Glanzmann's thrombasthenia (GT) is a severe autosomal recessive bleeding disorder with defective platelet surface αIIb-β3 integrin. Specifities of women with GT are menorrhagia, gynecological surgeries, pregnancies and the consequences of antiplatelet allo-immunization (anti-HLA antibodies) or iso-immunization (anti-αIIb-β3integrin antibodies), especially regarding the risk of neonatal/fetal thrombocytopenia.
The Glanzmann's Thrombasthenia Registry (GTR) is an international multicenter observational prospective registry, created to collect information on the effectiveness and safety of platelet transfusion (P), rFVIIa and other systemic hemostatic agents (mostly, antifibrinolytics [AF]) for the treatment of bleedings in GT patients. GTR offers a unique opportunity to collect data on gynecological issues in a large cohort of women with GT. In the following the terms “rFVIIa”, “P”, and “rFVIIa+P” may include use of AF. “AF” means AF only.
From 2004 to 2011, 218 GT patients from 45 sites in 15 countries from 4 continents were enrolled in the GTR. In the group of 127 females with a mean age of 22.4 years (y), 514 bleeding episodes and 114 surgical procedures were reported. The distribution according to age, type of GT, antiplatelet antibodies (AB) and platelet refractoriness (REF) was similar between females and males. However, the proportion of females with no AB and/or REF decreased with age especially after adolescence: 40/44 (91%) for patients <12 y, 12/15 (80%) for patients 12–17 y and 31/68 (45%) for patients ≥18 y.
Among the 83 females older than 12 y, 40 (48%) had 90 episodes of menorrhagia collected in the GTR while only 4 pregnancies were reported during the period of study. Menorrhagia accounted for 17.5% of the bleeding episodes in the female group. Two thirds of menorrhagia were moderate episodes. Treatments used were rFVIIa in 15 patients, platelets (P) in 22 patients, rFVIIa+P in 6 patients and AF in 11 patients. rFVIIa was used more frequently in patients with a history of AB and/or REF while platelets and AF were nearly always used in non-immunized patients. Treatment with rFVIIa, P, rFVIIa+P and AF was successful in 79% (23 out of 29), 85% (22 out of 26), 43% (3 out 7) and 93% (26 out of 28) of instances respectively. The median cumulative doses of rFVIIa or P were higher in menorrhagia compared to those in all other types of bleedings.
The 7 gynecological surgical procedures were 4 curettages (3 successfully treated with rFVIIa, 1 with P), and 3 caesarean sections successfully performed with P. The non-gynecological procedures were 77 dental, 7 gastrointestinal, 3 nasal, 3 orthopedic and 6 other surgeries. The rate of rebleedings was similar in admissions of females compared to all admissions.
In conclusion, compared to their male counterparts, females with GT presented a similar distribution of bleedings and surgeries, immunization/refractoriness status, dosing, treatment modalities and efficacy. Menorrhagia was observed globally in half of the females with GT ≥12 y and represented one-fifth of the bleeding episodes reported in women included in GTR.
d'Oiron:NovoNordisk: Honoraria. Off Label Use: rFVIIa (NovoSeven) in Glanzmann's thrombasthenia without antiplatelet antibodies or refractoriness to platelets. Poon:Novo Nordisk: Honoraria. Zotz:Novo Nordisk: Honoraria. di Minno:Novo Nordisk: Honoraria.
Asterisk with author names denotes non-ASH members.