Clinical Pattern of Glanzemnn Thrombathenia in Children Attending Assiut University Children Hospital

Glanzmann's thrombasthenia, which is a rare autosomal recessive inherited platelet disorder characterised by impaired platelet aggregation and due to defects in the platelet membrane glycoprotein (GP) IIb-IIIa(1)With a prevalence of 1:1 million, GT is rare, although the prevalence is higher in areas where marriage between relatives is common(2 ,3 )The exact incidence has been difficult to calculate, but is estimated at one in 1,000,000. With an autosomal recessive inheritance, males and females are affected equally. There is a worldwide distribution; however, a large proportion of the cases have been described in selected populations such as the French Romani(16)South Indian Hindus, Iraqi Jews, and Jordanian nomadic tribes(17).Type I is the most common subtype and accounts for around 78% of patients with GT type II and type III (functional variant in receptor) constituting around 14% and 8% of cases (19) most patients present with severe mucocutaneous bleeding at an early age. A classic pattern of abnormal platelet aggregation, platelet glycoprotein expression and molecular studies confirm the diagnosis. Bleeding manifestations range from easy bruising, purpura, epistaxis, gingival bleeds, haematuria, haemarthrosis, muscle haematomas to central nervous system bleed.( 1 )Epistaxis is the most common cause of severe bleeding,risk of severe nosebleeds decreases with age as the septal arterial plexus becomes less friable and children grow out of the habit of nose picking,Menorrhagia is highly prevalent in affected females and there is a higher risk of severe bleeding at the time of menarche due to the prolonged estrogen influence on the proliferative endometrium that occurs during anovulatory cycles.Several bleeding scores have been developed with the goal of standardizing the assessment of bleeding and facilitating the diagnosis of patients with a suspected inherited bleeding disorder.(18) which usually appear in early childhood , among the 187 patients with a known age of onset of bleeding, 53% had bleeding symptoms by 1 year of age and 85% by 14 years of age (median and mean ages of onset were 1 year and 5.6 years, respectively). ( 1 , 4 ,5 )Management of bleeding is based on a combination of hemostatic agents including recombinant activated factor VII with or without platelet transfusions and antifibrinolytic agents. Platelet transfusion is the standard of care if the bleeding is unresponsive to these conservative means. (5 ,6) However, platelet transfusion has several limitations including potential for blood-borne pathogen transmission, particularly bacterial infection. (7 , 8 )Patients may develop antibodies to human leucocyte antigen (HLA) or integrin α2bβ3, which can lead to platelet refractoriness, making future transfusions ineffective. (5 , 6)platelets may not be readily available in emergencies(.4). rFVIIa is being increasingly used in certain disorders of platelet dysfunction, particularly Glanzmann's thrombasthenia(1)The haemostatic effect of pharmacological doses of rFVIIa seems to be that of enhancing the rate of thrombin generation on thrombin-activated platelet surfaces, thus providing the thrombin necessary for the formation of a stable fibrin haemostatic plug. Based on this information, rFVIIa has also been employed in disorders characterised by impaired thrombin generation, such as quantitative and qualitative platelet defects.Recombinant activated factor VII (rFVIIa; eptacog alfa activated, NovoSeven, Novo Nordisk A/S, Bagsværd, Denmark) was approved by the European Medicines Agency (EMA) in 2004 for the treatment of bleeding episodes and for the prevention of bleeding during surgery or invasive procedures in patients with GT.

The GT Registry (GTR) was an international, multicenter, observational registry that focused on both adults and children, aims to evaluate rFVIIa effectiveness and safety as a treatment for young patients with GT. The GTR was set up as a part of an EMA regulatory commitment to collect postmarketing data on rFVIIa utilization in patients with GT. Data on the use of other therapeutic options (platelets and antifibrinolytics) were also collected.

Data from GTR found that rFVIIa, provided effective hemostasis with a low frequency of adverse events in surgical, as well as nonsurgical, bleeding in patients with GT. The data from GTR support the applicability of rFVIIa as a good alternative treatment to platelet transfusions for severe bleeding episodes .