Glanzmann Thrombasthenia: Perspectives from Clinical Practice on Accurate Diagnosis and Optimal Treatment Strategies

Abstract

Glanzmann thrombasthenia (GT) is a rare autosomal recessive disorder of fibrinogen-mediated platelet aggregation due to a quantitative or qualitative deficit of the α IIb β 3 integrin at the platelet surface membrane resulting from mutation(s) in ITGA2B and/or ITGB3 . Patients tend to present in early childhood with easy bruising and mucocutaneous bleeding. The diagnostic process requires consideration of more common disorders of haemostasis and coagulation prior to confirming the disorder with platelet light transmission aggregation, flow cytometry of CD41 and CD61 expression, and/or exon sequencing of ITGA2B and ITGB3 . Antifibrinolytic therapy, recombinant activated factor VII, and platelet transfusions are the mainstay of therapy, although the latter may trigger formation of anti-platelet antibodies in GT patients and inadvertent platelet-refractory disease. The management of these patients therefore remains complex, particularly in the context of trauma, labour and delivery, and perioperative care. Bone marrow transplantation remains the sole curative option, although the venue of gene therapy is being increasingly explored as a future alternative for definitive treatment of GT.

Double jeopardy, glomangiopericytoma and Glanzmann thrombasthenia resulting in recurrent epistaxis: a case report

“…Type I Glanzmann thrombasthenia as seen in our patient is characterized by less than 5% expression of the αIIbβ3 integrin and represents 62–78% of all Glanzmann thrombasthenia [6]. Screening for the pathogenic variants of the ITGA2B and ITGB3 genes confirms the diagnosis and allows for genetic counseling.…”

Glanzmann’s Thrombasthenia in a Young 11-Year-Old Girl Presenting with Menorrhagia: When to Suspect and How to Manage a Rare Disease

“…Gastrointestinal bleeding and hematuria are less common but they can lead to severe complications. Mucocutaneous bleeding can be spontaneous or occur after minimal trauma [3]. Epistaxis is the most frequent symptom especially during childhood.…”

“…The genetic diagnosis can help to improve disease management by directing genetic counseling, prenatal diagnosis, and carrier screening in asymptomatic family members, especially in regions with high consanguinity even if it is expensive (Figure 2). Management of bleeding is based on a combination of hemostatic agents including local measure such us fibrin sealants and topical thrombin, or with antifibrinolytics or desmopressin, rFVIIa with or without platelet transfusions [3]. Refractory bleeding and platelet alloimmunization are common complications during the course of the disease.…”

Glanzmann’s Thrombasthenia During Pregnancy: Case Report and Literature Review

“…[9,12] In the near future bone marrow transplant and gene therapy technology may guarantee an effective option to cure this otherwise lifelong disease. [13,14] Pregnancy and delivery should be managed in collaboration between haemophilia, anesthesia, neonatology and obstetric units. Glanzmann's thrombasthenia is characterized by an increased percentage of primary and secondary post-partum hemorrages.…”