Efficacy of the hemostatic device VasoSTAT and the study of hemostatic factor

Recently, trans-radial intervention has gained popularity as a common procedure to reduce hemorrhagic complications. However, the cuff-type hemostatic device (TR Band) previously used at our institution required 6 h to achieve hemostasis. Since July 2016, we have been using the VasoSTAT, a new hemostatic device that could achieve hemostasis in 4 h. In a verification study, we found that prolonged activated clotting time (ACT) was related to transient hemorrhage occurrence after the hemostatic procedure. Therefore, we designed a hemostatic protocol based on ACT and evaluated its efficacy. In this retrospective and observational study, 78 and 111 patients used the VasoSTAT and TR Band, respectively, from July 2015 to May 2017. In the VasoSTAT group, the ACTs were significantly lower in the hemostasis success (246 ± 46 s) than in the failure group patients (327 ± 59 s) (P < 0.01). Therefore, we applied the hemostatic protocol to 271 patients from May 2017 to March 2020. The hemostasis success rate was 96% in the post-protocol applied group patients, which was significantly higher than the 82% success rate in the pre-protocol applied group patients (P < 0.01). VasoSTAT resulted in adequate hemostasis in 4 h. Further, ACT was predictive of adequate hemostasis.


Results
From July 2015 to May 2017, 78 and 111 patients were treated with the VasoSTAT and TR Band, respectively. There were no significant differences in the patient backgrounds between the two groups. The ACTs were not significantly different between the VasoSTAT (261 ± 58 s) and TR Band group patients (269 ± 56 s) (P = 0.34). Similarly, the hemostasis success rate was not significantly different between the VasoSTAT (82%) and TR Band group patients (85%) (P = 0.31). The rate of 30-day radial artery occlusion (RAO) was lower in the VasoSTAT (0.6%) than in the TR Band group (4.5%) (P < 0.01).
The 78 patients that used the VasoSTAT were divided into the hemostasis success and failure groups. Patient characteristics are shown in Table 1. Baseline characteristics, procedural characteristics, antithrombotic therapy, and sheath size were similar in both groups. ACTs were significantly lower in the hemostasis success (246 ± 46 s) than in the failure group patients (327 ± 59 s) (P < 0.01). Therefore, based on this result, we designed a hemostasis protocol, based on ACTs.
The ROC curve is shown in Fig. 1. The cutoff for ACT, sensitivity, and specificity, were 299 s, 0.786, and 0.887, respectively. Considering this result, the cutoff value for ACT was set to 300 s for simplicity. When the ACT was more than 300 s, we neutralized heparin using protamine, as per the protocol (shown in Table 2).
From May 2017 to March 2020, 271 patients were treated with the protocol. Patient characteristics are shown in Table 3. Baseline characteristics, procedural characteristics, antithrombotic therapy, sheath size, and ACT were www.nature.com/scientificreports/ similar in both groups. The hemostasis success rate was significantly higher in the post-protocol applied group (96%) than in the pre-protocol applied group (82%) (P < 0.01). The results are shown in Fig. 2.

Discussion
This study primarily found that the hemostasis success rate in patients who used the VasoSTAT in 4 h was not significantly different from that of those who used the TR Band in 6 h. Further, ACTs were predictive of hemostasis, and good control of ACT led to improved hemostasis success rates. TRI has become an increasingly common PCI procedure in recent years, with endovascular therapy (EVT) also being performed by TRI. Therefore, it is widely acknowledged that the number of patients undergoing TRI continues to increase. Regardless of PCI and EVT, adequate hemostasis is achieved using the VasoSTAT.
The blood circulation in the puncture site is better with the use of VasoSTAT than TR Band; hence, primary and secondary hemostasis are readily obtained with the use of the former. Therefore, hemostasis time is shorter    8 . We set the hemostasis time as 4 h in our study, which was appropriate. The VasoSTAT also has several other general advantages. It does not compress surrounding vessels and nerves and can, therefore, reduce pain and numbness. Furthermore, a decompression protocol is unnecessary. As a result of these effects, patients and medical staff experience low stress levels. A study by Minor et al. indicated that the VasoSTAT could significantly increase patient-reported comfort compared with the TR Band 9 . The VasoSTAT could also stop bleeding by minimal pressure and results in a low rate of RAO, as demonstrated by previous studies [8][9][10] . The short duration of hemostatic compression 11 and non-occlusive compression of the puncture site 12,13 were the causes for decreased rates of early and chronic RAO, owing to the ability of VasoSTAT to lower the rate of RAO. Pancholy et al. reported that ipsilateral ulnar artery compression during radial artery hemostasis improved blood circulation through the radial artery, which reduced the incidence of RAO, compared with only radial compression in patients undergoing diagnostic cardiac catheterization 14,15 . However, Safirstein et al. reported that ulnar artery compression with simultaneous radial artery hemostasis did not improve hand perfusion and that the rate of RAO was not significantly different between the VasoSTAT and TR Band group patients 8 . In this study, we did not compress the ulnar artery or evaluate the circulation of the hand, although the rate of RAO was significantly lower in the VasoSTAT group than in the TR Band group patients. Further prospective studies may be necessary to evaluate the relationship between blood circulation and RAO, and the hemostasis device and RAO in patients undergoing PCI. In this study, ACT was found to be an indicator of adequate hemostasis. ACT can be easily measured in a laboratory. It is recommended that ACT be maintained between 250 and 400 s during the PCI procedure 16,17 . By measuring it from the start to the end of the PCI procedure, PCI safety and adequate hemostasis can be ensured. Patient age was not found to be significantly different between the hemostasis success and failure groups but tended to be higher in the latter. In general, due to the fragility of blood vessels and increased prevalence of hypertension, age is regarded as a risk factor for bleeding, as it is in patients undergoing PCI 18,19 . Therefore, it is necessary to be watchful of bleeding interventional procedures in elderly patients.
Distal TRI (d-TRI) is less invasive at the puncture site than TRI 20 , as a result of which, the number of d-TRI cases has increased. A previous study reported that the use of VasoSTAT in d-TRI and tibiopedal artery resulted in adequate hemostasis 10 ; thus, it may be the procedure of choice in these cases. Further studies are necessary to determine whether our hemostatic protocol applies to these cases as well.
This study has several limitations. First, this was a non-randomized, retrospective study. Second, this study was performed in a single center with a small sample size; therefore, the possibility of operator bias cannot be excluded. Third, owing to the prolonged study time, the possible contributive role of the operator's learning curve cannot be excluded. In the post-protocol group, the success rate was 89.5% from May 2017 to March 2018, 92.5% from April 2018 to March 2019, and 96.1% from April 2019 to March 2020.
In conclusion, adequate hemostasis can be achieved in lesser time (4 h vs. 6 h) using the VasoSTAT than using the TR Band. ACT can help indicate adequate hemostasis and, therefore, can be controlled to achieve an improved hemostasis success rate.

Data availability
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.