A fatal case of severe hemolytic disease of newborn associated with anti-Jk(b)

The Kidd blood group is clinically significant since the Jk antibodies can cause acute and delayed transfusion reactions as well as hemolytic disease of newborn (HDN). In general, HDN due to anti-Jk(b) incompatibility is rare and it usually displays mild clinical symptoms with a favorable prognosis. Yet, we apparently experienced the second case of HDN due to anti-Jk(b) with severe clinical symptoms and a fatal outcome. A female patient having the AB, Rh(D)-positive blood type was admitted for jaundice on the fourth day after birth. At the time of admission, the patient was lethargic and exhibited high pitched crying. The laboratory data indicated a hemoglobin value of 11.4 mg/dL, a reticulocyte count of 14.9% and a total bilirubin of 46.1 mg/dL, a direct bilirubin of 1.1 mg/dL and a strong positive result (+++) on the direct Coomb's test. As a result of the identification of irregular antibody from the maternal serum, anti-Jk(b) was detected, which was also found in the eluate made from infant's blood. Despite the aggressive treatment with exchange transfusion and intensive phototherapy, the patient died of intractable seizure and acute renal failure on the fourth day of admission. Therefore, pediatricians should be aware of the clinical courses of hemolytic jaundice due to anti-Jk(b), and they should be ready to treat this disease with active therapeutic interventions.     

A Delayed Hemolytic Transfusion Reaction (DHTR) with Multiple Alloantibodies (Anti-E, Jka, Dia, Fyb, and S) Induced by E-Antigen-Negative, Crossmatch-Compatible Blood

We describe the case of a 44-year-old woman with a delayed hemolytic transfusion reaction (DHTR). She had a history of two pregnancies and a blood transfusion, the details of which were unknown. At the time of her first vascular surgery on November 15, 1989, she received 1200 ml of crossmatch-compatible concentrated red blood cells (CRC). Before the first operation, screening for anti-RBC antibodies (Ab) was negative. At the time of the second admission on Feburary 15, 1996, anti-E Abs were detected by indirect antiglobulin test. She received 560 ml of E-antigen-negative, crossmatch-compatible, CRC for treatment of anemia on March 1 and 2, 1996. After this transfusion, total bilirubin (1.6 mg/dl) and lactate dehydrogenase (1355 IU/ml) were elevated on March 12, 1996. She had no evidence of clinical hemolysis. We suspected DHTR from these data, and therefore screened for anti-RBC Abs. Anti-E, Jk^a, Di^a, Fy^b, and S Abs were detected in blood samples obtained from the patient on March 12, 1996. Anti-E, Jk^a, Di^a, and S Abs were present more than 1 month and anti-Fy^b Ab was disappeared at 18 days after transfusion.     

Severe hemolytic disease of the newborn due to anti-Di b treated with phototherapy and intravenous immunoglobulin

The Di(b) antigen usually occurs with high incidence, except in certain Asian and South American Indian populations. In general, hemolysis caused by anti-Di(b) is not severe and its clinical course is benign. We report a Korean neonate with severe hemolytic disease of the newborn caused by anti-Di(b). The phenotype and genotype of the Diego blood group system of the patient and his mother were Di(a+b+) and Di(a+b-), respectively. The mother's serum and eluate from the neonate's erythrocytes contained anti-Di(b). This case was successfully managed with phototherapy and high dose iv immunoglobulin. Since most commercial antibody detection panels do not contain Di(b-) red cells, it is important to consider anti-Di(b) in cases of hemolytic disease of the newborn caused by an antibody against a high frequency antigen.     

Reactive lysis--a phenomenon of delayed hemolytic transfusion reactions

A 62-year-old female with Gaucher's disease demonstrated alloanti-c on pretransfusion testing. She was transfused with five units of c-negative red blood cells (RBCs) preoperatively and intraoperatively. The hemoglobin (Hb) level was slightly lower initially, hut was markedly lower on day 10 posttransfusion. Serologic results indicated a delayed hemolytic transfusion reaction (DHTR) due to alloanti-s, -Fya, and -Jkb, present both on the RBCs and in the serum. As late as day 35 posttransfusion, a mixed-field anti-IgG direct antiglobulin test (DAT) indicated that there were two cell populations present. The DAT remained positive with anti-C3b, -C3d throughout the course of the reaction. Because of the substantially lower Hb and the severity of symptoms, immunologic clearance of the antigen-positive donor RBCs was expected. However, we demonstrated their persistence. Our data corroborates the observation that complement activation occurring during DHTRs can result in the hemolysis of innocent bystander (autologous) cells.     

Severe hemolytic reaction due to anti-JK3.

A 35-year-old gravida 3, para 3 Filipino woman with a negative antibody screen, no prior history of transfusion, and no hemolytic disease of the newborn in her children suffered a massive postpartum hemorrhage requiring transfusion. A severe hemolytic transfusion reaction occurred 5 days after delivery. Subsequently, a panagglutinin on a routine antibody identification panel was identified as anti-Jk3. The patient's red blood cell phenotype was Jk(a-b-) and all of her children were Jk(a-b+), yet the antibody that formed reacted with equal strength against all Jk(a)- or Jk(b)-positive cells. The rare Jk(a-b-) phenotype is more common in Polynesians. Anti-Jk3, like other Kidd system antibodies, is difficult to detect because in vivo production may be absent between provocative episodes and because these antibodies often show weak in vitro reactions. The increasing numbers of Pacific Islanders in the United States could result in more frequent encounters with this rare phenotype. Increased awareness of ethnic variability in blood phenotypes and of the capricious nature of Kidd antibodies can help pathologists and technologists deal more effectively with these cases.     

Primary immune response to blood group antigens in burned children

Delayed hemolytic transfusion reactions (DHTRs) are generally attributed to an anamnestic immune response. Case reports of DHTRs due to a primary immune response are rare. Transfusion reactions occurring in patients on the pediatric burn unit from 1981 to September 1988 were reviewed, and additional information was obtained for patients for whom a DHTR was documented. Of 62 transfusion reactions, 11 were classified as a primary immune response (DHTR), with either a positive antibody screen, a positive direct antiglobulin test (DAT), or both. None of the 11 patients included in the study had been previously tranfused or pregnant. The average number of units transfused prior to antibody identification was 19. The average time elapsed between the first transfusion and antibody identification was 3.6 weeks. Anti-K and anti-E were the most frequently identified. Three patients had a decrease in hemoglobin (average 1.5 g/dL) and hematocrit at the time that a positive DAT was detected. Such changes could not be demonstrated for the remaining eight patients. The conclusion was that a DHTR may he caused by a primary immune response in burned children more often than expected, but DHTR signs and symptoms are often not apparent due to the complications of burn trauma.     

Two Cases of Transfusion-related Acute Lung Injury Triggered by HLA and Anti-HLA Antibody Reaction

Transfusion-related acute lung injury (TRALI) is a serious adverse transfusion reaction that is presented as acute hypoxemia and non-cardiogenic pulmonary edema, which develops during or within 6 hr of transfusion. Major pathogenesis of TRALI is known to be related with anti-HLA class I, anti-HLA class II, or anti-HNA in donor''s plasma. However, anti-HLA or anti-HNA in recipient against transfused donor''s leukocyte antigens also cause TRALI in minor pathogenesis and which comprises about 10% of TRALI. Published reports of TRALI are relatively rare in Korea. In our cases, both patients presented with dyspnea and hypoxemia during transfusion of packed red blood cells and showed findings of bilateral pulmonary infiltrations at chest radiography. Findings of patients'' anti-HLA antibodies and recipients'' HLA concordance indicate that minor pathogenesis may be not as infrequent as we''d expected before. In addition, second case showed that anti-HLA class II antibodies could be responsible for immunopathogenic mechanisms, alone.     

Étude d’une cohorte de 206 patients drépanocytaires adultes transfusés : immunisation,risque transfusionnel et ressources en concentrés globulaires

BackgroundPrevention of hemolytic transfusion reactions depends upon our capacity to prevent allo-immunization and conflicts between antigens of transfused red blood cells and antibodies produced by the recipient. In this study, we show that to secure transfusion of sickle cell disease patients, it is necessary to take into account their immunohematologic characteristics in the organization of transfusion.Methods and resultsImmunohematological data of 206 chronically transfused patients have been collected as well as phenotypes of transfused units. In order to prevent allo-immunization against C and E antigens for patients typed D+C−E−c+e+ (56%), 26% of the transfused units were D−C−E−c+e+. We found that 47% of the patients had a history of allo-immunization, whereas only 15% produced an antibody the day of inclusion in the study. The non-detectable antibodies were frequently known as dangerous for transfusion. Finally, this study shows the frequency of anti-D in D+ patients and anti-C in C+ patients, pointing out the question of partial antigens.ConclusionTo insure optimal transfusion safety for sickle cell disease patients, three points have to be improved: blood donation within the Afro-Caribbean community living in France, access to history of immuno-hematological data, detection of variant antigens, especially within the RH blood system.     

The clinical significance of antibody screening test including Dia+ panel cell in Asian-Mongoloid populations

The Di(a) antigen is well known as one of the antigens with low incidence among Caucasians; however, it has been discovered with a relatively higher incidence among Mongoloid populations. Thus, it has been speculated that the incidence of unexpected antibody against the Di(a) antigen might be relatively higher among these populations. Hemolytic transfusion reactions (HTRs) and hemolytic disease of the newborns (HDNs) caused by anti-Di(a) have been reported sporadically. However, there has been no prospective study on the incidence of anti-Di(a) in Mongoloid populations particularly. The authors conducted a series of antibody screening tests on 11,219 Korean individuals for 25 months, by using three kinds of screening cells including Di(a) cell. Anti-Di(a) was detected in 8 patients, seven of whom had a history of transfusions or were multigravida. The incidence of anti-Di(a) measured in this study was higher than expected, ranked third among unexpected antibodies identified during the period of the study, so it is strongly recommended that the Di(a+) panel cell must be incorporated into antibody screening test for safer transfusion in Asian-Mongoloid populations.     

A distinct pattern of cytokine production from blood mononuclear cells in multitransfused patients with β-thalassaemia

The unstimulated and induced production of granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), IL-3, IL-6, stem cell factor (SCF), IL-1β, tumour necrosis factor-alpha (TNF-α), TNF-β, interferon-gamma (IFN-γ) and transforming growth factor-beta (TGF-β) was determined after culture of blood mononuclear cells from 22 patients with severe β-thalassaemia in a regular transfusion programme, five non-regularly transfused patients with β-thalassaemia intermedia and nine normal persons. A distinct pattern of cytokine production in thalassaemic patients was detected, namely a low unstimulated production of all cytokines and a significant increase in the stimulated production of IFN-γ, TNF-α and IL-1β; these abnormalities were more pronounced in the more heavily transfused older patients. The increased production of the above cytokines, which usually characterize the acute response to infectious agents and have a negative effect on erythropoiesis, may explain the deterioration of anaemia found in thalassaemic patients during acute infections.     

Immune-mediated hemolysis in a postoperative patient Case report: anti-U and differential diagnosis

We present the differential diagnosis for a Coombs-positive immune hemolysis having onset during hospitalization and, in particular, during the postoperative period. The stimulus for this article was a delayed hemolytic transfusion reaction (DHTR) due to anti-U following open-heart surgery. The initial clinical and serologic findings led us to consider other causes of immune hemolysis which are reviewed in this article. To our knowledge, this is the fourth case of a DHTR due to anti-U to be reported in the medical literature.     

Transfusion related acute lung injury (TRALI): an unrecognised pathology

Transfusion related acute lung injury (TRALI) is a rare but potentially severe complication of blood transfusion, manifested by pulmonary oedema, fever and hypotension. The signs and symptoms are often attributed to other clinical aspects of a patient's condition, and therefore, TRALI may go unrecognised. It has been estimated to be the third cause of transfusion related mortality, so it should be better diagnosed. Cases are related to multiple blood units, such as white blood cells, red blood cells, fresh frozen plasma, platelets or intravenous immunoglobulins. Physiopathology of TRALI is poorly understood, and still controversial. It is often due to an immunological conflict between transfused plasma antibodies and recipients' blood cells. These antibodies are either HLA (class I or II) or granulocyte-specific. They appear to act as mediators, which result in granulocytes aggregation, activation and micro vascular pulmonary injury. Lipids or cytokines in blood units are also involved as TRALI priming agents. Diagnosis is based on antibody screening in blood components and on specific-antigen detection in the recipient. The screening of anti-HLA or anti-granulocytes is recommended as part of prevention for female donors who had been pregnant. Preventative measures should also include leucoreduction and measures to decrease the amount of priming agents in blood components. In this article, we summarise what is known about TRALI, and we focus attention on unanswered questions and controversial issues related to TRALI.     

Maternal Lymphocytotoxic Antibodies and Bilirubin Levels in the Postpartum Offspring

HLA antigens are present on immature red cells (Harris & Zervas 1969), but disappear from their surface when they become mature and enter into the circulation (Silvestre et al. 1970). Nevertheless some remnants of HLA substance may survive this antigenic switch and possibly persist on adult red cells (Morton et al. 1969, 1971, Doughty et al. 1973). A shortened survival of HLA incompatible reticulocytes has been reported when they are transfused into recipients with circulating anti-HLA antibodies (Zervas et al. 1972). As to anti-HLA antibodies possibly reacting with erythrocytes in cases of fetomaternal immunization, Moulinier (1970) claimed that they would potentiate any hemolytic process in newborns of Rh-immunized women, but successive investigations failed to confirm this (Ahrons & Glavind-Kristensen 1971, Nymand 1975). Also, Nymand (1975) found no association between lymphocytotoxic antibodies in mothers and high bilirubin levels in the umbilical cord blood collected at delivery. On the contrary, when the onset of neonatal jaundice in the postpartum offspring was monitored, newborns of mothers with lymphocytotoxins appeared to become jaundiced more frequently than expected (Reekers et al. 1975). The present study has been undertaken to investigate the relationships between complement dependent lymphocytotoxins (CdL) in the mothers and the bilirubin levels in the newborns during the first days of life.     

Effect of exchange transfusion with Fluosol DA 20% on splenic distribution and immunocompetence of rat lymphocytes

T- and B-splenic lymphocyte frequency, immune response 4 days after immunization with sheep red blood cells (SRBC), and proliferative response to concanavalin A (Con A) were determined 1, 3, and 5 days after exchange transfusion with Fluosol DA 20% (FDA) in adult, male Sprague-Dawley rats vs sham transfused rats. T-cell, T-helper, T-suppressor, and B-lymphocyte were reduced 1 day after transfusion (P less than or equal to 0.001). T- and B-lymphocyte frequencies were still reduced at day 3 (P = 0.0372). By day 5, there were no significant reductions in T-cell, T-helper, T-suppressor, and B-cell frequencies in the FDA-transfused rats. The frequency of cells with cytoplasmic IgG was reduced (P less than or equal to 0.025) in cells harvested from spleens of FDA-transfused rats and tested fresh. Proliferative response of splenic lymphocytes to Con A was unaffected by transfusion with FDA (P greater than or equal to 0.078). Splenic hemolytic plaques in response to SRBC were unaffected if rats were transfused 3 days after immunization with SRBC and 1 day prior to study (P = 0.941), enhanced if rats were transfused 1 day after SRBC immunization and 3 days prior to study (P = 0.0015), and suppressed if rats were transfused 1 day before SRBC immunization and 5 days before study (P less than 0.0001). Transfusion with FDA causes transient decreases in identifiable T and B lymphocytes, depresses cytoplasmic IgG-positive B cells, does not affect proliferative response to Con A, does not affect an ongoing specific immune response, enhances an early specific immune response, and inhibits the induction of a specific immune response.     

Delayed haemolytic transfusion reaction due to Kidd antibodies

A delayed haemolytic transfusion reaction (DHTR) encompasses a positive direct antiglobulin test (DAT) developed anytime between 24 hours to 28 days after cessation of transfusion, a positive eluate or a newly identified alloantibody in the plasma or serum along with features of haemolysis in the patient. Routinely, it is expected that with the transfusion of one unit of packed red cells in a patient of average height and weight, the haemoglobin level and hematocrit increase by 1 g/dL and 3% respectively. However, in a patient with DHTR, an inadequate rise of post-transfusion haemoglobin (< 1 g/dL) or rapid fall in haemoglobin back to pre-transfusion levels is observed. Kidd antibodies are particularly known to cause DHTR, maybe alone or in unison with other antibodies. Detection of these alloantibodies is consequential in providing good transfusion support to these patients. These events may be difficult to detect as they may present as varied clinical features or immunological nuisances. In this case series, we have presented three cases of DHTR with special emphasis on their clinical presentations, immunohaematological evaluations, laboratory parameters and the role of proper transfusion support in these patients to avoid further complications.     

Hemolytic transfusion reaction due to interdonor kell incompatibility. Report of two cases and review of the literature

A 74-year-old man experienced an acute hemolytic reaction following transfusion of 4 units of red blood cells. The recipient was K negative, one of the transfused units was K positive, and another contained a previously undetected anti-K with an indirect antiglobulin titer of 512. Further investigation led to the discovery of a hemolytic transfusion reaction in a second K-negative patient who received a platelet transfusion containing 50 mL of plasma from the same donor. The clinical and serologic features of these two cases and five previously reported cases of hemolytic transfusion reaction due to interdonor Kell incompatibility are summarized.     

Severe intravascular hemolysis due to autoantibodies stimulated by blood transfusion

Autoantibodies may cause severe hemolytic anemia, but only rarely are they the cause of a hemolytic transfusion reaction due to the destruction of transfused allogeneic blood. In two patients, autoantibody was detected shortly after blood transfusion. The first case was a D-negative patient who produced an autoanti-Ce and subsequently developed hemoglobinuria and hyperbilirubinemia. The second case was a patient who developed an autoanti-Wrb that caused severe hemolysis that resulted in death.     

Management of delayed hemolytic transfusion reaction in sickle cell disease: Prevention,diagnosis, treatment

Transfusion remains a key treatment of sickle cell disease complications. However, delayed hemolytic transfusion reaction, the most serious complication of transfusion, may be life-threatening if hyperhemolysis develops. This syndrome is generally underdiagnosed because its biological and clinical features resemble those of vaso-occlusive crisis, and red blood cell antibodies are frequently absent. Further transfusions may aggravate the symptoms, leading to severe multiple organ failure and death. It is therefore essential to prevent, diagnose and treat this syndrome efficiently. Prevention is based principally on the attenuation of allo-immunization through the provision of extended-matched RBCs or the use of rituximab. However, such treatment may be insufficient. Early diagnosis might make it possible to implement specific treatments in some cases, thereby avoiding the need for secondary transfusion. Diagnosis is dependent on the knowledge of the medical staff. Finally, many treatments, including steroids, immunoglobulins, erythropoietin and eculizumab, have been used to improve outcome. Improvements in our knowledge of the specific features of DHTR in SCD should facilitate management of this syndrome.     

Transfusion-related acute lung injury resulting from designated blood transfusion between mother and child: a report of two cases

Transfusion-related acute lung injury (TRALI) is an underdiagnosed serious complication of blood transfusion characterized by the rapid onset of respiratory distress, hypoxia, and noncardiogenic pulmonary edema during or soon after blood transfusion. The presence of anti-HLA and/or antigranulocyte antibodies in the plasma of donors is implicated in the pathogenesis of TRALI. We report 2 cases of TRALI that were caused by designated blood transfusion between mothers and their daughters; one in a 4-month-old girl who received designated packed RBCs donated by her mother and the second in a 78-year-old mother who received blood from her daughter. In both cases, examination of mother's serum revealed panel-reactive cytotoxic HLA antibodies. It is most likely that the mothers were sensitized from earlier pregnancy and produced HLA antibodies against the daughters' paternally derived HLA antigens. Designated blood transfusion between multiparous mothers and children might add an additional transfusion-related risk owing to the higher likelihood of the HLA antibody-antigen specificity between mother and child.     

Problem-solving in immunohematology: direct compatibility laboratory test ]

Cross-matching between the serum of a patient and the red blood cells to be transfused is most important for the prevention of hemolytic transfusion reactions in allo-immunized or new-born patients found positive with direct antiglobulin test. Cross-matching is a time-consuming and complex laboratory test. In order to obtain valid results, it is necessary to abide by some technical rules detailed in this article. The choice of the blood units to be cross-matched depends on the patient's clinical story and on the specificity of anti-erythrocyte antibodies present in the serum. The identification and the management of most frequent difficulties met by using the cross-match technique are discussed hereby.