Orthognathic surgery is a corrective intervention for various types of maxillofacial deformities and aims to readjust the anatomical and functional relationships through surgical manipulation of facial skeletal components¹.

Bleeding during orthognathic surgery is one of the main concerns of oral and maxillofacial surgeons². Owing to the high vascularity of the maxilla and mandible, significant bleeding may occur during orthognathic surgery³. In some patients, bleeding may necessitate blood transfusions during or after orthognathic surgery⁴.

Various agents have been developed to reduce intraoperative bleeding and transfusion, including hemocoagulase, tranexamic acid, and aprotinin⁵. Tranexamic acid inhibits the plasminogen activator, whereas hemocoagulase has a different mechanism that controls the conversion of fibrinogen to fibrin. Considering the different sites of action of the two drugs in the coagulation cascade, they have been reported to significantly reduce bleeding by complementing each other⁶. However, there are few studies of the effect of hemocoagulase or the combination of hemocoagulase and tranexamic acid on bleeding in orthognathic surgery. We investigated the effects of hemocoagulase, tranexamic acid, and their simultaneous use for reducing bleeding during orthognathic surgery.

1. Study participants

The study was approved by the Institutional Review Board of Dankook University Dental Hospital (DKUDH IRB 2022-11-014). Patients who underwent orthognathic surgery of the maxilla and mandible including conventional Le Fort I and bilateral sagittal split ramus osteotomies (BSSRO) at Dankook University Hospital between January 2013 and September 2022 were enrolled. We excluded 9 patients who underwent intraoral vertical ramus osteotomy, 5 patients who underwent coronoidectomy, and 5 patients who underwent anterior segmental osteotomy of the maxilla. None of the patients’ medications included antithrombotic agents.

2. Research methods

The following drugs were administered to all patients: hemocoagulase (Botropase; Hanlim Pharm.) 1 mL every 12 hours, and tranexamic acid (Shin Poong Pharm.) 500 mg every 24 hours. Patients were divided into three groups according to drugs received: Group T (tranexamic acid), Group B (Botropase), and Group BT (Botropase and tranexamic acid). According to each patient’s diagnosis, the maxilla and mandible were adjusted to the planned positions by the same surgeon. The mean arterial pressure during surgery was maintained at 90-100 mmHg. Age, sex, weight, blood loss, and duration of surgery were recorded in the surgical and anesthetic records, and red blood cells (RBC), hemoglobin (Hb), hematocrit (Hct), and platelet levels were measured before, immediately after, and one day after surgery. Total blood loss was calculated using the following formula:

Total amount of blood loss={amount of fluid collected in suction apparatus (mL)–amount of saline wash given (mL)}+amount of blood content in weighed swabs (mL).

where, 1 g of blood=1 mL of blood.

3. Statistical methods

Statistical analysis was performed using IBM SPSS software (ver. 28; IBM). ANOVA and repeated measures ANOVA were used as statistical methods. P<0.05 was considered statistically significant.

1. Characteristics of study participants

There were 26 patients in the tranexamic acid group (Group T; mean age, 24.65 years), 84 patients in the Botropase group (Group B; mean age, 23.73 years), and 72 patients in the Botropase+tranexamic acid combination group (Group BT; mean age, 22.69 years). The sex ratios (female:male) in Groups T, B, and BT were 14:12, 42:42, and 35:37, respectively. The mean weight of Groups T, B, and BT were 70.32 kg, 64.39 kg, and 64.25 kg, respectively. The mean operating time of Groups T, B, and BT were 208.23 minutes, 217.10 minutes, and 229.29 minutes, respectively. There was no significant differences between groups (P>0.05).(Table 1)

When preoperative RBC, Hb, Hct, and platelet levels were compared between the T, B, and BT groups, the P-values were 0.318, 0.234, 0.333, and 0.482, respectively, with no significant differences.(Table 2)

2. Bleeding volume, RBC, Hb, and Hct results

Intraoperative blood loss in T, B, and BT groups averaged 440.38 mL, 426.79 mL, and 450.69 mL, respectively. There were no significant differences between groups (P=0.649).(Table 3)

When RBC, Hb, and Hct levels were compared between the B, T, and BT groups before surgery, on the day of surgery, and the day after surgery, the P-values were 0.596, 0.468, and 0.466, respectively, with no significant differences.(Table 4)

3. Blood loss volume, RBC, Hb, and Hct results based on surgical methods

When comparing RBC, Hb, and Hct levels between the three groups, before and on the day of surgery, as well as one day after surgery for the patient group who underwent only Le Fort I and BSSRO, the P-values were 0.284, 0.508, and 0.357, respectively.(Table 5)

For the group that underwent Le Fort I and BSSRO, along with genioplasty, when the RBC, Hb, and Hct values were compared between the B, T, and BT groups before surgery, on the day of surgery, and the day after surgery, the P-values were 0.623, 0.897, and 0.833, respectively.(Table 6)

For the RBC, Hb, and Hct levels the day before, on the day, and the day after the surgery in the groups that underwent Le Fort Ⅰ and BSSRO with and without genioplasty, the P-value was <0.01 in all groups, with a significantly greater reduction in the group that underwent Le Fort I and BSSRO with genioplasty.(Table 7)

Orthognathic surgery can necessitate blood transfusion due to significant intraoperative bleeding, which can lead to the development of blood-borne infections, allergic reactions, and other complications⁷. Various methods have been proposed to reduce surgical bleeding and need for blood transfusions⁸.

Hemocoagulase (Botropase), a substance extracted from snake venom, promotes blood coagulation following a principle similar to thrombin⁹. Unlike thrombin, hemocoagulase affects only the fibrinogen conversion process and does not affect other factors. Therefore, the hemostatic effect appears only in the damaged area and does not cause coagulation in a wide range of blood vessels⁶. However, few studies have examined the effects of hemocoagulase on bleeding reduction in orthognathic surgery¹⁰.

Tranexamic acid is a synthetic analogue of lysine with an antifibrinolytic effect caused by reversibly inhibiting the binding of plasminogen and lysine on the plasmin molecule¹¹. Previous studies have reported that intraoperative administration of tranexamic acid can reduce intraoperative and postoperative bleeding and transfusion requirements in various surgeries¹².

A previous study showed that the two drugs act on different sites of the coagulation process and can reduce the need for blood transfusion by significantly reducing bleeding with complementary effects. However, no previous study has been conducted examining the use of this drug combination for reducing bleeding during orthognathic surgery¹³. Limited studies have been conducted to compare bleeding reduction in orthognathic surgery using hemocoagulase, tranexamic acid, and their simultaneous use.

Shetty and Sriram¹⁰ reported that hemocoagulase 1 mL was administered before orthognathic surgery to reduce blood loss. Christabel et al.¹⁴ and Choi et al.¹⁵ reported that administration of 10-20 mg/kg of tranexamic acid could reduce bleeding in orthognathic surgery. However, the appropriate dose for orthognathic surgery remains ambiguous, as the systemic use of this drug may increase the risk of thromboembolic complications. In the present study, a combination of 1 mL hemocoagulase and 500 mg tranexamic acid was administered in the simultaneous use patient group (Group BT). No drug side effects or thromboembolic complication occurred, consistent with the results of other surgical studies⁶.

Meta-analyses by Mei and Qiu⁵ and Song et al.¹⁶ confirmed that tranexamic acid can effectively reduce intraoperative bleeding. However, it was recommended to conduct larger scale studies to ascertain changes in blood loss during orthognathic surgery employing different surgical methods. Therefore, we included patients who underwent Le Fort I and BSSRO with and without genioplasty. There was no significant difference between the surgical methods in the tranexamic acid and hemocoagulase combination group based on the drug effects. The RBC, Hb, and Hct levels were significantly lower in Le Fort I and BSSRO combined with genioplasty group compared with those in the group without genioplasty.

This study had several limitations. First, the volume of blood loss during surgery does not necessarily measure the exact amount of blood lost by the patient in total. Second, this was a retrospective study without a control group in which hemostatic agents were applied to patients to reduce bleeding in orthognathic surgery. More accurate results may be obtained by conducting a larger randomized control trial in the future.

The use of tranexamic acid coupled with hemocoagulase had similar efficacy in patients who underwent Le Fort I and BSSRO both with and without genioplasty. This knowledge can equip oral and maxillofacial surgeons with information necessary to provide better medical care and avoid bleeding complications in their planned surgeries.

M.S.K. participated in data collection, study design, performed the statistical analysis and wrote the manuscript. S.J.H. participated in the study design and coordination and helped to draft the manuscript. All authors read and approved the final manuscript.

Ethical approval was provided by the Institutional Review Board of Dankook University Dental Hospital (DKUDH IRB 2022-11-014). The written informed consent was waived by the IRB due to the retrospective nature of the study.

No potential conflict of interest relevant to this article was reported.