Molecular analysis of a patient with type I Glanzmann thrombasthenia and clinical impact of the presence of anti-αIIbβ3 alloantibodies.
The occurrence of transfusion-related alloimmunization against αIIbβ3 is a major concern in patients with Glanzmann thrombasthenia (GT). However, few data are available about molecular defects of GT patients with anti-αIIbβ3 alloantibodies as well as clinical impact of these antibodies on platelet transfusion. Here, we report a case of type I GT with anti-HLA and anti-αIIbβ3 alloantibodies, who underwent laparoscopic total gastrectomy due to gastric cancer. We found a novel β3 nonsense mutation, 892C > T (Arg272X), and the patient was homozygous for the mutation. Laparoscopic gastrectomy was successfully performed with continuous infusion of HLA-matched platelet concentrates and bolus injection of recombinant factor VIIa at 2 h intervals. Total bleeding was 370 mL and no red-cell transfusion was necessary. Flow cytometric analysis employing anti-αIIbβ3 monoclonal antibody revealed that the transfused platelet count was maintained around 20-30 × 10⁹/L during the operation and 10 × 10⁹/L on the following day. Flow cytometric analysis also showed that transfused platelets retained normal reactivity to ADP stimulation. These results indicate that flow cytometry is useful to assess survival and function of transfused platelets in GT patients with anti-αIIbβ3 antibodies.
Department of Hematology and Oncology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
Hirokazu
H
Kashiwagi
Kazunobu
K
Kiyomizu
Tsuyoshi
T
Kamae
Tsuyoshi
T
Nakazawa
Seiji
S
Tadokoro
Shuji
S
Takiguchi
Yuichiro
Y
Doki
Yuzuru
Y
Kanakura
Yoshiaki
Y
Tomiyama
D044466:Asian People; D018389:Codon, Nonsense; D006801:Humans; D039661:Integrin beta3 / Q000235:genetics / Q000276:immunology; D007518:Isoantibodies / Q000276:immunology*; D007564:Japan; D008297:Male; D008875:Middle Aged; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000235:genetics / Q000276:immunology; D013915:Thrombasthenia / Q000235:genetics* / Q000276:immunology* / Q000628:therapy
D018389:Codon, Nonsense; D039661:Integrin beta3; D007518:Isoantibodies; D019039:Platelet Glycoprotein GPIIb-IIIa Complex