A split mouth randomized controlled trial was conducted in Department of Oral and Maxillofacial Surgery, Sri Siddhartha Dental College and Hospital, Tumkur, Karnataka, India, among 30 patients (sample size was determined from the findings of a pilot study with 80% power and 95% confidence levels 5 patients were involved in pilot study and were included in the study) aged 18 years to 90 years who required minor oral surgical procedures and were having two or more surgical sites [Table/Fig-1]. All consented patients taking OAT with INR less than 4 were included without altering their anticoagulant regimens. The study was registered under the Clinical Trial Research Institute of India with a registration number CTRI/2016/08/007174. Patients allergic to sea food and with severe medical illness, who were not fit for surgery, were excluded from the study [1]. Ethical clearance was taken from the Institutional Review Board before the start of the study. Two extraction sites, one each in separate quadrant or in same quadrant were randomly allocated into study and control sites [Table/Fig-1]. To reduce the study variability two contralateral sites or tissue in two different sites of any pathology were selected wherever possible. Neither patient nor surgeon could be blinded to the use of HDD versus control method. Patients were randomly divided into two groups by coin toss method.

[Table/Fig-1]:

Pre-operative.

1) Study site: Hemcon dental dressing was applied under finger pressure [Table/Fig-2].

[Table/Fig-2]:

Intra-operative.

2) Control site: The conventional method of pressure pack with a sterile gauze piece under biting pressure was used.

Under unavoidable circumstances if the hemostasis was not achieved at the control site after normal clotting time, then HDD was used to stop the bleeding. After recording complete history, patients were explained about the surgical procedure. Pre-operatively, bilateral Intra-Oral Periapical Radiograph (IOPAR), OPG, all necessary blood investigations were done. Surgical procedures were performed in single appointment; if possible the same tooth in the opposing quadrant or contralateral or same quadrant will be used as control to further minimize the study variability. Three patients were dropped out as they did not come back for the follow-up.

Procedure: HDD shown in [Table/Fig-3], with desired dimension 10mm×12mm was trimmed to fit any bleeding oral wound. Small amount of blood was intentionally left on surface as it was required to facilitate the unique adhesion process. Dressing was placed on the wound site with the dry instrument without packing the site. Direct finger pressure or dry instrument was applied on the dressing until it adheres and wound stabilization was achieved. Finger pressure or instrument was removed by lateral sweeping method to avoid dislodging of material. The top of the dressing should be at the level of crestal gingiva. Duration to achieve hemostasis was noted for HDD site and control site. If the surgical site was larger, then suture was used to stabilize the material if necessary. On the control site sterile cotton gauze dressing placed with biting pressure and time taken for hemostasis was noted. HDD sites were inspected to confirm correct positioning of the dressing on 1^st, 3^rd and 7^th post-operative days [Table/Fig-4,5]. If the material had not dissolved within 48 hours it was washed with irrigation. Post-operative photographs were taken on the 3^rd and 7^th day from the treatment. At one week post-operative appointment healing was evaluated using a scale as follows: 1(significantly worse than control), 2 (same as control), 3 (significantly better than control). Self reported pain scores were evaluated using Visual Analogue Scale (VAS) of 0 to 10 with 0 being no pain and 10 being the worst pain. Standardized Alveolar Osteitis Assessment Criteria [1,4] was used which included radiating pain, clot loss, dark coloration and fetid odour. All the patients were instructed about the oral hygiene maintenance and post-operative medications were prescribed. Patients were counselled for follow-up visits and then clinical evaluation of various parameters was done.

[Table/Fig-3]:

Hemcon Dental Dressing (HDD).

[Table/Fig-4]:

3^rd Post-operative day.

[Table/Fig-5]:

7^th Post-operative day.

Descriptive statistics were done and the data collected were subjected to statistical analysis using IBM SPSS (IBM SPSS Statistics for Windows, Version 21.0. Armonk, NY: IBM Corp). Unpaired t-test was used to compare means between the groups. A p-value <0.05 was considered statistically significant for all the comparisons.

Total 203 patients were assessed for eligibility and 162 patients were excluded as they did not meet the criteria and eight patients were excluded as they were not willing to participate in study and total 33 patients took part in study [Table/Fig-6].

[Table/Fig-6]:

Flowchart for allocation of subjects.

[Table/Fig-7] shows the distribution of study population according to age and gender. Majority of the study population were females with 40% of them were in the age range of 30-50 years.

Hemostasis: The time to achieve hemostasis was shorter using HDD than using pressure pack. The mean time to achieve hemostasis for control site was 4.06 minutes. Statistical significance was found in respect to hemostasis in HDD sites [Table/Fig-8].

Pain scores: Relative pain scores were assessed at day 1, day 3 and on day 7 of post-operative appointments and were based on a 0 to 10 self-reported pain score basis, with 0 being no pain and 10 being the worst pain the patient had ever experienced. HDD relative pain scores were significantly lower than control at day 1 and day 3 but these findings were not statistically significant at day 7 [Table/Fig-8].

Healing: Using a scale of 1 (significantly worse than control), 2 (the same as control), and 3 (significantly better than control), 22 of 30 HDD study sites demonstrated significantly improved healing compared with controls at day 1 and showed complete healing at day 3. HDD study sites healed comparatively better than control sites. There was statistically significant improved healing in HDD study sites compared with control sites [Table/Fig-9].

The possibility of post-surgical hemorrhage is a concern in any patient who is undergoing minor surgical procedure such as extraction, excision of oral lesions, etc. This possibility increases even more in patients taking anti-coagulant or anti-platelet therapy. The new generation HDD of hemostatic medical devices can achieve early hemostasis and improve post-operative healing in patients undergoing minor oral surgical procedures [1]. In the past, stopping anticoagulant treatment for 2-6 days before dental extractions has been suggested since severe hemorrhage may occur post-operatively. Recent research had advocated the continuation of anticoagulant therapy in oral surgical procedure which had gained more attention in the literature, emphasizing the role of local hemostasis [4]. Ferraris and Swason suggested that aspirin need not be stopped before any surgery [17]. Lawrence et al., recommended the continuation of aspirin therapy before elective dermatologic surgery if bleeding time is within normal limits [18]. Inspired by the above studies supporting our view point, we decided to conduct our own which, study included all patients of age group 18-90years taking anti-platelet therapy as well as who required minor surgical procedures. Investigations of PT, INR, bleeding time and clotting time were performed pre-operatively in all the patients. In the present study, sites receiving the HDD had improved post-operative wound healing with minimal complications when compared to the control site. In all sites receiving HDD had showed improved hemostasis (mean 1.49) and reduced pain (mean 1.87 and 1.27) on 1^st and 3^rd days respectively, but on 7^th day there was no significant difference in pain scores. The study also includes taking biopsy to the peripheral gaint cell granuloma in which two sites of the lesion was selected for biopsy out of which in one site HDD achieved hemostasis in 2 min10 sec, and in the other site even after 11 min 40 sec hemostasis was not achieved and later HDD material was used and achieved hemostasis in 2 min, which shows that HDD is a clinically effective haemostatic agent for arresting vessel bleed encountered during minor oral surgical procedures. The results of this study are similar to the study reported by Malliquist JP et al., which reaffirms the efficacy of HDD over conventional methods [1].

The use of antibiotics in conjunction with the HDD had no untoward effect on hemostasis, healing or pain scores. There was no incidence of dry socket, liver clot and untoward incidents in our study at the HDD site. The result of this study proved the fact that Hemcon is a new generation hemostatic agent with which facilitates early hemostasis, better pain control, along with improved wound healing and reduced post-operative pain. Chitin (poly-N acetylglucosamine) is a polysaccharide that is found in arthropod skeletons and produced by algae during fermentation. Both chitin and its deacetylated form chitosan have haemostatic properties. For chitin dressings, haemostatic properties are believed to result from vasoconstriction and mobilization of erythrocytes, clotting factors and platelets to the site of injury [1]. One of the most prominent chitin dressings is the Rapid Deployment Hemostat (RDH) made by marine polymer technologies. In animal studies, chitin is effective in treating minor wounds [2].

In one study, RDH applied to splenic lacerations in swine led to coagulation in 23 seconds, significantly faster than the 173 seconds with fibrin glue. In contrast other studies in swine indicated that RDH gave no statistically significant improvement in survival over a standard gauze dressing [2]. Chitosan dressing such as Hemcon appear to function through mechanically sealing wounds and adhering to surrounding tissue. Advantage of chitosan is natural antimicrobial property. Another advantage of chitosan is that its polycationic nature at acidic pH (like in Hemcon bandages which includes acetic acid) allows it to disrupt the membranes of gram-negative bacteria, giving it natural antimicrobial properties. It is worth noting that all the failures of Hemcon in that animal study were due to bandage not adhering to the tissue to which it was applied. Hemcon can effectively reduce blood loss when applied properly to a wound and has the added benefit of antimicrobial properties [2]. No side effects were reported in the present study and previous studies done. Further studies can be conducted with more number of subjects without keeping INR limitations. The present study material shows better hemostasis reduced pain, and good healing, in patients on AOT which can be used regularly.

The present study provides evidence that HDD can be used as a clinically effective haemostatic dressing material that significantly shortens bleeding time following minor oral surgical procedures. HDD also had better pain control, wound healing rates, improved surgical wound healing and reduced pain score compared to control sites. It also meets most of the criteria’s of ideal haemostatic agent. Furthermore, prospective clinical studies are required to study its efficacy in patients who are on OAT with higher INR values.