Bone marrow transplantation in severe Glanzmann's thrombasthenia with antiplatelet alloimmunization

Abstract

Summary:Glanzmann's thrombasthenia is an autosomal recessive disorder characterized by a lack of platelet aggregation due to the absence of platelet glycoprotein IIb and IIIa. Usually, the disease leads to mild hemorrhage but sometimes bleeding is severe enough to be life-threatening. We report the case of a 16-year-old girl, presenting with very severe type 1 Glanzmann's thrombasthenia, successfully treated with an HLA-identical sibling bone marrow transplant (BMT). We also update the clinical and laboratory data of her brother, who had received a BMT 16 years ago for the same disease. In the light of these two cases and two others published in the literature, we discuss the indications for BMT from HLAidentical sibling donors in Glanzmann's thrombasthenia. Alloimmunization against the missing platelet GPIIb/IIIa complex and severity of bleeding episodes may constitute sufficient criteria for allogeneic BMT after careful assessment of the risk-benefit of such a procedure, although this remains exceptional in this disease. Bone Marrow Transplantation (2000) 25, 327-330.

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

“…The most serious bleeding episodes often occur after trauma or are aggravated episodes of normal physiologic bleeding. The management of GT is mainly supportive with hemostatic procedures, antifibrinolytic agents, desmopressin for minor hemorrhages and packed red cells or platelet concentrates for major hemorrhages [5]. Some patients with severe clinical history and/or the development of anti-platelet antibodies (either anti-GP aIIbb3 or against other epitopes, such as human leukocyte antigen (HLA) or human platelet antibody molecules) render the patient refractory to platelet transfusions [5].…”

“…The management of GT is mainly supportive with hemostatic procedures, antifibrinolytic agents, desmopressin for minor hemorrhages and packed red cells or platelet concentrates for major hemorrhages [5]. Some patients with severe clinical history and/or the development of anti-platelet antibodies (either anti-GP aIIbb3 or against other epitopes, such as human leukocyte antigen (HLA) or human platelet antibody molecules) render the patient refractory to platelet transfusions [5]. In these patients, stem cell transplantation can be considered as a curative treatment, but the potential late effects of transplantation must be balanced against the benefits of this therapy [6].…”

“…Type III is considered a variant of GT and is characterized by 420% of the normal amount of GP aIIbb3 on platelets, but the complex is qualitatively abnormal [4]. The severity of bleeding complications is unpredictable and is independent of the type of defect [5].…”

Successful unrelated donor cord blood transplantation for Glanzmann’s thrombasthenia

“…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.…”

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“…6 Since then, hematopoietic stem cell transplant has been reported sporadically. [7][8][9][10][11] A literature search showed 18 cases of Glanzmann thrombasthenia treated with allogeneic hematopoietic stem cell transplant. 12 We report an 18-year-old woman who presented with severe, repeated bleeding.…”