Signa Vitae. 2023; 19(4): 104-108. doi: 10.22514/sv.2023.054
Original Research

Effect of hemocoagulase on the coagulation parameters, blood transfusion volume and bleeding volume of patients with severe traumatic fractures

Haiyang Zhao1,*,, Jingyuan Si2, Hongmin Guo3, Xiaoming Li4, Jinzhu Wang1

1Department of Severe Trauma Orthopedics, The Affiliated Hospital of Chengde Medical University, 067000 Chengde, Hebei, China

2Operating Room, The Affiliated Hospital of Chengde Medical University, 067000 Chengde, Hebei, China

3Department of Emergency, Chengde Central Hospital, 067000 Chengde, Hebei, China

4Department of Orthopedics, Xinglong Count People’s Hospital, 067399 Chengde, Hebei, China

*Corresponding Author(s):zhaohaiyang_vv@163.com (Haiyang Zhao)

History Submitted: 28 September 2022 | Accepted: 12 December 2022 | Published: 08 July 2023
Copyright:  ©2023 The Author(s). Published by MRE Press.
This is an open access article under the CC BY 4.0 license (https://creativecommons.org/licenses/by/4.0/).

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Abstract

To investigate the effect of hemocoagulase on coagulation parameters, blood transfusion volume and bleeding volume in patients with severe traumatic fractures. A total of 116 patients with severe traumatic fractures admitted to our hospital. These patients were randomly divided into the study group (hemocoagulase injection) and control group (normal saline injection), with 58 patients in each group. The bleeding time, coagulation time, perioperative bleeding volume, blood transfusion volume, hematology and coagulation parameters of the two groups were observed and compared. At 24 h post-surgery, the bleeding time and coagulation time were significantly shorter in the study group than in the control group (p < 0.05). The intraoperative bleeding volume, 24 h postoperative drainage volume, and blood transfusion volume were significantly lower in the study group than in the control group (p < 0.05). In addition, the 24 h postoperative levels of hematology parameters were significantly higher in the study group than in the control group (p < 0.05). However, coagulation parameters were similar in both groups before and at 24 h after surgery. Hemocoagulase has a better hemostatic effect and can effectively reduce perioperative bleeding without affecting the coagulation functions of patients with severe traumatic fractures. Therefore, hemocoagulase is a reliable treatment regimen in clinical practice.

Keywords:Hemocoagulase;Severe traumatic fracture;Coagulation function;Blood transfusion volume;Bleeding volume
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Cite this article

Haiyang Zhao, Jingyuan Si, Hongmin Guo, Xiaoming Li, Jinzhu Wang. Effect of hemocoagulase on the coagulation parameters, blood transfusion volume and bleeding volume of patients with severe traumatic fractures. Signa Vitae. 2023; 19(4): 104-108. doi: 10.22514/sv.2023.054

1. Introduction

There are clinical evidences [1, 2] indicating that patients often suffer bone, tendon and other deep tissue injuries during severe trauma to the limbs, and bone fractures are the most common outcome of these traumatic events. In some serious cases, severe trauma can lead to massive hemorrhage and pose a direct threat to the life and health of the patients. Emergency repair surgery is currently the mainstay of treatment for severe traumatic fracture, as this approach can quickly improve the patient’s conditions and promote early functional recovery of the patient’s limbs. Clinical studies [3, 4] have demonstrated that uncontrolled massive bleeding following a severe traumatic fracture can cause hemorrhagic shock in patients. In addition, patients with severe traumatic fractures have been reported to have clinically abnormal coagulation functions such as hypercoagulability and hyperfibrinolysis, leading to adverse reactions including venous thrombosis and gastrointestinal bleeding [5, 6]. These conditions not only affect the surgical treatment of patients, but also are extremely detrimental to their postoperative recovery [7, 8]. Therefore, how to effectively control the postoperative bleeding volume and improve coagulation functions in patients with severe traumatic fractures is an important issue that needs to be addressed in the clinical treatment and postoperative recovery of these patients. Hemocoagulase, an enzyme preparation isolated from snake venom, has demonstrated significant efficacy in treating bleeding disorders and improving bleeding in patients [9, 10]. In this comparative study, the effect of hemocoagulase on the coagulation parameters, blood transfusion volume, and bleeding volume were examined in patients with severe traumatic fractures admitted to hospital.

2. Subjects and methods

2.1 General subject information

A total of 116 patients with severe traumatic fractures admitted were selected in this study. These patients were randomly divided into study group and control group with 58 patients per group using the random number table (Supplementary Table 1). In the study group, there were 30 males and 28 females, with a mean age of 34.26 ± 1.21 years (31–37 years), an average weight of 65.34 ± 3.15 kg (58–71 kg), and an average height of 168.24 ± 5.26 cm (153–177 cm). There were 22 cases of femur and tibia-fibula fractures, 18 cases of tibia-fibula and ulna-radius fractures, 15 cases of femur and humerus fractures, and 3 cases of humerus and ulna-radius fractures. Causes of trauma included traffic injuries (n = 31), crush injuries (n = 14), fall injuries (n = 11), and others (n = 2). General clinical data were comparable for both two patient groups.

2.1.1 Inclusion criteria

(1) Patients who meet the criteria for severe trauma: Injury severity score (ISS) is >16 on the Abbreviated Injury Scale (AIS); (2) Has bone fractures; (3) Underwent open reduction and internal fixation; (4) Patients who are conscious and have normal cognition; (5) Patients who signed the informed consent form.

2.1.2 Exclusion criteria

(1) Open bone fractures; (2) Impaired central nervous system; (3) Severe stress response during treatment.

2.2 Methods

All participants received basic integrative therapy, including symptomatic treatment of injuries, open reduction internal fixation surgery for limb fractures, blood transfusion and fluid replacement to stabilize the circulatory system, and protective mechanical ventilation to maintain normal respiration and correct symptoms of hypoxia. In addition, hemostasis, analgesia, sedation, and measures to prevent gastrointestinal hemorrhage and infection were also provided.

2.2.1 Study group

Patients were intramuscularly injected with one unit of hemocoagulase solution for injection (Manufacturer: Zhaoke Pharmaceutical (Hefei) Co., Ltd., Anhui province, China; Approval document no.: CYFYLL2022494; NMPA approval no. H20060895; Strength: 1 mL: 1 unit) at 30 min before surgery. Patients were also intravenously injected with one unit of hemocoagulase solution for injection at 15 min before incision and on the evening of the day of surgery and 1 d after surgery.

2.2.2 Control group

Patients were given the same dose of normal saline in the same manner at the same time points as the study group.

2.3 Observation parameters

The bleeding time, coagulation time, perioperative bleeding volume, blood transfusion volume, hematology and coagulation parameters of the two groups were observed and compared.

(1) Hematology parameters include hemoglobin (Hb) and platelet count (PLT);

(2) Coagulation parameters include thrombin time (TT), fibrinogen (Fib), prothrombin time (PT), and activated partial thromboplastin time (APTT).

(3) Collect venous blood (2 mL) from patients before and at 24 h after surgery and the relevant parameters were measured using the Sysmex XE-2100 Automated Hematology System (Sysmex, Kobe, Japan) in strict accordance with the instrument procedures.

2.4 Statistical analysis

Statistical analysis was performed using SPSS (version 14.0, IBM, Chicago, IL, USA). Measured data was expressed as mean ± standard deviation (x̄ ± s) and compared using the independent sample t-test between groups and paired t-test within a group. Count data was expressed as a percentage (%) and compared using a χ2 test. p < 0.05 was considered statistically significant.

3. Results

3.1 Comparison of bleeding time and coagulation time in the study and control groups

The bleeding time and coagulation time were not significantly different between the study and control groups before surgery. However, the bleeding time and coagulation time were significantly shorter in the study group than that in the control group at 24 h after surgery (both p < 0.05) (Table 1).

Table 1.Comparison of bleeding time and coagulation time (x̄ ± s).
GroupNBleeding time (s)t valuep valueCoagulation time (s)t valuep value
Pre-surgery24 h post-surgeryPre-surgery24 h post-surgery
Study group58116.34 ± 15.23108.02 ± 11.253.34640.0011354.24 ± 20.20334.25 ± 16.525.8340<0.001
Control group58115.91 ± 14.97116.05 ± 14.990.05030.9599355.64 ± 19.98354.26 ± 18.630.38470.7012
t value—0.15333.2630——0.37536.1203——
p value—0.88<0.001——0.71<0.001——

3.2 Comparison of perioperative bleeding volume and blood transfusion volume in the study and control groups

Intraoperative bleeding volume, 24 h postoperative drainage volume, and blood transfusion volume were significantly lower in the study group than that in the control group (all p < 0.05) (Table 2).

Table 2.Comparison of perioperative bleeding volume and blood transfusion volume (x̄ ± s).
GroupNIntraoperative bleeding volume (mL)24 h postoperative drainage volume (mL)Blood transfusion volume (mL)
Study group58526.34 ± 22.3292.16 ± 8.10123.16 ± 11.02
Control group58963.14 ± 47.14158.28 ± 11.03264.28 ± 19.11
t value—63.779836.796948.7194
p value—<0.001<0.001<0.001

3.3 Comparison of hematology parameters in the study and control groups

Hematology parameters, including Hb level and PLT level, were similar between the two groups before surgery (all p < 0.05). However, levels of hematology parameters at 24 h post-surgery were significantly higher in the study group than in the control group (all p < 0.05) (Table 3).

Table 3.Comparison of hematology parameters (x̄ ± s).
GroupNHb (g/L)t valuep valuePLT (109/L)t valuep value
Pre-surgery24 h post-surgeryPre-surgery24 h post-surgery
Study group58131.24 ± 9.23121.93 ± 8.255.7274<0.001183.84 ± 7.26173.25 ± 6.228.4362<0.001
Control group58132.03 ± 8.96101.24 ± 7.9419.5868<0.001184.00 ± 8.05160.24 ± 5.1418.9457<0.001
t value—0.467713.7614——0.112412.2793——
p value—0.64<0.001——0.91<0.001——
Hb: hemoglobin; PLT: platelet count.

3.4 Comparison of coagulation parameters in the study and control groups

Coagulation parameters were not significantly different between the two groups before and at 24 h after surgery. However, Fib level was significantly decreased in both groups at 24 h post-surgery (p < 0.05) (Supplementary Table 2).

4. Discussion

Previous clinical studies [11, 12] have shown that patients with severe limb trauma are often hypercoagulable due to abnormal changes in the coagulation system. Both intrinsic coagulation factors and extrinsic coagulation pathways are considered to play a role in this phenomenon, with the latter being a key contributing factor. Therefore, activation of extrinsic coagulation pathway is an important method for initiating blood coagulation during clinical treatment in patients with severe limb trauma. When an individual is healthy, the relevant substances in the blood, including platelets, various coagulation factors and anticoagulation factors, are in a relatively stable equilibrium [13]. However, this equilibrium is disrupted when an individual experiences trauma, especially severe trauma. During acute severe bone fracture, rupture of local blood vessel wall disrupts the equilibrium among coagulation, anticoagulation and fibrinolysis, ultimately leading to hemorrhage [14, 15]. In the case of minor trauma, intrinsic coagulation factors can be self-activated to promote coagulation. On the other hand, since patients with severe traumatic fractures have more severe and complicated trauma, drug intervention is required to activate extrinsic coagulation pathway to achieve effective hemostasis.

Given that wound and incisions are a source of bleeding in patients undergoing orthopedic surgery, it is also necessary to consider the effect of hemostatic agent on perioperative coagulation functions of the patient when selecting a reasonable hemostatic agent. This is because patients may develop hypercoagulability due to postoperative pain and inflammation. In addition, since bone fracture patients require long-term bed rest after surgery, the incidence of venous thrombosis can be greatly increased if hypercoagulability cannot be effectively controlled. Therefore, the impact on coagulation function is an important factor to be considered when choosing a hemostatic agent [16, 17].

Hemocoagulase is a hemostatic agent extracted from Bothrops jararaca venom that is extensively used in general surgery, gynecology, and thoracic surgery. The clinical hemostatic effect of hemocoagulase has also been widely recognized by patients and clinicians [10, 18]. Previous studies [19, 20] have demonstrated that the application of hemocoagulase during hepatobiliary surgery can effectively reduce intraoperative bleeding volume without affecting the coagulation functions of patients. Furthermore, other studies [21, 22] have shown that injection of hemocoagulase into rabbits accelerated blood coagulation without affecting platelet concentration. A study by Nascimento da Costa et al. [23] found that hemocoagulase therapy does not confer the risk of deep vein thrombosis in the lower limb and is clinically safe and highly reliable in elderly patients.

Hemocoagulase plays both “thrombin-like” and “thromboplastin-like” roles in clinical practice [24, 25]. Hemocoagulase acts similarly to human thrombin in that it causes platelet aggregation and white thrombus formation at the bleeding site without affecting the patient’s other healthy sites [26, 27]. On the other hand, hemocoagulase can also act as thromboplastin in the degradation of fibrin to fibrinopeptide A, which forms soluble fibrin I with fibrin to achieve coagulation in patients with injury-induced bleeding [28, 29]. Collectively, these findings [30, 31] showed that the coagulation and hemostatic effects of hemocoagulase are specific only to the bleeding site and not to blood vessels in other healthy tissues.

In the present study, the 24 h postoperative bleeding time and coagulation time were significantly shorter in the study group than in the control group (both p < 0.05). Patients in the study group had significantly lower intraoperative bleeding volume, 24 h postoperative drainage volume, and blood transfusion volume than that in the control group (all p < 0.05). In addition, the levels of 24 h postoperative hematology parameters were markedly higher in the study group than in the control group (all p < 0.05). However, coagulation parameters were similar between the study and control groups both before and at 24 h after surgery. Further study revealed that administration of a small dose of hemocoagulase promoted local platelet aggregation and thrombus formation specifically at the site of vascular damage without disrupting the coagulation/fibrinolysis balance in the patients. Hemocoagulase does not activate fibrin stabilizing factor, indicating stable maintenance of overall coagulation function. Consistent with previous findings [32, 33], our results further confirmed the superior efficacy of hemocoagulase in the clinical treatment of severe traumatic fractures. Limitations of this study included a small sample size and a lack of patients with open fractures. Therefore, a large-cohort study of a wider patient population is warranted to determine the efficacy and scope of application of hemocoagulase.

5. Conclusions

In summary, hemocoagulase is a better hemostatic agent that can effectively reduce perioperative bleeding without affecting coagulation functions in patients with severe traumatic fractures. Therefore, hemocoagulase is a reliable treatment regimen in clinical practice.

Availability of Data and Materials

The authors declare that all data supporting the findings of this study are available within the paper and any raw data can be obtained from the corresponding author upon request.

Author contributions

HYZ—designed the research study. HYZ, JYS, HMG, XML and JZW—performed the research. HYZ, JYS, HMG, XML and JZW—analyzed the data. HYZ, JYS, HMG, XML and JZW—wrote the manuscript. All authors read and approved the final manuscript.

Ethics approval and consent to participate

Ethical approval was obtained from the Ethics Committee of the Affiliated Hospital of Chengde Medical University (Approval no. CYFYLL2022494). Written informed consent was obtained from a legally authorized representative(s) for anonymized patient information to be published in this article.

Acknowledgment

Not applicable.

Funding

This research received no external funding.

Conflict of interest

The authors declare no conflict of interest.

Supplementary material

Supplementary material associated with this article can be found, in the online version, at https://oss.signavitae.com/mre-signavitae/article/1677194327244062720/attachment/Supplementary%20material.docx.

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