Allogeneic stem cell transplantation for Glanzmann thrombasthenia

Abstract

Glanzmann thrombasthenia (GT) is a rare autosomal recessive bleeding disorder characterized by normal platelet count, but lack of platelet aggregation. The molecular basis is linked to quantitative and/or qualitative abnormalities of the membrane glycoprotein IIb/IIIa complexes. Usually it is associated with mild bleeding but may lead to severe and potentially fatal hemorrhages. Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment. However, because of the risks associated with HSCT, it is generally not recommended unless there are life threatening hemorrhages, or the patient has developed refractoriness to platelet transfusion due to antibody formation. Herein, we report an 11-year-old female from United Arab Emirates (UAE) with severe GT and anti platelet alloimmunization successfully treated with HSCT from her HLA-identical sibling.

Successful Management of Acute Catastrophic Juvenile Vaginal Bleeding in Glanzmann’s Thromboasthenia by Uterine Tamponade: A Case Report and Review of The Literature

“…There are reports of successful allogenic hematopoietic bone marrow transplant for GT, in cases of early life-threatening events [15]. …”

Successful unrelated donor cord blood transplantation for Glanzmann’s thrombasthenia

“…First, the risk of placing a tunneled CVC in patients who are refractory to platelet transfusions cannot be underestimated. At the time of CVC placement for the 14 reported patients, five fortunately remained responsive to platelet transfusions (1–8). Among the remaining nine patients, only four were clearly stated to be refractory to platelet transfusions, and rfVIIa was the mainstay for achieving hemostasis in this group (1, 6, 8, 9).…”

“…Intense cytotoxic conditioning appears to have controlled this problem in the small number of cases where platelet alloimmunization was present, but rituximab offers an additional and more targeted B cell approach to reducing alloantibodies. It is of interest that two reports included alemtuzumab with conditioning, which also achieves prolonged host B cell depletion (7, 8). One patient who did not receive anti‐B cell serotherapy developed anti‐GPIIb/IIIa antibodies on D+5 and became unresponsive to platelet transfusions but did respond to IVIG (6).…”

“…Fatal hemorrhages may occur in severe cases because bridging of GPIIa/IIIb complexes with fibrinogen is required for primary hemostasis. Marrow transplantation from HLA‐matched siblings, and less commonly from unrelated donors, has been curative but is reserved for severe cases, especially when alloimmunization has rendered platelet transfusions ineffective (1–8). Paradoxically, life‐threatening hemorrhage may be precipitated during the peritransplant period, especially when anti‐GPIIb/IIIa antibodies coincide with routine procedures including CVC placement or conditioning‐associated mucosal disruption.…”

Use of allogeneic stem cell transplantation for moderate–severe Glanzmann thrombasthenia

“…GT is a result of mutations across the ITGA2B and ITGB3 genes; nonsense mutations, splice mutations with frameshifts and missense mutations causing amino acid substitutions are common [2]. GT is characterized by a normal platelet count and morphology, prolonged bleeding time, absent or diminished clot retraction and defective platelet aggregation [3]. The diagnosis is confirmed by platelet flow cytometry demonstrating the absence of normal GP aIIbb3 complexes.…”