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Glanzmann thrombasthenia: genetic basis and clinical correlates

Management of bleeding is based on a combination of hemostatic agents including recombinant activated factor VII with or without platelet transfusions and antifibrinolytic agents.

Recombinant activated factor VII (rFVIIa) is approved by the European Medicines Agency (EMA) and the FDA for the treatment of patients with GT. The approval of this drug has changed the landscape of treatment of GT and has allowed for better hemostatic outcomes in all patients, especially those who do not respond to platelet transfusions. Optimal dosing and interval of doses vary by center and clinical situation. Typical doses for acute bleeding are 90 mcg/kg intravenous (IV) every 2-6 hours until hemostasis…

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 Learning the signs is the first step toward recognizing Glanzmann’s thrombasthenia

GT: a rare bleeding disorder that’s challenging to diagnose.

 Management of Glanzmann's Thrombasthenia...

Experts panel elected to use recombinant activated factor VII (rFVIIa) as the first line of treatment of acute bleeds and reserve platelets transfusion for nonresponding patients or severe bleeds, rFVIIa at high dose (270 μg/kg body weight) may tried upfront. rFVIIa may be tried as prophylactic treatment in patients with frequents bleeds.

Articles of Interest

Medication & Remedies

It’s important to be familiar with your options when it comes to medications and remedies.

Glanzmann's Thrombasthenia (GT): You Are Not Alone

GT is an inherited bleeding disorder, meaning that it is passed on from biological parents to child at the time of conception. It is caused by a change (mutation) in the DNA sequence (a gene located on chromosome 17) that instructs the production of a protein that is important for the platelet function called integrin αIIbβ3 (previously known as glycoprotein IIb or IIIa).

Mother hopes her efforts lead to cure for disorder

Mrs. Smith believes that one day there will be a cure for GT. "I'm excited about that," she said. "I hear about things and feel I can help make a difference. We're going to conquer it, get rid of it. I'm sure of it."

New Insights Into the Treatment of Glanzmann Thrombasthenia

rFVIIa is effective whether antibodies/refractoriness to platelets is present. rFVIIa’s mechanisms of action in Glanzmann thrombasthenia are now well understood. A few patients have been cured by transplant; gene therapy remains a prospect.

Case Study: Intermittent Epistaxis in a Young Boy

Glanzmann’s is caused by a deficiency of the platelet fibrinogen receptor GPIIb-IIIa present on the platelet surface and undergoes conformational change when platelets are activated. Fibrinogen binds to GIIb-IIIa and causes platelets to aggregate, thus a defect in this receptor predisposes to bleeding. Glanzmann’s can be distinguished from other platelet function disorders

Emergency management of patients with Glanzmann thrombasthenia

Caution should be taken regarding the risk for thrombosis when using rFVIIa, and thrombosis prophylaxis should be decided on an individual basis. Administration of intravenous or oral tranexamic acid may also be used.

Glanzmann thrombasthenia: an editorial perspective

Glanzmann’s thrombasthenia (GT) is a rare recessively inherited disorder of platelet function due to absence or abnormal structure of one of the two important platelet glycoproteins (GPIIb and GPIIIa which in activated platelet heterodimerizes and forms high affinity receptor for fibrinogen). Platelet count and morphology in this disease is normal and a patient with this disease can have a variety of bleeding from mucosal surfaces of nose, oral cavity, gastrointestinal tract, and genitourinary tract.

Glanzmann’s Thrombasthenia: An Overview

Glanzmann’s thrombasthenia (GT) is an autosomal recessive inherited bleeding disorder due to a defect in platelet function. The hallmark of this disease is severely reduced/absent platelet aggregation in response to multiple physiological agonists. Bleeding signs in GT include epistaxis, bruising, gingival hemorrhage, gastrointestinal hemorrhage, hematuria, menorrhagia, and hemarthrosis.

Prophylactic Therapy for Glanzmann Thrombasthenia Moves Towards Clinical Trials

GT is an ultra-rare inherited bleeding disorder that is characterized by poorly functioning platelets due to a particular protein deficiency – this results in inadequate clotting and greater susceptibility to bleeding. People with GT may experience mild-to-severe bleeding symptoms some of which can be life threatening if not promptly treated. Existing therapies employed to treat bleeding associated with GT include antifibrinolytics, platelet transfusions, and recombinant factor VIIa.

Resources

Glanzmann's Research Foundation

Glanzmann's Research Foundation is a dedicated platform providing comprehensive information and support to patients, families, and healthcare providers affected by the rare inherited blood clotting disorder, Glanzmann's Thrombasthenia (GT).

Amicar

AMICAR (aminocaproic acid) is 6-aminohexanoic acid, which acts as an inhibitor of fibrinolysis. AMICAR is useful in enhancing hemostasis when fibrinolysis contributes to bleeding. In life-threatening situations, fresh whole blood transfusions, fibrinogen infusions, and other emergency measures may be required.

NovoSeven

NovoSeven® RT is the only recombinant treatment indicated for Glanzmann's thrombasthenia (GT) with refractoriness to platelets.

Eduard Glanzmann

Glanzmann described Hereditäre hämorrhagische Thrombasthenie in 1918, a condition which now bears his name. Glanzmann was an outstanding clinician and paediatrician with special interests, including haematology, infectious diseases, psychopathology, growth and development.

NORD

Glanzmann thrombasthenia is inherited in an autosomal recessive pattern. An abnormality in either the gene for aIIb (glycoprotein IIb; GPIIb) or the gene for β3 (glycoprotein IIIa; GPIIIa) results in an abnormal platelet aIIbβ3 (GPIIb/IIIa) integrin family receptor and prevents platelets from forming a plug when bleeding occurs.

StatPearls

Glanzmann thrombasthenia is a congenital bleeding disorder caused by a deficiency of the platelet integrin alpha IIb beta3. This integrin is the platelet fibrinogen receptor and is thus essential to platelet aggregation and hemostasis. Patients with Glanzmann thrombasthenia have lifelong bleeding episodes that often involve the mucocutaneous membranes.