Glanzmann's thrombasthenia, Glanzmann's Research Foundation, blood, blood disorder, blood disease, fibrinogen bridging, prolonged bleeding, autosomal recessive, platelets, hematologists, hemophelia, Haemophilia, nose bleeds

Sustained Engraftment Post Bone Marrow Transplant Despite Anti-Platelet Antibodies in Glanzmann Thrombasthenia

Veronica M. Flood, MD., F. Leonard Johnson, MD, Lynn K. Boshkov, MD, Gregory A Thomas, MD, Diane J. Nugent, MD, Antony C. Bakke, PhD, H. Stacy Nicholson, MD, MPH, David Tilford, MD, Mary P. Brown, MD, and Kamar T. Godder, MD, MPH.

Background. Patients with Glanzmann thrombasthenia (GT) have normal platelet counts but abnormal platelet aggregation and carry the risk of life-threatening bleeding. We report three patients who received bone marrow transplantation (BMT) for type 1 GT and discuss the risk and management of anti-platelet antibodies. Patients and Results. Diagnosis of GT was made through abnormal platelet aggregation studies or the absence of GPIIb/IIIa by flow cytometry. All patients had severe bleeding requiring multiple red blood cell transfusions. One patient received an unrelated donor transplant and two received matched sibling donor transplants following conditioning therapy with busulfan, cyclophosphamide, and fludarabine. Two patients developed an anti-platelet antibody, treated in one with intravenous immune

globulin (IVIG). Engraftment of white blood cells and platelets was achieved on day +13 to +14 and +17 to +25, respectively. Complete donor chimerism and GPIIb/IIIa+ platelets are sustained at +22 to +30 months post transplant. Conclusions. In summary, patients with GT and history of severe hemorrhage can be cured with BMT, but the presence of anti-platelet antibodies should be sought and platelet transfusions minimized prior to transplant. IVIG may be helpful in cases of refractory immune thrombocytopenia related to anti-platelet antibodies. Improvement in transplant-related complications with current transplant regimens allows consideration of BMT for life-threatening non-malignant disorders such as GT.

Pediatric Blood Cancer 2005; 45;971-975.

INTRODUCTION

Glanzmann thrombasthenia (GT) is an inherited bleeding disorder resulting from either qualitative or quantitative abnormalities in the glycoprotein IIb/IIIa complex located on the platelet membrane. Glanzmann first reported a series of patients with muco-cutaneous bleeding, normal platelet counts, and prolonged bleeding times in 1918. Later, it was discovered that these patients lacked functional GPIIb/IIIa on their platelets. This defect prevents adequate formation of the platelet plug, which then leads to increased bleeding at sites of injury. GT patients can be classified as type I, with less than 5% GPIIb/IIIu and absent clot retraction; or type II. with 10-20% GPIIb/IIIa and minimal clot retraction. Qualitative defects manifest as variants with abnormal function despite normal or near-normal levels of GPIIb/IIIa.

The clinical spectrum of GT is variable, with symptoms ranging from minimal bleeding to significant epistaxis, menorrhagia, and life-threatening hemorrhage. Treatment typically consists of local control measures. Systemic and topical antifibrinolytic therapy may be helpful, while platelet transfusions are reserved for severe bleeding. Although, the infusion of normal donor platelets will initially allow hemostasis, GT patients may develop

antiplatelet antibodies against the GPIIb/IIIa complex, decreasing the efficacy of transfusion and creating the risk of poor response to future transfusions. While aiding in temporary hemostasis, none of the measures described above address the underlying defect. The only curative treatment to date has been bone marrow transplantation (BMT). Four previous transplants for GT have been reported, all with matched sibling donors.
We report three patients who received BMT for GT at our institution. All patients had type I GT and had experienced severe bleeding requiring multiple transfusions. One patient received a transplant from a human

1 Pediatric Stem cell Transplant Program. Division of Pediatric Hematology/Oncology. Oregon Health & Science University, Portland, Oregon

2 Department of Pathology. Oregon Heath& Science University, Portland, Oregon

Division of Hematology, Children's Hospital of Orange County, Orange California

3 Central Oregon Pediatrics, Bend. Oregon

4 Correspondence to: Victoria H. Flood. Kamar T Godder, Division of Pediatric Hematology / Oncology, DCRCP, Oregon Health and Science University. 3181 SW Sam Jackson Park Road, Portland, OR 97239