What is the management of Glanzmann thrombasthenia?

Management of Glanzmann Thrombasthenia

For patients with Glanzmann thrombasthenia (GT), recombinant activated Factor VII (rFVIIa) at a dose of 80-120 μg/kg is the recommended treatment for bleeding episodes or perioperative management in patients with antibodies to HLA and/or GPIIb/IIIa, with doses given before and during interventions at 2-hour intervals. 1

Understanding the Condition

• GT is a rare autosomal recessive bleeding disorder characterized by qualitative or quantitative defects of platelet surface glycoprotein IIb/IIIa (integrin αIIbβ3), resulting in faulty platelet aggregation and diminished clot retraction 2
• Patients typically present with spontaneous mucocutaneous bleeding that can range from mild to severe and potentially life-threatening 3

First-Line Management Approach

For Minor Bleeding Episodes:

• Local measures including pressure, ice, and topical hemostatic agents 4
• Antifibrinolytic agents (tranexamic acid) as adjunctive therapy 3
• Hormone therapy may be considered for menorrhagia in female patients 4

For Moderate to Severe Bleeding Episodes:

• Platelet transfusions remain the standard first-line treatment for bleeding that is unresponsive to conservative measures 5
• Recommended dose: Typically 1 unit of platelets per 10kg body weight 4
• Monitor for development of antiplatelet antibodies, which may lead to refractoriness 3

Management of Platelet Refractoriness

• Patients who develop antibodies to GPIIb/IIIa and/or HLA may become refractory to platelet transfusions 5
• Early recognition of refractoriness is critical - watch for continued bleeding despite adequate platelet transfusion 3
• For GT patients with antibodies to HLA and/or GPIIb/IIIa, rFVIIa is the treatment of choice 1

rFVIIa Protocol for GT Patients

• Dosing for patients with antibodies: 80-120 μg/kg given as bolus doses before and during interventions with 2 hours between doses 1
• For perioperative management, the same dosing regimen should be used 1
• rFVIIa works by enhancing thrombin generation at the site of vascular injury 1
• For optimal efficacy, rFVIIa requires:
  • Fibrinogen concentrations ≥1 g/L
  • Platelet counts ≥ 50 × 10⁹/L
  • pH ≥ 7.2
  • Body temperature > 34°C 1

Surgical Management

For Major Surgery:

• rFVIIa at 80-120 μg/kg before and during surgery for patients with antibodies 1
• For patients without antibodies, platelet transfusions remain first-line therapy 5
• Tranexamic acid can be used as adjunctive therapy 1

For Minor Surgery and Dental Procedures:

• Antifibrinolytic agents may be sufficient for minor procedures 4
• For patients with history of significant bleeding, consider prophylactic rFVIIa or platelet transfusion depending on antibody status 3

Important Clinical Considerations

• Consultation with a hematologist experienced in platelet function disorders is strongly recommended 3
• Regular assessment of antibody development is important in patients receiving multiple platelet transfusions 5
• The efficacy of rFVIIa has been documented in registry data and international surveys, showing good response rates in treating and preventing hemorrhage in GT patients 2, 6
• Early intervention is critical to prevent life-threatening bleeding complications 3

Emerging Treatment Options

• Gene therapy and stem cell transplantation represent potential curative approaches but remain experimental and costly 2
• The Glanzmann's Thrombasthenia Registry (GTR) is collecting prospective data on treatments to optimize clinical management 5