Alloimmunization in Congenital Deficiencies of Platelet Surface Glycoproteins: Focus on Glanzmann's Thrombasthenia and Bernard–Soulier's Syndrome

2018 ◽  
Vol 44 (06) ◽  
pp. 604-614 ◽  
Author(s):  
Roseline d'Oiron ◽  
Man-Chiu Poon
Keyword(s):  
Platelet Transfusion ◽  
Clinical Laboratory ◽  
Human Leukocyte ◽  
Factor Vii ◽  
Platelet Glycoprotein ◽  
Recombinant Activated Factor Vii ◽  
Platelet Surface ◽  
Glanzmann’S Thrombasthenia ◽  
Platelet Antibodies ◽  
Glanzmann's Thrombasthenia

AbstractGlanzmann's thrombasthenia (GT) and Bernard–Soulier's syndrome (BSS) are well-understood congenital bleeding disorders, showing defect/deficiency of platelet glycoprotein (GP) IIb/IIIa (integrin αIIbβ3) and GPIb-IX-V complexes respectively, with relevant clinical, laboratory, biochemical, and genetic features. Following platelet transfusion, affected patients may develop antiplatelet antibodies (to human leukocyte antigen [HLA], and/or αIIbβ3 in GT or GPIb-IX in BSS), which may render future platelet transfusion ineffective. Anti-αIIbβ3 and anti-GPIb-IX may also cross the placenta during pregnancy to cause thrombocytopenia and bleeding in the fetus/neonate. This review will focus particularly on the better studied GT to illustrate the natural history and complications of platelet alloimmunization. BSS will be more briefly discussed. Platelet transfusion, if unavoidable, should be given judiciously with good indications. Patients following platelet transfusion, and women during and after pregnancy, should be monitored for the development of platelet antibodies. There is now a collection of data suggesting the safety and effectiveness of recombinant activated factor VII in the management of affected patients with platelet antibodies.

Glanzmann’s thrombasthenia (defective platelet integrin αIIb-β3): proposals for management between evidence and open issues

2009 ◽  
Vol 102 (12) ◽  
pp. 1157-1164 ◽  
Author(s):  
Giovanni Di Minno ◽  
Matteo Di Minno ◽  
Man-Chiu Poon ◽  
Antonio Coppola
Keyword(s):  
Clinical Management ◽  
Factor Vii ◽  
Major Surgery ◽  
Clinical Settings ◽  
Minor Bleeding ◽  
Antifibrinolytic Agents ◽  
Recombinant Activated Factor Vii ◽  
Platelet Surface ◽  
Glanzmann’S Thrombasthenia ◽  
Glanzmann's Thrombasthenia

SummaryGlanzmann’s Thrombasthenia (GT) is a rare autosomal recessive bleeding disorder, characterized by a quantitative or qualitative defect of platelet surface αIIb-β3 integrin. Presently, no specific guideline/algorithm for clinical management for GT is available. Due to the rarity and heterogeneity of inherited platelet abnormalities, recommendations and guidelines are based on reports from opinions and clinical experience of panel of experts, and refer to the general management of platelet disorders. Based on the limited evidence in the area and on the strategies in clinical settings of inherited/acquired platelet defects, proposals for management of minor bleeding; moderate/major bleeding unresponsive to conservative management; major surgery; minor surgery and dental procedures for GT patients without, or with anti-platelet isoantibodies are reported. In addition to life-style advices and continuous patient education programs, when and how to employ/combine local measures, antifibrinolytic agents, hormone treatment, platelet transfusions and recombinant activated Factor VII is described. The prospective collection of treatments in GT patients recently established (Glanzmann’s Thrombasthenia Registry, GTR), based on a careful definition of clinical settings and outcomes, is likely to provide newer insight for optimising clinical management in GT.

scholarly journals Type-1 Glanzmann’s thrombasthenia: a rare cause of epistaxis in a child

2021 ◽  
Vol 8 (2) ◽  
pp. 374
Author(s):  
Saumil M. Patel ◽  
Rekha Thaddanee ◽  
Ajeet Kumar Khilnani ◽  
Gurudas Khilnani
Keyword(s):  
Adenosine Diphosphate ◽  
Membrane Receptors ◽  
Factor Vii ◽  
Definitive Treatment ◽  
Cell Transplant ◽  
Recombinant Activated Factor Vii ◽  
Platelet Surface ◽  
Glanzmann’S Thrombasthenia ◽  
Glanzmann's Thrombasthenia ◽  
Recurrent Epistaxis

Glanzmann’s thrombasthenia (GT) is a rare genetic platelet surface disorder of glycoprotein IIb/IIIa receptor presenting with muco-cutaneous bleeding of varying severity. We are reporting an unusual case of a child presenting with recurrent epistaxis with prolonged bleeding time, moderate thrombocytopenia and giant platelet size. GT was suspected because the platelet aggregation was abnormal with adenosine diphosphate, epinephrine, collagen, and thrombin; but normal with ristocetin. Diagnosis was confirmed by flow cytometry which showed deficiency of platelet membrane receptors CD 41 (Gp IIb) and CD 61 (GpIIIa) with normal expression of CD 42b (GpIb). Platelets transfusions and antifibrinolytics were given to manage bleeding. Due to repeat platelets transfusions patients with GT can develop anti-platelet antibodies for which rFVIIa (recombinant activated factor VII) is effective. Definitive treatment includes stem cell transplant or gene therapy.

GLANZMANN'S THROMBASTHENIA: HEMOSTATIC EFFECTIVENESS OF PLASMA CRYOPRECIPITATE TRANSFUSION

1987 ◽  
Author(s):  
W L Nichols ◽  
T M Habermann ◽  
S E Kaese ◽  
E J W Bowie
Keyword(s):  
Topical Therapy ◽  
Platelet Glycoprotein ◽  
Type I ◽  
Glanzmann’S Thrombasthenia ◽  
Platelet Antibodies ◽  
Glanzmann's Thrombasthenia ◽  
Before And After ◽  
Severe Epistaxis ◽  
Initial Hospitalization ◽  
Apheresis Platelets

A 39-year-old 75 kg man with Type I Glanzmann's thrombasthenia developed recurring severe therapy-refractory nosebleeds, associated with nasal septal deformity, synechial scarring, and previous radiotherapy. During a 21 month period he required 16 hospitalizations for treatment of severe epistaxis. At initial hospitalization it was observed that his epistaxis ceased shortly after transfusion of 10 bags (units) of plasma cryoprecipitate (cryo), although transfusion with HLA-matched apheresis platelets from 3 donors, and topical therapy (cautery, packing), had been ineffective. Serum anti-platelet antibodies were not detectable by indirect immunofluorescence. During 9 subsequent hospitalizations his epistaxis stopped promptly (usually within 1 hour) following cryo transfusion (10 or 20 bags), including 6 occasions when cryo was the only therapy. On 6 additional occasions his epistaxis did not stop following cryo transfusion, but did stop after subsequent platelet transfusions or topical therapy. Eventually he underwent nasal septal reconstructive surgery surgery, and severe epistaxis has not recurred. Hemostatic studies, before and after cryo transfusions on 5 occasions, did not show improvement of platelet aggregation defects nor of Ivy bleeding times, although occasionally the volume of blood emanating from bleeding time punctures appeared decreased following cryo transfusion. Platelet glycoprotein (GP) IIb/IIIa antigen was measured in aliquots of 10 of the pools of cryo received by the patient (representing 100 bags of total volume 2200 ml), using an immunoradiometric assay (Nichols et al, Blood 68:300a, 1986). On average, the transfused cryo pools contained GP IIb/IIIa equivalent to 1.1 x 108 platelets/ml (range 0.6-1.7 x 108/ml. Our recently reported studies of blood bank cryo documented similar GP IIb/IIIa levels, and revealed that >93% of GP IIb/IIIa in cryo is present in the form of sedimentable membranous platelet macroparticles and microparticles. We hypothesize that the GPIIb/IIla-bearing platelet particles in transfused cryo might account for the improvement in hemostasis we frequently observed. We conclude that cryo transfusion deserves further study as a potentially useful therapeutic adjunct in promoting hemostasis in individuals with Glanzmann's thrombasthenia.

scholarly journals A Cys374Tyr homozygous mutation of platelet glycoprotein IIIa (beta 3) in a Chinese patient with Glanzmann's thrombasthenia

Blood ◽  
1996 ◽  
Vol 88 (5) ◽  
pp. 1666-1675 ◽  
Author(s):  
CM Grimaldi ◽  
F Chen ◽  
LE Scudder ◽  
BS Coller ◽  
DL French
Keyword(s):  
Platelet Aggregation ◽  
Receptor Expression ◽  
Hunan Province ◽  
Initial Slope ◽  
Platelet Glycoprotein ◽  
Homozygous Mutation ◽  
Binding Studies ◽  
Platelet Surface ◽  
Glanzmann’S Thrombasthenia ◽  
Glanzmann's Thrombasthenia

A 20-year-old woman from a consanguineous family in the Hunan Province of the People's Republic of China was diagnosed as having Glanzmann's thrombasthenia based on (1) nearly a lifelong history of epistaxis, gum bleeding, petechiae, and purpura; (2) severe menorrhagia resulting in anemia and need for whole-blood transfusion; (3) normal coagulation assays; (4) prolonged bleeding time; (5) absent clot retraction; (6) decreased glass bead retention; (7) absent platelet aggregation in response to adenine diphosphate, epinephrine, and collagen; and (8) normal initial slope of platelet aggregation in response to ristocetin, but with a diminished maximal extent. The patient's platelets had a decreased level of platelet fibrinogen, but the deficiency was not as severe as in other Glanzmann's thrombasthenia patients. As judged by monoclonal antibody binding studies, surface glycoprotein (GP) IIb/IIIa (alpha IIb beta 3) expression was less than 15% of normal and alpha v beta 3 vitronectin receptor expression was 15% to 19% of normal, suggesting that the defect was in GPIIIa (beta 3). Immunoblotting of platelet lysates demonstrated decreased levels of GPIIb (approximately 30% to 35% of normal) and GPIIIa (approximately 10% of normal), and the GPIIb had undergone normal maturational processing into GPIIb heavy and light chains. Sequence analysis of the patient's GPIIIa RNA identified a G to A mutation at nucleotide 1219, predicting a Cys to Tyr substitution at residue 374. The patient's parents, who are first cousins, are asymptomatic and have only minor reductions in platelet aggregation. Direct sequencing of polymerase chain reaction-amplified cDNA and GPIIIa exon VIII indicated that the patient is homozygous and her parents are heterozygous for the mutation. Transient transfection studies in Chinese hamster ovary cells indicated that the mutation results in an 85% to 90% reduction in GPIIb/IIIa surface expression, but these cells retain the ability to mediate adhesion to immobilized fibrinogen. The relative preservation of platelet fibrinogen despite the very low level of platelet surface GPIIb/IIIa expression in this patient raises some interesting questions regarding the mechanism of fibrinogen uptake and the pathophysiology of Glanzmann's thrombasthenia.

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