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Biomedical subjects

K Kario

Publications and source records attributed to K Kario.

At least 163 records · Page 9Linked to original sources
PubMed1992

Prophylactic antithrombin III administration during pregnancy immediately reduces the thrombin hyperactivity of congenital antithrombin III deficiency by forming thrombin-antithrombin III complexes.

We examined the changes of haemostatic molecular markers after antithrombin III (AT III) administration in a 22-year-old woman with congenital AT III deficiency in the third trimester of pregnancy who did not have thrombosis. Various markers including fibrinopeptide A (FPA), thrombin-antithrombin III complex (TAT), prothrombin fragment F1 + 2 (F1 + 2), plasmin-alpha 2antiplasmin, D-dimer, beta-thromboglobulin, and platelet factor 4 were measured before and just after 3,000 U of AT III concentrate, which was given three times per week from the 34 week of pregnancy until delivery. Just after AT III administration, F1 + 2 and FPA levels decreased on most occasions, while TAT sometimes increased. Plasma FPA levels were markedly decreased on all 8 occasions when the plasma FPA levels was above 2.0 ng/ml before AT III administration. Plasma FPA levels were always greater than or equal to 6.4 ng/ml before AT III administration on the 4 occasions when TAT increased to above 115%. The changes of plasma F1 + 2 levels were significantly correlated with the AT III level. These results suggest that prophylactic AT III administration in the third trimester immediately inactivates intravascular thrombin to form TAT and reduce the plasma FPA level. Thus, the transient TAT elevation following AT III administration may not only be due to extraction of thrombin from the fibrin clots of thrombi but also to intravascular thrombin which is not attached to thrombi. FPA is the best molecular marker for thrombin hyperactivity and it should be monitored in AT III-deficient pregnant women in the third trimester.

Adult↗
PubMed1992

Preferential consumption of heparin cofactor II in disseminated intravascular coagulation associated with acute promyelocytic leukemia.

We measured plasma heparin cofactor II (HC II) activity in patients with disseminated intravascular coagulation (DIC) due to various underlying diseases together with the levels of antithrombin III (AT III), pseudocholinesterase (a marker of hepatic synthesis), and various haemostatic molecular markers. Both HC II and AT III were decreased in DIC secondary to all the underlying diseases studied, except acute promyelocytic leukemia (APL), when compared with healthy subjects. The lowest HC II and AT III levels was observed in coagulopathy secondary to liver disease, the HC II level in sepsis was the second lowest. In DIC due to APL, the decrease in HC II was not accompanied by a decrease in AT III. Thus, we divided all 124 samples tested into APL and non-APL groups. The HC II level correlated positively with fibrinogen and plasminogen in both the APL and non-APL groups. In the APL group, the HC II level had a significant negative correlation with the thrombin-AT III complex (TAT), fibrinogen/fibrin degradation products, and D-dimer levels as well as the prothrombin time, while AT III showed no correlations with any of the haemostatic parameters. These results suggest that HC II may be consumed preferentially by thrombin in APL patients with DIC, and thus may spare the consumption of AT III. Accordingly, HC II seems to be a superior indicator of DIC than AT III in APL patients. Moreover, replacement therapy with HC II instead of AT III may be useful to treat DIC associated with APL. In the non-APL group, the HC II levels were positively correlated with the levels of AT III and pseudocholinesterase activity. This indicates that plasma HC II levels are closely related not only to consumption coagulopathy but also to hepatic synthetic activity, as is the case for plasma AT III.

Adult↗
PubMed1992

Rapid quantitative evaluation of plasma D-dimer levels in thrombotic states using an automated latex photometric immunoassay.

To evaluate a recently developed latex photometric immunoassay (LPIA) that which can measure 40 samples quantitatively within 30 minutes, we measured D-dimer levels in blood samples obtained from patients with disseminated intravascular coagulation (DIC). Linearity of D-dimer determination was shown over the range from 0.5 to 36 micrograms/ml, and recovery studies demonstrated 94 to 108% recovery. The intra-assay and inter-assay coefficients of variation ranged from 0.6 to 11.3% at plasma D-dimer levels of 0.54 to 30.1 micrograms/ml. No interference by lipids, bilirubin, haemoglobin, rheumatoid factor, or gamma-globulin was noted. The normal D-dimer range was less than 0.5 microgram/ml in healthy ambulatory subjects, while the level in elderly subjects with atherosclerosis (14%) or in immobilized subjects (38%) was well above this limit. There was a strong correlation between plasma and serum D-dimer levels (r = 0.993). D-dimer levels measured by this LPIA showed a good correlation with those determined using two kinds of ELISA. The LPIA D-dimer levels were elevated in some subjects with diseases predisposing to DIC, but remained below 10.0 micrograms/ml. On the other hand, the LPIA D-dimer levels in DIC subjects were almost always above 10.0 microgramS/ml. Our study showed that a hypercoagulable state should be suspected when the LPIA D-dimer level is greater than 0.5 microgram/ml and that DIC should be diagnosed when the level is greater than 10.0 micrograms/ml in the presence of an appropriate underlying disease. This LPIA system can rapidly evaluate the presence of a hypercoagulable state as accurately as any ELISA, and thus seems potentially valuable for both emergency and routine laboratory use.

Adult↗
PubMed1992

Hereditary heparin cofactor II deficiency and coronary artery disease.

We here present a Japanese family with type I hereditary heparin cofactor II (HC II) deficiency. The propositus (a 61-year-old man) suffered from angina pectoris and coronary artery disease was confirmed by coronary angiography. He underwent percutaneous transluminal coronary angioplasty (PTCA) four times in one year. Combined use of heparin, aspirin, and nitrates could not prevent the return of his symptoms and restenosis of segment 6 of the left anterior descending artery. His HC II activity and antigen levels were 49% and 50%, respectively, and his daughter also showed similar low levels. Cerebral infarction had occurred in two family members. Argatroban, a selective potent thrombin inhibitor, was administered after the fourth PTCA for the purpose of preventing reocclusion and achieved a successful outcome. A relationship between HC II deficiency and thrombosis has not yet been established. Our case suggests that standard heparin therapy is not effective in preventing restenosis in such individuals, in whom the process is accelerated by thrombin generation at the site where PTCA produces rupture of the atherosclerotic plaque. Argatroban may be more effective under low HC II conditions because of its potent inhibition of thrombin activity at sites of vascular wall damage.

Angina Pectoris↗
PubMed1992

Reduced erythropoietin secretion in senile anemia.

To investigate the etiology of the age-related decrease in hemoglobin (Hb) concentration, we measured serum erythropoietin (EPO), serum iron, total iron binding capacity, and serum ferritin levels in 247 elderly subjects aged 60-99 years. EPO levels were determined by radioimmunoassay. An age-related increase in the serum EPO concentration (r = 0.220; P < 0.01) and a significant inverse relationship between EPO and Hb concentrations were found in normal elderly subjects without anemia (r = -0.302; P < 0.001), but not in 111 younger controls. Serum EPO levels were slightly higher in elderly subjects with pre-anemic iron deficiency than in the normal elderly subjects (P < 0.05). These results suggest that the EPO secretion is accelerated in the elderly even though the Hb remains above 12.0 g/dl, probably as a compensatory mechanism for peripheral tissue hypoxia. An inverse relationship between the EPO and Hb concentrations was found in the elderly subjects with iron deficiency anemia, but not in those with unexplained senile anemia. The changes of EPO levels were also assessed in 20 elderly subjects who had developed anemia when reviewed after 12 months. Serum EPO levels increased in relation to the decrease in Hb concentration in those with iron deficiency anemia, but not in those with unexplained senile anemia. Reduced EPO secretion thus seems to play a role in the progression of unexplained senile anemia, and recombinant human EPO may possibly be effective for treating this type of anemia by mobilizing excess iron.

Aged↗
PubMed1992

Cigarette smoking increases the mean platelet volume in elderly patients with risk factors for atherosclerosis.

To study the effects of cigarette smoking and atherosclerosis on platelet size, we measured the mean platelet volume (MPV) and other platelet parameters in 142 elderly smokers and nonsmokers with or without atherosclerotic risk factors. The MPV and the platelet count were highest and their inverse correlation was strongest in the atherosclerotic smokers (r = 0.54, P < 0.05) when compared with the nonsmoking and non-atherosclerotic groups. A 10% decrease of MPV was found in 8 smoking subjects in the atherosclerotic group, who successfully discontinued smoking (P < 0.05). These results suggest that smoking may increase platelet consumption in atherosclerotic vessels and that subsequently megakaryocytes are activated to produce larger platelets, which are more active. Thus, an increase in MPV due to smoking may also contribute to the acceleration of atherosclerosis and should be considered as a risk factor for atherosclerotic disease.

Aged↗
PubMed1992

Imbalance between thrombin and plasmin activity in disseminated intravascular coagulation. Assessment by the thrombin-antithrombin-III complex/plasmin-alpha-2-antiplasmin complex ratio.

We investigated the imbalance between thrombin and plasmin activity in vivo with various grades of severity of disseminated intravascular coagulation (DIC) in relation to the underlying diseases. Plasma thrombin-antithrombin-III complex (TAT) and plasmin-alpha 2-antiplasmin complex (PAP) levels were measured in 133 blood samples obtained from patients with DIC. The TAT/PAP ratio was higher in patients with sepsis or solid cancer than in those with hematologic malignancies. In acute promyelocytic leukemia (APL), the TAT levels were the highest, but the PAP levels were even higher and the TAT/PAP ratio was the lowest. As for the severity of DIC, in mild DIC, both thrombin and plasmin activities were increased. In moderate DIC, the TAT/PAP ratio increased, and thrombin activity was much more predominant. However, in severe DIC, the ratio decreased, and plasmin activity became excessive. In 3 patients with acute myeloblastic leukemia, APL and pancreatic cancer, respectively, the PAP level remained high during heparin therapy although the TAT level was decreased. When tranexamic acid was given, the PAP level was selectively reduced, and the TAT/PAP ratio was markedly decreased along with clinical improvement. These results indicate that monitoring of the TAT/PAP ratio may contribute to decisions regarding the institution and performance of combination therapy for DIC using anticoagulants and antifibrinolytic agents.

Adenocarcinoma↗
PubMed1991

Which factors affect high D-dimer levels in the elderly?

To study the age-related changes in plasma D-dimer levels and the effect of atherosclerotic disease and long-term immobilization on haemostasis the elderly, we measured plasma D-dimer levels in 148 subjects aged from 60 to 94 years using an ELISA. We also measured plasma fibrinogen, serum uric acid, total cholesterol, triglycerides, HDL cholesterol, beta-lipoprotein fractions, and apolipoproteins (A-I, A-II, B, E). Plasma D-dimer levels (326 +/- 148 ng/ml) were significantly higher in the healthy elderly subjects than in younger controls (180 +/- 58 ng/ml, p less than 0.01) and increased further with age (r = 0.344, p less than 0.01). D-dimer levels were significantly higher in elderly women than in elderly men (p less than 0.05). The D-dimer level correlated significantly with both the fibrinogen antigen level (r = 0.286, p less than 0.001) and the clotting activity (r = 0.275, p less than 0.01), and also correlated with apolipoprotein E levels. There were no correlations with the other parameters assessed. The D-dimer levels were significantly higher in the elderly subjects with atherosclerotic disease (516 +/- 285 ng/ml) than in healthy elderly subjects (p less than 0.001). Moreover, the levels were even higher in elderly subjects with long-term immobilization (866 +/- 408 ng/ml) than in subjects with atherosclerosis, even after age, sex and underlying diseases were taken into consideration. These results indicate that coagulation and fibrinolysis activity are increased in the elderly, especially those with atherosclerotic disease and that moreover long-term immobilization further accelerates their haemostatic hyperactivity.

Aged↗
PubMed1991

Factor VII hyperactivity in the elderly.

To investigate the age-related increase in coagulation factor VII (FVII) and its significance in the elderly, we measured FVII coagulation activity (FVIIc), FVII antigen (FVIIag), and D-dimer levels in 150 normal subjects ranging in age from 60 to 98 years. We also measured blood lipid fractions and serum cholinesterase activity (ChE), as an indicator of hepatic protein synthesis. FVIIc (141 +/- 36%), FVIIag (136 +/- 28%), and D-dimer (0.150 +/- 0.372 microgram/ml) levels were significantly higher in the elderly than in younger controls (p less than 0.01). Both FVIIc and FVIIag levels were significantly higher in elderly women than in elderly men (p less than 0.01). FVIIc levels significantly correlated with FVIIag levels, but not with D-dimer levels. FVIIag was more closely correlated with ChE levels in both sexes (men: r = 0.425, women: r = 0.365, p less than 0.001) than with the lipid fractions. When the elderly subjects were divided into atherosclerotic and non-atherosclerotic groups, both FVIIc (p less than 0.01) and FVIIag (p less than 0.05) levels were higher in the former group. Moreover, the FVIIc/FVIIag ratio and ChE levels were higher in both the elderly men and women with atherosclerosis. These results suggest that in elderly subjects, especially with atherosclerosis, hepatic FVII synthesis and the activation of FVII zymogen are both accelerated.

Aged↗
PubMed1991

Xanthine urolithiasis: ultrastructure analysis of renal and bladder calculi.

The surface structure of a xanthine stone from a patient with hereditary xanthinuria was examined using scanning electron microscopy. This revealed that the xanthine stone was composed of at least two very different structures. One was a spherical protrusion with craters and a fine granular surface and the other consisted of a granular growth of plate-like crystals.

Aged↗
PubMed1991

Serum erythropoietin levels in the elderly.

We evaluated the relationship between erythropoietin (EPO) and hemoglobin (Hb) concentrations in 156 normal subjects ranging from 60 to 98 years old. EPO was determined by a radioimmunoassay. The serum EPO concentration in subjects with Hb concentrations greater than 12.0 g/dl (26.9 +/- 15.2 mU/ml), was significantly higher than that in younger controls (15.8 +/- 5.0 mU/ml, p less than 0.001). No sex difference in serum EPO level was detected. In addition, there was an inverse semilogarithmic relationship between EPO and Hb concentrations in subjects with Hb concentrations less than 12.0 g/dl (r = -0.559, p less than 0.001). EPO concentrations in the elderly were lower than those in young subjects with iron deficiency anemia with the same Hb level. Thus, in the elderly, a high EPO concentration may be preventing a decrease in the Hb concentration. However, a decreased EPO response to low Hb concentrations may be a contributing factor in anemia in the elderly.

Aged↗
PubMed1991

[An aged case of hereditary xanthinuria with xanthine urinary calculi].

A 74-year-old female with hereditary xanthinuria and xanthine stones is reported. She has a family history of consanguineous parents and a past history of right side nephrectomy due to a xanthine renal stone and vesicolithotomy of 3 bladder stones approximately 5 X 4 X 4 cm in size at the age of 58 and 71, respectively. Her young brother exhibited a slightly elevated urinary excretion of oxypurines. Laboratory examination showed a low serum level (0.3 mg/dl) and urinary excretion (1.56 mg/day) of uric acid, and high plasma and urine levels of oxypurines. No xanthine oxidase activity was detectably in duodenal mucosa by biopsy specimen obtained by duodenofiberscopy. Now she has another stone approximately 5 X 4 X 4 cm in her bladder. There have been are few elderly cases of hereditary xanthinuria with recurrent giant urolithiasis.

Aged↗