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Toshiyuki Sakata

Publications and source records attributed to Toshiyuki Sakata.

8 recordsLinked to original sources
PubMed2006

Genetic risk factors for deep vein thrombosis among Japanese: importance of protein S K196E mutation.

There is mounting evidence that mutations associated with a given disease arise with different frequencies among ethnic groups, thus ethnicity-specific studies are needed to identify causative mutations and properly assess risk. In particular, ethnic differences in the genetic background of thrombophilia have been reported. We recently conducted a large-scale analysis of the plasma activities of proteins C, S, antithrombin, and plasminogen within the Japanese general population. We found age- and sex-related differences and estimated the prevalence of deficiencies of protein C (0.13%), antithrombin (0.15%), protein S (1.12%), and plasminogen (4.29%). We also evaluated the genetic contribution to deep vein thrombosis and found that protein S mutation K196E is a genetic risk factor in the Japanese population. We estimated allele frequency to be 0.009, suggesting that 1 of 12,000 Japanese may be homozygous for the E allele, thus possibly as many as 10,000 individuals. Accordingly, a substantial proportion of the Japanese population carries the protein S E allele and is at risk of developing deep vein thrombosis. Given the frequency of this mutation and its strong correlation with deep vein thrombosis, it may be valuable to conduct a large-scale screening for this allele and advise concerned persons to avoid environmental risk factors known to be associated with deep vein thrombosis.

Age Factors↗
PubMed2005

Optimal dose of prothrombin complex concentrate for acute reversal of oral anticoagulation.

We investigated optimal dose of prothrombin complex concentrate (PCC) for acute reversal of oral anticoagulation in patients with major hemorrhagic complications or who required invasive procedures. We also checked how rapidly international normalized ratio (INR) was reversed after PCC administration. INR was measured before and 10-60 min after administration of PCC with or without vitamin K in 42 patients (men 28, women 14, median age of 70 years old) who had received warfarin but required rapid reversal of INR because of a hemorrhagic complication or medical procedure. The amount of PCC administered was 200 IU in six patients, 500 IU in 30, 1000 IU in 3, and 1500 IU in the other 3. Additional administration of PCC was performed when the correction of INR was inadequate. In 10 of the 42 cases, INR was measured serially, before, 10 and 60 min and 12-24 h after the administration of PCC and vitamin K. In the six patients who received PCC of 200 IU, INR values of 3.34 median (range 2.06 to 5.08) decreased to 1.85 (range 1.23 to 2.43) significantly (Wilcoxon's rank sum test, p=0.028), but in three patients (50%), INR values were still above 2.0 after the administration. In 30 patients treated with PCC of 500 IU, values decreased from 2.49 median (range 1.54 to 10.00) to 1.19 (range 0.87 to 1.55) significantly (p<0.0001). The corrected INR values were below 1.5 in 25 of 26 patients (96%) who had initial INR values from 2.0 to 4.9. In four patients with initial INR of 5.0 or more, the reversed INR was below 1.5 in one (25%), between 1.5 and 2.0 in two (50%), and above 2.0 in one (25%) who had additional administration of 500 IU PCC lowering INR from 2.01 to 1.48. Values of INR in the six patients receiving 1000 IU or 1500 IU, INR decreased from 2.33 median (range 1.96 to 4.00) to 0.96 (range 0.87 to 1.24, p=0.028). In the 10 patients with serial measurement, INR changed from 2.67 median (range 2.05 to 10.00) to 1.17 (range 0.99 to 1.60) 10 min after the administration. The INR values remained stable 60 min and 12-24 h after the PCC administration. The 500 IU of PCC is likely to be optimal dose of PCC for emergent reversal of INR in patients requiring rapid correction of INR below 5.0, but to be inadequate dose in patients with INR of 5.0 or more. PCC administration with vitamin K may finish reversing INR rapidly within 10 min and keep the reversed INR values for 12-24 h.

Administration, Oral↗
PubMed2004

Potential of free-form TFPI and PAI-1 to be useful markers of early atherosclerosis in a Japanese general population (the Suita Study): association with the intimal-medial thickness of carotid arteries.

This study assessed markers of vascular endothelial cell dysfunction associated with early atherosclerosis in carotid arteries. We measured the plasma levels of free-form tissue factor pathway inhibitor (free TFPI), plasminogen activator inhibitor-1 (PAI-1), and von Willebrand factor (vWF) in 522 adults without cardiovascular disease enrolled in the Suita Study. For each sex, we analyzed the association of the degree of intimal-medial thickness (IMT) with hemostatic markers using logistic regression analysis considering potential confounding risk factors, including age, body mass index, lifestyle (current smoking and drinking), illness (diabetes mellitus and hyperlipidemia), systolic blood pressure, and antihypertensive drug use. The age-adjusted levels of free TFPI and PAI-1 were positively and independently associated with the degree of IMT for men. Even after adjustment for all confounding factors, the level of PAI-1 was positively associated with the degree of IMT. These results indicate that measurement of the levels of free TFPI and PAI-1 is a potentially useful tool for the detection of early atherosclerosis in men.

Adult↗
PubMed2003

Predisposing factors for enlargement of intracerebral hemorrhage in patients treated with warfarin.

To elucidate predisposing factors for enlargement of intracerebral hematoma (ICH) during warfarin therapy, we reviewed 47 patients on warfarin who developed acute ICH and determined relationships among ICH enlargement, INR reversal and clinical data. Among 36 patients treated to counteract the effects of warfarin within 24 h of onset, ICH increased in 10 patients (enlarged group), but remained unchanged in the remaining 26 (unchanged group), while ICH remained unchanged in another 11 patients in whom the effect of warfarin was reversed after 24 h. The international normalized ratio (INR) was counteracted immediately in 11 patients treated with prothrombin complex concentrate (PCC) but gradually in the other 36 treated by reducing the dose of warfarin, or by administering vitamin K or fresh frozen plasma. Multivariate analysis with a logistic regression model showed an INR value <2.0 at admission or for 24 h after immediate INR correction with PCC prevented ICH enlargement (OR 0.069, 95%CI 0.006-0.789, p = 0.031). An INR value of >2.0 within 24 h of ICH seems an important predisposing factor for ICH enlargement.

Adolescent↗
PubMed2002

Correction of INR by prothrombin complex concentrate and vitamin K in patients with warfarin related hemorrhagic complication.

We investigated the effect of prothrombin complex concentrate (PCC, median 500 IU) and vitamin K (10-20 mg) or either on blood coagulation and clinical findings in 17 patients with major hemorrhagic complication during warfarin treatment. Their international normalized ratio (INR) at admission was median 2.7 (2.0-above 10.0). In 11 patients treated with PCC and vitamin K, INR decreased to median 1.13 (0.91-1.36) 10 min after the administration with elevation of plasma levels of coagulant factors II, VII, IX, X and protein C.INR decreased abruptly after the administration of PCC without vitamin K in two patients but it increased again 12-24 h after, with decrease of coagulant factors levels. In one of them, a hematoma of the brain enlarged with INR re-increase 12-24 h after the administration. In four patients treated with vitamin K alone, INR decreased slowly from 2.69 (1.03-3.35) to 1.28 (1.25-1.44) 12-24 h after the administration in parallel with gradual increase of the coagulant factors.PCC administration with or without vitamin K seems to be more effective in rapidly correcting increased INR levels than vitamin K treatment without PCC. PCC without vitamin K may result in re-increase of INR and clinical deterioration.

Aged↗