심장판막치환수술후 항혈소판제의 혈전방지 효과에 관한 임상관찰 및 실험적 연구 = A Clinical and Experimental Study on Prevention of Thromboembolism with Antiplatelet Drugs after Cardiac Valve Replacement

다국어 초록 (Multilingual Abstract)

Thromboembolism is one of the main complications in the course of patients having prosthetic cardiac valve replacement. Prevention of thromboembolism after prosthetic cardiac valve replacement is mandatory for patient. The thromboembolic events of 54 patients who were treated with ticlopidine and aspirin after cardiac valve replacement were evaluated and compared with that of patients who were treated with warfarin and aspirin after same type operation. The follow-up period ranged from 4 to 110 months (mean of 48 months).
There were 11 major thromboembolic episodes including three deaths in the warfarin group during mean follow-up period of 56 months. Two cases of cerebrovascular accident and one hemarthrosis were noted due to overdose of warfarin. In ticlopidine + aspirin group, there was only one fatal thromboembolic episode three months after mitral valve replacement during mean follow-up period of 18 months.
Although the exact mechanism of the thromboembolic events is incompletely understood, it is clear that interaction of platelets with prosthetic surface results in adhesion and aggregation.
We measured the parameters of platelet function in aggregation curve of platelet with platelet aggregometer (Chrono-log aggregometer, model No.430). Aggregation test was performed with three final concentrations of epinephrine in 10 μM/L, adenosine diphosphate in 5 μM/L and 10 μM/L. Twenty eight patients with prosthetic cardiac valves and 35 healthy volunteers were subgrouped as follows to evaluate the effect of antithrombotic drugs used.
GroupⅠ; Eleven patients treated with 250-500㎎ of ticlopidine and 0.5gm of aspirin as a daily single dose after cardiac valve replacement (14 St. Jude Medical and 1 Carpentier-Edwards, 9 patients with atrial fibrillation among them).
Group Ⅱ; Ten patients treated with 3-5㎎ of warfarin and 0.75gm of aspirin 6 months and single aspirin dose was matained afterwards as a life long regimen (3 St. Jude Medical, 1 Hall-Kaster and 7 Carpentier-Edwards valve, 9 patients in atrial fibrillation).
Group Ⅲ; Seven patients who abandoned anticoagulant treatment (warfarin + aspirin) 6-12 months after the regimen as group Ⅱ(3 St. Jude Medical, 1 Bjo¨rk-Shiley, 1 Hall-Kaster, 3 Carpentier-Edwards valve, 2 of them are with atrial fibrillation). Normal control group; 35 healthy volunteers (28 males and 7 females)
The following results were obtained.
1. The mean maximal platelet aggregability in groupⅠinduced by 10 μM/L epinephrine was 15.6% and 17.5 and 18.7% in B.M. in proportion to the induction by 5 and 10 μM/L ADP.
2. The mean maximal platelet aggregability in group Ⅱ induced by 10 μM/L epinephrine was 16.5% and 27.4 and 44.7% in B.M. in proportion to the induction by 5 and 10 μM/L ADP.
3. The mean maximal platelet aggregability in group Ⅲ induced by 10 μM/L epinephrine was 65% and 56.5 and 51.8% in B.M. in proportion to the induction by 5 and 10 μM/L ADP.
4. The mean maximal platelet aggregability in the normal subjects induced by 10 μM/L epinephrine was 64% and 65 and 69% in B.M. in proportion to the induction by 5 and 10 μM/L ADP.
5. Reversible change of platelet aggregation curve induced by 5 and 10 μM/L was noted all of the patients in group Ⅰ.
Ticlopidine and aspirin produced a significant inhibition of platelet aggregation in the presence of ADP and epinephrine in this study.
To evaluate the effectiveness of aspirin and ticlopidine as a antithromboembolic agents after cardiac valve replacement, an animal experiment was performed in 5 dogs. In 5 dogs,18mm polytetrafluoroethylene conduits containg home-made prosthetic cardiac valve were implanted between right ventricle and pulmonary artery. As antiplatelet agent, ticlopidine 200 ㎎/day was used in the post operation period during which time monthly laboratory parameters were obtained including hemoglobin, hematocrit, white cell count, lactic acid dehydrogenase, platelet count. Among the survived 4 dogs after conduit graft implantation two dogs died of the thromboermbolic complication. The two remaining dogs were investigated post operative 3 months period. Died dogs were autopsied at 4 and 6th week postoperatively and the heart and lungs were excised and examined grossly. Both valves had thrombus formation on the valve ring and disc.
In conclusion, according to our clinical data and animal experimental data maintenance with combined therapy of aspirin and ticlopidine was effective in prevention of thromboembolism after cardiac valve replacement and hemorrhagic complication was negligible compared to the anticoagulant therapy with warfarin.