An Unusual Case of Fetal/Neonatal Alloimmune Thrombocytopenia

2019 ◽  
Vol 152 (Supplement_1) ◽  
pp. S151-S152
Author(s):  
Maryna Vazmitsel ◽  
Dong Chen ◽  
Barbara Gruner ◽  
Emily Coberly
Keyword(s):  
Platelet Count ◽  
Hla Class I ◽  
Maternal Blood ◽  
Term Infant ◽  
Blood Type ◽  
Class I ◽  
Severe Thrombocytopenia ◽  
Antibody Testing ◽  
Torch Infection ◽  
Alloimmune Thrombocytopenia

Abstract Objectives Fetal/neonatal alloimmune thrombocytopenia (FNAIT) occurs when maternal IgG alloantibodies against paternal human platelet antigens (HPA) cross the placenta and cause the destruction of fetal platelets. The vast majority (up to 95%) of FNAIT cases are caused by antibodies against HPA-1a or HPA-5b antigens, while the remaining cases are usually due to antibodies against a variety of other HPA antigens. Cases of FNAIT due to anti-HLA antibodies are extremely uncommon and have only rarely been reported. We present a case of FNAIT suspected to be caused by anti-HLA class I alloantibodies. Methods The patient is a term infant boy born to a 32-year-old G2T2L2 mother. The mother had a previous diagnosis of Still disease (an adult form of systemic juvenile rheumatoid arthritis) but experienced complete resolution of symptoms and was off all treatment during the pregnancy. At birth, laboratory testing revealed isolated severe thrombocytopenia (platelet count 38,000/mcL) in an otherwise healthy-appearing infant. Results The infant had no evidence of bleeding, and testing for TORCH infection, sepsis, and DIC was negative. The maternal blood type was O positive. The maternal platelet count was normal. FNAIT was suspected and the infant was given two platelet transfusions from the same HPA 1a and 5b antigen-negative donor with no significant or sustained improvement in platelet count. Maternal platelet antibody testing subsequently revealed an absence of HPA antibodies, but anti-HLA class I alloantibodies were present. The infant was treated with three subsequent doses of IVIg with improvement in platelet count. No significant hemorrhage occurred. Conclusion HLA class I antibodies are commonly found in multiparous women but are not generally thought to cause significant fetal complications during subsequent pregnancies. This case suggests that, although rarely reported, HLA class I alloantibodies may be capable of causing FNAIT.

scholarly journals Anti-HLA Antibodies in Neonatal Alloimmune Thrombocytopenia - Is There Any Clinical Significance?

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4647-4647 ◽  
Author(s):  
Lilach Bonstein ◽  
Nardeen Atweh ◽  
Nuhad Haddad ◽  
Yariv Fruchtman
Keyword(s):  
Platelet Count ◽  
Antibody Titer ◽  
Conflicts Of Interest ◽  
Hla Class I ◽  
Class I ◽  
Hla Antibodies ◽  
Neonatal Thrombocytopenia ◽  
Alloimmune Thrombocytopenia ◽  
Sample Case ◽  
Hla Antibody

Abstract Background: Neonatal alloimmune thrombocytopenia (NAIT) is caused by maternal alloantibodies raised against paternally inherited alloantigens carried on fetal platelets. Platelets express both HLA class I and specific human platelet antigens (HPA). Although anti-HLA class I antibodies are often detectable in pregnant women, NAIT is considered to be mainly associated with antibodies against HPA. Cases where NAIT has been caused by antibodies against HLA class I are relatively rare and the role of these antibodies in NAIT remains debatable. We hereby describe a sample case of NAIT proved to be caused solely by anti-HLA antibodies and discuss laboratory measures aimed at identification of pregnancies at risk of NAIT related to anti-HLA class I antibodies based on a series of similar cases. Methods: This sample case presents laboratory work-up on a young mother who delivered her first son with a platelet count of 20x109/L, minor petechiae and normal WBC count. Thrombocytopenia in the newborn resolved spontaneously two weeks after birth. Laboratory investigation included platelet immunofluorescence test (PIFT), monoclonal antibody-specific immobilization of platelet antigens (MAIPA) assay, genotyping of both parents and the newborn for platelet antigens, including rare antigens, and HLA antibody identification using the panel reactive antibodies (PRA) assay (Luminex, USA). A serum sample of this mother, drawn during her second pregnancy, and those of ten other women referred to our laboratory with a similar obstetric history of neonatal thrombocytopenia, were evaluated for the anti-HLA antibody titer using the MAIPA assay. Results: The Rambam Platelet & Neutrophil Immunology Laboratory, as well as 32 other laboratories worldwide, that participated in the 2014 International Workshop organized by the ISBT Platelet Immunobiology Working Party failed to detect anti-HPA antibodies in the mother's serum during her second pregnancy, despite using the most sensitive serological analysis and molecular methods. Only strong anti-HLA antibodies with no single specificity were found in the analyzed samples by all the laboratories. Her second child was born by caesarean section with a platelet count of 50x109/L and maternal anti-HLA antibodies were found in his serum and on his platelets. The anti-HLA antibody titer of the mother, determined by the MAIPA assay, was greater than 1:1024, with antibodies being multi-specific, as demonstrated by PRA. The anti-HLA antibody titer ≥1:16 was found to correlate with low platelet counts in the additional ten cases tested, as opposed to the titer of ≤1:4 in cases with mild and not clinically significant neonatal thrombocytopenia. Conclusions: The presence of anti-HLA class I antibodies should be considered as a potential cause of NAIT, especially in cases with a very high titer of antibodies. The mechanism underlying the effect of these antibodies on fetal platelets needs to be further investigated. Disclosures No relevant conflicts of interest to declare.

scholarly journals Case Of NAIT Causing Severe Thrombocytopenia due to Anti-HLA Class I

2021 ◽  
Vol 5 (0-2) ◽  
pp. 21
Author(s):  
Noor Aqilah Binti Ashamuddin ◽  
Sabariah Binti Mohd Noor ◽  
Irni Binti Mohd Yasin
Keyword(s):  
Placental Transfer ◽  
Serum Antibody ◽  
Hla Class I ◽  
Premature Baby ◽  
Maternal Serum ◽  
Class I ◽  
Severe Thrombocytopenia ◽  
Platelet Antigen ◽  
Obstetric Management ◽  
Alloimmune Thrombocytopenia

Neonatal alloimmune thrombocytopenia (NAIT) is the leading cause of thrombocytopenia in otherwise healthy new-born. (1,2) Maternal antibodies raised against paternally inherited alloantigen carried on fetal platelet causing NAIT. Maternal IgG antibodies passed through to the fetal via the placenta, attack and cause the destruction of the fetal platelet. (3) We present a case of NAIT without any complications in a premature baby (35 weeks) with VACREL association, G6PD deficiency, left calcified cephalohaematoma, cardiomegaly and hypospadias with severe thrombocytopenia (platelet counts is 23 109/L) at day two of life and received twice platelet transfusion. Platelet count initially 123 109/L at birth but significantly drop and persistently less than 50 109/L until day 10 of life before it normalized. Maternal serum antibody screening was negative, but platelet immunology test detected maternal platelet-reactive antibody Anti-HLA Class I and correlates with incompatible parental crossmatch indicating that parent had “platelet-antigen incompatibility”. The goal of obstetric management is to identify pregnancies at risk and prevent intracranial haemorrhage. (4) There is no evidence to support routine screening for pregnancies as per current practice. (2, 5) The latest treatments include maternal administration of intravenous immunoglobulin to suppress maternal antibody production and or to reduce placental transfer of antibodies; with or without steroids during antepartum period besides planning of mode, timing and method of delivery. (2, 5, 6, 7) This is a rare and unique case of NAIT secondary to Anti-HLA Class I antibody and hence clinician should be au fait with the diagnosis and management as it is infrequent among Malaysian.International Journal of Human and Health Sciences Supplementary Issue-2: 2021 Page: S21

HLA class I expression on the erythrocytes of cord and maternal blood — Flow cytometric analysis

1996 ◽  
Vol 47 (1-2) ◽  
pp. 110
Author(s):  
G. Paterakis ◽  
A. Germenis ◽  
D. Skoumi ◽  
N. Koutsodimas ◽  
C. Stavropoulos-Giokas
Keyword(s):  
Blood Flow ◽  
Flow Cytometric Analysis ◽  
Hla Class I ◽  
Maternal Blood ◽  
Class I ◽  
Flow Cytometric

HLA class I and HPA9b related fetal‐neonatal alloimmune thrombocytopenia

2021 ◽  
Author(s):  
Sara Barbieri ◽  
Alessandro Copeta ◽  
Nicoletta Revelli ◽  
Alberto Malagoli ◽  
Alessia Montani ◽  
...  
Keyword(s):  
Hla Class I ◽  
Class I ◽  
Alloimmune Thrombocytopenia

A Screening and Intervention Program Reducing Mortality and Serious Morbidity Associated with Neonatal Alloimmune Thrombocytopenia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1232-1232
Author(s):  
Jens Kjeldsen-Kragh ◽  
Mette K. Killie ◽  
Geir Tomter ◽  
Elzbieta Golebiowska ◽  
Helene Pedersen ◽  
...  
Keyword(s):  
Platelet Count ◽  
Intervention Program ◽  
Human Platelet ◽  
Fetal Brain ◽  
University Hospital ◽  
Severe Thrombocytopenia ◽  
Platelet Antigen ◽  
Human Platelet Antigen ◽  
Alloimmune Thrombocytopenia

Abstract Background: Neonatal alloimmune thrombocytopenia (NAIT) is most frequently caused by antibodies against the human platelet antigen (HPA) 1a. The objective of the present study was to identify HPA 1a negative women, and to offer them an intervention program aimed to reduce morbidity and mortality of NAIT. Methods: A total of 100,448 pregnant women were HPA 1 typed. The HPA 1a negative women were screened for anti-HPA 1a, which was quantified when present. Immunized women were referred to a university hospital for clinical follow-up, including ultrasonographic examination of the fetal brain. Caesarean section was performed 2–4 weeks prior to term with platelets from HPA 1bb donors reserved for immediate transfusion if petechiae were present and/or if platelet count was < 35 × 109/L. Results: Of all women typed 2.1% were HPA 1a negative. Anti-HPA 1a was detected in 210 of 1,990 HPA 1a negative women. A total of 170 pregnancies in 154 HPA 1a negative women were managed according to the intervention program. These women gave birth to 161 HPA 1a positive children of whom 55 had severe thrombocytopenia (<50 × 109/L) including two with ICH. There were no intrauterine deaths. In 13 previously published prospective studies comprising 131,465 women of whom 2,290 were HPA 1a negative, there were 10 cases with severe NAIT-related complications (3 intrauterine deaths and 7 neonates with ICH), which are significantly higher than in our study (p < 0.05). Conclusions: The screening and intervention program seems to reduce mortality and serious morbidity associated with NAIT.

scholarly journals Generation of iPSC-Derived Human Megakaryocytes for Flow Cytometric Detection of Platelet-Specific Alloantibodies

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 740-740
Author(s):  
Nanyan Zhang ◽  
Peter Newman
Keyword(s):  
Conflicts Of Interest ◽  
Flow Cytometric Analysis ◽  
Hla Class I ◽  
Blood Type ◽  
Class I ◽  
Antibody Detection ◽  
Enzyme Linked Immunosorbent Assay ◽  
Transfusion Therapy ◽  
Flow Cytometric ◽  
Simple Flow

Abstract Antibodies that form against human platelet alloantigens (HPAs) are responsible for several clinically important alloimmune bleeding disorders, including fetal and neonatal alloimmune thrombocytopenia, posttransfusion purpura, and multitransfusion platelet refractoriness. Some of HPAs are relatively rare in the population, and difficult to obtain for purposes of transfusion therapy and diagnostic testing. In addition, HPA alloantisera often contain antibodies against human leucocyte antigen (HLA) class I, thereby limiting antibody detection to glycoprotein (GP)-specific assays such as the modified antigen capture enzyme-linked immunosorbent assay (MACE) and the monoclonal immobilization of platelet antigen (MAIPA), which are tedious and require solubilization of platelet GPs that may cause the loss of epitopes. In this study we aimed to generate gene-edited, HPA-specific, megakaryocytes (MKs) derived from human induced pluripotent stem cells (iPSCs) that could be used for simple flow cytometric detection of specific HPA alloantibodies present in patient sera. The HPA-3a/HPA-3b alloantigen system, also known as Baka/Bakb, is caused by a single T13809G nucleotide substitution in the ITGA2B gene, resulting in an Ile874Ser amino acid polymorphism near the C terminus of the integrin αIIb subunit (GPIIb). Here we targeted HPA-3 system because alloantibodies targeting HPA-3 are often hard to detect with current detection methods, in part due to the requirement for cell type-specific glycosylation. To prevent interference of anti-A or anti-B antibodies in patient sera, a blood type O iPSC line (OT1-1) was generated from human peripheral blood mononuclear cells derived from a healthy donor using integration-free episomal vectors. The gene for β2 microglobulin (B2M) was first ablated from the OT1-1 iPS cell line using CRISPR/Cas9 to prevent binding of HLA class I alloantibodies. The resulting B2M knockout (B2MKO) cells were then additionally gene edited to convert the endogenous HPA-3a alloantigenic epitope present on B2MKO OT1-1 cells to HPA-3b. Two different guide RNAs targeting sequences that flank exon 26 of the ITGA2B gene were designed such that the entire exon harboring the HPA-3 polymorphic site was removed. A plasmid harboring a template replacing exon 26 with the G13809 mutation, flanked by 600 bp homology arms, was cotransfected into the B2MKO OT1-1 iPSCs together with the two CRISPR/Cas9 guide RNA constructs. iPSC clones containing the desired targeted T13809G mutation were identified by a diagnostic MfeI digestion specific for the G13089-bearing HPA-3b allele. Sequence analysis confirmed conversion of T13089 to G in these HPA-3b clones. Flow cytometric analysis showed the HPA-3a iPSCs, when differentiated into CD41+/CD42b+ MKs, specifically reacted with HPA-3a, but not HPA-3b, patient sera, while the HPA-3b iPSC-derived MKs lost reactivity with HPA-3a patient serum, and gained the reactivity with HPA-3b patient sera. Taken together, we have established genetically modified iPSC-derived MKs expressing specific HPAs that are suitable for simple flow cytometry-based detection of HPA alloantibodies in patient sera, with low non-specific background binding. This system provides intact antigens on the cell surface with carbohydrate moieties that likely mimic those found on human platelets, thus facilitating the detection of HPA alloantibodies that are normally hard to detect with current methods. Application of this strategy to genetically edit this and other clinically-important HPAs holds great potential for producing Designer Platelets for diagnostic, investigative and ultimately therapeutic use. Disclosures No relevant conflicts of interest to declare.

scholarly journals Thrombocytopenia caused by passive transfusion of anti-glycoprotein Ia/IIa alloantibody (anti-HPA-5b)

Blood ◽  
1992 ◽  
Vol 79 (9) ◽  
pp. 2480-2484 ◽  
Author(s):  
TE Warkentin ◽  
JW Smith ◽  
CP Hayward ◽  
AM Ali ◽  
JG Kelton
Keyword(s):  
Platelet Count ◽  
Copy Number ◽  
Severe Thrombocytopenia ◽  
Count Nadir ◽  
Low Copy Number ◽  
Plasma Donor ◽  
Alloimmune Thrombocytopenia ◽  
Platelet Count Nadir

We describe a patient who developed transient and moderately severe thrombocytopenia (platelet count nadir 35 x 10(9)/L) after the transfusion of plasma. Using the technique of direct radioimmunoprecipitation, we showed that during the thrombocytopenia episode, the patient's platelets had IgG specifically bound to the glycoprotein (GP) Ia/IIa complex. Indirect radioimmunoprecipitation using serum from the plasma donor confirmed that anti-HPA-5b (anti- Zava) was the cause of GP Ia/IIa sensitization. The relatively mild thrombocytopenia, compared with passive alloimmune thrombocytopenia caused by anti-HPA-1a (anti-P1A1), may reflect the low copy number of HPA-5 compared with HPA-1. Direct radioimmunoprecipitation permits the detection of the GPs carrying the known platelet alloantigen systems, and this study suggests that this technique can be used to diagnose passive alloimmune thrombocytopenia.

scholarly journals Thrombocytopenia caused by passive transfusion of anti-glycoprotein Ia/IIa alloantibody (anti-HPA-5b)

Blood ◽  
1992 ◽  
Vol 79 (9) ◽  
pp. 2480-2484 ◽  
Author(s):  
TE Warkentin ◽  
JW Smith ◽  
CP Hayward ◽  
AM Ali ◽  
JG Kelton
Keyword(s):  
Platelet Count ◽  
Copy Number ◽  
Severe Thrombocytopenia ◽  
Count Nadir ◽  
Low Copy Number ◽  
Plasma Donor ◽  
Alloimmune Thrombocytopenia ◽  
Platelet Count Nadir

Abstract We describe a patient who developed transient and moderately severe thrombocytopenia (platelet count nadir 35 x 10(9)/L) after the transfusion of plasma. Using the technique of direct radioimmunoprecipitation, we showed that during the thrombocytopenia episode, the patient's platelets had IgG specifically bound to the glycoprotein (GP) Ia/IIa complex. Indirect radioimmunoprecipitation using serum from the plasma donor confirmed that anti-HPA-5b (anti- Zava) was the cause of GP Ia/IIa sensitization. The relatively mild thrombocytopenia, compared with passive alloimmune thrombocytopenia caused by anti-HPA-1a (anti-P1A1), may reflect the low copy number of HPA-5 compared with HPA-1. Direct radioimmunoprecipitation permits the detection of the GPs carrying the known platelet alloantigen systems, and this study suggests that this technique can be used to diagnose passive alloimmune thrombocytopenia.

Clinical Experience of Transfusion of Plasma from HLA Immunized Donors

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4317-4317
Author(s):  
Fleur M Aung ◽  
Benjamin Lichtiger
Keyword(s):  
Whole Blood ◽  
Blood Donors ◽  
Hla Class I ◽  
Class Ii ◽  
Hla Class Ii ◽  
Biologically Active ◽  
Class I ◽  
Antibody Testing ◽  
Hla Antibodies ◽  
Male Donor

Abstract Transfusion-related acute lung injury (TRALI) is a serious complication of plasma-containing blood components. Studies have implicated HLA antibodies along with biologically active lipids in stored blood in the pathogenesis of TRALI. We reviewed the HLA Antibody testing of our whole blood donors during a three month period who were tested for HLA Class I and HLA Class II antibodies by the DONORSCREEN-HLA Class I and Class II ELISA from GTI Diagnostics @ Waukesha, WI. The testing for HLA Antibodies in our donors was implemented as both HLA Class I and HLA Class II antibodies have been implicated in TRALI. The goal was to quarantine the plasma from these donors in order to reduce the exposure to patients to plasma from HLA Immunized Donors. Of 4056 whole blood donors, there were twenty-two donors of which 21 female and one male who tested positive for either HLA Class I or HLA Class II antibodies whose plasma was transfused. Of the twenty two donors, twenty one were females and one was male. Of the twenty one females, fifteen tested positive for HLA Class I antibodies and seven tested positive for HLA Class II antibodies. The single male donor tested positive for HLA Class II antibodies. The cause of the HLA immunization of these donors was unknown (as to whether they were caused by multiparity or blood transfusions). The plasma from the HLA Immunized female donors were transfused to ten female patients and eleven male patients. The plasma from the male donor was transfused to a male patient. All of the plasma from the HLA immunized donors was pooled with other plasma products in pools ranging from three to eight. All of the plasma products were irradiated and transfused via Fenwal Sepacell Reduction Filter for Red cells and all of the patients were premedicated prior to transfusion. One male and one female patient received plasma on two occasions from two donors both of whom were positive for HLA Class I antibodies. The twenty two patients consisted of four with hematological malignancies, one with a lymphoid malignancy and seventeen with malignancies of solid organs. Three of the patients had received an autologous transplant and one had received an allogeneic unrelated transplant. None of the patients had received IVIG therapy. The transfusions reactions reported for the three months of this review was also reviewed. None of the patient that received the HLA immunized plasma products was reported to have suffered a transfusion reaction. Although we did not meet our goal of reserving 100% of our plasma products from HLA immunized donors as recovered plasma, we discovered that the plasma products that were transfused from the HLA immunized donors were not associated with transfusion reactions in our patient population. The reason for not meeting our goal was the test results for the HLA Class I and HLA Class II antibodies were received after the plasma products were released for transfusion, due to logistical limitations in the performance of the testing. Although the number is small, we feel that the results may be significant in light of the current thinking of accepting only male donors for plasma products.

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