for this function are available in relatively few hospital laboratories in the United States because of logistic and fiscal impediments.

Nonhemolytic passenger lymphocyte syndrome: donor-derived anti-M in an M+ recipient of a multiorgan transplant.

Passenger lymphocyte syndrome (PLS) is a well-recognized complication that may follow a hematopoietic progenitor cell or solid-organ transplant. Typically, the syndrome presents as acute hemolysis of the recipient's RBCs, which have become serologically incompatible with blood group antibodies formed by passively transfused donor-origin B lymphocytes. Most cases involve anti-A or anti-B. However, there are cases involving non-ABO serologic incompatibility, as well as cases in which the serologic incompatibility was not associated with clinical evidence of hemolysis. This report describes a case of passenger lymphocyte syndrome in an M+ recipient who developed anti-M after receiving a multiorgan transplant from an M- cadaver donor. Although the temporal events and serologic findings were consistent with a diagnosis of PLS, there was no evidence of in vivo hemolysis associated with the identification of a newly formed anti-M. This report includes a literature review of other case reports of PLS associated with non-ABO antibodies in solid-organ and hematopoietic progenitor cell transplant recipients.

Human platelet alloantigen systems in three Chinese ethnic populations.

Knowledge of the prevalence of human platelet antigens (HPA) in different populations is important for effective diagnosis and management of immune-mediated platelet disorders. The purpose of this study was to determine HPA gene frequencies in the majority Han ethnic population of China and in ethnic She and Tajik minority populations. Using PCR sequence specific primers, HPA- 1, -2, -3, -4, -5, and -6, we determined genotypes for ethnic Han, She, and Tajik blood donors. HPA gene frequencies for Chinese Han were found to be similar to those of She, reflecting the historic affinities of these two populations. HPA gene frequencies for Tajik were closer to those for Caucasians than to Chinese Han, She, or other Asian populations, reflecting their disparate origin and historic geographic isolation. HPA gene frequencies in these Chinese populations reflect their historic origins. Knowledge of these findings may be used to better understand and treat immune-mediated platelet disorders in these populations.

Treatment of immune thrombocytopenic purpura in children : current concepts.

Treatment of immune thrombocytopenic purpura (ITP), the most common bleeding disorder of childhood, is a controversial subject for most practitioners. Diagnosis and management of ITP has historically been based primarily on expert opinion rather than on evidence. Due to a paucity of carefully conducted clinical trials in children, the management of ITP varies widely, ranging from observation only, to aggressive management with intravenous immunoglobulin (IVIG), intravenous anti-D rhesus (Rh)0 immunoglobulin (IV RhIG), corticosteroids, and splenectomy. To address the controversies, the American Society of Hematology (ASH) and the British Society for Hematology (BSH) have developed ITP practice guidelines. These guidelines, based on expert opinion, differ in their recommendations for treatment. The ASH guidelines favor therapy based on a low platelet count, and the more current BSH guidelines recommend a more conservative 'wait and watch' approach. In addition to treating children with severe bleeding symptoms, there is a tendency (not evidence based) to treat early in order to prevent a life-threatening bleeding episode, including intracerebral hemorrhage. Corticosteroids are a highly effective therapy, inexpensive, and can usually increase the platelet count within hours to days. However, chronic or prolonged use is associated with toxicity. In the US, based on the knowledge of known toxicities of corticosteroids, as well as the efficacy of alternative treatments (IV RhIG, IVIG), many pediatricians prefer to treat with IVIG and IV RhIG, reserving corticosteroid treatment for serious bleeding or refractory disease. However, in the UK, for the most part, corticosteroids are used as first-line therapy in children with ITP. Splenectomy is rarely indicated in children except for those with life-threatening bleeding and chronic, severe ITP with impairment of quality of life. For children who develop chronic or refractory ITP, immunosuppressive drugs and/or chemotherapy agents may offer some promise. However, the long-term effects of these drugs in children are unknown and they should not be considered unless there is unequivocal evidence that the patient is refractory to IV RhIG, IVIG, and corticosteroids. To date, virtually all of the randomized clinical trials conducted in children with ITP have focused on platelet counts as the sole outcome measure. Only carefully designed, multicenter, randomized clinical trials comparing the effects of different treatment modalities in terms of bleeding, quality of life, adverse effects, and treatment-related costs will be able to address the controversies surrounding childhood ITP treatment and allow management of this condition to be based on scientific data rather than treatment philosophy.

Bar code technology improves positive patient identification and transfusion safety.

As a result of human error, an estimated 1 in 12,000 blood transfusions is given to the wrong patient. The cause of nearly all of these errors is failure of hospital personnel to identify positively intended transfusion recipients, their blood samples for cross-matching, or their correct blood components. We describe our experience using a point-of-care bar code transfusion safety system that links patients' bar-coded wristbands, with bar-coded labels on blood sample tubes, blood component bags, and nurses' identification badges. The result was 100 % accuracy of matching patients, their blood samples, and components for transfusions. For verifying information before starting blood transfusions, nurses preferred bar code "double checks" to conventional visual "double checks" by a second nurse. Methods are needed to reinforce nurses' proficiency with technological approaches to transfusion safety, such as software-driven bar code scanning, in situations where transfusions are administered infrequently.

Review: immune thrombocytopenic purpura: an update for immunohematologists.

Immune thrombocytopenic purpura (ITP) is an acquired disease in which autoantibodies to platelets cause their sequestration and destruction by mononuclear macrophages, principally in the spleen. If increased production of platelets by megakaryocytes does not compensate for platelet destruction, the number of circulating platelets decreases (thrombocytopenia), resulting in a characteristic bleeding tendency (purpura). While most children with the disease experience a relatively short and benign clinical course, ITP in adults often lasts more than 6 months (chronic ITP) and is resistant to conventional treatment (corticosteroids, intravenous immune globulin, or splenectomy). The goal of medical management is to increase the platelet count to a safe level, without the risks of bacterial infections associated with splenectomy or toxicity from prolonged corticosteroid therapy. Splenectomy increases platelet counts in hours to days in most patients with acute ITP, but nearly 50 percent experience recurrent thrombocytopenia by 5 years postsplenectomy.

Equivalence of spray-dried K2EDTA, spray-dried K3EDTA, and liquid K3EDTA anticoagulated blood samples for routine blood center or transfusion service testing.

We compared the results of routine blood tests for 102 blood donors' samples and 100 patients' samples collected in spray-dried K2EDTA, spray-dried K3EDTA, and liquid K3EDTA blood collection tubes to evaluate the impact of changes in formulation of the anticoagulant (K2EDTA vs.K3EDTA), its application (liquid vs. spray-dried), and tube material (glass vs. plastic). Methods for ABO/D testing, antibody screening, and antibody identification included direct hemagglutination/microplate (Olympus(R) PK 7200) and gel column methods (Ortho ID-Micro Typing System/Gel Test). Additional studies on blood donors' samples included time delayed antigen testing and antibody identification and half-draw/half-evacuated collections. Also, we compared the results of routine ABO/D testing and antibody screening for 50 patients' samples collected in spray-dried K2EDTA and spray-dried K3EDTA and for an additional 50 patients' samples collected in spray-dried K2EDTA tubes from two different manufacturers. All patients' samples were tested in parallel by solid phase/microplate method (Immucor ABS 2000) and the standard manual tube method. All test results for routine blood bank tests on donors' and patients' samples were concordant, demonstrating the equivalence of spray-dried K2EDTA, spray-dried K3EDTA, and liquid K3EDTA blood collection tubes for routine donor center or transfusion service testing.

Intravenous Rh immune globulin for treating immune thrombocytopenic purpura.

Intravenous Rh [corrected] immune globulin was licensed by the U. S. Food and Drug administration in 1995 for the treatment of acute and chronic immune thrombocytopenic purpura in children and chronic immune thrombocytopenic purpura in adults. In 1996, the American Society of Hematology published a practice guideline for immune thrombocytopenic purpura, but treatment recommendations of necessity were formulated using only results of early clinical trials with intravenous Rh immune globulin. To date, there are no published results of large-scale clinical trials comparing conventional doses of intravenous immune globulin with the most promising dose range for intravenous Rh immune globulin (50-75 microg/kg). However, clinical experience is accumulating to indicate that intravenous Rh immune globulin is as effective, probably safer, and easier to administer than intravenous immune globulin. Acute intravascular hemolysis after infusions of intravenous Rh immune globulin for immune thrombocytopenic purpura has been reported with an estimated incidence of 1 in 1,115 patients. The risk factors for this adverse event have not been defined.

Serologic aspects of treating immune thrombocytopenic purpura using intravenous Rh immune globulin.

In patients with immune thrombocytopenic purpura (ITP), IgG autoantibody-coated platelets are phagocytized by mononuclear macrophages, primarily in the spleen. Intravenous Rh immune globulin (IV RhIG) has been used since 1983 to treat D(+), nonsplenectomized patients with ITP. The beneficial therapeutic effect of IV RhIG is attributed to competitive inhibition of phagocytosis of IgG-coated platelets by IgG anti-D-coated D(+) red blood cells (reticuloendothelial or Fc receptor blockade). Following infusions of IV RhIG in D(+) ITP patients, the direct and indirect antiglobulin tests become transiently positive, reflecting passively transferred anti-D and other alloantibodies that were present in the infused IV RhIG. These consistent and predictable serologic findings contrast with the inconsistent and weak anti-D reactivity observed when D(-) women are treated with relatively small doses of intramuscular RhIG for Rh immunoprophylaxis. The pathophysiology of ITP and the effect of infusing IV RhIG in patients with ITP are illustrated in this review, using computer-generated figures.

A solid phase and microtiter plate hemagglutination method for pretransfusion compatibility testing.

Most hospital blood transfusion services perform routine pretransfusion compatibility tests (ABO/D typings, antibody detection tests and crossmatches) using standard test tube methods. Recently, alternative technologies, including microtiter plate methods, solid phase red cell adherence (SPRCA) assays, gel tests, microbead columns and affinity column assays have become available. While the increased sensitivity of these new serological technologies is an important advantage, cost savings and automated testing are also important benefits. Our hospital's Transfusion Service converted from manual test tube methods for compatibility testing to manual microtiter plate and SPRCA methods and, subsequently, to automated microtiter plate and SPRCA methods. The conversion was facilitated by using commercially-marketed reagent kits and a fully-automated blood typing analyzer. The automated blood typing system was linked electronically to a hand-held combination bar code reader/portable data terminal that enabled positive identification of patients' bar code wrist bands, personal identification badges, and bar code labels on patients' blood samples and blood components. This bar code identification system has been implemented in the hospital's outpatient Infusion Service. Thus, the conversion to microtiter plate and SPRCA assays enhanced transfusion safety not only by increasing the sensitivity of serological testing, but also by standardizing compatibility testing, supporting electronic record keeping, and linking the laboratory analyzer to a bar code identification system.