Maternal HLA genotyping is not useful for predicting severity of fetal and neonatal alloimmune thrombocytopenia

Lack of reliable laboratory parameters is the main challenge in the management of fetal and neonatal alloimmune thrombocytopenia (FNAIT ). Despite the long‐known association between the HLA ‐DRB 3* 01:01 allele and human platelet antigen 1a (HPA ‐1a) alloimmunisation, maternal human leucocyte antigen (HLA ) typing has been of little clinical value. Recently, other DRB 3 allele variants have been suggested to predict the severity of FNAIT . In this nationwide population‐based retrospective cohort study, we performed extensive HLA typing of 96 women, accounting for 87% of our cohort of 110 families with confirmed or possible HPA ‐1a‐immunisation. The HLA type was compared with anti‐HPA ‐1a levels, severity of neonatal disease and responsiveness to maternally administrated intravenous gammaglobulin (IVIG ). HLA haplotypes were constructed to investigate further HLA associations. Despite significantly lower anti‐HPA ‐1a levels in DRB 3* 01:01‐negative women, the carrier status of this particular allele could not be used to confirm or rule out FNAIT in the absence of detectable antibodies. In the haplotype analysis, the DRB 3* 01:01 allele was the actual factor associated with FNAIT . No other HLA allele was shown to be of additional value as a predictor of severe FNAIT or non‐responsiveness to IVIG treatment. Thus, HLA genotyping was not found useful in differentiating high‐ and low‐risk pregnancies or in guiding antenatal treatment in affected families.     

Human platelet antigens – 2013

To date, 33 human platelet alloantigens (HPAs) have been identified on six functionally important platelet glycoprotein (GP) complexes and have been implicated in alloimmune platelet disorders including foetal and neonatal alloimmune thrombocytopenia (FNAIT), posttransfusion purpura (PTP) and multitransfusion platelet refractoriness (MPR). The greatest number of recognized HPA (20 of 33) resides on the GPIIb/IIIa complex, which serves as the receptor for ligands important in mediating haemostasis and inflammation. These include HPA‐1a, the most commonly implicated HPA in FNAIT and PTP in Caucasian populations. Other platelet GP complexes, GPIb/V/IX, GPIa/IIa and CD109, express the remaining 13 HPAs. Of the recognized HPAs, 12 occur as six serologically and genetically defined biallelic ‘systems’ where the –a form designates the higher frequency allele and the –b form, the lower. Twenty‐one other HPAs are low‐frequency or rare antigens for which postulated higher frequency –a alleles have not yet been identified as antibody specificities. In addition to the HPA markers, platelets also express ABO and human leucocyte antigen (HLA) antigens; antibodies directed at the former are occasionally important in FNAIT, and to the latter, in MPR.     

Maternal antibodies against paternal class I human leukocyte antigens are not associated with foetal and neonatal alloimmune thrombocytopenia

The causative role of maternal, anti-human leukocyte antigen (anti-HLA) class I antibodies in foetal and neonatal alloimmune thrombocytopenia (FNAIT) remains controversial. Furthermore, in FNAIT cases caused by anti-human platelet antigen-1a (anti-HPA-1a) antibodies, the possible additive effect of maternal anti-HLA class I antibodies on outcomes is unclear. Among 817 mother–father–neonate trios of suspected FNAIT, we assessed the possible association of maternal anti-HLA class I antibodies with neonatal platelet count, and the incidence of FNAIT caused by anti-HPA-1a antibodies. In 144 FNAIT cases caused by anti-HPA-1a antibodies, we investigated the possible association of maternal anti-HLA class I antibodies with neonatal platelet count, birth weight, and the incidence of intracranial haemorrhage (n = 16). Maternal anti-HLA class I antibodies were not associated with neonatal platelet count in suspected cases of FNAIT. There was no significant interaction between the presence of anti-HLA class I antibodies and anti-HPA-1a antibodies. In FNAIT cases caused by anti-HPA-1a antibodies, there was no association between the presence of anti-HLA class I antibodies and neonatal platelet count, birth weight, or occurrence of intracranial haemorrhage. This study’s findings do not support the concept that maternal anti-HLA class I antibodies represent a risk factor of FNAIT or disease severity.     

A new efficient tool for non-invasive diagnosis of fetomaternal platelet antigen incompatibility

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is the consequence of platelet destruction by maternal alloantibodies against fetal human platelet antigens (HPA). This may result in intracranial haemorrhages (ICH) or even fetal death. Currently, fetal HPA genotyping is performed using invasive procedures. Here, we carried out a proof-of-concept study for non-invasive prenatal diagnosis of fetal platelet genotyping in four HPA systems (HPA-1, -3, -5 and-15) by droplet digital polymerase chain reaction (ddPCR) using cell-free DNA extracts from the plasma of 47 pregnant women with suspected, or history of, FNAIT. Results showed that 74% (35/47) of pregnant women presented incompatibility in at least one HPA system, and 38% (18/47) of cases presented HPA-1 incompatibility, including nine women with multiple incompatibilities. ICH occurred in one case of profound fetal thrombocytopenia with HPA-15 incompatibility, confirming the need for non-invasive prenatal genotyping in systems other than HPA-1. Fetal HPA genotypes predicted by ddPCR were confirmed in all FNAIT cases after amniocentesis or delivery. Fetal HPA genotyping on maternal plasma based on ddPCR is a fast, safe and reliable non-invasive method. This technique will be useful for the early identification of pregnancies at high risk of FNAIT requiring antenatal management to minimize the risk of fetal/neonatal haemorrhage.     

Fetal and neonatal alloimmune thrombocytopenia: No evidence of systemic inflammation as a modulator of disease severity. Could placental inflammation be key?

In fetal/neonatal alloimmune thrombocytopenia (FNAIT), maternal alloantibodies against paternal human platelet antigens (HPA) cross the placenta and lead to platelet destruction. The extent of thrombocytopenia varies among neonates, and inflammation may constitute an important trigger. A set of stable inflammatory markers was measured in serum samples from neonates with low platelet counts, of which n = 50 were diagnosed with FNAIT due to anti-HPA-1a antibodies and n = 50 were thrombocytopenic without detectable maternal HPA antibodies. Concentrations of C-reactive protein, soluble CD14, procalcitonin, and sFlt-1 did not differ between the two cohorts. There was no correlation between C-reactive protein or soluble CD14 and the platelet count, but a negative correlation between procalcitonin concentrations and the neonatal platelet count in both cohorts. sFlt-1 concentration and the platelet count were correlated in FNAIT cases exclusively. None of the inflammatory markers was statistically different between cases with and without intracranial haemorrhage. We were unable to identify systemic inflammation as a relevant factor for thrombocytopenia in FNAIT. The antiangiogenic enzyme sFlt-1, released by the placenta, did correlate with the platelet count in FNAIT cases. Our findings may give rise to the hypothesis that placental inflammation rather than systemic inflammation modulates disease severity in FNAIT.     

Glycosylation pattern of anti‐platelet IgG is stable during pregnancy and predicts clinical outcome in alloimmune thrombocytopenia

Fetal or neonatal alloimmune thrombocytopenia (FNAIT) is a potentially life‐threatening disease where fetal platelets are destroyed by maternal anti‐platelet IgG alloantibodies. The clinical outcome varies from asymptomatic, to petechiae or intracranial haemorrhage, but no marker has shown reliable correlation with severity, making screening for FNAIT impractical and highly inefficient. We recently found IgG Fc‐glycosylation towards platelet and red blood cell antigens to be skewed towards decreased fucosylation, increased galactosylation and sialylation. The lowered core‐fucosylation increases the affinity of the pathogenic antibodies to FcγRIIIa and FcγRIIIb, and hence platelet destruction. Here we analysed the N‐linked glycans of human platelet antigen (HPA)‐1a specific IgG1 with mass spectrometry in large series of FNAIT cases (n = 166) including longitudinal samples (n = 26). Besides a significant decrease in Fc‐fucosylation after the first pregnancy (P = 0·0124), Fc‐glycosylation levels remained stable during and after pregnancy and in subsequent pregnancies. Multiple logistic regression analysis identified anti‐HPA‐1a –fucosylation (P = 0·006) combined with galactosylation (P = 0·021) and antibody level (P = 0·038) correlated with bleeding severity , making these parameters a feasible marker in screening for severe cases of FNAIT.     

The unique immunological features of heparin‐induced thrombocytopenia

Heparin‐induced thrombocytopenia (HIT) is a serious drug reaction that leads to a decrease in platelet count and a high risk of thrombosis. HIT patients produce pathogenic immunoglobulin G (IgG) antibodies that bind to complexes of platelet factor‐4 (PF4) and heparin. HIT immune complexes crosslink Fc‐receptors resulting in platelet and monocyte activation. These events lead to the release of procoagulant chemokines and tissue factor, which together create an intensely prothrombotic state. HIT represents an atypical immune response because it has features of both T cell‐dependent and T cell‐independent mechanisms. The disorder is characterized by newly formed anti‐PF4/heparin IgG antibodies, which are characteristic of a T cell‐dependent mechanism; however, re‐exposure to heparin, months after HIT, does not lead to a memory response, which is consistent with a T cell‐independent mechanism. In this review, we discuss the immunobiological events that can explain these features, including the role for T cell‐dependent and T cell‐independent mechanisms in HIT antibody generation, the immunogenic characteristics of the PF4/heparin antigen, and the concept of a temporary loss in immune regulation contributing to the onset of HIT. We also present a novel immunobiological model to explain the atypical immune response that is characteristic of HIT.     

A novel murine model of fetal and neonatal alloimmune thrombocytopenia: response to intravenous IgG therapy

Fetal and neonatal alloimmune thrombo cytopenia (FNAITP) is a life-threatening bleeding disorder caused by maternal antibodies directed against fetal platelet antigens. The immunoreactive epitopes in FNAITP are primarily located in the extracellular regions of the platelet glycoprotein IIIa (beta3 integrin). Here we have established a novel animal model of FNAITP using beta3 integrin-deficient (beta3-/-) mice. We demonstrated first that these mice are immunoresponsive to beta3 integrin; beta3-/- mice transfused with wild-type platelets generated specific anti-beta3 antibodies which were able to induce thrombocytopenia in wild-type mice. Subsequently, beta3-/- female mice (both naive and immunized) were bred with wild-type male mice to recapitulate the features of FNAITP. The titer of generated maternal antibodies correlated with the severity of FNAITP. High titer maternal anti-beta3 anti-bodies caused severe fetal thrombocytopenia, intracranial hemorrhage, and even miscarriage. Furthermore, maternal administration of intravenous immunoglobulin G (IgG) ameliorated FNAITP and down-regulated pathogenic antibodies in both the maternal and fetal circulations.     

Report on the 14th international society of blood transfusion platelet immunology workshop

Background and Objectives The aims of the 14th ISBT Platelet Immunology Workshop were to evaluate in‐house methods for detection of antibodies to human platelet antigens, to compare the sensitivity and specificity of antibody detection using a panel of monoclonal antibodies and to evaluate genotyping methods and establish procedures for drug‐dependent antibody detection. Materials and Methods Forty‐two laboratories from 23 countries participated. Samples and reagents provided for the five different exercises. Results The ability of participating laboratories to correctly identify the HPA antibody specificity in the nine samples ranged from 20% to 97%. The greatest difficulty was observed with samples that contained antibodies against HPA‐3b and GPIV. The significant differences in optical density values by monoclonal antibody of immobilization of platelet antigens (MAIPA) assay were observed when testing the same platelet‐specific antibodies. HPA genotyping of DNA with novel mutations did not significantly affect the results. The overall average discrepancy rate was 2·15% for genotyping of 10 DNA samples from well‐characterized Epstein–Barr virus transformed cell lines. For detection of drug‐dependent antibodies, excellent results for specificity and sensitivity were obtained by the laboratories using the MAIPA and flow cytometry. Conclusions Most laboratories were able to identify the majority of HPA antibodies; however, significant disparities were observed in proficiency testing. MAIPA assay sensitivity is influenced by the monoclonal antibody clone used. DNA with new mutations and EBV cell lines are valuable samples to ensure accurate genotyping. A sensitive and specific drug‐dependent antibody assay performed well in the hands of participants.     

Fetal and neonatal alloimmune thrombocytopenia: recommendations for evidence-based practice,an international approach

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) may result in severe bleeding, particularly fetal and neonatal intracranial haemorrhage (ICH). As a result, FNAIT requires prompt identification and treatment; subsequent pregnancies need close surveillance and management. An international panel convened to develop evidence-based recommendations for diagnosis and management of FNAIT. A rigorous approach was used to search, review and develop recommendations from published data for: antenatal management, postnatal management, diagnostic testing and universal screening. To confirm FNAIT, fetal human platelet antigen (HPA) typing, using non-invasive methods if quality-assured, should be performed during pregnancy when the father is unknown, unavailable for testing or heterozygous for the implicated antigen. Women with a previous child with an ICH related to FNAIT should be offered intravenous immunoglobulin (IVIG) infusions during subsequent affected pregnancies as early as 12 weeks gestation. Ideally, HPA-selected platelets should be available at delivery for potentially affected infants and used to increase the neonatal platelet count as needed. If HPA-selected platelets are not immediately available, unselected platelets should be transfused. FNAIT studies that optimize antenatal and postnatal management, develop risk stratification algorithms to guide management and standardize laboratory testing to identify high risk pregnancies are needed.     

Frequencies of maternal platelet alloantibodies and autoantibodies in suspected fetal/neonatal alloimmune thrombocytopenia, with emphasis on human platelet antigen-15 alloimmunization

BACKGROUND AND OBJECTIVES: Serological evaluation of maternal sera for platelet antibodies in suspected fetal/neonatal alloimmune thrombocytopenia (FNAITP) discloses in only approximately 30% of individuals a platelet-specific antibody. Transfusion-induced alloimmunization against human platelet antigen-15 (HPA-15) has been reported to be about as common as against HPA-5, the second most common platelet antibody. Thus, anti-HPA-15 may also contribute significantly to yet-unclear cases of FNAITP. MATERIALS AND METHODS: In this retrospective analysis, we provide data on maternal platelet antibodies from 309 mothers who delivered an offspring with suspected FNAITP. RESULTS: Genotyping maternal and paternal samples (together n = 573) revealed a gene frequency of 0.496 for HPA-15a and a gene frequency of 0.504 for HPA-15b. HPA-15 antibodies were detected in 2% of all samples. Anti-HPA-15a and -15b were detected in two and three samples, respectively. One serum reacted equally with HPA-15a and -15b platelets. The most frequent platelet-specific antibodies were anti-HPA-1a (22%), but anti-HPA-5b (8.4%) were more frequent than anti-HPA-15. In addition, panreactive (5.5%) or autoreactive (5.2%) anti-GPIIb/IIIa or anti-GPIb/IX were detectable in maternal samples. CONCLUSIONS: These data indicate that HPA-15 alloimmunization needs only to be considered in subjects with suspected FNAITP if no other platelet-specific antibody is detectable. The presence of panreactive or autoreactive antibodies should also be considered in neonatal thrombocytopenia.     

Antibody‐mediated transfusion‐related acute lung injury; from discovery to prevention

Transfusion‐related acute lung injury (TRALI), a syndrome of respiratory distress caused by blood transfusion, is the leading cause of transfusion‐related mortality. The majority of TRALI cases have been related to passive infusion of human leucocyte antigen (HLA) and human neutrophil antigen (HNA) antibodies in donor blood. In vitro, ex vivo and in vivo animal models have provided insight in TRALI pathogenesis. The various classes of antibodies implicated in TRALI appear to have different pathophysiological mechanisms for the induction of TRALI involving endothelial cells, neutrophils, monocytes and, as very recently has been discovered, lymphocytes. The HLA and HNA‐antibodies are found mainly in blood from multiparous women as they have become sensitized during pregnancy. The incidence of TRALI has decreased rapidly following the introduction of a male‐only strategy for plasma donation. This review focuses on pre‐clinical and clinical studies investigating the pathophysiology of antibody‐mediated TRALI.     

The IgG subclasses of platelet-associated autoantibodies directed against platelet glycoproteins IIb/IIIa in patients with idiopathic thrombocytopenic purpura

The majority of patients with idiopathic thrombocytopenic purpura (ITP) have antiplatelet autoantibodies that are most frequently directed against platelet glycoproteins IIb/IIIa or Ib/IX/V. However, there is some debate whether the immune response is oligoclonal or polyclonal in nature. We investigated the subclass distribution of anti-IIb/IIIa IgG autoantibodies in 59 prospectively studied patients with ITP. We also tested patients with a variety of thrombocytopenic disorders (n=31) and healthy controls (n=30). Platelet lysates were tested for IgG anti-IIb/IIIa autoantibodies, and the specific IgG subclass distribution was measured using antigen capture assays. All testing was done blinded to diagnosis and other assay results. After unblinding, we found that 43 of the 59 ITP patients had anti-IIb/IIIa autoantibodies (sensitivity=73%). Anti-IIb/IIIa autoantibodies were also detected in five of the 31 non-ITP patients, but in none of the 30 healthy controls (specificity=91%). The IgG subclass assay was positive in 39 of the 43 ITP patients with anti-IIb/IIIa antibodies (sensitivity=92%) and in 12 samples that had no detectable anti-IIb/IIIa antibodies including two ITP patients (specificity=83%). The most common subclass in the ITP patient samples was IgG1 (77%), either alone (n=14) or with other IgG subclass antibodies (n=19). However, there were also patients with only IgG2 (n=2), IgG3 (n=3) or IgG4 (n=3) antibodies. Our results are consistent with the hypothesis that ITP is a heterogeneous disorder and that some patients have evidence of oligoclonality, whereas other patients have polyclonal autoantibodies.     

The relevance of HPA-15 antigen expression for anti-HPA-15 antibody detection

Introduction: The HPA‐15 antigen system is characterized by a low antigen expression on platelets. The antibodies against this antigen are implied in fetal/neonatal alloimmune thrombocytopenia (F/NAIT), post‐transfusion purpura, and refractoriness to platelet transfusions. Detection of these antibodies appears to be related to the level of HPA‐15 expression on the platelets used in the monoclonal antibody–specific immobilization of platelet antigen (MAIPA) assay. Methods: We performed genotyping of 300 healthy blood donors for HPA‐15 by TaqMan real‐time PCR technology, and the HPA‐15 antigen expression was investigated in 13 HPA‐15aa and 19 HPA‐15bb individuals. We also investigated the relevance of HPA‐15 antigen expression on donor platelets used in MAIPA for antibody detection in 223 multitransfused hematological patients and 271 women with suspected F/NAIT. Results: In Polish donors, the HPA‐15a allele frequencies were lower than the HPA‐15b (0.480 vs. 0.515). We identified three HPA‐15 expression groups: high (36.7 ± 8.36 MFI – eight cases), medium (19.5 ± 6.2 MFI – 21 cases), and low (6.5 ± 5.9 MFI – three cases). The HPA‐15 expression was stable over time. The HPA‐15aa and HPA‐15bb platelets with high antigen expression were used for anti‐HPA‐15 antibody detection; anti‐HPA‐15 antibodies were detected in 4/223 (1.8%) patients receiving multiple transfusions but in none of the 271 women with suspected F/NAIT. Further examination of the four sera by MAIPA with various platelets revealed the optical density in the assay to be closely related to the level of HPA‐15 antigen expression. Conclusion: Anti‐HPA‐15 antibody detection should be based on carefully selected platelets with high HPA‐15 expression level.     

Quantitation of platelet-specific autoantibodies in platelet eluates of ITP patients measured by a novel ELISA using the purified glycoprotein complexes GPIIb/IIIa and GPIb/IX as antigens

Immune thrombocytopenic purpura (ITP) is a disorder caused by anti-platelet autoantibodies (Ab), most of which are directed against epitopes on platelet membrane glycoprotein complexes GPIIb/IIIa and GPIb/IX. To detect platelet Ab, reliable techniques, such as MAIPA or immunobead assay, have been developed. They all achieve their selective specificity by the use of monoclonal antibodies (MoAb) against defined glycoproteins of the platelet membrane. In order to determine the most frequent Ab-specificities, a novel enzyme-linked immunosorbent assay, named platelet-glycoprotein-ELISA (P-GP-ELISA), has been developed. It uses purified GPIIb/IIIa and GPIb/IX complexes, respectively, as antigens and enables determination of platelet-associated as well as circulating Ab (IgG, IgM). MoAbs are not required and therefore there is no risk of competition between MoAb and Ab. Levels of Ab in patients with the clinical diagnosis of an idiopathic thrombocytopenic purpura were analysed. 92.7% (76/82) platelet eluates with significantly increased levels of Ab against at least one of the glycoproteins were found, whereas no sample from healthy volunteers (0/37) gave a positive result, pointing to a high sensitivity and specificity of the test system. Since its application is also easy and quick, P-GP-ELISA should facilitate detection of Ab against platelet membrane proteins in routine determinations.     

Management of Alloimmune Neonatal and Antenatal Thrombocytopenia

Neonatal and antenatal alloimmune thrombocytopenia is induced by maternal antibodies against platelet-specific fetal antigens. This disease is rare but potentially severe because of intracranial bleedings which may occur during pregnancy or around birth. In the last decade our knowledge of this disorder has markedly advanced. New techniques are used in platelet immunology. New platelet antigens involved in these perinatal thrombocytopenias have recently been discovered. A group of women likely to produce the responsible platelet antibodies has been genetically defined as regards the PLA1 antigen. The quality of the sonographies and the possibility of performing cord vein puncture in early pregnancy afford a new approach in the management of perinatal alloimmune thrombocytopenias. But more must be done to prevent the complications of this disease.     

Living donor liver transplantation for patients immunized against human leukocyte antigen

Background/purpose

The clinical features and perioperative management of liver transplant recipients who are already sensitized against human leukocyte antigen (HLA) prior to transplantation are not yet clear.

Materials and methods

Medical records of living donor liver transplant recipients were reviewed and clinical features of the patients possessing anti-HLA antibodies were studied.

Results

Among the 470 consecutive living donor liver transplant recipients, 6 patients (1.3%) had preformed anti-HLA antibodies. A review of the postoperative courses of these patients revealed that the problems included platelet transfusion refractoriness (PTR) due to immune-mediated destruction of platelet and thrombotic microangiopathy (TMA). PTR was observed in patients with anti-HLA class I antibodies and only HLA-matched platelet concentrate (HLA-matched PC) relieved thrombocytopenia. Intravenous gammaglobulin had an additive effect to HLA-matched PC in some cases, and platelet transfusion from close relatives might be a substitute for HLA-matched PC in life-threatening situations. Although the etiology of TMA is unremarkable, the incidence was high (67%, 4/6) compared with that in patients who were not sensitized against HLA (5.6%, 26/464; p < 0.01). Of the four patients, three were complicated with late-onset TMA.

Conclusions

Considering these clinical features, careful preparation and postoperative management are needed for liver transplant candidates with anti-HLA antibodies.     

Platelet and granulocyte alloimmunisation in multitransfused Tunisian patients

We determined the frequency of post-transfusion alloimmunisation against platelet and granulocyte antigens in 51 Tunisian polytransfused patients with haematological diseases. Serum samples were analysed by a standard and an antiglobulin-augmented lymphocytotoxicity technique, a granulocyte agglutination test, a granulocyte immunofluorescence test, a platelet immunofluorescence test and the monoclonal antibody-specific immobilisation of platelet antigens assay. No granulocyte-specific antibodies were detected. HLA antibodies were found in 58.8% of patients. Platelet-specific antibodies were detected in four patients and were directed against human platelet antigen (HPA)-5b, HPA-1b and HPA-3a. The three patients with Glanzmann's thrombasthenia developed anti-GPIIb/IIIa antibodies. This study provides immunogenetic information that could improve the management of transfusion therapy in Tunisia.     

Collaborative studies to establish the first WHO Reference Reagent for detection of human antibody against human platelet antigen-5b

BACKGROUND AND OBJECTIVES: This report describes the production of a freeze-dried preparation of pooled human plasma, coded 99/666, containing immunoglobulin G (IgG) antibodies against human platelet antigen 5b (HPA-5b). MATERIALS AND METHODS: The material is intended for use as a minimum sensitivity reagent in the assays currently used for detection of antibodies to HPA-5b. Laboratories can use it to assess the sensitivity of their 'in-house' assays for antibodies to HPA-5b and to calibrate local controls for routine use in each batch of tests. RESULTS: Two collaborative studies demonstrated that the two candidate materials contained antibodies to HPA-5b and that there were no other HPA or human leucocyte antigen (HLA) antibodies which might confuse the detection of antibodies to HPA-5b. The two samples were pooled and freeze-dried in 1-ml ampoules. CONCLUSIONS: The minimum dilution of the antibody against 5b required to yield a positive result was determined, by two international collaborative studies involving a total of 49 laboratories in 26 countries, to be 1 in 2.     

Advances in alloimmune thrombocytopenia: perspectives on current concepts of human platelet antigens,antibody detection strategies,and genotyping

Alloimmunisation to platelets leads to the production of antibodies against platelet antigens and consequently to thrombocytopenia. Numerous molecules located on the platelet surface are antigenic and induce immune-mediated platelet destruction with symptoms that can be serious. Human platelet antigens (HPA) cause thrombocytopenias, such as neonatal alloimmune thrombocytopenia, post-transfusion purpura, and platelet transfusion refractoriness. Thirty-four HPA are classified into 28 systems. Assays to identify HPA and anti-HPA antibodies are critically important for preventing and treating thrombocytopenia caused by anti-HPA antibodies. Significant progress in furthering our understanding of HPA has been made in the last decade: new HPA have been discovered, antibody-detection methods have improved, and new genotyping methods have been developed. We review these advances and discuss issues that remain to be resolved as well as future prospects for preventing and treating immune thrombocytopenia.