Subamniotic haemorrhage, a possible new presentation of fetal and neonatal alloimmune thrombocytopenia

Fetal Diagnosis and Therapy ◽

10.1159/000521866 ◽

2022 ◽

Author(s):

Steven Giesbers ◽

Manon Bos ◽

Johan Bulten ◽

Lotte van der Meeren ◽

Joris van Drongelen

Keyword(s):

Intravenous Immunoglobulin ◽

Human Platelet ◽

Maternal Antibodies ◽

Histopathological Analysis ◽

Germinal Matrix ◽

Fetal Origin ◽

Alloimmune Thrombocytopenia

Background: Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a rare fetal disease in which maternal antibodies directed towards fetal human platelet antigens (HPA) are formed during pregnancy and cause fetal thrombocytopenia. The diagnosis FNAIT is suspected when a fetus or neonate presents with signs of bleeding. Case: We describe a pregnancy complicated by a placental hematoma in the 20th week of gestation as the first manifestation of FNAIT. Further evaluation showed signs of germinal matrix haemorrhage and HPA-5b allo-antibodies. After the diagnosis, intravenous immunoglobulin was administered weekly and a healthy daughter was born at 37 weeks. Histopathological analysis revealed that the hematoma was caused by a subamniotic haemorrhage of fetal origin. Conclusion: A subamniotic hematoma appears to be the first manifestation of FNAIT.

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Localization of the Br Polymorphism on a 144 bp Exon of the GPIa Gene and Its Application in Platelet DNA Typing

Thrombosis and Haemostasis ◽

10.1055/s-0038-1642498 ◽

1994 ◽

Vol 71 (05) ◽

pp. 651-654 ◽

Cited By ~ 50

Author(s):

Rainer Kalb ◽

Sentot Santoso ◽

Katja Unkelbach ◽

Volker Kiefel ◽

Christian Mueller-Eckhardt

Keyword(s):

Genomic Organization ◽

Fragment Length Polymorphism ◽

Human Platelet ◽

Dna Typing ◽

Rflp Analysis ◽

Serological Typing ◽

Allele Specific ◽

Polymerase Chain ◽

Alloimmune Thrombocytopenia ◽

Rflp Typing

SummaryAlloimmunization against the human platelet alloantigen system Br (HPA-5) is the second most common cause of neonatal alloimmune thrombocytopenia (NAIT) in Caucasian populations. We have recently shown that a single base polymorphism at position 1648 on platelet mRNA coding for GPIa results in an aminoacid substitution at position 505 on the mature GPIa which is associated with the two serological defined Br phenotypes.Since DNA-typing of platelet alloantigens offers possibilities for useful clinical applications, we designed genomic DNA-based restriction fragment length polymorphism (RFLP) typing for Br alloantigens. To establish this technique we analyzed the genomic organization of GPIa adjacent to the polymorphic base. Using the polymerase chain reaction (PCR) of blood cell DNA we have identified two introns (approximately 1.7 and 1.9 kb) flanking a 144 bp coding sequence of the GPIa gene encompassing the polymorphic base 1648. Based on the in- tron sequence, a PCR primer was constructed to amplify a 274 bp fragment which was used for allele-specific RFLP to determine the Br genotypes. The results of RFLP analysis using Mnll endonuclease obtained from 15 donors (2 Br37*, 2 Br^ and 11 Brb/b) correlate perfectly with serological typing by monoclonal antibody-specific immobilization of platelet antigens (MAIPA) assay.

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Maternal intravenous immunoglobulin treatment does not prevent intracranial haemorrhage in fetal alloimmune thrombocytopenia

Transfusion Medicine ◽

10.1111/j.1365-3148.1994.tb00266.x ◽

1994 ◽

Vol 4 (4) ◽

pp. 293-296 ◽

Cited By ~ 63

Author(s):

H. Kroll ◽

V. Kiefel ◽

G. Giers ◽

R. Bald ◽

J. Hoch ◽

...

Keyword(s):

Intravenous Immunoglobulin ◽

Intracranial Haemorrhage ◽

Immunoglobulin Treatment ◽

Alloimmune Thrombocytopenia

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Chronic villitis in untreated neonatal alloimmune thrombocytopenia: An etiology for severe early intrauterine growth restriction and the effect of intravenous immunoglobulin therapy

American Journal of Obstetrics and Gynecology ◽

10.1016/j.ajog.2005.06.043 ◽

2005 ◽

Vol 193 (3) ◽

pp. 1100-1104 ◽

Cited By ~ 33

Author(s):

Janyne Althaus ◽

Edward G. Weir ◽

Fred Askin ◽

Thomas S. Kickler ◽

Karin Blakemore

Keyword(s):

Intravenous Immunoglobulin ◽

Intrauterine Growth Restriction ◽

Immunoglobulin Therapy ◽

Growth Restriction ◽

Intravenous Immunoglobulin Therapy ◽

Intrauterine Growth ◽

Chronic Villitis ◽

Alloimmune Thrombocytopenia

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

Blood ◽

10.1182/blood-2005-06-2562 ◽

2006 ◽

Vol 107 (7) ◽

pp. 2976-2983 ◽

Cited By ~ 60

Author(s):

Heyu Ni ◽

Pingguo Chen ◽

Christopher M. Spring ◽

Ebrahim Sayeh ◽

John W. Semple ◽

...

Keyword(s):

High Titer ◽

Maternal Antibodies ◽

Platelet Glycoprotein ◽

Wild Type ◽

Wild Type Male ◽

Glycoprotein Iiia ◽

Life Threatening ◽

Β3 Integrin ◽

Pathogenic Antibodies ◽

Alloimmune Thrombocytopenia

AbstractFetal 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 (β3 integrin). Here we have established a novel animal model of FNAITP using β3 integrin–deficient (β3-/-) mice. We demonstrated first that these mice are immunoresponsive to β3 integrin; β3-/- mice transfused with wild-type platelets generated specific anti–β3 antibodies which were able to induce thrombocytopenia in wild-type mice. Subsequently, β3-/- 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–β3 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.

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