No increased risk of thrombosis in heterozygous congenital dysplasminogenemia.

To assess the risk of thrombosis in congenital dysplasminogenemia, we studied 10 unrelated families with this disorder. The probands were excluded from the analysis of data to prevent bias in the selection of subjects. Positive thrombotic histories were found in 1 of the 25 family members determined to have heterozygous congenital dysplasminogenemia and in 2 of their 41 biochemically unaffected relatives. The percentages of family members with no history of thrombosis up to a given age among subjects with and without congenital dysplasminogenemia were analyzed by the Kaplan-Meier method. No significant difference between the 2 groups was observed by generalized Wilcoxon test (P = .32) or Cox-Mantel test (P = .62). These findings suggest that heterozygous congenital dysplasminogenemia is not associated with an increased risk of thrombosis.

Increase in plasma thrombomodulin level in patients with vibration syndrome.

To determine whether endothelial cells are injured in vibration syndrome, we measured plasma levels of thrombomodulin (TM) in 100 patients with this syndrome using one-step sandwich enzyme immunoassay. Plasma level of TM in patients with vibration syndrome was significantly higher than that in normal control (p < 0.0001). There was no significant difference in the plasma TM level between patients with vibration syndrome and those with collagen disease. Plasma TM concentration in chain-saw operators was significantly higher than that in rock-drill operators (p < 0.05). Plasma TM value did not significantly differ between patients with vibration-induced white finger (VWF) and those without VWF. These results suggest that endothelial injury is present in patients with vibration syndrome, the degree of endothelial injury in patients with vibration syndrome equals that in patients with collagen disease, and the endothelial injury in chain-saw operators is greater than that in rock-drill operators. However, there was no difference in the degree of endothelial injury between patients with VWF and those without VWF.

Congenital deficiency of histidine-rich glycoprotein: failure to identify abnormalities in routine laboratory assays of hemostatic function, immunologic function, and trace elements.

Histidine-rich glycoprotein (HRGP) has many biologic activities, but its physiologic function is still unclear. To show the physiologic function of HRGP, we studied five patients with congenital HRGP deficiency. Hemostatic screening tests, activities of natural anticoagulants and fibrinolytic proteins, markers of thrombin and plasmin generation, plasma levels of platelet-specific proteins, thrombin times with various concentrations of bovine thrombin, prolongation of thrombin time after addition of heparin or demartan sulfate, and contact activation of blood coagulation were normal or nearly normal in these patients. Serum concentrations of immunoglobulin, functional activity of the classical and the alternative pathway of complement, lymphocyte subsets, and serum concentrations of soluble interleukin-2 receptor were approximately normal in all patients, and serum concentrations of copper and zinc were completely normal. These results suggest that the physiologic functions of HRGP are limited when compared with its biologic activities. However, because the patients examined had plasma HRGP levels of 20% to 35% of normal, it is possible that 20% of normal HRGP level is sufficient for its physiologic functions.

High level of plasma thrombomodulin (TM) concentration and correlation with endothelin (ET)-1 in vibration-exposed patients.

We measured plasma level of TM and ET-1 in vibration exposed patients. The results showed the plasma level of TM in vibration exposed patients was significantly higher than in normal controls. The present findings showed relatively wide damage of endothelial cells in the vascular bed of vibration-exposed patients. On the other hand, the mean level of ET-1 in these patients tended to be higher than in normal controls, though there was no difference. Further studies are necessary about the mechanism of endothelial damage in vibration syndrome patients and its contribution to peripheral circulatory disturbance of vibration syndrome including the role of ET-1.