Effects of hyaluronic acid on bleeding following third molar extraction

Abstract Objective To explore the effects of hyaluronic acid (HA) on bleeding and associated outcomes after third molar extraction. Methods Forty patients who had undergone molar extraction were randomly divided into two groups; 0.8% (w/v) HA was applied to the HA group (n=20) whereas a control group (n=20) was not treated. Salivary and gingival tissue factor (TF) levels, bleeding time, maximum interincisal opening (MIO), pain scored on a visual analog scale (VAS), and the swelling extent were compared between the two groups. Results HA did not significantly affect gingival TF levels. Salivary TF levels increased significantly 1 week after HA application but not in the control group. Neither the VAS pain level nor MIO differed significantly between the two groups. The swelling extent on day 3 and the bleeding time were greater in the HA group than in the control group. Conclusions Local injection of HA at 0.8% prolonged the bleeding time, and increased hemorrhage and swelling in the early postoperative period after third molar extractions.

Introduction effect during oral wound-healing, and is commonly applied after tooth extraction. Generally, previous studies about the subject have focused on tissue It has been hypothesized that HA of appropriate consistency increases cell motility 1,13 .
Tissue factor (TF) is best known as the primary cellular initiator of blood coagulation. TF levels vary as the need for hemostatic protection changes 4,10 . The changes in tissue TF levels. The bleeding time may also be an objective measure of HA activity. Swelling, pain scored on a visual analog scale (VAS), and the hemorrhage extent.
positive outcomes of HA treatment, may cause researchers to overlook potential side effects.
process, hemostatic effects of HA should also be considered. Our hypothesis was that HA might modulate hemostasis and bleeding. Additionally its therapeutic effect and relationship with side effects can also compromise its use in surgical procedures.  Gengigel, Ricerfarma, Italy) following tooth removal (n=20) 5,6 . A 0.2 ml HA gel was applied immediately after M3 removal to the edge of the extraction socket.
The control group was not treated.
Before each surgical procedure, MIO was recorded (in mm) and the mouth was rinsed with distilled water. (thus from the most inferior region of the tragus to the oral commissure, and to the soft tissue margin, respectively) on the operated side were noted 11 . VAS pain scores were recorded 1 h, and 3 and 7 days, after surgery. At 1 week (T2), the mouth was rinsed with distilled water and 2-mL saliva samples collected once more as described above. The sutured regions were locally anesthetized and tissue samples were obtained from sites very close to the initial sampling sites. Mann-Whitney U test were used to assess differences between the HA and control groups. A p value <0.05

Results
The mean patient age was 24.8 years (range:

18-35 years). Comparison of the gingival TF between
difference with TF when compared to the control group's mean values.
In the control group, there was no statistically week in HA group in One-Way ANOVA for Repeated Measurement test (p<0,05). In this group, binary Difference) test. In which, mean of T2 was less then  measurements (p<0.05). However 3rd day outcomes of orotragus and mentotragus measurements showed more swelling in the HA group (p<0.05)( Table 3).

Discussion
We explored whether HA affected hemostasis after M3 extraction. We used the TF level and bleeding time as primary outcomes and VAS-measured pain, MIO, and swelling as secondary outcomes. To the best of our knowledge, the effect of high-molecular weight HA on hemostasis after M3 extraction has not previously been examined.
HA inhibits platelet aggregation and adhesion and, at high concentrations, prolongs bleeding times.
As HA exerts antithrombotic effects, the material is used to coat endovascular devices 15 . HA plays two very important roles during wound-healing. First, it creates a temporary structure during the early stages of healing. Second, and most importantly, it triggers cell proliferation and migration 14 . Therefore, HA is often used to aid oral wound-healing and increases 12 .
However, although HA aids wound-healing, this may be associated with increased bleeding (an antithrombotic effect) 2,15 . We measured the TF levels, the blood coagulation cascade initiator, to explore the relationship between HA application and bleeding.
TF is often overexpressed after wounding, trauma, or surgery. TF-induced hypercoagulability encourages wound-healing 3 . However, we found that HA did not increase gingival TF activity. The salivary TF level controls at 1 week after operation, when we expected a reduction. This may be associated with prolongation of bleeding in the HA group. HA increased salivary but not gingival TF levels, perhaps because physiological changes in the salivary glands and gingiva differ.