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.

Diversity of Glycoprotein Deficiencies in Glanzmann’s Thrombasthenia

1985 ◽  
Vol 54 (03) ◽  
pp. 626-629 ◽  
Author(s):  
M Meyer ◽  
F H Herrmann
Keyword(s):  
High Resolution ◽  
Gel Electrophoresis ◽  
Type Ii ◽  
Two Dimensional ◽  
Two Dimensional Gel Electrophoresis ◽  
Structural Variant ◽  
Glanzmann’S Thrombasthenia ◽  
Crossed Immunoelectrophoresis ◽  
Glanzmann's Thrombasthenia ◽  
Platelet Proteins

SummaryThe platelet proteins of 9 thrombasthenic patients from 7 families were analysed by high resolution two-dimensional gel electrophoresis (HR-2DE) and crossed immunoelectrophoresis (CIE). In 7 patients both glycoproteins (GPs) IIb and Ilia were absent or reduced to roughly the same extent. In two related patients only a trace of GP Ilb-IIIa complex was detected in CIE, but HR-2DE revealed a glycopeptide in the position of GP Ilia in an amount comparable to type II thrombasthenia. This GP Ilia-like component was neither recognized normally by anti-GP Ilb-IIIa antibodies nor labeled by surface iodination. In unreduced-reduced two-dimensional gel electrophoresis two components were observed in the region of GP Ilia. The assumption of a structural variant of GP Ilia in the two related patients is discussed.

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.

Additional Glycoprotein Defects In Glanzmann’s Thrombasthenia Platelets

1981 ◽  
Author(s):  
J L McGregor ◽  
K J Clemetson ◽  
E James ◽  
A Capitanio ◽  
M Dechavanne ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Gel Electrophoresis ◽  
Lens Culinaris ◽  
Polyacrylamide Gel Electrophoresis ◽  
Sodium Dodecyl ◽  
Platelet Surface ◽  
Glanzmann’S Thrombasthenia ◽  
Healthy Donors ◽  
Glanzmann's Thrombasthenia ◽  
Dimensional Electrophoresis

Glanzmann’s thrombasthenia (G.T.) platelets are deficient in 2 major membrane GP (IIb and IIIa). In order to investigate if these are the only defects in this disorder, platelets from G.T. patients and from healthy donors were isolated, washed and surface-labelled by techniques specific for protein or for sugars (sialic acid or penultimate galactose/N-acetylgalactosamine residues). Labelled or unlabelled platelets were solubilized in sodium dodecyl sulphate (SDS) and separated by 2-dimensional polyacrylamide gel electrophoresis, first according to isoelectric point and then according to molecular weight. Glycoproteins from unlabelled platelets separated by 2-dimensional electrophoresis were identified by binding of 125I-labelled Lens culinaris lectin (mannose, glucose specific) GPIIbA1 and IIIaA1 were absent in one G.T. patient while in others lower amounts of 2 GP were found in positions similar to these GP. Major membrane GP (IbA1, IbA2, IbB1 and IIIbA1) had more intensely labelled terminal sialic acid moieties in G.T. platelets than in normals. A major membrane GP designated Ic had an altered pi and its penultimate galactose/N-acetyl galactosamine residues labelled more intensely in G.T. platelets than in controls. One high M.Wt. GP and a number of lower M.Wt. GP (IVa, IVb and VII) normally found in platelets of healthy donors were absent in G.T. platelets. These results indicate strongly that there is a major perturbation of the platelet surface in G.T.

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.

THE ARG-GLY-ASP(SER) SEQUENCE OF FIBRONECTIN, AND THE GLYCOPROTEIN IIB-IIIA COMPLEX ARE NOT INVOLVED IN FIBRONECTIN DEPENDENT PLATELET ADHESION IN FLOW

1987 ◽  
Author(s):  
P F E M Nievelstein ◽  
M Ottenhof-Rovers ◽  
M D Pierschbacher ◽  
J J Sixma
Keyword(s):  
Platelet Adhesion ◽  
Cell Attachment ◽  
Blood Platelets ◽  
Attachment Site ◽  
Type I ◽  
Shear Rates ◽  
Glanzmann’S Thrombasthenia ◽  
Glanzmann's Thrombasthenia ◽  
Static Conditions ◽  
Induced Aggregation

Activated blood platelets interact with fibronectin through it to the glycoprotein IIb-IIIa(GPIIb-IIIa)-complex. The cell attachment site of fibronectin with its crucial arg-gly-asp-(-ser) (RGD(S))sequence is involved in this binding. We have studied the importance of this interaction for the fibronectin dependence of platelet adhesion under flow conditions. An RGDS-containing hexapeptide (GRGDSP) was compared with a non-reactive control peptide (GRGESP). The GRGDSP-peptide inhibited thrombin induced aggregation and adhesion under static conditions at 0.1 mM. This concentration had no effect on platelet adhesion to nonfibrillar collagen type I in flow. GRGDSP at 1 mM had a significant inhibitory effect at 1500 s™1 (8.8 ± 1.4 111In platelets* 105 /cm2, versus 19.8 ± 0.5 for the control). At lower shear rates of 800 and 300 s™1 , where platelet adhesion is also fibronectin dependent, no significant differences were obtained (respectively 11.7 ± 1.1 versus 15.2 ± 2.1, and 11.4 ± 1.0 versus 13.1 ± 0.7).The relation between GPIIb-IIIa and fibronectin dependence was investigated with platelets of a patient with Glanzmann’s thrombasthenia and monoclonal antibodies to GPIIb-IIIa, using endothelial cell matrix (ECM) as a surface. Platelets of normal controls or a patient with Glanzmann’s thrombasthenia showed a inhibition of adhesion in fibronectin free plasma, after the ECM had been preincubated with anti-fibronectin F(ab’)2, of respectively _J5 and 30 percent at 300 s™1 , and 43 and 65 percent at 1300 s™1 . Incubation of platelets with anti GPIIb-IIIa showed inhibition of platelet adhesion at high shear rates. Dependence on fibronectin for platelet adhesion was still observed, even though separate experiments had shown that these anti GPIIb-IIIa antibodies could block binding of radiolabeled fibronectin to thrombin activated platelets. These data suggest the existence of a second binding system from the RGD/GPIIb-IIIa system separate for the interaction of platelets with fibronectin, which may only function when fibronectin is present on a surface.

Crossed Immunoelectrophoresis In The Identification Of Platelet Membrane Glycoproteins And Complexes

1981 ◽  
Author(s):  
S Karpatkin ◽  
S Shulman ◽  
L Howard ◽  
S Sadanandan
Keyword(s):  
Concanavalin A ◽  
Surface Antigens ◽  
Platelet Membrane ◽  
Surface Proteins ◽  
Membrane Glycoproteins ◽  
Glanzmann’S Thrombasthenia ◽  
Crossed Immunoelectrophoresis ◽  
Platelet Membranes ◽  
Glanzmann's Thrombasthenia ◽  
Major Antigen

Human platelet membranes were solubilized in 1% Triton X-100 and subjected to crossed immunoelectrophoresis, employing a rabbit anti-piatelet membrane antibody. Ten different antigens were observed fairly consistently; one could be identified as albumin, the other as fibrinogen. Surface antigens were determined by antibody adsorbtion experiments, and cell surface labeling with 125I-lactoperoxidase. Four surface antigens reacted with concanavalin A, when this was employed as an intermediate spacer gel. A major surface antigen, 10, was present on all preparations and was inversely related to antigens 13 and 18, which moved more cathodally. Membranes from preparations with full 10 antigen peaks had absent or diminished 13 and 18 antigen peaks, whereas preparations with absent to incomplete cathodal curves had increased 13 and 18 antigen peaks. Digestion of intact washed platelets with α chymotrypsin resulted in a decrease in the 10 antigen peak and an increase in 13 and 18, suggesting a structural relationship. Extraction of platelet membranes in EDTA or EGTA resulted in the disappearance of 10 and appearance of 13 and 18 (which react with concanavalin A) and 15 and 16 (which do not). Splitting of the major antigen into 13, 18, 15 and 16 could be prevented by addition of excess Ca++ relative to EGTA (but not by excess Mg++). Similar results were obtained in the absence of chelating agents following dialysis at 60-200 hrs against ‘Ca++-free’ buffer. Five patients with Glanzmann’s thrombasthenia have been studied. All k components of the major membrane antigen are missing. We conclude that the major antigen, 10, is composed of 2 glycoproteins, 13 and 18, and 2 other surface proteins, 15 and 16, which are held together by Ca++. It is conceivable that patients with Glanzmann’s thrombasthenia are lacking a membrane receptor for Ca++ or the platelet membrane (glyco)protein which anchors these A components.

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.

Effects of Ticlopidine and Indobufen on Platelet Aggregation Induced by A23187 and Adrenaline in the Presence of Different Anticoagulants

1989 ◽  
Vol 17 (6) ◽  
pp. 514-520 ◽  
Author(s):  
C. Cimminiello ◽  
M. Milani ◽  
T. Uberti ◽  
G. Arpaia ◽  
G. Bonfardeci
Keyword(s):  
Platelet Aggregation ◽  
Platelet Function ◽  
Sodium Citrate ◽  
Platelet Rich Plasma ◽  
Antiplatelet Agents ◽  
Ionophore A23187 ◽  
Tyrode Solution ◽  
Low Levels ◽  
Induced Aggregation ◽  
Aggregation Of Platelets

As Ca2+ is known to play a fundamental role in platelet function, the effect of combining two platelet aggregating agents (adrenaline and the ionophore A23187) with different effects on Ca2+ was studied at levels subthreshold for aggregation using platelet-rich plasma from eight atherosclerotic patients. Adrenaline lowered the A23187 threshold required to induce aggregation. The effects of treating patients with the antiplatelet agents, indobufen and ticlopidine, on A23187 and adrenaline induced aggregation of platelets prepared in hirudin or sodium citrate was also evaluated. Aggregation was also studied using platelets resuspended in Ca2+-free and Ca2+-enriched Tyrode solution. Before treatment hirudin treated platelet-rich plasma, which has physiological extraplatelet Ca2+ levels, was more sensitive to A23187 and adrenaline than was citrated platelet-rich plasma, which has suppressed Ca2+ levels. Ticlopidine significantly raised the concentration of A23187 required to induce aggregation in citrated but not hirudin treated platelet-rich plasma. Indobufen did not significantly affect A23187 induced aggregation. Ticlopidine acts by inhibiting the glycoprotein IIb – IIIa complex on the platelet membranes. Low levels of extracellular Ca2+ and ticlopidine may act synergistically to reduce the aggregatory response of stimulated platelets.

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