Katsuo Koie

Congenital Deficiency of α2-Plasmin Inhibitor Associated with Severe Hemorrhagic Tendency *

alpha(2)-Plasmin inhibitor (alpha(2)PI) is a recently characterized, fast-reacting plasmin inhibitor in human plasma that appears to play an important role in regulation of in vivo fibrinolysis. We report here a case of complete deficiency of alpha(2)PI in man. The patient, a 25-yr-old Japanese man, had a life-long severe bleeding tendency (hemarthrosis and excessive bleeding after trauma). The following tests were within normal limits: platelet count, bleeding time, thrombin time, prothrombin time, partial thromboplastin time, titers of known clotting factors, platelet glass bead retention, Factor VIII-related antigen, platelet aggregation by ADP, collagen and ristocetin, and clot retraction. Routine liver function tests were also normal. The only abnormal finding was that whole blood clot lysis was extemely rapid and was complete in 4-8 h. The concentration of plasma protease inhibitors, including alpha(2)-macro-globulin, antithrombin III, alpha(1)-antitrypsin, and C1INH, were all normal. The concentration of alpha(2)-PI in the patients plasma, assayed by immunological methods, was <0.1 mg/100 ml (normal concentration, 6.1+/-0.88 mg/100 ml [mean+/-SE]) and functional assays showed a complete deficiency of alpha(2)PI. Addition of purified alpha(2)PI to the patients whole blood completely corrected the accelerated fibrinolysis. The patients parents, four siblings, and four other members of this family were asymptomatic, but the titers of alpha(2)PI in their plasmas were congruent with50% of normal pooled plasma. There were three consanguineous marriages in this family, and the alpha(2)PI deficiency appears to have been inherited as an autosomal recessive trait. We speculate that alpha(2)PI deficiency in this patient has led to uninhibited in vivo fibrinolysis that probably causes the severe hemorrhagic tendency. Thus, this study indicates the important role of alpha(2)PI in hemostasis.

α2-PLASMIN-INHIBITOR DEFICIENCY (MIYASATO DISEASE)

A 25-year-old man, born in Okinawa, Japan, had a haemorrhagic diathesis characterised by prolonged bleeding and ecchymoses after minor trauma and spontaneous joint haemorrhage. The frequency and severity of these episodes were reduced by an antiplasminic drug. Routine coagulation studies revealed no abnormalities except for significantly sshortened euglobulin-lysis time and whole-blood clot lysis time. Activities of all known clotting and fibrinolytic factors were within normal ranges but no circulating alpha2-plasmin inhibitor was found in the plasma. alpha2-plasmin inhibitor is a potent and fast-acting protease inhibitor. Studies of family members indicated that this abnormality was inherited as an autosomal and recessive gene.

Cytogenetic characterization of a T-cell line, ATN-1, derived from adult T-cell leukemia cells

A T-cell line, ATN-1, was established by culturing peripheral blood mononuclear cells derived from a patient with adult T-cell leukemia/lymphoma (ATL/L). Identities of the patterns of chromosomal abnormalities, cell surface phenotypes, morphologic findings, rearrangement patterns of T-cell receptor beta chain gene, and an integration site of human T-cell leukemia virus I proviral genome indicated that ATN-1 was derived from original leukemic cells. Both ATN-1 and the original leukemic cells showed a variety of patterns of chromosomal abnormalities that include 3q-, 6q-, rearrangements involving 2q31, 7q11.2, 8q11, 8q24, 19p13.3, and also 14q11 and 14q32, where genes for the T-cell receptor alpha chain and the immunoglobulin heavy chain are located. Availability of a genuine ATL/L cell line with these chromosomal abnormalities may greatly facilitate the biologic analysis of ATL/L.

Daunorubicin, cytosine arabinoside, 6-mercaptopurine riboside, and prednisolone (DCMP) combination chemotherapy for acute myelogenous leukemia in adults.

Thirty‐seven adults with acute myelogenous leukemia (AML) were treated with a combination of daunorubicin, cytosine arabinoside, 6‐mercaptopurine riboside, and prednisolone (DCMP) for remission induction. Twenty‐three of 37 patients (62.2%) achieved complete remission, three, partial remission and 11, failure. Patients with prior therapy responded as well as patients without it. The median survival time of the patients who received DCMP for their initial remission induction therapy was 10.3 months and that of the patients who obtained complete remission was 17 months. Complete remission occurred in 21 out of 28 patients (75%) less than 40 years old but in only two out of nine patients (22.2%) more than 40 years old. The most common toxic effects were severe myelosuppression and liver function abnormalities. DCMP therapy is an effective remission induction chemotherapy for adults with AML.

Sensitive Solid Phase Enzyme Immunoassay for Factor IX Antigen and Classification of Hemophilia B

A sensitive solid phase enzyme immunoassay (EIA) was developed for the measurement of factor IX antigen (IX:AG), using rabbit antihuman factor IX antiserum and beta-D-galactosidase, which enabled us to detect IX:AG as low as 10(-4)U/ml. 37 patients with severe hemophilia B have been investigated by EIA, inhibitor neutralization assay and bovine brain prothrombin time. They could be divided into four genetic variants. 25% had normal levels of IX:AG but decreased levels of factor IX clotting activity. On crossed immunoelectrophoresis of the hemophilia B+ and hemophilia BM, we could not find abnormalities in electrophoretic mobilities compared to normal subjects in the presence of 1 mM Ca++ lactate.

Pregnancy complicated by idiopathic thrombocytopenic purpura

SummaryThe findings on 30 women with 48 pregnancies complicated by idiopathic thrombocytopenic purpura (ITP) have been analysed. The criteria for advising whether or not pregnancy complicated by ITP should be allowed to continue are as follows. When the onset of ITP precedes pregnancy and pregnancy occurs without any remission, termination of the pregnancy should be considered because in these circumstances ITP commonly runs a poor course. When the onset of ITP has preceded pregnancy, and is in remission at the time of conception, pregnancy can be continued. In those cases where ITP develops during pregnancy, it is generally possible to continue pregnancy.Haemorrhage during pregnancy can be controlled with corticosteroids and blood transfusion. In those cases with decreased platelet counts, bleeding from the uterine cavity after labour is not a problem but haemorrhage from lacerated wounds is difficult to control. Therefore, vaginal delivery is preferred unless there is an absolute indication for caesarea...