| Objective: To study the clinical significance of warfain and PIVKA-II 's plasma concentration in oral anticoagulati--on monitoring following mechanical heart valve replace--ment.Methods: Sixteen patients following mechanical heart valve replacement were choiced randomly . They all had rheumatic heart disease. Plasma concentration of warfarin and PIVKA-II international normalized ratio(INR),prothrombin time (PT) and oral dosage of warfarin were determined respectively. Blood samples were taken from patients at the following time points:(l) o hour before taking warfarin. (2) 2 hours after taking warfarin. (3) 4 hours. (4) 6 hours. (5) 8 hours. (6) 12 hours. (7) 24 hours . (8) 36 hours . (9) 48 hours . (10) 72 hours . (11) 96 hours. (12) 192 hours. (13) 1 month. (14) 2 months. 5ml blood was taken from patients' elbow vena at each time point. Heparin was added into 3ml blood. The plasma concentration of warfarin and PIVKA-II were determined by RP-HPLC and ELISA method respectively. Sodium citrate (0.13mol/L) was added into the other 1.8 mlblood. INR and PT were determined by using the first phase method of Quick. Changes and correlationships of all the above indexes were compared before and after taking warfarin. At the same time, the clinical complications, such as blooding and thromboembolism were observed.Results: (1) Plasma concentration of warfarin increased significantly and reached 0.437mg/L at the time point of 2 hours after initial dose administration of warfarin (P <0.05). It reached its first peak at 8 hours and the concentration was 0.647mg/l (P <0.01),then the concentration depressed a little. At 24 hours, the concentration reached a lower level which was 0.600mg/L. The warfarin's plasma concentration increased again after taking the second dose of warfarin. At 72 hours, the concentration reached its second peak (0.773mg/L). Then depressed a little and tended to remain constant after 192 hours.(2) The plasma concentration of PIVKA-II had not any difference in 4 hours after initial dose administration of warfarin (P >0.05). 6 hours later the PIVKA-II 's concentration had a statistic difference and reached 0.535Au/ml (P <0.05). 12 hours later, the concentration reached 1.696Au/ml (P <0.01). After 36 hours, there was a very significant difference. Compared with 0 hours (P O.001) and the concentration reached 4.480Au/ml. The PIVKA-II 's concentration tended to remain constant after 72 hours.(3) After the initial dose of warfarin ,there were notsignificant changes of INR and PT until 36 hours (P <0.05).At 36 hours, INR increased greatly and reached 1.52, PT prolonged significantly and reached 16.7s 72 hours later, INR and PT had very significant difference compared with 0 hour (P <0.001) and tended to remain constant. The steady therapeutic range of INR and PT were 1.50-2.50 and 16.7s -22.2s is respectively.(4) By comparing all the above indexes of 2m after taking the first dose of warfarin with those of 192 hours (the indexes of those two time points were all in steady therapeutic range), we found that the plasma concentration of warfarin and PIVKA-II had not significant difference (P >0.05), whereas the difference of INR and PT were significant (P <0.05).(5) The dosage of warfarin had not any significant effect on plasma concentration of warfarin and PIVKA-II, INR and PT (P >0.05).(6) There were not significant correlationships between warfarin's plasma concentration with INR and PT. The correlation coefficient were 0.274 and 0.276 respectively (P >0.05). However, analysis showed a significant relationship between the logarithm of the warfrain concentration with INR and PT after 36 hours. The correlation coefficient were 0.594 and 0.980(P<0.05). There were not any correlation between warfarin concentration and its logarithm with the dosage of warfarin. The correlation coefficient were 0.284 and 0.229 respectively (P >0.05).(7) The were not any correlationships between PIVKA-II 's plasma concentration with INR and PT in 24 hours after taking the first...
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