A Randomized Controlled Trial of the Chinese Herbal Medicine Keisi-bukuryo-gan (Gui-Zhi-Fu-Ling-Wan) in the Treatment of Deep Vein Thrombosis

Abstract

Keisi-bukuryo-gan was first described in Chinese medical classics Chin-Kuei-Yao-Lueh (金匱要略，200A. D.) and known as one of the most important “kampoh” prescriptions used as a remedy for the “oketsu” syndrome. This prescription contains Moutan Cortex, Persicae Semen and Paeoniae Radix, which are all thought to be improve the “oketsu” syndrome. Keisi-bukuryo-gan possesses the potential to improve peripheral microcirculation by reducing blood viscosity and platelet aggregation. In this paper, we have investigated the effects of oral administration of Keisi-bukuryo-gan on the improvement of the swelling of the lower extremity in the patients with deep vein thrombosis. A prospective controlled trial was devised.

The subjects were consecutive 12 patients with acute symptomatic proximal deep vein thrombosis diagnosed between January 2003 and December 2007. There were 5 men and 7 women and their ages ranged from 30 to 89 years old, with a mean of 65.8 years old. The affected limbs were 9 left lower and 3 right lower extremities. All patients were treated with intravenous drip infusion of heparin (10,000 units /day) and urokinase (240,000 units/day) for 5 to 7 days. Oral anti-coagulant therapy with warfarin sodium was continued for six months. The patients were categorized as follows: Group A–6 patients treated with Keisi-bukuryo-gan; Group B–6 patients treated without Keisi-bukuryo-gan. The two groups were comparable with respect to ages, sex and laterality. To eliminate bias during the period of study. selection of patients was randomized. Consent was obtained from individuals. A granulated preparation of Keisi-bukuryo-gan extract (Tsumura. Inc, Tokyo) was used for this study. The subjects ingested 7.5g of Keisi-bukuryo-gan extract t.i.d. for six months. Each patient was evaluated for the difference of the maximum calf circumference between the affected and the normal limbs. Improvement rate was defined as the following equation. Improvement rate = (Circumference difference before treatment - Circumference difference after treatment)/ Circumference difference before treatment x 100%. The values are expressed as mean±S.D. Statistical evaluation was performed by analysis of the paired Student’s t test.

The difference of the circumference between the affected and the normal limbs in Group A were 5.6±1.3cm (before treatment) and 1.8±1.1cm (after treatment). Those in Group B were 5.2±2.3cm and 3.5±1.9cm, respectively. The circumference difference were significantly decreased after treatment in both groups (p<0.05). The improvement rates of Group A and Group B were 66.1±20.5% and 34.0±13.7%,respectively. The former was significantly higher than the latter (p<0.05).

The results obtained suggest that Keisi-bukuryo-gan has a salutary effect on the improvement in the swelling of the limbs. Catheter directed thrombolysis therapy is more effective than conventional systemic therapy, however, it has some contraindications. Oral administration of Keisi-bukuryo-gan is easy and effective for the treatment of deep vein thrombosis. This result must he evaluated more strictly after collecting more cases in the future.