Katsumi Nakamura

Hemostatic studies in patients with carbohydrate-deficient glycoprotein syndrome

The carbohydrate deficient glycoprotein (CDG) syndrome is a newly described disorder characterized by impaired glycosylated molecules. It has been reported that transient stroke-like episodes appear in half of the patients. We performed hemostatic studies on three CDG syndrome patients belonging to two unrelated families. The most characteristic findings were decreases in antithrombin III (AT III), protein C and alpha 2 plasmin inhibitor to nearly half normal levels. Protein S was reduced in two (siblings) patients. Isoelectric focusing of AT III in native plasma revealed decreased intensity of the major band and increased intensity of a minor cathodal band. These minor AT III molecules were considered to lack an oligosaccharide sidechain. A 12-year-old girl defective not only for AT III but also protein C and protein S developed disseminated intravascular coagulation accompanied by arterial thrombosis in her left hand following dyspnea associated with bronchial asthma. These findings suggest that thrombotic predisposition in patients with CDG syndrome is due to decreased levels of major coagulation inhibitors, particularly as a result of impaired glycosylation of AT III.

Measurements of tissue factor-like activity in plasma of patients with DIC

Tissue factor-like activity was measured in the plasma of 30 patients with disseminated intravascular coagulation(DIC) and 22 patients without DIC using a chromogenic substrate. Twenty-three of the 30 patients with DIC (77%) exhibited tissue factor-like activity levels above normal range (greater than 3.0 U/L), and in eleven of these patients, the levels were more than 10 U/L. Of the 22 patients without DIC, seven patients had elevated levels (3-10 U/L), and had a possibility to be developing DIC. So, we considered them to be in a pre-DIC state. No correlation was found between tissue factor-like activity and alpha 2 plasmin inhibitor-plasmin complex or FDP-D dimer. In a patient with acute monocytic leukemia, the elevated tissue factor-like activity (84.4 U/L) rapidly decreased after the initiation of chemotherapy, whereas in a patient with pancreatic cancer, the level remained elevated (67.4-79.2 U/L). These results suggested that the plasma tissue factor-like activity is differ from the other parameters reflecting the process of DIC and is a useful indicator of the presence of an initiating factor of blood coagulation in some selected patients with DIC or pre-DIC.

A new hereditary abnormal protein C (protein C Yonago) with a dysfunctional Gla-domain

A familial abnormal protein C most probably with the dysfunctional Gla domain was found in a 60-year-old man with recurrent thrombosis. Namely, the anticoagulant activity as measured by the APTT method and the antigen level by an ELISA utilizing a calcium-dependent antibody were reduced to nearly half of normal, 43.5% and 2.1 micrograms/ml (normal range: 2.8-5.0 micrograms/ml), respectively. On the other hand, the amidolytic activity determined on a synthetic chromogenic substrate, S-2366, and the total antigen measured by an ELISA utilizing a polyclonal antibody were both in the normal range, 74.1% and 83% of normal, respectively. Crossed immunoelectrophoresis showed more anodal migration than the normal control in the presence of calcium ions, and adsorption of protein C to barium citrate was insufficient. These data altogether indicated that a half population of protein C in the patients plasma was dysfunctional in the Gla domain or its related structures. Four other members of his immediate family were found to have the same abnormality of protein C, although they had been all asymptomatic. We thus conclude that the dysfunctional protein C is hereditary, and that the abnormalities noted in several tests are most likely due to a structural defect residing in the Gla or its related regions. We hereby designate this abnormal protein C as protein C Yonago.

Immunological evaluation after splenectomy for hairy cell leukemia--a case report.

Immunocompetence is generally reduced in patients with hairy cell leukemia (HCL)1, and splenectomy is advocated by many authorities as being the initial treatment of choice for HCL.2–4 A 46-year-old Japanese man with HCL underwent a splenectomy and was studied, with respect to immunological parameters, pre- and post-operatively. Preoperative analysis of the T cell subsets showed decreases in the proportions of OKT3 positive cells, OKT4 positive cells and OKT8 positive cells; a decrease in the OKT4/OKT8 ratio; and a markedly reduced lymphocyte blastic response in peripheral blood. After splenectomy, the increase in the proportion of OKT4 positive cells was greater than in that of OKT8 cells and the lymphocyte blastic response was also improved. The patients post-operative course has been uneventful and immunological improvement is still recognizable now, 1 year after splenectomy.