Tateo Sugiyama

Antibody Removal Therapy Used Successfully at Delivery of a Pregnant Patient with Glanzmann's Thrombasthenia and Multiple Anti‐Platelet Antibodies

Abstract. A 31‐year‐old Japanese woman with Glanzmanns thrombasthenia became pregnant voluntarily. She had had transfusions with more than 60 units for severe bleeding. She had multiple antibodies against HLA antigens and platelet glycoprotein Ilb/IIIa. No compatible platelets were available. To prevent serious hemorrhage during her delivery, antibody removal therapy was carried out three times. Large molecules including immunoglobulins were removed from more than 3 liters of plasma each time. After the titer of antiplatelet antibodies had decreased in the patients blood, antihuman globulin‐lymphocyte cytotoxicity test compatible platelets were transfused. Her bleeding time improved and delivery was induced successfully despite atonic hemorrhage of about 2,000 g of blood. Her infant had no bleeding problems. This patient is the first with Glanzmanns thrombasthenia to receive antibody removal therapy at delivery.

Chronic myeloid leukemia with minor‐bcr breakpoint developed hybrid type of blast crisis

Although a breakpoint in the minor breakpoint cluster region (m‐bcr) of the BCR gene is observed in about two‐thirds of patients with Philadelphia chromosome‐positive acute lymphoblastic leukemia, this type of genomic rearrangement occurs very rarely in chronic myeloid leukemia (CML). We describe here the eighth case of m‐bcr CML, and delineate unique clinical characteristics found in common to the 7 cases reported previously. Monocytosis with a low neutrophil/monocyte ratio resembling chronic myelomonocytic leukemia was the most striking feature of m‐bcr CML. Splenomegaly and basophilia were not conspicuous in chronic phase. A high percentage of immature granulocytes and low neutrophil alkaline phosphatase score were the findings in common with classical CML. Lymphoid and myeloid blast changes have been observed at and shortly after presentation so far. We found a hybrid type of blast crisis in the course of m‐bcr CML.Thus, m‐bcr CML may be a definite subtype of CML, exhibiting distinct clinical characteristics. The presence of fusion product of m‐bcr mRNA in an earlier myeloid cell may involve monocytic lineage in addition to myeloproliferative defects. Am. J. Hematol. 57:320–325, 1998.

Requirement of free arachidonic acid for leukotriene B4 biosynthesis by 12-hydroperoxyeicosatetraenoic acid-stimulated neutrophils

Stimulation of human neutrophils with 12-hydroperoxyeicosatetraenoic acid (12-HPETE) led to formation of 5S, 12S-dihydroxyeicosatetraenoic acid (DiHETE), but leukotriene B4 (LTB4) or 5-hydroxyeicosatetraenoic acid (5-HETE) was not detectable by reversed-phase high-performance liquid chromatography analysis. N-formylmethionylleucylphenylalanine (FMLP) induced the additional synthesis of small amounts of LTB4 in 12-HPETE-stimulated neutrophils. The addition of arachidonic acid greatly increased the synthesis of LTB4 and 5-HETE by neutrophils incubated with 12-HPETE. In experiments using [1-14C]arachidonate-labeled neutrophils, little radioactivity was released by 12-HPETE alone or by 12-HPETE plus FMLP, while several radiolabeled compounds, including LTB4 and 5-HETE, were released by A23187. These findings demonstrate that LTB4 biosynthesis by 12-HPETE-stimulated neutrophils requires free arachidonic acid which may be endogenous or exogenous.

Platelet prostaglandin D2 dehydrogenase in patients with myeloproliferative disorders.

NADP-linked 15-hydroxyprostaglandin dehydrogenase for prostaglandin D2 (PGD2DH) transforms prostaglandin D2 (PGD2) to inactive 15-keto-PGD2. This enzyme activity was spectrophotometrically determined in the cytosol of platelets and platelet sensitivities to PGD2 were studied in patients with myeloproliferative disorders (MPD) as well as in normal subjects. Platelet sensitivities to exogenous and endogenous PGD2 were estimated by IC50 of added PGD2 for platelet aggregation and by the inhibitory effect of a specific thromboxane synthetase inhibitor (OKY-046) on collagen-induced aggregation, respectively. PGD2DH activities of MPD patients were significantly higher than those of normal subjects (p less than 0.01). Although decreased sensitivity to exogenous PGD2 was detected in some MPD patients, they were not always associated with the increased enzyme activities. Furthermore, no specific correlation was found between PGD2DH activities and the inhibitory effects of OKY-046. Thus, PGD2DH seems to have little effect on the action of PGD2 against platelet aggregation in MPD patients and normal subjects.