Glanzmann's Thrombasthenia , Correlation by Flow , Platelet Aggregometry and Platelet Function Assay ( PFA )

Epistaxis in children is one of the important presenting symptoms for attending emergency department in paediatric patients. Recurrent epistaxis is common in children. Although epistaxis in children usually occurred due to different benign conditions, it may be one of the important presenting symptoms of some inherited bleeding disorder. Whereas most bleeding disorders can be diagnosed through different standard hematologic assessments, diagnosing rare platelet function disorders may be challenging. In this article we describe one case report of platelet function disorders on Glanzmann’s thrombasthenia (GT). Our patient was a 10-year old girl who presented to us with history of recurrent severe epistaxis. She had a bruise on her abdomen and many scattered petechiae in different parts of the body. Her previous investigations revealed no demonstrable haemostatic anomalies. After performing platelet aggregation test, she was diagnosed as GT.

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Absence of the Complete Platelet-Specific Alloantigens Zw (PlA) On Platelets in Glanzmann’S Thrombasthenia and the Effect of Anti-Zwa Antibody on Platelet-Function

10.1055/s-0039-1687067 ◽

1979 ◽

Author(s):

E.F. von Leeuwen ◽

G.T.E. Zonneveld ◽

L.E. von Riesz ◽

C.S.P Jenkins ◽

J.A. van Mourik ◽

...

Keyword(s):

Platelet Function ◽

Gel Electrophoresis ◽

Family Members ◽

Glanzmann’S Thrombasthenia ◽

Platelet Membranes ◽

Glanzmann's Thrombasthenia ◽

The Family ◽

Induced Aggregation ◽

Aggregation Of Platelets ◽

Slight Inhibition

The expression of the platelet-speciftc alloantigens on the platelets from 6 patients with Glanzmann’s Thrombasthenia (G.T.) and their nearest relatives was studied. The alloantigens Zwa (PIAl) and Zwb(PIA2) were found to be completely absent from thrombasthenic platelets while the alloantigens of the Ko-system were found to be normally expressed. The alloantigen Baka(phenotypefrequency 90.2%) was absent on the platelets from 4 studied G.T. patients. The platelets of all the family members reacted positively with anti-Zwa, negatively with antt-Zwb serum. SDS-PA gel electrophoresis of G.T. platelet membranes demonstrated a marked deficiency of the glycoproteins IIb and IIIa. Glycoprotein analysis of the platelet membranes from the family members of 3 of the 6 patients reveoled no apparent abnormalities.Pre-incubation with anti-Zwa containing plasma strongly inhibits ADP-and collagen induced aggregation of platelets from normal Zwa homozygous individuols with a slight inhibition of the aggregation induced by ristocetin. Zwa antibodies did not affect the functions of platelets from ZWb homozygous individuals. Thus binding of Zwa antibodies induces a thrombosthenis-like state.

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Case 6: A 2-year-old boy with mucocutaneous bleeding – Glanzmann’s Thrombasthenia. The role of the fibrinogen-receptor glycoprotein IIb–IIIa in platelet function

Therapeutische Umschau ◽

10.1024/0040-5930.56.9.495 ◽

1999 ◽

Vol 56 (9) ◽

pp. 495-498

Author(s):

Alberio ◽

Hirt

Keyword(s):

Platelet Function ◽

Glanzmann’S Thrombasthenia ◽

Fibrinogen Receptor ◽

Glanzmann's Thrombasthenia ◽

Diagnostik Und Therapie ◽

Mucocutaneous Bleeding

Der Fall eines Patienten mit einer seit Geburt vorhandenen mukokutanen Blutungsneigung wird vorgestellt. Es wurde eine Thrombasthenie Glanzmann diagnostiziert. An diesem Beispiel werden wichtige Aspekte der Diagnostik und Therapie von Thrombozytenfunktionsstörungen beschrieben. Zudem wer-den die Thrombozytenbeteiligung im Blutstillungsvorgang sowie die Rolle des thrombozytären Fibrinogen-Rezeptors Glykoprotein IIb–IIIa im Rahmen der primären Hämostase dargestellt.

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PARTIAL PLATELET FUNCTION DEFECT IN A VARIANT OF GLANZMANN'S THROMBASTHENIA WITH INTERMEDIATE LEVELS OF GP IIb/IIIa

10.1055/s-0038-1644743 ◽

1987 ◽

Author(s):

R M Hardisty ◽

A Pannocchia ◽

N Mahmood ◽

T J C Nokes ◽

D Pidard ◽

...

Keyword(s):

Platelet Function ◽

Binding Sites ◽

Adenine Nucleotide ◽

Bleeding Tendency ◽

Binding Studies ◽

Platelet Factor ◽

Glanzmann’S Thrombasthenia ◽

Fibrinogen Binding ◽

Glanzmann's Thrombasthenia ◽

Sds Page

A 17-year-old Italian boy has had a lifelong bleeding tendency, with frequent epistaxes and gum bleeding. The bleeding time is prolonged and the platelet count low normal. Electron microscopy showed a wide diversity of platelet size with many giant forms. In citrated PRP, ADP and other agonists induce slow and incomplete aggregation. The response of washed platelets varied with the agonist but ranged from subnormal to almost normal. Fibrinogen binding to washed platelets occurred slowly in response to ADP but eventually approached normal levels. No significant abnormality was observed of 5HT uptake, adenine nucleotide content, platelet factor-3 availability, β-thromboglobulin content or release, or malonyldialdehyde production. Clot retraction was normal. SDS-PAGE showed reduced amounts of GPIIb and GPU Ia. Crossed immunoelectrophoresis of Triton X-100 extracts of washed platelets showed the presence of GPIIb/IIIa complexes at 25-50% of normal levels. SDS-PAGE combined with an immunoblot procedure confirmed unchanged mobilities of GPIIb and GPIIIa and a normal proportion of GPIIb to GPIIIa. However, binding studies with radiolabelled monoclonal antibodies showed that intact washed platelets expressed only 12-20% of the normal binding sites for M148, AP-2 and Tab. These antibodies recognize different epitopes on GPIIb/lIIa complexes. Similar levels of these glycoproteins were detected by autoradiography after SDS-PAGE of radio-iodinated patient's platelets. GP lb was normally present. A possible defect in the exposure of fibrinogen binding sites might contribute to the altered platelet function. Meanwhile, the patient appears to be a unique variant of Glanzmann's thrombasthenia with GP IIb/IIIa complexes at the borderline of those able to support platelet aggregation.

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Platelet function assessment in Glanzmann's thrombasthenia

British Journal of Anaesthesia ◽

10.1093/bja/aef545 ◽

2002 ◽

Vol 89 (3) ◽

pp. 525-525 ◽

Cited By ~ 1

Author(s):

W. Marchant

Keyword(s):

Platelet Function ◽

Glanzmann’S Thrombasthenia ◽

Glanzmann's Thrombasthenia ◽

Function Assessment

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Platelet Function, Ultrastructure and Management in Glanzmann’s Thrombasthenia

10.1055/s-0039-1680788 ◽

1977 ◽

Author(s):

J.M. Lusher ◽

M.I. Barnhart ◽

J. Pullen ◽

A.I. Warrier

Keyword(s):

Electron Microscopy ◽

Platelet Function ◽

Surface Membrane ◽

Severe Bleeding ◽

Contact Activation ◽

Clot Retraction ◽

Platelet Function Test ◽

Platelet Factor ◽

Glanzmann’S Thrombasthenia ◽

Glanzmann's Thrombasthenia

This exhibit will demonstrate laboratory abnormalities found in longitudinal studies on six patients with Glanzmann’s thrombasthenia. All have had mucous membrane bleeding (predominantly epistaxis) since infancy. In addition to prolonged bleeding times, absent clot retraction and little or no platelet retention in a glass bead column, all six have defective platelet factor 3 release with Kaolin and their platelets do not aggregate with ADP, epinephrine or collagen. The platelets of all six do aggregate with ristocetin, however. Transmission electron microscopy (TEM) of thin sectioned platelets revealed normal ultrastructure. However, in the TEM platelet function test (Thromb. Diath. Haemorrh., Suppl. 42:321-344, 1970) there was difficulty in capturing the thrombasthenic platelets even on the formvar surface. Those platelets which did adhere to the formvar exhibited normal percentages of dendritic and spread forms although pseudopod detail was unusual. Inspection by scanning electron microscopy (SEM) of surfaces of platelets responding to contact activation and captured on companion formvar coverslips revealed surface membrane features consistent with inhibition of membrane activation. Platelets were swollen with convoluted membranes while pseudopod outgrowth from discrete regions was not prominent. Suppression of membrane activation was also noted by SEM of platelets obtained by cytocentrifugation of buffy coat preparations. Upon exposure to collagen platelet adhesion and morphologic features of aggregation were abnormal under our test conditions.In addition to local measures, recommended management of severe bleeding episodes is infusion of single donor platelet concentrates, obtained from an HLA matched donor by plateletpheresis.

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Epistaxis as a Common Presenting Symptom of Glanzmann’s Thrombasthenia, a Rare Qualitative Platelet Disorder: Illustrative Case Examples

Case Reports in Emergency Medicine ◽

10.1155/2017/8796425 ◽

2017 ◽

Vol 2017 ◽

pp. 1-6 ◽

Cited By ~ 1

Author(s):

Michael Recht ◽

Meera Chitlur ◽

Derek Lam ◽

Syana Sarnaik ◽

Madhvi Rajpurkar ◽

...

Keyword(s):

Platelet Function ◽

Case Reports ◽

Microcytic Anemia ◽

Laboratory Evaluation ◽

Illustrative Case ◽

Glanzmann’S Thrombasthenia ◽

Glanzmann's Thrombasthenia ◽

Platelet Function Disorders ◽

Platelet Disorder ◽

Recurrent Epistaxis

Children often present to emergency departments (EDs) with uncontrollable nose bleeding. Although usually due to benign etiologies, epistaxis may be the presenting symptom of an inherited bleeding disorder. Whereas most bleeding disorders are detected through standard hematologic assessments, diagnosing rare platelet function disorders may be challenging. Here we present two case reports and review diagnostic and management challenges of platelet function disorders with a focus on Glanzmann’s thrombasthenia (GT). Patient 1 was a 4-year-old boy with uncontrolled epistaxis. His medical history included frequent and easy bruising. Previous laboratory evaluation revealed only mild microcytic anemia. An otolaryngologist stopped the bleeding, and referral to a pediatric hematologist led to the definitive diagnosis of GT. Patient 2 was a 2.5-year-old girl with severe epistaxis and a history of milder recurrent epistaxis. She had a bruise on her abdomen with a palpable hematoma and many scattered petechiae. Previous assessments revealed no demonstrable hemostatic anomalies. Platelet aggregation studies were performed following referral to a pediatric hematologist, leading to the diagnosis of GT. As evidenced by these cases, the ED physician may often be the first to evaluate severe or recurrent epistaxis and should recognize indications for coagulation testing and hematology consultation/referral for advanced hematologic assessments.

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Inherited abnormalities of platelet glycoproteins

Philosophical Transactions of the Royal Society of London Series B Biological Sciences ◽

10.1098/rstb.1981.0106 ◽

1981 ◽

Vol 294 (1072) ◽

pp. 281-290 ◽

Cited By ~ 2

Keyword(s):

Platelet Aggregation ◽

Platelet Function ◽

Membrane Glycoproteins ◽

Blood Disorders ◽

Glanzmann’S Thrombasthenia ◽

Glanzmann's Thrombasthenia ◽

Bernard Soulier Syndrome

Glanzmann’s thrombasthenia and the Bernard-Soulier syndrome are inherited blood disorders characterized by abnormalities in different aspects of platelet function during haemostasis. Platelets from patients with thrombasthenia do not aggregate in response to the normal physiological platelet aggregation inducing stimuli, while Bernard-Soulier platelets have a reduced capacity to adhere to exposed subendothelium. Deficiencies of different membrane glycoproteins have been located in the platelets of both disorders and suggest specific roles for membrane glycoproteins in different aspects of platelet function.

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Glanzmann's Thrombasthenia: A rare platelet functional disorder

Faridpur Medical College Journal ◽

10.3329/fmcj.v15i2.53898 ◽

2021 ◽

Vol 15 (2) ◽

pp. 103-105

Author(s):

Muhammad Kamruzzaman ◽

Mohammad Iqbal Hossain ◽

Mohammad Ashiqur Rahman ◽

Sharifunnesa

Keyword(s):

Supportive Care ◽

Platelet Function ◽

Platelet Transfusion ◽

Autosomal Recessive ◽

Good Prognosis ◽

Bleeding Disorder ◽

Functional Disorder ◽

Glanzmann Thrombasthenia ◽

Glanzmann’S Thrombasthenia ◽

Glanzmann's Thrombasthenia

Glanzmann's Thrombasthenia (GT) is a rare inherited autosomal recessive platelet functional disorder. Due to the deficiency of platelet function, it manifests as a bleeding disorder characterized by mucocutaneous hemorrhage of varying severity. It is difficult to diagnose as it closely mimics with others bleeding disorder, so it can be diagnosed after investigations & exclusion of others. Treatment is supportive care with platelet transfusion & proper counseling. With careful supportive care, GT has a very good prognosis. In this report, we describe a 13 years old female with Glanzmann Thrombasthenia. Faridpur Med. Coll. J. 2020;15(2): 103-105

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Detection of the Glanzmann's Thrombasthenia Mutations in Arab and Iraqi-Jewish Patients by Polymerase Chain Reaction and Restriction Analysis of Blood or Urine Samples

Thrombosis and Haemostasis ◽

10.1055/s-0038-1646446 ◽

1991 ◽

Vol 66 (04) ◽

pp. 500-504 ◽

Cited By ~ 28

Author(s):

H Peretz ◽

U Seligsohn ◽

E Zwang ◽

B S Coller ◽

P J Newman

Keyword(s):

Polymerase Chain Reaction ◽

Base Pair ◽

Restriction Analysis ◽

Urine Samples ◽

Chain Reaction ◽

Base Pairs ◽

Glanzmann’S Thrombasthenia ◽

Glanzmann's Thrombasthenia ◽

Base Pair Deletion ◽

Polymerase Chain

SummarySevere Glanzmann's thrombasthenia is relatively frequent in Iraqi-Jews and Arabs residing in Israel. We have recently described the mutations responsible for the disease in Iraqi-Jews – an 11 base pair deletion in exon 12 of the glycoprotein IIIa gene, and in Arabs – a 13 base pair deletion at the AG acceptor splice site of exon 4 on the glycoprotein IIb gene. In this communication we show that the Iraqi-Jewish mutation can be identified directly by polymerase chain reaction and gel electrophoresis. With specially designed oligonucleotide primers encompassing the mutation site, an 80 base pair segment amplified in healthy controls was clearly distinguished from the 69 base pair segment produced in patients. Patients from 11 unrelated Iraqi-Jewish families had the same mutation. The Arab mutation was identified by first amplifying a DNA segment consisting of 312 base pairs in controls and of 299 base pairs in patients, and then digestion by a restriction enzyme Stu-1, which recognizes a site that is absent in the mutant gene. In controls the 312 bp segment was digested into 235 and 77 bp fragments, while in patients there was no change in the size of the amplified 299 bp segment. The mutation was found in patients from 3 out of 5 unrelated Arab families. Both Iraqi-Jewish and Arab mutations were detectable in DNA extracted from blood and urine samples. The described simple methods of identifying the mutations should be useful for detection of the numerous potential carriers among the affected kindreds and for prenatal diagnosis using DNA extracted from chorionic villi samples.

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