New Insights Into the Treatment of Glanzmann Thrombasthenia

Transfus Med Rev. 2016 Apr;30(2):92-9. doi: 10.1016/j.tmrv.2016.01.001. Epub 2016 Jan 30.


Glanzmann thrombasthenia (GT) is a rare inherited autosomal recessive bleeding disorder of platelet function caused by a quantitative or qualitative defect of platelet membrane glycoprotein IIb/IIIa (integrin αIIbβ3), a fibrinogen receptor required for platelet aggregation. Bleeds in GT are variable and may be severe and unpredictable. Bleeding not responsive to local and adjunctive measures, as well as surgical procedures, is treated with platelets, recombinant activated factor VII (rFVIIa), or antifibrinolytics, alone or in combination. Although platelets are the standard treatment for GT, their use is associated with the risk of blood-borne infection transmission and may also cause the development of platelet antibodies (to human leukocyte antigens and/or αIIbβ3), potentially resulting in platelet refractoriness. Currently, where rFVIIa is approved for use in GT, this is mostly for patients with platelet antibodies and/or a history of platelet refractoriness. However, data from the prospective Glanzmann's Thrombasthenia Registry (829 bleeds and 206 procedures in 218 GT patients) show that rFVIIa was frequently used in nonsurgical and surgical bleeds, with high efficacy rates, irrespective of platelet antibodies/refractoriness status. The mechanisms underpinning rFVIIa effectiveness in GT have been studied. At therapeutic concentrations, rFVIIa binds to activated platelets and directly activates FX to FXa, resulting in a burst of thrombin generation. Thrombin converts fibrinogen to fibrin and also enhances GT platelet adhesion and aggregation mediated by the newly converted (polymeric) fibrin, leading to primary hemostasis at the wound site. In addition, thrombin improves the final clot structure and activates thrombin-activatable fibrinolysis inhibitor to decrease clot lysis.

Keywords: Gene therapy; Glanzmann thrombasthenia; Hematopoietic stem cell transplantation (HSCT); Platelet glycoprotein GPIIb-IIIa complex; Platelets; Recombinant activated factor VII (rFVIIa).

Publication types

  • Review

MeSH terms

  • Antigens, Human Platelet / immunology
  • Blood Safety
  • Blood-Borne Pathogens
  • Disease Management
  • Factor VIIa / pharmacokinetics
  • Factor VIIa / therapeutic use
  • Female
  • Genetic Therapy
  • Hematopoietic Stem Cell Transplantation
  • Hemorrhage / etiology
  • Hemorrhage / therapy
  • Hemostatic Techniques
  • Humans
  • Male
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • Platelet Transfusion / adverse effects
  • Recombinant Proteins / pharmacokinetics
  • Recombinant Proteins / therapeutic use
  • Thrombasthenia / complications
  • Thrombasthenia / drug therapy
  • Thrombasthenia / therapy*
  • Thrombin / biosynthesis


  • Antigens, Human Platelet
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • Recombinant Proteins
  • recombinant FVIIa
  • Factor VIIa
  • Thrombin