Glanzmann Thrombasthenia

Hematology

OverviewWhoPresentationMechanismWorkupManagementPivots

Illness script · Hematology

Glanzmann Thrombasthenia

Autosomal recessive deficiency/dysfunction of platelet GPIIb/IIIa (αIIbβ3) causing failure of platelet aggregation despite normal platelet count.

This illness script for Glanzmann Thrombasthenia covers predisposing factors, classic presentation, mechanism, workup, management, and the clinical pivots that separate it from look-alikes—written for USMLE Step 1 and clerkship reasoning.

Updated Aug 16, 2026All scripts

01

Predisposing factors

  • Autosomal recessive inheritance; consanguineous families at highest risk
  • Enriched in Middle Eastern, South Asian, and Roma (Gypsy) populations
  • Presents in early childhood with first hemostatic challenge
  • Affects males and females equally
  • Rare (~1 per million), but most common inherited platelet function disorder

02

Presentation

  • Mucocutaneous bleeding: epistaxis, gingival bleeding, petechiae, easy bruising
  • Menorrhagia is a major presenting symptom in adolescent females
  • Onset in infancy/childhood, often triggered by minor trauma or dental procedures
  • Normal platelet count and normal platelet morphology on peripheral smear
  • Prolonged bleeding time; normal PT and aPTT
  • Absent clot retraction (GPIIb/IIIa also mediates clot retraction)

03

Pathophysiology

  • GPIIb/IIIa (αIIbβ3 integrin) is absent or nonfunctional on platelet surface
  • GPIIb/IIIa is the obligate receptor for fibrinogen cross-linking between platelets
  • Without fibrinogen bridging, platelets cannot aggregate despite normal adhesion
  • Platelet adhesion via GPIb–vWF axis is intact; aggregation step is the sole defect

04

Diagnostics

  • Platelet aggregation studies: absent aggregation to ALL agonists (ADP, collagen, epinephrine, thrombin) — key finding
  • Ristocetin-induced aggregation is NORMAL (GPIb–vWF axis intact) — critical differentiator
  • Flow cytometry: absent/markedly reduced CD41 (GPIIb) and CD61 (GPIIIa)
  • PFA-100 closure time prolonged; PT/aPTT normal; platelet count normal
  • Clot retraction assay: absent — useful bedside clue

05

Management

  • Avoid antiplatelet agents (aspirin, NSAIDs) strictly
  • Antifibrinolytics (tranexamic acid) for mucosal/dental bleeding — first-line adjunct
  • Platelet transfusions for significant bleeding; risk of alloimmunization with repeated use
  • Recombinant FVIIa (NovoSeven) for refractory or surgical bleeding, especially if alloimmunized
  • HSCT is the only curative option; reserved for severe, refractory cases

06

Clinical pivots

How to separate this script from the look-alikes that show up on exams and on the wards.

  • Bernard-Soulier Syndrome

    BSS has GIANT platelets, mild thrombocytopenia, and absent ristocetin aggregation (abnormal GPIb); GT has normal platelet size/count with absent non-ristocetin aggregation.

  • von Willebrand Disease

    vWD shows reduced ristocetin aggregation and low vWF levels; GT has normal ristocetin aggregation with absent aggregation to all other agonists.

  • Immune Thrombocytopenic Purpura (ITP)

    ITP causes mucocutaneous bleeding via low platelet COUNT; GT has a normal platelet count with functional (aggregation) defect only.

  • Uremic Platelet Dysfunction

    Uremic dysfunction is acquired in the setting of renal failure with elevated BUN; GPIIb/IIIa is present on flow cytometry, and aggregation defects are partial/variable.

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Educational use only. This illness script is a study framework, not medical advice. Confirm decisions with current guidelines and your clinical supervisors.