The change of fibrinogen level and the problem of its measurements were investigated on 16 patients suffered from peripheral vascular occlusive diseases (DVT, ASO, TAO, CAT, etc.).
Plasma fibrinogen level decreased to 60±55mg/dl 24 hours after the initial intravenous infusion of Batroxobin in doses of 30 to 60μl/kg. And it recovered to the pre-treatment level 6 to 8 days after the termination of Batroxobin administration.
Fibrinogen level measured by thrombin time method was lower than that measured by gravimetric method within 24 hours after the initial Batroxobin infusion. Fibrinogen levels measured by nephelometry (T-G meter) and immunological method (M-Partigen) were higher than that measured by gravimetry and thrombin time method. Prothrombin time was prolonged at a fibrinogen level of below 100μg/dl.
The dose of Batroxobin which decreases fibrinogen level below 60mg/dl 24 hours after the initial infusion of Batroxobin, correlated well with the pre-treated fibrinogen level (r=0.952, Y=21.2X-511.4).
It was suggested from these results as follows:
1) Fibrinogen level measured by thrombin time method might be lowered due to FDP which increased markedly within 24 hours after the initial Batroxobin infusion.
2) Fibrinogen levels measured by nephelometry and immunological method were inaccurate, because of being affected by fibrin monomer or des A fibrin.
3) It is possible to fix a dose of Batroxobin correctly that controls the fibrinogen level below 60mg/dl, with the use of the formula as
μl/kg=pre-treated fibrinogen level/20+25
4) The maintenance dose of Batroxobin might be approximately 25μl/kg, if the plasma fibrinogen level decreases to unmeasurable level just before the Batroxobin administration.

抄録全体を表示

腸骨腿動脈領域の閉塞疾患22名に23回のバイパス手術が行われた. 男性20人, 女性2人で, 41-89歳(68.9±11.4歳)であった. 解剖学的再建は大動脈大腿動脈が6例, 腸骨動脈-大腿動脈が3例の9例であり, 非解剖学的再建は大腿- 大腿が8例, 腋下-大腿が6例の14例であった. 非解剖経路の選択は高齢など全身的理由が8例, 再手術などの局所的理由が6例で, この両者の年齢間に有意差がみられた. 5年開存率は
解剖経路で83%, 非解剖経路で59%であり, 両群間に差は認められなかった. 本領域の解剖学的再建の成績は良好であるが, 全身および局所的理由から非解剖経路が選択される例も多く, 慎重な対応が要請される. 解剖経路再建後早期に閉塞した例の検討から, 動脈硬化の危険因子は若年層で増加している部分もあり, 厳しい日常生活のコントロールは高年者より若年層に必要との意見に同意できる結果であった.

抄録全体を表示

Defibrinogenation therapy is expected to be a new type of anticoagulant therapy without serious bleeding complications. However, it appears to be dangerous to perform surgical procedure in the defibrinogenated state.
In order to investigate the causes of the bleeding tendency which occurs during defibrinogenation therapy, the following clinical study was undertaken.
Twelve patients were treated with Batroxobin (Bothrops atrox moojeni and marajoensis). Eight out of 12 patients were suffering from venous thrombosis of ilio-femoral vein. Another 2 patients were suffering from arteriosclerosis obliterans (ASO). And finally, 2 patients were suffering from cerebral artery thrombosis.
Batroxobin was given in doses of 30 to 115μl/kg/day diluted 200 to 500ml of phisiological NaCl-solution as intravenous infusion for 2 to 8 hours. Eight out of 12 patients were treated concervatively with Batroxobin and Urokinase. On the other 4 patients, surgical procedure was performed during defibrinogenation therapy.
On 8 patients who were treated concervatively with Batroxobin and Urokinase, Red blood cell and platelet counts were not changed. Plasma fibrinogen concentration decreased between 40 to 80mg%. FDP level tended to be moderate after the 3rd or 4th infusion. Platelet adhesiveness and ADP-induced platelet aggregation was not decreased markedly. No bleeding complications were found. The other 4 patients were operated during defibrinogenation therapy. Red blood cell, platelet counts, platelet adhesiveness, and ADP-induced platelet aggregation were not changed. Fibrinogen concentration ranged between 0 and 80mg% at the time of the operation. There was no bleeding tendency on these patients with the exception of patient No. 12.
Tracheostomy was performed as an emergency measure on the patient No. 12, 3 hours after the end of the Batroxobin infusion (It is not considered the Batroxobin to have played any causative role). Fibrinogen concentration was decreased beyond measure ability during and after the operation. There was severe bleeding from the wound.
It is concluded from these results as follows:
(1) Platelet adhesion to the grass and ADP-induced platelet aggregation are not influenced extremely by the decreased fibrinogen concentration during the defibrinogenation therapy.
(2) Batroxobin could be used as a conservative therapeutic drug without haemorrhagic risk even if fibrinogen concentration is markedly decreased.
(3) To insure haemostasis, it is necessary to control the fibrinogen concentration above 60mg% during and after the operation.

抄録全体を表示

心臓大血管手術症例11例の術中出血(1,440±650ml)を洗浄式自己血回収装置(Cell Saver 4)で回収した際に生じた廃液を, 選択的遊離Hb吸着剤(HR-O)を充填したカラム(HR-300:遊離Hb約10g吸着可能)および限外濾過装置を用いて処理した. カラム1本使用群8例においては, 廃液中の遊離Hb含有量がカラムの吸着能である10g以下の6例で, 遊離Hbは良好に吸着され, アルブミン, 免疫グロブリン(IgG, IgA)の70～90%回収が可能であった. カラム2本使用群3例では, 遊離Hbはほぼ良好に吸着されたが, アルブミンの回収率が約50%に低下した. 洗浄式回収式自己血輸血において破棄されている血漿蛋白成分は, 遊離Hb吸着剤により有効再利用が可能と考えられた.

抄録全体を表示

Batroxobin is a thrombin-like enzyme from Bothrops atrox venom which causes hypofibrinogenemia by splitting off only fibrinopeptide A from fibrinogen. Defibrinogenation with this enzyme is expected to be a new type of anticoagulation therapy without serious bleeding complications.
In this paper, the changes in blood coagulation systems, specifically platelet function, during defibrinogenation therapy with Batroxobin (B. moojeni) were investigated.
Two out of 3 patients suffered from iliofemoral vein thrombosis were treated with 30 to 40μl/kg/day of Batroxobin and 30, 000u/day of urokinase for 8 to 16 days. In the other one, thrombectomy was performed after the initial administration of Batroxobin, and the defibrinogenation therapy was continued for 15 days after the operation. In these 3 patients, Warfarin sodium was administered 2 days prior to the time when defibrinogenation therapy was discontinued, and it was continued for 1 to 3 months after the therapy.
Red blood cell, platelet count and coagulation factors (II, V, VII-X, VIII, IX) were unchanged during the treatment. Fibrinogen concentration varied between 0 and 80mg% during the defibrinogenation therapy. The maximum level of FDP was found to occure 4 to 6 hours after the initial administration of Batroxobin, and it was gradually restored after that. Prothrombin time was prolonged at a fibrinogen level of below 100mg%. Partial thromboplastin time shortend slightly. Platelet adhesion to glass and ADP induced platelet aggregation were not changed after Batroxobin administration. There was no corelation between platelet function and fibrinogen concentration. No bleeding complications were observed in all patients.
These results suggest as follows:
1) Batroxobin from B. moojeni induces longer lasting defibrinogenation than Batroxobin from B. marajoensis.
2) Platelet adhesion to glass and ADP induced aggregation are not influenced by the decreased fibrinogen concentration nor the increased level of FDP during defibrinogenation therapy with Batroxobin.
3) It is an imporatant factor in certain hemostasis that normal platelet function is maintained during defibrinogenation therapy.
4) It is possible to use defibrinogenation therapy with Batroxobin as a postoperative anticoagulat therapy in vascular surgery.

抄録全体を表示