Glanzmann Thromboasthenia with Isolated Amegakaryocytic Thrombocytopenia.

Glanzmann thromboasthenia is an autosomal recessive bleeding disorder caused by a quantitative and/or qualitative defect of the platelet glycoprotein GPalfaIIb/betaIIIa (IIb/IIIa integrin ITGA2B-ITGB3) complex. We have studied a 24 years old patient (exon 2113 T-C substitution missense C705F/C674R) with refractory bleeding platelet count above 25.000, and a very prolonged bleeding time, extensive mucocutaneous petechiae, nosebleeds, and bleeding gums, marked spenomegaly, and conjunctival hemorrage with a prevalence of HLA-DRw2 and DRB1-0410 and a severely decreased platelet production. Immunophenotyping of lymphocytes showed a relative increase of the subset of gamma/delta T-cell receptor (TCR) positive, and CD4 CD8 negative T lymphocytes; expression of c-Mpl and TPO were down-regulated. The bone marrow examination revealed extremely scarce and small megakaryocytes (with a great reduction of CD34+ and CD41+ and a small fraction of CD42+) and with normal marrow cellularity regarding other cellular lines; chromosomal analysis was also normal, while there was an associated severe anaemia with elevated HbF without any history of alcohol use or drugs ingestion. The important observation in this case was the need of many platelet trasfusions, and of fresh frozen plasma (FFP); the functional consequences of this kind of therapy include the induction of abnormalities of the hormones or their receptors (TPO/c-Mpl) that can be decreased in these patients; in addition, platelet mass blocks the biologic effects of SDF-1/CXCR4 receptor and the degree of this inhibition is correlated inversely with platelet count, and supports the evidence that the thrombocytopenia may be related to the inhibition of transcription factors (GATA-1, NF-E2, TAL-1, ETS family), and it directly correlates with the excess of platelet transfusions as an inducible knock-out in MK differentiation. Moreover, this findings indicate that when the receptors (c-Mpl) is saturated, the JAK-2 activation is neutralized and subsequent phosphorylation of STAT-3 and STAT-5 are down-regulated. This patient responded to treatment with danazol 200 mg daily and desmopressin (DDAVP) 0.3 mg/kg, while an additional therapy with traxenamic acid and recombinant FVIIa reduced mucosal bleeding.