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

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.

scholarly journals Platelet Function, Ultrastructure and Management in Glanzmann’s Thrombasthenia

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.

Detection of Carriers in Glanzmann's Thrombasthenia

1983 ◽  
Vol 49 (03) ◽  
pp. 182-186
Author(s):  
G T E Zonneveld ◽  
E F van Leeuwen ◽  
A Sturk ◽  
J W ten Cate
Keyword(s):  
Bleeding Time ◽  
Periodic Acid ◽  
Type I ◽  
Clot Retraction ◽  
Periodic Acid Schiff ◽  
Glanzmann’S Thrombasthenia ◽  
Aggregation Response ◽  
Glanzmann's Thrombasthenia ◽  
Sds Page ◽  
Reduced State

SummaryQuantitative glycoprotein (GP) analysis of whole platelets or platelet membranes was performed by SDS-polyacrylamide gelelectrophoresis (SDS-PAGE) and periodic acid Schiff staining in the families of two unrelated Glanzmann’s thrombasthenia (GT) patients. Each family consisted of two symptom free parents, a symptom free daughter and a GT daughter. All symptom free members had a normal bleeding time, clot retraction and platelet aggregation response to adenosine 5’-diphosphate (ADP), collagen and adrenalin. Platelet Zw* antigen was normally expressed in these subjects. GT patiens, classified as a type I and II subject, showed reduced amounts of GP lib and of GP nia. Analysis of isolated membranes in the non-reduced state, however, showed that the amount of GP Ilia was also reduced in three of the four parents, whereas one parent (of the GT type I patient) and the two unaffected daughters had normal amounts of GP Ilia. Quantitative SDS-PAGE may therefore provide a method for the detection of asymptomatic carriers in GT type I and II.

A Case Report on Glanzmann’s Thrombasthenia: A Rare Platelet Function Disorder

2018 ◽  
Vol 2 (02) ◽  
pp. 59-60
Author(s):  
Farida Yasmin ◽  
Md. Anwarul Karim ◽  
Chowdhury Yakub Jamal ◽  
Mamtaz Begum ◽  
Ferdousi Begum
Keyword(s):  
Case Report ◽  
Platelet Function ◽  
The Body ◽  
Presenting Symptoms ◽  
Glanzmann’S Thrombasthenia ◽  
Glanzmann's Thrombasthenia ◽  
Platelet Function Disorders ◽  
Recurrent Epistaxis ◽  
Severe Epistaxis ◽  
History Of

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.

scholarly journals Impaired function of platelet membrane glycoprotein IIb-IIIa in end-stage renal disease.

1994 ◽  
Vol 5 (1) ◽  
pp. 36-46
Author(s):  
M P Gawaz ◽  
G Dobos ◽  
M Späth ◽  
P Schollmeyer ◽  
H J Gurland ◽  
...  
Keyword(s):  
Renal Failure ◽  
Chronic Renal Failure ◽  
Platelet Aggregation ◽  
Platelet Function ◽  
Uremic Toxin ◽  
Bleeding Tendency ◽  
Fibrinogen Receptor ◽  
Fibrinogen Binding ◽  
Uremic Patients ◽  
Stage Renal Disease

Impaired platelet function and a bleeding tendency are well-recognized complications of chronic renal failure. Because the fibrinogen receptor GPIIb-IIIa plays a central role in platelet aggregation and adhesion to the subendothelium, it was reasoned that a defect in this receptor may underlie the impaired platelet function in uremia. To test this hypothesis, the function of this receptor in the platelets of 11 uremic patients was studied. Aggregation studies were performed with flow cytometric techniques with anti-GPIIb-IIIa conformation-specific monoclonal antibodies (mAb) (anti-LIBS1 and anti-PMI-1). Antifibrinogen and antithrombospondin mAb were used to characterize fibrinogen binding to GPIIb-IIIa and the release of alpha-granules, respectively. Platelets from patients with chronic renal failure showed significantly decreased binding of conformation-dependent anti-LIBS1 mAb after ADP, phorbol myristate acetate, or RGD-peptide stimulation compared with normal controls, suggesting a defect related to the ability of the fibrinogen receptor to undergo a conformational change. Moreover, antifibrinogen and antithrombospondin binding to activated platelets were reduced in uremic patients, implying impairment of both ligand-binding and alpha-granule release. Hemodialysis partially restored GPIIb-IIIa function, which may account for the observed effects of this therapy in restoring platelet aggregation. These findings indicate that platelets of patients with chronic renal failure reveal an aggregation defect at least partially due to an intrinsic GPIIb-IIIa dysfunction and the presence of a putative uremic toxin that inhibits fibrinogen binding to GPIIb-IIIa.

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

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.

Diagnosis of Heterozygotes in Glanzmann’s Thrombasthenia

1982 ◽  
Vol 48 (02) ◽  
pp. 217-221 ◽  
Author(s):  
H Stormorken ◽  
G O Gogstad ◽  
N O Solum ◽  
H Pande
Keyword(s):  
High Reliability ◽  
Type I ◽  
Bleeding Tendency ◽  
Glanzmann’S Thrombasthenia ◽  
Glanzmann's Thrombasthenia ◽  
Immunochemical Methods

SummaryA study of a family with a propositus suffering from classical thrombasthenia type I has shown that the new immunochemical methods detect heterozygotes with high reliability. There was no overlapping between heterozygotes and normals, and the concentration of the glycoprotein IIb-IIIa-complex is remarkably constant around 50–60% in the heterozygotes. Furthermore, heterozygotes as a group show an increased bleeding tendency.

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

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.

Arachidonate-Induced Fibrinogen Binding To Thrombin-Degranulated Rabbit Platelets Is Independent Of Released ADP

1981 ◽  
Author(s):  
E J Harfenist ◽  
M A Guccione ◽  
M A Packham ◽  
R L Kinlough-Rathbone ◽  
J F Mustar
Keyword(s):  
Binding Sites ◽  
Creatine Phosphokinase ◽  
Synergistic Effects ◽  
Creatine Phosphate ◽  
Dense Granule ◽  
Binding Studies ◽  
Fibrinogen Binding ◽  
Low Concentrations ◽  
Rabbit Platelets ◽  
Stimulation Of

When human or rabbit platelets are stimulated with ADP, fibrinogen (Fbg) binding sites are revealed, the platelets bind Fbg and aggregate. Since stimulation with other aggregating agents (arachidonate, collagen or ionophores) releases platelet granule contents, including ADP and Fbg, it is difficult to determine whether these agents cause aggregation or Fbg binding that is independent of ADP. Therefore we treated rabbit platelets with thrombin (0.73 U/ml) to release at least 90% of their dense granule contents, as measured by 14C-serotonin, washed and resuspended them, and studied aggregation and Fbg binding upon stimulation with ADP or arachidonate. In the presence of Fbg, thrombin-degranulated platelets (TDP) aggregate in response to ADP or arachidonate at concentrations that aggregate untreated platelets, although TDP aggregate somewhat less extensively. When TDP are aggregated with 50 μM arachidonate, they lose up to 9% of their remaining serotonin, corresponding to a concentration of ADP in the suspending medium of not more than0.06μM, which does not aggregate TDP or cause detectable Fbg binding. When creatine phosphate/creatine phosphokinase (CP/CPK) is added at a concentration that abolishes aggregation in response to 1 μM ADP, it reduces aggregation caused by arachidonate by only 18%. Binding studies with 125I-Fbg show that stimulation of TDP with either ADP or arachidonate results in specific Fbg-binding similar to the binding to ADP-stimulated normal platelets. CP/CPK almost completely inhibits binding induced by ADP but reduces binding induced by arachidonate by only 30%. Aggregation and binding studies with TDP using a combination of arachidonate with low concentrations of ADP failed to show synergistic effects. Thus arachidonate causes aggregation and Fbg binding to TDP that are independent of ADP, although the magnitude of these effects may be increased by released ADP.

Sign in / Sign up

Export Citation Format

Share Document