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.

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.

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.

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.

Seroprevalence and epidemiological correlates of HTLV-I infection in U.S. blood donors.

Screening for human T-lymphotropic virus type I (HTLV-I) antibodies was performed on sera from 39,898 blood donors at eight blood centers in geographically distinct areas of the United States. Ten donors (0.025 percent) showed evidence of HTLV-I seropositivity by enzyme immunoassays; this was confirmed by protein immunoblot and radioimmunoprecipitation. Seroprevalence rates ranged from 0 to 0.10 percent at the locations sampled, with HTLV-I antibodies found predominantly in donors from the southeastern and southwestern United States. Matched case-control interviews and laboratory studies were performed on five seropositive women and two seropositive men who participated in an identity-linked collection of sera from a subset of 33,893 donors at six of the eight blood centers. Four of the women and both men are black; one woman is Caucasian. Four of the seven seropositive individuals admitted to prior intravenous drug abuse or sexual contact with an intravenous drug user. Sexual contact with native inhabitants of an HTLV-I endemic area was the only identified risk factor for one male. The distribution of HTLV-I antibodies in this U.S. blood donor sample corroborates the previously reported epidemiology of this agent and suggests that additional donor screening measures, including the testing of donated blood for HTLV-I markers, may be necessary to prevent the spread of HTLV-I to transfusion recipients.

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.

IgA deficiency and autoimmune hemolytic disease.

A case of familial selective IgA deficiency associated with autoimmune hemolytic disease is reported that illustrates the therapeutic implications when these two entities coexist. Immunoglobulin screening is recommended for patients with AHD who require blood transfusions, in order to identify IgA-deficient patients who may have anti-IgA anaphylactic reactions.

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.

The spleen and splenectomy in immune (idiopathic) thrombocytopenic purpura.

The benefits of surgical splenectomy in patients with immune (Idiopathic) thrombocytopenia purpura (ITP) probably reflect the combined effects of eliminating a source of antiplatelet antibody synthesis as well as the primary site of platelet destruction. The recent availability of intravenous Rho(D) Immune globulin (WinRho SDF; Nabi, Boca Raton, FL) presents an opportunity to extend the duration of nonsurgical (spleen-sparing) management of chronic ITP by inducing reversible Fc blockade. While new methods for laparoscopic splenectomy may offer improved surgical outcomes and reduced costs for ITP patients in the near-term, the long-term consequences of splenectomy remain to be determined. Partial splenectomy has been shown to be effective in the management of anemia in hereditary spherocytosis and elliptocytosis, while preserving vital splenic phagocytic and immune functions. The concept that cell destruction occurs in reticuloendothelial cells has been updated with recognition that the mononuclear phagocyte is neither a reticular nor an endothelial cell. Immune phagocytosis is now understood to be mediated by macrophage IgG Fc and complement receptors. A key factor for devising a strategy for selecting medical or surgical splenectomy, or postponing splenectomy, is an assessment of the relative importance of splenic immune versus phagocytic function in the pathogenesis of ITP.

Intraoperative autotransfusion in cardiac operations. Effect on intraoperative and postoperative transfusion requirements.

The Southern Arizona Regional Red Cross Blood Program, in cooperation with two cardiac surgery groups, examined the effect of intraoperative autotransfusion on red cell, plasma, and platelet usage during and after cardiac operations. The study evaluated whether intraoperative autotransfusion influenced intraoperative or postoperative blood usage and whether regular use was more effective than selective use. The study demonstrated that intraoperative autotransfusion reduces intraoperative and postoperative blood use and that regular use of intraoperative autotransfusion is more effective than selective use.

Human T-cell lymphotropic virus type I and II in transfusion medicine.

As a consequence of migrating populations, IV drug use and, to a lesser extent, blood transfusions, endemic HTLV-I and HTLV-II infections have spread to nonendemic geographic regions. Although the risk that a person infected with HTLV-I will develop significant disease--even over a lifetime--is estimated to be relatively low, our awareness of the serious diseases associated with other retroviruses requires a cautious approach to blood transfusion. Reports from Japan and the United States indicate that programs testing donated blood and excluding units with HTLV-I antibodies have been highly successful in interrupting the spread of HTLV-I by transfusions. One unanticipated outcome of testing large numbers of people in the United States for HTLV-I antibodies has been recognition of the relatively high prevalence of HTLV-II infection, particularly among IV drug users. The long-term effects of HTLV-II infection are also unknown. Until the natural history and clinical consequences of HTLV-II infection are clearly understood, it is only prudent that blood donated by persons identified to be HTLV-II carriers also be excluded.

IgA anaphylactic transfusion reactions.

IgA anaphylactic transfusion reactions are rare events, estimated to occur in 1 in 20,000 to 47,000 transfusions. The signs and symptoms of these reactions do not differentiate them from other causes of anaphylaxis. The diagnosis of an anaphylactic transfusion reaction is established by showing an IgA-antibody in the patient's serum. Most laboratories that test for IgA antibodies rely on the PHA method, which uses red blood cells that are coated with serologically defined IgA multiple myeloma proteins. We tested sera referred from Red Cross regional blood centers and hospitals from patients with suspected IgA anaphylactic reactions and found an IgA antibody in 76.3% of IgA-deficient patients. However, only 17.5% of all samples referred contained an IgA antibody, indicating that most persons with suspected IgA anaphylactic reactions had experienced acute generalized reactions that were from causes other than anti-IgA transfusion. Using PHIA to measure serum concentrations of IgA and PHA to detect IgA antibodies, we found the frequency of IgA deficiency (< 0.05 mg/dL) and class-specific anti-IgA in random blood donors to be approximately 1 in 1,200. Titers of anti-IgA did not distinguish these seemingly healthy blood donors from patients with a history of an anaphylactic transfusion reaction. Because the frequency of 1 in 1,200 greatly exceeds the observed frequency of anaphylactic reactions in transfused persons, we conclude that using PHA for anti-IgA does not reliably predict risk for an anaphylactic transfusion reaction. Additional research is needed to define a more specific marker to identify those persons who are truly at risk for these serious, but rare, complications of blood transfusion.

Autologous blood transfusions and pregnancy.

The application of autologous and frozen red blood cell (RBC) programs is described for 3 pregnant women with antibodies to high-incidence blood group antigens (anti-Lutheranb, anti-Cellano, anti-Vel). The cases illustrate how readily available supplies or rare blood types can be maintained throughout pregnancy using autologous and frozen RBC techniques, including selective predeposit, "family-sharing," and intensive phlebotomy with fluid replacement. The RBC phenotypes described in this paper are exceedingly rare since they occur in only 0.1-0.001% of random donors. However, the principles of autologous blood transfusions are universal and they can be applied to the general problems of blood group incompatibility in pregnancy.

Impact of innovations on transfusion medicine.

The final decade of the last century of the second millennium ad has seen dramatic changes in all aspects of science and health care. In transfusion medicine, the blood supply is the safest it has ever been. Newer refinements and innovations are continuously being researched and implemented to achieve and further enhance safety. Advances in blood conservation, pharmacologic manipulation, engineered blood derivatives, and recombinant growth factors can now provide safer and more effective alternatives to blood transfusions for many patients. This overview highlights selective innovations in transfusion medicine and emphasizes some significant advances that have occurred in blood donor screening, blood component collections and therapy, and laboratory testing. Newer technologies are anticipated that will further enhance the safety of blood and transfusions and potentially augment annually the blood supply on a worldwide basis.

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.

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.