Glanzmann thrombasthenia.
Glanzmann thrombasthenia (GT) is a rare autosomal recessive bleeding syndrome affecting the megakaryocyte lineage and characterized by lack of platelet aggregation. The molecular basis is linked to quantitative and/or qualitative abnormalities of alphaIIb beta3 integrin. This receptor mediates the binding of adhesive proteins that attach aggregating platelets and ensure thrombus formation at sites of injury in blood vessels. GT is associated with clinical variability: some patients have only minimal bruising while others have frequent, severe and potentially fatal hemorrhages. The site of bleeding in GT is clearly defined: purpura, epistaxis, gingival hemorrhage, and menorrhagia are nearly constant features; gastrointestinal bleeding and hematuria are less common. In most cases, bleeding symptoms manifest rapidly after birth, even if GT is occasionally only diagnosed in later life. Diagnosis should be suspected in patients with mucocutaneous bleeding with absent platelet aggregation in response to all physiologic stimuli, and a normal platelet count and morphology. Platelet alphaIIb beta3 deficiency or nonfunction should always be confirmed, for example by flow cytometry. In order to avoid platelet alloimmunisation, therapeutic management must include, if possible, local hemostatic procedures and/or desmopressin (DDAVP) administration. Transfusion of HLA-compatible platelet concentrates may be necessary if these measures are ineffective, or to prevent bleeding during surgery. Administration of recombinant factor VIIa is an increasingly used therapeutic alternative. GT can be a severe hemorrhagic disease, however the prognosis is excellent with careful supportive care.
Nurden
Alan T
AT
IFR No4/CRPP, Laboratoire d'Hématologie, Hôpital Cardiologique, 33604 Pessac, France. Alan.Nurden@cnrshl.u-bordeaux2.fr
D001792:Blood Platelets / Q000378:metabolism; D015942:Factor VIIa / Q000627:therapeutic use; D006470:Hemorrhage / Q000378:metabolism / Q000473:pathology; D006801:Humans; D039661:Integrin beta3 / Q000378:metabolism / Q000502:physiology; D017713:Platelet Transfusion; D013915:Thrombasthenia / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy
D039661:Integrin beta3; D015942:Factor VIIa