title: Human platelet alloantigen polymorphism in Glanzmann's thrombasthenia and its impact on the severity of the disease.
abstract: Glanzmann's thrombasthenia (GT) is an autosomal recessive disorder of platelets caused by the deficiency or abnormality of platelet receptors. Several platelet alloantigen systems reside on glycoprotein (GP) IIb and GPIIIa, of which the human platelet antigen 1 (HPA-1) system is important. Studies have shown that, in the normal population, the HPA-1b phenotype results in increased platelet aggregation and increased fibrinogen binding, increasing the risk of myocardial infarction. GT produces severe bleeding, but in a subset of patients has a relatively milder course. Forty-one GT patients and 100 healthy control subjects were genotyped for platelet alloantigens HPA-1 to HPA-6, using PCR-ASA (polymerase chain reaction-allele-specific amplification), and for GPIIb-IIIa expression and fibrinogen binding using flow cytometric techniques. Platelet alloantigen distributions were similar in the patient and control groups. With the exception of the two HPA-1b/1b homozygous patients (> 10%), 25 GT patients had less than 5% aggregation to 6 micro mol/l ADP, and 16 patients showed between 5% and 10% aggregation to 6 micro mol/l ADP. Seven out of 37 patients with HPA-1a/1a phenotype showed 1-5% fibrinogen binding and GPIIb-IIIa receptors. The two HPA-1b/1b patients showed 34.6% and 32% fibrinogen binding and > 10% GPIIb-IIIa receptors. This study determined the platelet alloantigen distribution in a large cohort of unrelated GT patients from western India. GT patients homozygous for HPA-1b/1b had higher levels of platelet aggregation and fibrinogen binding as well as a milder course, as evidenced by infrequent epistaxis and no transfusion requirement to date.
authors.affiliation: Institute of Immunohematology (ICMR), KEM Hospital, Parel, Mumbai, India.
authors.forename: Kanjaksha
authors.initials: K
authors.lastname: Ghosh
authors.forename: Bipin
authors.initials: B
authors.lastname: Kulkarni
authors.forename: Sona
authors.initials: S
authors.lastname: Nair
authors.forename: Shrimati
authors.initials: S
authors.lastname: Shetty
authors.forename: Dipika
authors.initials: D
authors.lastname: Mohanty
mesh_terms: D000293:Adolescent; D016824:Antigens, Human Platelet / Q000235:genetics* / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D039661:Integrin beta3; D007519:Isoantigens / Q000235:genetics*; D008297:Male; D040201:Platelet Membrane Glycoprotein IIb / Q000378:metabolism; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D011485:Protein Binding; D013915:Thrombasthenia / Q000235:genetics* / Q000276:immunology
chemical_list: D016824:Antigens, Human Platelet; C061248:ITGB3 protein, human; D039661:Integrin beta3; D007519:Isoantigens; D040201:Platelet Membrane Glycoprotein IIb; D005340:Fibrinogen