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,
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
(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.
Blood Cancer 2005; 45;971-975.
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
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
Pediatric Stem cell Transplant Program. Division of Pediatric
Hematology/Oncology. Oregon Health & Science University,
Department of Pathology. Oregon Heath& Science University,
of Hematology, Children's Hospital of Orange County, Orange
Central Oregon Pediatrics, Bend. Oregon
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
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