TRALI-risk-reduction strategies: Japanese approach

Transfusion-related acute lung injury (TRALI) is one of the most serious complications of blood transfusion. We have been gathering information about TRALl in Japan since 1997 through our national haemovigilance system. Recently, we have 20–40 TRALI cases per year (five million bags issued per year). Although TRALI is a rare complication of transfusion, it may become severe and may sometimes be fatal. A substantial number of TRALI cases have been caused by donor HLA or HNA antibodies, which were generated in alloimmunized, i.e. parous females. Considering this mechanism, TRALI mitigation strategies such as the use of male-only-plasma have been implemented in many blood centres or countries. Because of the availability of male plasma and the time limit for the production of fresh frozen plasma (FFP), we first tried to prepare FFP-LR2 derived from 400 ml whole blood only from male donors. FFP-LR2 accounts for 75% of FFP in Japan. (Six per cent of FFP products are from 200 ml whole blood and 19% from apheresis plasma.) A preliminary project on male-predominant plasma was started at several core blood centres. To minimize the burden on nurses regarding marking bags collected from males or females, which might lead to serious errors in collection sites, we updated the computer system that allows the staff members in the production department to sort male and female blood automatically. In a month after the system implementation nationwide, we successfully increased the production rate of male plasma for FFP-LR2 product by up to more than 98%. Regarding FFP-LR1 derived from 200 ml whole blood, the percentage of female donors is approximately 75%. One of the core blood centres has successfully implemented the same strategy for producing FFP-LR1, but others have not done so yet. Although male-only-plasma strategies achieved good results without any expensive screening tests to reduce TRALI incidence in some countries, the standard measures for other plasma rich blood products such as platelet concentrates or apheresis plasma have not been established yet. There are some measures to consider reducing the risk of TRALI caused by other plasma-rich products – recruiting only males as apheresis platelet donors, testing a certain number of donors for HLA antibodies, replacing the supernatant of a platelet pool with male plasma and excluding female donors from apheresis donations. Some blood centres adopted some of these measures, but so far there is little evidence for the efficacy of these measures for reducing the risk of TRALI. We have recently conducted research about the relationship between strength of HLA antibodies and TRALI development. On the basis of the results of the research, we can set the cut-off level in HLA antibody tests, which can reduce the risk of TRALI by eliminating strong HLA antibodies that presumably cause TRALI development if the specificity of an antibody matches the patient’s antigen. Preliminary screening for donor HLA antibodies is ongoing in three core blood centres in Japan, results of which enable us to establish effective and feasible screening strategies for HLA antibodies in the near future.     

Transfusion related acute lung injury (TRALI) caused by red blood cell transfusion involving residual plasma anti-HLA antibodies: a report on two cases and general considerations

TRALI is considered a serious hazard among immune complications of blood transfusion and its occurrence is admitted to be globally underestimated. Each type of blood product is likely to cause TRALI. We report here on two consecutive observations of TRALI caused by red blood cell concentrates, in which anti-HLA class I and class II antibodies resulting from post-gravitational allo-immunization were evidenced in donors. HLA class I and II antigenic community between recipients and donors' husbands were found and strong reacting IgG antibodies directed at several of those common antigens were detected in the donors' serum. Both donors had more than 3 pregnancies, raising the issue of blood donor selection or of plasma reduction for cellular products.     

New insights in mechanisms of transfusion-related acute lung injury

Transfusion-related acute lung injury (TRALI) is a syndrome characterized by acute respiratory distress following the transfusion of blood components. The pathophysiological hallmark of TRALI is an increased pulmonary microvascular permeability. Several reports demonstrate that the majority of TRALI cases are precipitated by the transfusion of donor antibodies directed against HLA (human leukocyte antigens) or HNA (human neutrophil antigens) expressed on the neutrophils’ surface of the recipient. This antibody- antigen interaction is thought to directly cause neutrophil activation and release of cytotoxic agents, with subsequent endothelial damage and capillary leak. Recent observations, however, indicate that other cells may also play a significant role in TRALI. This review will introduce several possible mechanisms of TRALI including the involvement of other blood cells and of the pulmonary endothelium.     

Transfusion-related acute lung injury: Current understanding and preventive strategies

Transfusion-related acute lung injury (TRALI) is the most serious complication of transfusion medicine. TRALI is defined as the onset of acute hypoxia within 6 hours of a blood transfusion in the absence of hydrostatic pulmonary oedema. The past decades have resulted in a better understanding of the pathogenesis of this potentially life-threating syndrome. The present notion is that the onset of TRALI follows a threshold model in which both patient and transfusion factors are essential. The transfusion factors can be divided into immune and non-immune mediated TRALI. Immune-mediated TRALI is caused by the passive transfer of human neutrophil antibodies (HNA) or human leukocyte antibodies (HLA) present in the blood product reacting with a matching antigen in the recipient. Non-immune mediated TRALI is caused by the transfusion of stored cell-containing blood products. Although the mechanisms behind immune-mediated TRALI are reasonably well understood, this is not the case for non-immune mediated TRALI. The increased understanding of pathways involved in the onset of immune-mediated TRALI has led to the design of preventive strategies. Preventive strategies are aimed at reducing the risk to exposure of HLA and HNA to the recipient of the transfusion. These strategies include exclusion of “at risk” donors and pooling of high plasma volume products and have shown to reduce the TRALI incidence effectively. This review discusses the current understanding of TRALI and preventive strategies available.     

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.     

TRALI-new challenges for histocompatibility and immunogenetics in transfusion medicine

Antibodies against human leukocyte antigens (HLAs) have long been associated with transfusion-related acute lung injury (TRALI). In contrast to febrile transfusion reactions and refractoriness to platelet transfusions in immunized patients, the causative antibodies in TRALI are present in the transfused blood component, i.e. they are formed by the blood donor and not by the recipient. Consequently, blood components with high plasma volume are particularly associated with TRALI. In addition to antibodies against HLAs, antibodies directed against human neutrophil antigens (HNAs) present in the plasma of predominantly multiparous female blood donors can induce severe TRALI reactions. Especially, antibodies to HLA class II and HNA-3a antigens can induce severe or even fatal ALI in critically ill patients. Over the last decade, the clinical importance of TRALI as major cause for severe transfusion-related morbidities has led to the establishment of new guidelines aimed at preventing this condition, including routine testing for HLA and -HNA antibodies for plasma donors with a history of allogeneic sensitization. This, in turn, poses new challenges for close collaboration between blood transfusion centers and histocompatibility and immunogenetics laboratories, for sensitive and specific detection of the relevant antibodies.     

Transfusion-related acute lung injury: past, present, and future

Noncardiogenic pulmonary edema caused by transfusion has been observed for almost 60 years. Today, we know this entity as transfusion-related acute lung injury (TRALI). TRALI is an uncommon but potentially fatal adverse reaction to transfusion of plasma-containing blood components. It is typified by dyspnea, cough, hypoxemia, and pulmonary edema within 6 hours of transfusion. Most commonly, it is caused by donor HLA antibodies that react with recipient antigens. It may also be caused by biologically active compounds accumulated during storage of blood products, which are capable of priming neutrophils. Without a "gold standard," the diagnosis of TRALI relies on a high index of suspicion and on excluding other types of transfusion reactions. Although current definitions of TRALI depend on symptoms, laboratory parameters can aid in the diagnosis and frequently identify the causative donor unit. As our understanding of TRALI deepens, risk reduction or prevention may become possible.     

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.     

Recent insights into the mechanism of TRALI

This paper will summarize the experimental and clinical literature on the pathogenesis of transfusion-related acute lung injury (TRALI). Several mechanisms by which leukocyte antibodies including, HLA class I, HLA class II, and HNA-3a antibodies, induce TRALI have been unraveled, although some aspects remain a matter of debate. Significant advances have also been made in the field of recipient-related factors that contribute to the development of TRALI. In contrast, the pathomechanism behind antibody-negative TRALI (associated with the transfusion of blood components which do not contain antibodies) is less well understood, and further research is urgently required.     

Diagnosis of transfusion-related acute lung injury: TRALI or not TRALI?

TRALI is a challenging diagnosis for both the transfusion specialist and the clinician. A Canadian consensus panel has recently proposed guidelines to better define TRALI and its implications. The guidelines recommend classifying each suspected case in one of the following 3 categories: (1) "TRALI," (2) "Possible TRALI," or (3) "Not TRALI." We report the clinical presentation, laboratory evaluation, and management of 3 patients with respiratory failure (RF) following allogeneic blood transfusions. These patients all experienced RF within 6 hr post-transfusion. Based on a review of the clinical and laboratory data and applying the Canadian guidelines, the first patient, a 67-yr-old man with chronic myelomonocytic leukemia, was diagnosed as "TRALI" due to the sudden onset of RF requiring intensive resuscitation. The second patient, a 55-yr-old man with aplastic anemia, was diagnosed as "Possible TRALI" due to pre-existing RF that worsened after blood transfusion. The third patient, a 1-yr-old male, was diagnosed as transfusion associated circulatory overload (TACO) and "Possible TRALI," although his RF improved after treatment with diuretics. In all 3 cases, the blood donor center was informed of the suspected TRALI reactions. The remaining blood products from the donors associated with these reactions were quarantined. After review of the clinical data, the donors associated with cases #1 and #3 were screened by the blood center for granulocyte and HLA antibodies. Using a Luminex flow bead array, the following class I and class II antibodies specific for patient #1 were identified in the respective donor: anti-A25, B8, B18, and anti-DR15, DR 17. Subsequently, donor #1 was permanently deferred. A non-specific IgM anti-granulocyte antibody was identified in the donor associated with case #3, and this donor was subsequently disqualified from plasma and platelet donations. In conclusion, the Canadian guidelines to categorize patients suspected of TRALI provide a useful framework for evaluation of these patients and their respective blood donors.     

Aktualny stan wiedzy na temat patofizjologii,diagnostyki i zapobiegania TRALI

Transfusion-related acute lung injury (TRALI) is the leading cause of mortality following transfusion of blood components. Characteristic for TRALI is acute hypoxemia during or up to 6 h after transfusion provided that cardiogenic respiratory failure and transfusion-associated circulatory overload (TACO) are excluded.In this article we present: 1) Etiology and pathomechanism of TRALI syndrome including the numerous issues that are still unresolved. Currently accepted is the multiple-event model which involves both the patient and the transfused blood components. The TRALI syndrome may be either immunological or nonimmunological dependant on the various factors that activate neutrophils – the main cells in TRALI pathogenesis. 2) TRALI diagnosis should be based mainly on the clinical presentation due to the variety of pathomechanism of the syndrome; however testing of anti-leukocyte antibodies in transfused blood components, according to ISBT guidelines, is recommended in order to prevent TRALI incidence. 3) Different strategies of TRALI prevention, although up to date no ultimate provisions have been accepted. Transfusion of plasma collected only from men seems to be a promising solution as in many countries that adapted this preventive measure the number of TRALI cases has substantially decreased. 4) Different methods of proceeding with donors who donated blood components that were the cause of TRALI in transfused patients. It still remains an open question whether to defer donors with anti-leukocyte antibodies or multi pregnant women.     

Transfusion-related acute lung injury investigation insights

Background From 2005 to 2009 transfusion-related acute lung injury (TRALI) has maintained its ranking as the number one cause of transfusion-related fatalities reported to the FDA. This confirms that TRALI remains a serious and potentially fatal transfusion complication. As over 80% of TRALI events have been attributed to donor derived leucocyte antibodies the detection and management of donors with these antibodies is crucial to reducing the TRALI risk. Objective Because blood is a precious medical commodity in limited supply, it would be more effective to exclude only those donors with a risk of triggering TRALI substantiated by objective laboratory evidence (i.e. implicated). This would allow implicated donors to be confidently excluded and would allow other donors only clinically associated with TRALI to be reassessed for continuing to donate. Therefore, the design of an effective and objective TRALI laboratory investigation strategy has to be based on current knowledge of the mechanism of antibody mediated TRALI. Discussion Leucocyte antibodies in the transfused blood product are thought to activate neutrophils in the pulmonary microvasculature. The by-products of neutrophil activation (e.g. reactive oxygen species and enzymes) consequently cause injury to the pulmonary microvasculature resulting in respiratory distress. There is strong evidence for the role of neutrophil reactive antibodies to human neutrophil antigen (HNA)-3a and human leucocyte antigen (HLA)-A2 in serious TRALI events. HLA Class II antibodies have also been implicated and they are thought to activate monocytes, which subsequently activate neutrophils. Neutrophils, which express human neutrophil antigens (HNA) and HLA Class I, are thus key effector cells in TRALI injury. Because of the pivotal role of neutrophils, effective TRALI investigations must include well validated neutrophil assays such as the granulocyte immunofluorescence test (GIFT) and granulocyte agglutination test (GAT). This article will discuss: – TRALI investigation strategy, – assays for detection of antibodies to HNA and HLA, – how to differentiate associated from implicated donors, – and provide thoughts on the remaining 20% of TRALI events (i.e. non-immune mediated).     

Evidence behind the pathophysiology of TRALI

Transfusion-related acute lung injury (TRALI) is a serious transfusion complication that may lead to significant morbidity and mortality. This has driven a significant research effort focused on understanding why and how TRALI develops. The ultimate goal must be prevention or at least mitigation of the clinical consequences of TRALI. The underlying pathophysiology of TRALI is presently best described by two hypotheses which are not mutually exclusive. These are the antibody mediated TRALI mechanism and the two-event or priming TRALI mechanism. One of the key initial findings in TRALI research was the frequent presence of leucocyte antibodies in associated blood products, providing strong evidence for an antibody driven pathogenesis. In contrast, the two-event mechanism proposed that these transfused antibodies activated neutrophils that had first been primed by the patient’s clinical condition. Together, data from haemovigilance programs, clinical reports and experimental findings have led several countries to introduce TRALI risk-reduction strategies. These include either limiting the transfusion of plasma from female donors or, screening female donors for the presence of leucocyte antibodies. Both approaches are justified by adoption of the immune mechanism as the prime driver of the pathogenesis of TRALI. TRALI incidence has gratifyingly been reduced by these measures. Nevertheless, TRALI cases persist and they remain a major concern because of continuing significant morbidity and mortality. While the majority of earlier TRALI research has focused on the role of antibodies in TRALI, evidence for the role of non-antibody factors in TRALI is now growing, based on an increasing number of in vitro, ex vivo and in vivo models. This review aims to present data from such models, which are the foundation for our current understanding of the pathophysiology behind antibody mediated and non-antibody mediated TRALI.     

Transfusion‐related acute lung injury and transfusion‐associated circulatory overload

Pulmonary complications of transfusion were once believed to be infrequent and relatively unimportant in terms of morbidity. Transfusion‐related acute lung injury (TRALI) and transfusion‐associated circulatory overload (TACO) are now appreciated as being relatively common and clinically important. TRALI is one of the two most frequent causes of transfusion‐associated death and patients with TACO have longer hospitalizations and increased morbidity. Both entities are diagnosed primarily on clinical grounds but laboratory tests are available which can confirm or supplement the clinical impression. The high‐risk patient for TRALI has not been identified but in TACO, very young or older patients who are transfused too rapidly or with too much volume are the most vulnerable. The mechanism of TRALI is incompletely understood but antibodies in stored blood components certainly play an important role. In TACO, the problem is primarily a mechanical issue. Prompt recognition is the key to successful treatment for both entities.     

Transfusion and lung injury.

The respiratory tree has been viewed as an infrequent site of injury arising as a complication of transfusion. In recent years, this view has changed as investigators have shown that two complications--circulatory overload and transfusion-related acute lung injury--are relatively frequent events. Circulatory overload is a result of hypertransfusion to individuals at risk, the very young or old recipient. The reaction is due to fluid infusion which overwhelms the capacity of the left ventricle, resulting in pulmonary edema. While rarely fatal, studies have shown that such incidents result in intensive care and extended hospitalization. In the setting of orthopedic surgery, 1% of elderly patients undergoing hip or knee surgery experience circulatory overload. These events are associated with autologous, as well as allogeneic red blood cells (RBC) and fresh frozen plasma. Transfusionists need to be vigilant with transfusion therapy in this population. Phlebotomy and supplemental oxygen are the key therapies. Transfusion-related acute lung injury (TRALI) is the adult respiratory distress syndrome due to transfusion. It is associated with a significant morbidity and mortality of 5-14%, making it the third most common cause of death from transfusion in developed countries. It is characterized by the onset of acute respiratory distress, bilateral pulmonary edema and hypoxemia. It occurs within 1-2 hours of transfusion of a plasma-containing blood product. All blood components have been associated with the reaction, and rarely, intravenous immune globulin. There is no recognized profile of individuals at increased risk for TRALI. There are two purported mechanisms of injury; the vast majority of cases are associated with passively transfused complement-activating antibodies. These antibodies are either HLA (Class I or II) or granulocyte-specific. These antibodies appear to act as mediators, which result in granulocyte aggregation, activation, and microvascular pulmonary injury. With appropriate respiratory intervention, 80% of patients recover within 96 hours of the original insult. There are no permanent pulmonary sequelae.     

Effect of one-HLA-DR-antigen-matched and completely HLA-DR-mismatched blood transfusions on survival of heart and kidney allografts

Blood transfusions can influence the survival of organ allografts favorably, in spite of the danger of sensitization. We investigated the influence of HLA compatibility between blood donors and transfusion recipients on the production of HLA antibodies and on graft survival. Among recipients of transfusions who shared one HLA-DR antigen with their respective donors, antibodies developed in 6 of 28 who had received one transfusion, in 2 of 16 who had received three transfusions, and in 4 of 24 who had undergone renal transplantation. Among recipients who were mismatched with their donors for both HLA-DR antigens, the rate of sensitization was significantly higher in all three of these groups (18 of 30, P = 0.02; 12 of 16, P = 0.0007; and 12 of 22, P = 0.001). The survival of kidney allografts among graft recipients who were given transfusions and shared one HLA-DR antigen with their blood donors (81 percent at five years) was significantly higher than among recipients who were given transfusions and were mismatched for both HLA-DR antigens (57 percent; P = 0.02) or among recipients who were not given transfusions (45 percent; P = 0.001). There was no difference in graft survival between patients who received transfusions mismatched for two HLA-DR antigens and those who were not given transfusions. We conclude that allograft survival can be improved by pretransplantation blood transfusion when the transfusion recipients share at least one HLA-DR antigen with their donors. In view of the increased rate of sensitization and the lack of improvement in graft survival, the transfusion of blood mismatched for two HLA-DR antigens appears to be contraindicated in candidates for transplantation.     

Presence of HLA antibodies in single‐donor‐derived fresh frozen plasma compared with pooled,solvent detergent‐treated plasma (Octaplas®)

Adverse reactions to plasma transfusion are well documented. One of the most serious hazards of transfusion, transfusion‐related acute lung injury (TRALI), has nearly as high an incidence of mortality and major morbidity as that reported for the transfusion of incorrect blood components. The specific mechanisms of plasma component‐induced adverse reactions remain unclear, but a major contribution may be related to the presence of alloantibodies. In this study, a laboratory analysis was undertaken to determine the presence of HLA antibodies in leucodepleted single‐donor‐derived fresh frozen plasma (FFP). A comparison was made with a pooled plasma product that has undergone solvent detergent treatment. In total, 58 plasma samples from single‐donor units of leucodepleted FFP were tested along with samples from 12 units (three for each ABO blood group) of the pooled plasma (Octaplas^®; Octapharma Ltd, Coventry, UK), for the presence of HLA antibodies. HLA‐specific enzyme‐linked immunosorbent assay (ELISA) methods were used to screen for their presence, and complement‐dependent cytotoxicity and flow cytometry analyses were used to further define their presence, specificity and class [immunoglobulin G (IgG)/IgM]. In the study groups, HLA antibodies were found to be present in five of the single‐donor units (9%) while the pooled plasma samples tested negative.     

Further characterization of transfusion-related acute lung injury: demographics, clinical and laboratory features, and morbidity

According to Food and Drug Administration data, transfusion-related acute lung injury (TRALI) is the third most frequent cause of transfusion-associated death in the United States and is characterized by an acute respiratory distress syndrome-like clinical picture following transfusion of plasma-containing blood components. It may be underdiagnosed due to unfamiliarity of clinicians with the syndrome. This report describes the largest series to date, 46 cases, occurring between 1992 and 1998. The male-to-female ratio was approximately 1:1. The mean age at diagnosis was 54 years. The most frequent presenting symptom or signs were acute respiratory distress, hypotension, and hypertension. Antibodies to human leukocyte antigens or granulocytes were identified in 61 percent of cases, with 50 percent associated with antibodies in a donor whose blood had been transfused to a patient developing TRALI. Clinical recovery occurred in 87 percent of patients, but TRALI contributed to deaths in 13 percent. Clinicians need to recognize and diagnose this syndrome in order to respond with appropriate interventions.     

Unappreciated risk factors for transplant patients: HLA antibodies in blood components

One of the more aggressive approaches in renal transplantation is the use of plasmapheresis (PP) and intravenous immunoglobulin to eliminate donor-directed human leukocyte antigen (HLA) alloantibodies. A potential complication of a PP protocol is iatrogenic hypocoagulability resulting from the removal of coagulation factors. To prevent bleeding, hypocoagulable patients may require transfusions with fresh frozen plasma (FFP) and/or cryoprecipitate (Cryo). Although HLA alloantibodies in these components have been linked to complications, such as transfusion-related acute lung injury (TRALI), whether they cause complications following transfusion into allograft recipients is unknown. The incidence of complications would be dependent, in part, upon the frequency of HLA alloantibodies in the various blood components. In this study, segments from 77 units of FFP, 66 units of Cryo, 106 units of packed red blood cells (RBCs), and 59 units of apheresis platelets (Plts) were tested for antibodies to HLA class I and class II antigens using FlowPRA, an HLA antigen-specific flow cytometric assay. On average, 22% of blood components tested contained HLA alloantibodies, tenfold greater than previously reported. This unappreciated frequency of HLA alloantibodies in blood components may pose a risk to transplant patients requiring transfusions by promoting allograft dysfunction or loss.     

The role of HLA antibodies in neonatal thrombocytopenia: a prospective study

The role of HLA antibodies in neonatal alloimmune thrombocytopenia is controversial. We prospectively studied the sera of obstetric patients at delivery for HLA antibodies and correlated their presence with umbilical cord blood platelet counts. We studied 493 births at The Johns Hopkins Hospital comprising of 357 African American, 115 Caucasian, and 21 babies of other racial groups. One hundred and thirty nine mothers had HLA antibodies. Of these HLA alloimmunized mothers, only ten infants had platelet counts of 150,000/μL or less. Three hundred and eight mothers with no detectable antibodies gave birth to 27 infants with platelet counts of 150,000/μL or less. Yates corrected Chi square analysis showed no significant relationship between maternal HLA alloimmunization and baby platelet count (p=0.709). Only 8 of sixty cord sera from babies of HLA alloimmunized mothers were positive for HLA antibodies. The HLA cord blood antibody results were then correlated with the neonatal platelet counts. The Fisher's exact test showed no significant relationship between the presence of HLA antibodies in cord blood samples and neonatal platelet counts (p=0.232). Although one third (31%) of mothers have HLA antibodies, neonatal thrombocytopenia is rarely associated with this finding. However, HLA antibodies can cross the placenta, and in these unusual cases, may be associated with a higher risk of neonatal thrombocytopenia.