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Assessment of the hemostatic and osteopromotive action of a local hemostatic agent in hepatitis patients

Abdel-Alim, Hala M.; Abdel-Dayem, Hassan

Egyptian Journal of Oral & Maxillofacial Surgery: April 2012 - Volume 3 - Issue 1 - p 16–22
doi: 10.1097/01.OMX.0000412426.71329.19
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Background Patients suffering from hepatitis require special care for controlling bleeding after dental extractions. Although fibrin glue has been widely used, autologous platelet gel with its recognized advantages can be considered as its alternative. However, limited attention has been given in the literature to the use of blood-banked platelet gel as a hemostatic osteopromoter.

Objectives The present work aimed at evaluating the hemostatic effect of blood-banked rich plasma and calcified thrombin on patients suffering from chronic hepatitis B and C and undergoing dental extraction.

Materials and Methods After conducting proper history and laboratory investigations, extractions were performed atraumatically, and local hemostasis was achieved using surgicel for the control group and using blood-banked plasma-rich gel for the study group.

Results The patients were closely observed, and the results proved that platelet gel acted as a successful local hemostatic agent, which was superior in its effect to surgicel with the added advantage of being a healing promoter.

Oral and Maxillofacial Surgery, King Abdelaziz University, Jeddah, Saudi Arabia

Corresponding to Hala M. Abdel-Alim, Department of Oral and Maxillofacial Surgery, King Abdel-Aziz University, Jeddah, Saudi Arabia Tel: + 966 0533482015; e-mail: hala.mokhtar@live.com

Received December 25, 2011

Accepted January 13, 2012

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Introduction

Dental surgeons are faced with medically compromised patients. An accurate medical history is the most useful information a clinician can have when deciding whether a patient can safely undergo planned dental therapy 1.

Patients suffering from liver disease require special consideration before undergoing oral surgery. Liver damage could be the result of infectious disease, ethanol abuse, or biliary congestion or could be drug induced. Hepatitis B virus, which can be transferred through blood and body fluids, is a major concern of every healthcare provider 2.

To fully assess liver function, liver function tests, including analyses of aspartate aminotransferase, alanine aminotransferase, γ-glutamyl transpeptidase, bilirubin, alkaline phosphatase, lactate dehydrogenase, and albumin levels, and a coagulation profile, are conducted when indicated 2.

Liver disease may alter clotting function considerably. With liver failure, clotting factors II, VII, IX, and X are produced in much lower amounts, and patients may experience severe bleeding problems during surgery. The prothrombin time (PT), partial thromboplastin time (PTT), international normalized ratio (INR), and platelet levels should be monitored. If the PT and PTT are more than 1.5 times the control values or if the INR is at least 1.5 times normal, replacement of clotting factors with fresh frozen plasma is necessary 3.

The liver is closely involved in carbohydrate and fat metabolism. Dysfunction may lead to malnutrition and poor wound healing. Laboratory values may reveal clotting abnormalities and impairment of protein synthesis 3,4.

The literature has mainly focused on infection control measures and systemic management of patients with liver disease, and only minor attention has been given to local management of patients undergoing minor oral surgical procedures. Local measures to control operative bleeding include placement of hemostatic agents such as regenerated oxidized cellulose or topical thrombin with a collagen plug, microfibrillar collagen, collagen tape, or resorbable gelatin sponge. These materials should be held in the socket with sutures 2. Fibrin glue (tisseel) has gained more recognition in managing local bleeding in the maxillofacial region 5,6.

The use of autologous platelet-rich plasma in the field of cosmetic surgery started in 1997. It was applied in the fields of periodontal surgery and implant dentistry around the root surface of natural teeth that are prone to bone loss, as well as in implants with a minor interface defect to enhance bone regeneration 7.

Autologous platelet gel has been considered as an alternative to fibrin glue, with applications in oral and maxillofacial surgery. To make the gel ready for use, calcified thrombin is added in predetermined proportions just before application. These applications include the following: bone grafting for dental implants; sinus lift procedures; particulate grafts; and oral/nasal fistula repair in hemophiliacs undergoing surgery 7.

Platelet gel has the following positive effects: first, a large number of platelet cells needed for clot formation are found in the platelet gel, which leads to the formation of a firm, nonfriable clot. Second, thrombin activates factor XIII, which in turn allows for a stable fibrin crosslinkage in the presence of ionized calcium; it speeds up mineralization of the collagen matrix because of the presence of a platelet-derived growth factor (PDGF), which is a beneficial effect that occurs right from the start instead of taking place during the second phase of osteogenesis. Third, trabecular bone density is improved by 15–30% when platelet-rich plasma is added to bone grafts; this has been reported in the literature. Fourth, it enhances osteoconduction; osteoblasts are normally nonmotile cells in that will not normally move across a distance greater than 0.4 mm. As osteoblasts participate in ‘endocytosis’ there is a slow movement of the cells through the fibrin network. Because PDGF enhances the fibrin network, movement of osteoblasts along the fibrin network (osteoconduction) is enhanced, resulting in the formation of woven bone much earlier than normal. Fifth, it promotes earlier availability of growth factors and bone morphogenic protein. Sixth, PDGF is chemotactic for monocytes and macrophages. Seventh, PGDF is an activator of collagenase in the later stages of wound healing, which allows remodeling of collagen to promote wound strength. Tissue growth factor β1 activates fibroblasts to form procollagen, which results in collagen deposition within the wound. Eighth, it facilitates local release of thrombin; thromboxane A2 and adenosine diphosphate cause intense vasoconstriction, which enhances hemostatic response and attracts additional platelets to the developing clot 8.

In the reviewed literature, the use of blood-banked platelet concentrate as a substitute for autologous platelet-rich plasma was mentioned but not seriously tried and tested 9.

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Aim of the work

The present work aimed to evaluate the hemostatic and osteopromotion effects of blood-banked platelet-rich plasma and calcified thrombin in patients suffering from chronic hepatitis B and C who were undergoing dental extractions.

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Materials and methods

This study is a prospective, randomized, controlled evaluation, consisting of 30 patients suffering from chronic hepatitis B and C, having severely damaged teeth with indication for extraction. The patients were randomly divided into two equal groups: the control group and the study group, each consisting of 15 patients.

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Preoperative management

All patients underwent comprehensive and thorough history taking and clinical examinations, as well as preoperative assessment of their liver condition. Their coagulation profile was assessed (24–48 h) preoperatively according to their medical reports and results of laboratory investigations by carrying out the following tests:

  • Determination of the type of the presenting hepatic viral disease and analysis of blood group, complete blood count, PT, PTT, bleeding time, and INR were carried out 24–48 h before dental extraction.
  • Liver function tests were assessed preoperatively, including assessment of alanine aminotransferase, aspartate aminotranserase, γ-glutamyl transpeptidase, alkaline phosphatase, and albumin levels. Values of bilirubin were also checked to exclude patients with active jaundice from the research sample.
  • Only patients with INR values not exceeding 2.5 and PT less than 20 s were selected for dental extraction.

A detailed written consent was signed and obtained after providing a clear explanation about the use of the platelet concentrate or surgicel in the extraction sockets following dental extraction.

Radiological study: preoperative periapical images were taken of the damaged tooth or teeth before extraction. Postoperative images were taken 3 months after extraction to assess bone healing.

An aseptic surgical technique and universal infection control precautionary measures were strictly followed throughout the whole procedure, which included the following:

  • Disposable materials such as gloves, needles, patient’s towel and cup, sutures, suction tips, etc. were used. All surfaces were disinfected with gluteraldehyde 2%; all reusable instruments were soaked in 1% chlorohexidine for 20 min immediately after their use, then rinsed with running water, dried, and packed in sterilization pouches for sterilization in an autoclave at 121°C, 15 psi for 24 min.
  • When handling contaminated objects during surgery or during cleanup, a barrier technique was used (gloves, facemask, and eye protection).
  • All sharp objects were promptly disposed of into well-labeled protective containers. All infected nonsharp materials were disposed of into special disposal yellow bags marked as containing biohazard items.
  • All patients were given mepivacaine 3% as a local anesthetic.
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Local hemostatic factors

For the control group

Oxidized regenerated cellulose (surgicel; Johnson and Johnson, Ethicon, Inc. Sommerville, New Jersey, US) of 1/2×2 inch (Fig. 1) was used in the control group.

Fig. 1

Fig. 1

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For the study group

Platelet-rich plasma

The gel was prepared at the Alexandria Regional Blood Transfusion center (Fig. 2).

Fig. 2

Fig. 2

Each platelet bag contained 40–60 ml plasma (from a single donor): 50–60×109/packed platelets with a few red blood cells and a few white blood cells, labeled according to the A–B–O blood grouping system. The platelet bags were stored in blood banks at +22°C or −2°C with constant gentle agitation (or using a mechanical agitator) for 3–5 days according to the type of material of the bag. Blood belonging to group AB, either Rh negative or Rh positive, was used as the source of platelet-rich plasma.

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Calcified thrombin

  • A measure of 1 mg of thrombin was prepared by mixing thrombin, bovine, and lyophilized powder (freeze dried), in vials.
  • A measure of 1 mg of thrombin powder was dissolved in 5 ml of calcium chloride (CaCl, 0.02 mol/l; 10% concentration; Dia Med, Geneva, Switzerland), and 1 ml was aspirated in a 10 ml plastic syringe

Hemostasis relied exclusively on the local measures to control operative and postoperative readings without any systemic replacement therapy.

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Operative procedures

Infection control and universal precautionary measures were implemented during the surgical procedures and postoperative cleanup. After administration of local anesthesia, extraction was performed atraumatically, and the local hemostatic agent was placed in the socket to control bleeding and initiate local coagulation. Thereafter, 3-0 black sutures were used to hold the edges of the wound together.

The local hemostatic was applied for the study and control groups in the following manner:

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For the control group

After performing the extraction, oxidized regenerated cellulose ‘surgicel’ was placed on the rim of the socket, with the edges tucked under the gingival margins; the suture was then used as a figure eight on top of the cellulose piece to hold the surgicel in place along with the edges of the extraction socket for proper healing. A gauze pack was then placed on the socket in the conventional manner.

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For the study group

After tooth extraction, the dental assistant isolated the socket with a gauze surgical dressing and placed a dry gauze pack inside the empty socket while the surgeon prepared the local hemostatic.

The platelet-rich plasma (PRP) was used as a local hemostatic in the following manner: a measure of 7 ml of PRP was collected in a 10 ml syringe and then added to1 ml of calcified thrombin; 1 cm3 of air was then drawn into the syringe. The syringe was tilted three to four times to ensure that the contents were mixed well, and the gel was rapidly applied onto the isolated extraction socket immediately after removing the gauze from the socket. Thereafter, the socket was sutured with 3-0 black silk sutures using the horizontal mattress technique. A gauze pack was then placed on the socket in the conventional manner.

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Postoperative phase

The patients were checked 15 s, 30 min, and 60 min postoperatively, and information pertaining to bleeding and coagulation was recorded. The patients were then discharged after 1 h of postoperative observation with accurate postextraction instructions. All patients were prescribed amoxicillin (500 mg), to be taken orally three times daily for 4 days, starting 1 day preoperatively, as a prophylactic antibiotic. Paracetamol tablets were also prescribed as an analgesic to be taken when needed in divided doses as one or two tablets three times per day, with a maximum dose of six tablets per day.

Postoperative findings and complications including secondary hemorrhage, pain, localized edema, and socket healing were measured and assessed regularly for every patient on the second, seventh, 14th, and 21st postoperative days. Sutures were removed on the seventh postoperative day.

At the end of the 3-month postoperative period, clinical and radiological follow-up investigations were conducted as follows.

Clinical examination of the extraction area was carried out to evaluate the healing of the soft tissue and the condition of the gingival covering the surgical site.

Radiographic evaluation was carried out and images in periapical and/or panoramic views were taken 12 weeks postoperatively to evaluate the healing of the bone.

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Results

The results of this study were analyzed and are tabulated as follows:

The oral condition of all patients who participated in this research was recorded, and the results varied from poor oral hygiene showing signs of generalized gingivitis with calculus deposits, many carious teeth, many severely damaged teeth and roots to good oral hygiene with few carious teeth that needed filling and a mild form of chronic gingivitis, as summarized in Fig. 3.

Fig. 3

Fig. 3

The age range of all 30 patients varied from 40 to 70 years (Fig. 4).

Fig. 4

Fig. 4

The sex distribution of all 30 patients showed a female predominance: 19 patients were female and 11 were male, as presented in Fig. 5.

Fig. 5

Fig. 5

The results of PT showed prolonged time above normal levels for all patients, as presented in Table 1.

Table 1

Table 1

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Results of the immediate postoperative phase

Patients were assessed after placement of surgicel for the control group and PRP for the study group.

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Results 15 s postoperatively

Good homeostasis was observed in both groups; bleeding was similar for all patients; gauze packs showed only blood stains rather than being completely blood soaked (Figs 6 and 7).

Fig. 6

Fig. 6

Fig. 7

Fig. 7

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Results 30 min postoperatively

The successful coagulation resulted in the formation of a blood clot in all patients with only a small amount of blood on the gauze packs, especially when compared with gauze packs removed at an interval of 15 s. Gauze packs removed from extraction sockets of single-rooted teeth showed a similar amount of blood in patients of both groups, but those removed from multirooted extraction sockets showed less amount of blood in patients of the study group when compared with the control group (Fig. 8).

Fig. 8

Fig. 8

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Results 60 min postoperatively

A stabilized clot was achieved in all patients of both groups 1 h after the placement of the local hemostatic. All patients were then discharged without further complications.

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Results of the intermediate postoperative phase

Results of postoperative localized edema and redness for both groups

Examination of the gingival tissue around the extraction site showed mild gingival edema and redness on the second postoperative day in two patients from the control group and in one patient from the study group, which disappeared on the seventh postoperative day.

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Postoperative pain in both groups

Pain was assessed quantitatively for both groups by recording the number of analgesic tablets consumed per day by every patient at the onset of pain: zero to one tablet represented no pain; two to three tablets represented mild pain; four tablets represented moderate pain; and five to six tablets represented severe pain (results are summarized in Tables 2 and 3).

Table 2

Table 2

Table 3

Table 3

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Results of postoperative healing

There were no signs of infection, disintegrated clot, or wound dehiscence in any of the patients in either the control group or the study group. However, socket closure in a significant number of patients of the study group showed signs of improved soft tissue healing and faster closure of the socket when compared with sockets of the control group during the first and second postoperative weeks. By the end of the third week of postoperative clinical assessment, all 30 patients revealed complete socket closure with good gingival healing. No signs of delayed wound healing were observed in any patient of either group.

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Results of the delayed postoperative phase

During the 3 months of postoperative clinical follow-up, it was evident that the local hemostatics used in this study helped in the process of healing of oral wounds. The results were comparable in both groups as regards the small-sized sockets (those of anterior teeth and premolars); better hemostatic and healing results were achieved with PRP when applied to the sockets of the posterior teeth (molars have a greater surface area) especially during the first 3 postoperative weeks.

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Radiological evaluation

All radiographic views showed signs of bone trabeculation in the previously empty sockets with varying signs of resorbing of the lamina dura from the walls of the sockets. No significant difference could be detected in the pattern of bone trabeculation seen in radiographic views of sockets receiving platelet-rich plasma as the local hemostatic compared with those receiving surgicel (Figs 9 and 10).

Fig. 9

Fig. 9

Fig. 10

Fig. 10

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Discussion

It has been stated by Little et al.10 that, when afflicted with chronic liver disease, patients suffer from neglected and poor oral hygiene. This agrees with our present study, as 70% of the whole sample representing both the study group and the control group showed signs of poor oral hygiene. This finding might be attributed to the debilitating nature of the chronic liver disease, which adversely affects many systems and organs of the body, among which are the oral cavity and its structures. Another important reason is the suffering endured by many patients when they seek dental care, as many healthcare providers refuse to carry out any dental treatment on patients suffering from hepatitis.

As regards the laboratory investigations, they were indicative in our study as the PT values revealed obvious altered clotting function, as all patients had elevated PT values that were above the control levels. More than 50% of patients constituting the whole sample from both groups had PT values ranging from 15 to 16.9 s, which indicates increased risk of operative bleeding with decreased clotting function. This agrees with the results of previous researchers 11 who concluded that patients with elevated PT and INR values are susceptible to serious bleeding following dental extraction, and controlling hemorrhage necessitates the use of a powerful local hemostatic as an adjunctive therapy.

With regard to the use of prophylactic antibiotics, amoxicillin was chosen primarily because it is not metabolized in the liver and hence does not add more load on a diseased liver. Second, amoxicillin has a broad spectrum bactericidal effect against Gram-positive cocci and oral anaerobes 1. This agrees with the study by Sweeneyl et al.12 whose goal was to achieve sufficient concentration of the antibiotic at the potential site of infection (tissue or blood) before the spread of the organism. This could support our findings as no postoperative infection was noticed in any patient of both groups. This result was achieved not only by prescribing a prophylactic antibiotic but also by strict adherence to infection control and universal precautionary measures.

The need for a local hemostatic with healing properties for patients with liver disease might be explained by the statement made by O’Connor et al.13, who reported that liver dysfunction may lead to malnutrition and poor wound healing. Therefore, the use of a platelet gel, containing numerous viable platelets, with calcified thrombin (activator and accelerator for PRP) as the local hemostatic in our study seemed to be a suitable solution, helping this category of patients to not only control postoperative bleeding but also promote the process of wound healing 5.

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Conclusion

Blood-banked platelet-rich plasma proved to be an effective local hemostatic for operative bleeding following dental extraction in patients suffering from altered clotting functions, such as in patients suffering from liver disease.

It also showed significant acceleration of soft tissue healing in chronic liver disease patients, who are liable to suffer from delayed wound healing, postoperative pain, and infection.

Postextraction complications including pain, infection, and delayed healing were overcome in this study through the occluding effect of the local hemostatic, the strict infection control measures, the prophylactic use of antibiotics, and finally by the healing effect of the PRP.

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Acknowledgements

Conflicts of interest

There are no conflicts of interest.

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