Glanzmann’s thrombasthenia: strategies for identification and management

ABSTRACT

Introduction: Glanzmann’s thrombasthenia (GT) is a rare inherited platelet disorder with deficient/dysfunctional fibrinogen receptor αIIbβ3 important for platelet aggregation. Bleeding is mostly mucocutaneous, but can be severe.

Area covered: We review the pathobiology, diagnosis and management of GT. Diagnosis requires the demonstration of absent/defective platelet aggregation to physiologic stimuli but normal to ristocetin (gold standard). Flow cytometry can confirm αIIbβ3 deficiency but not dysfunction. Platelet transfusion is the standard of care for bleeding and trauma/surgery not responsive to conservative treatment, but there are potential complications with clinical consequences such as development of platelet-antibodies. Results from a previous international survey and the GT Registry suggest rFVIIa may be effective with few safety concerns in GT patients with and without platelet antibodies and/or platelet refractoriness.

Expert opinion: Whenever possible, rFVIIa should be preferred in patients with past or present platelet-antibodies and/or platelet-refractoriness or when platelet concentrates are not immediately available. rFVIIa is preferred over platelet transfusion in type I GT with severe mutation (or when molecular diagnosis is not available) to prevent anti-αIIbβ3 development. This is particularly important for women of reproductive age and prepubertal girls, given that anti-αIIbβ3 has the potential to cross the placenta during pregnancy, resulting in fetal/neonatal thrombocytopenia and bleeding.

KEYWORDS:

• Glanzmann’s thrombasthenia
• diagnosis
• management
• platelet transfusion
• rFVIIa
• αIIbβ3 (GPIIb/IIIa)
• HLA
• Genetics

Article highlights

• Glanzmann’s thrombasthenia is one of the more common and well-understood congential bleeding disorder of platelet surface integrin αIIbβ3 (deficiency or dysfunction) with salient clinical, laboratory, biochemical and genetic features.

• Diagnosis requires platelet studies showing absent/defective aggregation to physiologic stimuli but normal agglutination to ristocetin. Deficiency (but not dysfunction) of αIIbβ3 can also be confirmed using flow cytometry.

• Management of these patients in a comprehensive care setting is important

• Platelet transfusion remains a standard of care for bleeding and for trauma/surgery unresponsive to conservative treatment – but development of anti-platelet antibodies may complicate care.

• rFVIIa is emerging as an important alternative therapeutic agent to platelet transfusion and its mechanism of action has been well studied

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Declaration of interest

MC Poon was chair of Novo Nordisk’s expert panel on the GTR (2007-2011), has been an ad hoc speaker for Bayer, Novo Nordisk, and Pfizer, has attended advisory board meetings of Biogen Idec, CSL Behring, Novo Nordisk, Octapharma, Pfizer and Shire, and received grant funding from Bayer and CSL Behring . RB Zotz was member of Novo Nordisk’s expert panel on the GTR (2007-2011), and has been a speaker for Sanofi-Aventis, LEO Pharma, GlaxoSmithKline, Bayer, Boehringer Ingelheim, Pfizer, Novo Nordisk, CSL Behring, MEDA, Novartis, Octapharma, Biotest, Wyeth, and AstraZeneca, has received fees from Biotest, CSL Behring, GlaxoSmithKline, Novartis, Sanofi-Aventis, and Wyeth, is a member of the advisory boards at Novo Nordisk, Pfizer, and Bayer, and has received research funding from CSL Behring. G Di Minno was member of Novo Nordisk’s expert panel on the GTR (2007-2011) and has been a speaker or a member of a speakers’ bureau for Boehringer Ingelheim, Sanofi-Aventis, Bayer, Novo Nordisk, Pfizer, Biotest, and Grifols, and has also acted as a consultant or ad hoc speaker/consultant for Boehringer Ingelheim, Eli Lilly, Sanofi-Aventis, Bayer, CSL Behring, Novo Nordisk, Pfizer, Biotest, and Grifols. R d’Oiron was member of Novo Nordisk’s expert panel on the GTR (2007-2011) and has received fees or honoraria for attending advisory boards, or speaking at symposia from Baxter, Bayer, Pfizer, Sobi and CSL Behring. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This paper was not funded