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Biomedical subjects

K Kario

Publications and source records attributed to K Kario.

At least 145 records · Page 8Linked to original sources
PubMed1995

[Activated factor VII as a new cardiovascular risk factor of atherothrombotic disease].

Factor VII (FVII) is a plasma vitamin K-dependent glycoprotein that plays an important role in the initiation of tissue factor-induced coagulation (extrinsic pathway of blood coagulation). An increase in FVII coagulant activity (FVIIc) has been proposed as an independent risk factor for coronary artery disease. Recently, the coagulation assay using soluble tissue factor(sTF) enables us to measure the plasma levels of the activated form of factor VII(FVIIa) without the effect of the FVII zymogen form. We have developed the fluorogenic assay for FVIIa using sTF and measured the plasma FVIIa in atherosclerotic diseases. The FVIIa level in the Japanese was lower than that reported in Caucasians, suggesting that the incidence of ishemic heart disease is lower in the former. The FVIIa level was higher in the patients with cardiovascular diseases (ischemic heart disease and cerebral infarction), non-insulin-dependent diabetic mellitus, hypertension with microalbuminuria, and renal failure than in the healthy controls. The FVIIa levels were also increased in non-insulin-dependent diabetic patients, and this FVIIa increase was positively correlated with urinary albumin excretion. Furthermore, FVIIa levels were not correlated with the levels of lipids and the activity of hepatic synthesis, indicating that FVIIa may be an independent risk factor for cardiovascular disease.

Biomarkers↗
PubMed1995

[Some aspects of newly developed instruments for blood coagulation tests].

Five newly developed instruments for five routine blood coagulation tests including prothrombin time, APTT, thrombotest, normotest and fibrinogen assay and the other specialized tests were introduced by each manufacturer. In four instruments, the principal of clot detection is based on the change of optical density due to fibrin thread. One instrument detects viscosity change. All instruments were easy to use due to full-automation, and the precision and accuracy in one laboratory use were high in quality. There were difficult problems when a user switches from the reagent recommended by the manufacturer to another commercially available one. The user needs to re-evaluate the standard curve using international reference plasma. In Japan, international normalized ratio (INR) presentation of prothrombin time is not common even in a large scale laboratory. When a patient with warfarin moves to another hospital, the presentation of prothrombin time from the former laboratory can not be used because of the difference in reagent and equipment. Much confusion concerning prothrombin time occurred due to differences in reagent and equipment after the Hanshin-Awaji earthquake. Many patients taking warfarin had to evacuate under severe stress condition, and had prothrombin time out of the optimal therapeutic range not knowing whether it was due to quake-stress or intra-laboratory difference. Selection of automated coagulation instrument which can easily print out the INR in prothrombin time is recommended.

Blood Coagulation Tests↗
PubMed1995

An inappropriate erythropoietic response to iron deficiency anaemia in the elderly.

This study was carried out to clarify the features of iron deficiency anaemia in the elderly. Subjects were chosen from residents undergoing an annual health check in a home for the aged and the features of anaemia in the elderly were compared with those in middle-aged adults under 60 years old. The red cell count, red cell size and haemoglobin content in an elderly group with iron-deficiency anaemia did not differ from those in middle-aged adults. No significant differences of the serum ferritin and iron levels were noted between the two groups. Total iron binding capacity was higher in the middle-aged adults than in the elderly, while the reticulocyte count was significantly lower in the elderly group. Immature reticulocytes showing a considerable amount of residual RNA by flow cytometry with fluorescent staining were also lower in the elderly group than in the middle-aged adults. Serum erythropoietin levels in both groups were significantly higher than in non-anaemic age-matched controls and no difference in erythropoietin levels was noted between them. The ratio of the reticulocyte count to the log-transformed erythropoietin level was low in the elderly group with iron-deficiency anaemia compared with the middle-aged adults with iron deficiency anaemia. The same result was seen when the immature reticulocyte count was related to the log-transformed erythropoietin level. These findings suggest that the red cell production response to erythropoietin in the elderly with iron-deficiency anaemia might be inappropriate compared with both non-anaemic and anaemic middle-aged adults.

Aged↗
PubMed1994

Close relation between lipoprotein (a) levels and atherothrombotic disease in Japanese subjects > 75 years of age.

Levels of lipoprotein (a) (Lp[a]) and various hemostatic factors were studied in 132 Japanese aged > 75 years (mean 83). The group consisted of 50 healthy persons, 36 hypertensive subjects, 31 patients with chronic cerebral infarction, and 15 with coronary artery disease. Lp(a) levels were slightly lower in the healthy "old old" subjects than in the 184 healthy younger adults (mean +/- SD: 10.7 +/- 7.9 vs 12.1 +/- 10.1 mg/dl). There were no gender-related differences in the Lp(a) levels of healthy adults and healthy old old subjects. Lp(a) levels were higher in the hypertensive old old subjects (14.6 +/- 15.4 mg/dl) and the old old patients with cerebral infarction (21.3 +/- 16.2 mg/dl) and coronary artery disease (26.5 +/- 20.4 mg/dl). The prevalence of subjects with high Lp(a) levels (> 30 mg/dl) was the greatest among old old patients with coronary artery disease (27%). Lp(a) levels in the 132 old old subjects showed positive correlations with sialic acid, fibrinogen, factor VII activity, and D-dimer levels. These results indicate a close association between Lp(a) levels and atherothrombotic disease as well as the characteristics of Lp(a) as an acute phase reactant in old old Japanese. Subjects with higher Lp(a) levels may develop cardiovascular disease later in life, whereas the remaining healthy old old subjects have lower Lp(a) levels.

Aged↗
PubMed1994

Fluorogenic assay of activated factor VII. Plasma factor VIIa levels in relation to arterial cardiovascular diseases in Japanese.

Factor VII (FVII) plays an important role in initiation of the tissue factor-induced coagulation pathway. An increase in FVII coagulant activity (FVIIc) has been proposed as an independent risk factor for coronary artery disease. However, it remains uncertain whether high FVIIc levels are due to an increase in the activation of FVII or an increase in the concentration of FVII mass. We developed a new fluorogenic assay for plasma activated FVII (FVIIa) that used soluble tissue factor. The sensitivity of this assay ranged from 0.2 to 1000 ng FVIIa per milliliter of plasma. Plasma FVIIa levels were measured in 110 healthy subjects and 93 patients with hypertension, diabetes mellitus, and/or cardiovascular disease. The mean plasma FVIIa level in healthy Japanese individuals was 2.5 ng/mL, which was lower than that in Western subjects. Gel filtration analysis showed that most of the circulating FVIIa was in a free form, and binding of FVIIa to tissue factor in plasma was not detected. Aging increased both the FVIIa level and FVII mass, whereas menopause increased mainly the FVII mass. Elderly patients with arterial cardiovascular diseases showed increases in plasma FVIIa levels and FVIIa to FVII antigen (FVII:Ag) ratios. Among the elderly, arterial cardiovascular disease was more common in a high-FVIIa than a low-FVIIa group. Plasma FVIIa levels were not correlated with serum levels of total cholesterol or triglycerides. The FVIIa level and the FVIIa-to-FVII:Ag ratio were positively correlated with fibrinogen level and negatively correlated with body mass index and serum albumin level in the elderly. In conclusion, aging, cardiovascular disease, and malnutrition increased plasma FVIIa levels. FVIIa levels were not correlated with lipid levels or hepatic synthesis, suggesting that FVIIa may be an independent risk factor for cardiovascular disease.

Adolescent↗
PubMed1994

High factor-VII activity in the elderly is related to vascular disease through activation of the coagulation system.

BACKGROUND: High factor-VII activity has recently been recognized as an independent risk factor for coronary artery disease. The aim of the present study was to determine whether high levels of factor-VII activity in elderly patients are caused by endothelial cell injury and are related to vascular disease through activation of the coagulation system. METHODS: We studies 27 asymptomatic healthy elderly men with high factor-VII activity (155-206%) and 22 healthy elderly men with low factor-VII activity (96-122%) selected from 246 men over 60 years of age attending annual health examinations. We also studied 36 patients with vascular disease (22 with coronary artery disease and 14 with chronic cerebral infarction). RESULTS: The levels of endothelium-derived markers (thrombomodulin, tissue plasminogen activator-plasminogen activator inhibitor-1 complex, active plasminogen activator inhibitor 1 and tissue factor pathway inhibitor) did not differ between the subjects with high and those with low factor-VII activity. We therefore conclude that high factor-VII activity is not primarily caused by endothelial cell injury. The high-factor-VII group had higher levels of coagulation inhibitors (protein C, antithrombin III and heparin cofactor II), coagulation activation markers (prothrombin fragment 1 + 2, D-dimer and plasmin-alpha2- plasmin-inhibitor complex), lipoprotein (a) and total cholesterol than the low-factor-VII group. The coagulation and lipid profiles of the group with vascular disease were closer to those of the high-factor-VII group than to those of the low-factor-VII group; the same was true of elevated active plasminogen activator inhibitor-1 levels. CONCLUSION: High factor-VII activity in the elderly is accompanied by hyperlipidaemia, including increased levels of lipoprotein (a), and leads to coagulation activation in vivo. Thus, elderly people with high factor-VII activity are predisposed to vascular disease.

Aged↗
PubMed1994

Increased tissue factor pathway inhibitor levels in uremic patients on regular hemodialysis.

We investigated tissue factor pathway inhibitor (TFPI) levels in 44 non-dialysis uremic patients and 36 chronic dialysis patients, as well as the changes of TFPI levels during hemodialysis sessions using heparin (n = 14), low molecular weight heparin (n = 7), nafamostat mesilate (n = 5), and argatroban (n = 2). In non-dialysis uremic patients, TFPI levels increased (mean +/- SD: 178 +/- 37% of control pooled plasma) along with the impairment of renal function. In chronic hemodialysis patients, TFPI levels were even higher (265 +/- 72%) before dialysis, but did not depend on the etiology of renal failure (diabetic or non-diabetic), the interval between dialysis sessions (twice or three times a week), and the duration of hemodialysis. During hemodialysis sessions using heparin, TFPI levels increased 1.2- to 3.5-fold compared with the level before hemodialysis and the degree of increase in TFPI was correlated with the heparin concentration (r = 0.648, p = 0.0001, n = 29). During dialysis sessions using low molecular weight heparin, TFPI levels also increased, but the change was less marked than during dialysis with heparin. TFPI levels did not change during dialysis sessions using nafamostat mesilate or argatroban. In conclusion, TFPI levels were increased by renal failure and by long-term repeated injection of heparin, but the hemodialysis procedure itself did not alter the TFPI level.

Adolescent↗
PubMed1993

Lipid-related hemostatic abnormalities in the elderly: imbalance between coagulation and fibrinolysis.

To clarify age-related and lipid-related hemostatic abnormalities in the elderly, we measured the plasma levels of active PAI-1 antigen (aPAI-1), tPA-PAI-1 complex (TPC), plasminogen, alpha 2-plasmin inhibitor (alpha 2-PI), plasmin-alpha 2-PI complex (PIC), and D-dimer, together with the plasma levels of fibrinogen, factor VII (F VII), and thrombin-antithrombin III complex (TAT) and the serum lipid levels in 68 hyperlipidemic and 82 normolipidemic elderly subjects. The aPAI-1 ratio was calculated as aPAI-1/(aPAI-1 + TPC). In the normolipidemic elderly subjects, plasma PIC and D-dimer levels were much higher when compared with healthy young controls, and there was also a decrease in plasma plasminogen and alpha 2-PI levels, an increase in plasma TPC levels, and high plasma F VII and fibrinogen levels. In elderly subjects with type IIb hyperlipidemia, both the plasma aPAI-1 level and the aPAI-1 ratio were significantly increased, while the plasma PIC and D-dimer levels were reduced despite higher plasma F VII, fibrinogen and TAT levels. Both serum total cholesterol and triglyceride levels were correlated positively with plasma F VII and TAT levels and with the TAT/PIC ratio, while only serum triglyceride levels showed a positive correlation with plasma TPC and aPAI-1 levels and with the aPAI-1 ratio. Thus, an increase of fibrinolytic activity appears to occur as part of normal aging to balance the increase of procoagulant activity. However, an imbalance between thrombin activity (increased procoagulant activity) and plasmin activity (hypofibrinolysis) appears to occur in elderly individuals with hyperlipidemia, perhaps resulting in a predisposition to thromboembolic disease.

Aged↗
PubMed1992

Congenital protein C deficiency and myocardial infarction:concomitant factor VII hyperactivity may play a role in the onset of arterial thrombosis.

A 29-year-old man with congenital protein C deficiency and acute myocardial infarction is reported. Four hours after the onset of chest pain, he was treated intravenously with tissue-type plasminogen activator. Subsequent coronary angiography revealed only slight stenosis of the left anterior descending coronary artery without any atherosclerosis. The propositus, his brother, and his mother, showed low levels of both protein C activity and antigen, while plasma thrombomodulin levels were normal. His grandfather had died from acute myocardial infarction at 38 years of age. We investigated several other risk factors for arterial thrombosis, including factor VII, fibrinogen, heparin cofactor II, lipoprotein (a), and anticardiolipin antibodies. No other haemostatic abnormalities apart from factor VII hyperactivity were detected in this family. To study the effects of protein C and factor VII on procoagulant activity, prothrombin time was measured after the addition of activated protein C and factor VII to protein C-deficient plasma. The prothrombin time ratio decreased along with an increase in the factor VII level. It also decreased with a decrease in the activated protein C level. These findings indicated that the procoagulant activity of factor VII was enhanced by low protein C levels, suggesting that concomitant factor VII hyperactivity may cause acute myocardial infarction in patients with protein C deficiency.

Adult↗
PubMed1992

Factor VII hyperactivity in chronic dialysis patients.

To study factor VII (F VII) hyperactivity in chronic dialysis patients, we measured the plasma levels of F VII activity (F VII c) and antigen (F VII Ag), prothrombin activation fragments 1 + 2 (F1 + 2), thrombin-antithrombin III complexes (TAT), and thrombomodulin in 28 patients on hemodialysis. Marked elevation of F VII c was found in long-term dialysis patients (185 +/- 30%). This hyperactivity was accompanied by both elevation of the F VII Ag level (153 +/- 28%) and enhanced activation of F VII zymogen, expressed as the F VII c/F VII Ag ratio (1.23 +/- 0.23), but pseudocholinesterase activity was decreased. The 6 patients with ischemic heart disease had slightly higher F VII c (200 +/- 25%) than those without ischemic heart disease (181 +/- 30%), although the difference was not significant. Increased F VII c was accompanied by factor Xa hyperactivity (a high plasma F1 + 2 level) in the long-term dialysis patients, but there was no significant elevation of plasma TAT levels when compared with controls matched for age, sex, and the presence or absence of diabetes mellitus. Plasma TAT levels were significantly correlated with plasma thrombomodulin levels, suggesting that thrombin generation in blood as a result of hemodialysis could induce systemic endothelial cell injury.

Aged↗
PubMed1992

Heparin cofactor II deficiency in the elderly: comparison with antithrombin III.

We investigated heparin cofactor II (HC II) levels and their relationship to other haemostatic factors in the elderly in comparison with antithrombin III (AT III). We measured plasma HC II activity levels in 166 subjects aged from 61 to 99 years using a chromogenic method. HC II levels (94.4 +/- 18.5%) in the healthy elderly subjects were significantly (p less than 0.001) lower than in 40 healthy adult controls under 60 years of age (mean age: 51.5 years; 111.6 +/- 21.2%). HC II levels in the elderly subjects decreased further with age (r = 0.308, p less than 0.001) and the extent of the decrease was more marked than that for AT III (r = 0.179, p less than 0.05). There was no significant sex difference in HC II levels in the elderly. HC II levels correlated significantly with AT III levels and with acute phase reactants including sialic acid, fibrinogen, and PAI-1. HC II levels also correlated with factor VII, plasminogen, alpha 2-plasmin inhibitor, serum lipid, pseudocholinesterase, and albumin levels. These correlations were also found for AT III except active PAI-1 and tPA-PAI-1 complexes, but the correlations with acute phase reactants were stronger for HC II than AT III. We divided 154 elderly subjects into 4 groups by their pseudocholinesterase and albumin levels to estimate the effect of nutritional status on antithrombin activity in the elderly. HC II levels were normal in the elderly subjects with a good nutritional state (103 +/- 18%), but were significantly decreased in those with malnutrition (85 +/- 15%, p less than 0.001). AT III levels also showed the same tendency. These results indicate a decrease in the reserve capacity to inhibit thrombin generation at sites of atherosclerosis in response to trigger events. The deficiency of two major antithrombin factors in the elderly may indicate a tendency to thrombosis, especially in individuals with malnutrition. When considering the clinical significance of HC II, several other parameters, including age, nutritional status, hepatic synthetic ability, and the presence or absence of acute phase reaction should also be assessed.

Acute-Phase Proteins↗