Dental implants and bleeding disorders: review and clinical indications

1. Introduction

Bleeding disorders are a group of conditions when blood cannot clot properly. They can be congenital or acquired. The congenital ones are inherited and are quite rare. The acquired ones can develop from a pathological condition or can be caused by the intake of drugs belonging to the category of anti-platelet or to the inhibitors of coagulation factors.

Among congenital bleeding disorders the most common is Von Willebrand’s disease, caused by diminished quantity or by a structural defect of the von Willebrand factor [1]. Von Willebrand disease is primarily a hereditary disease, but an acquired variant of von Willebrand disease has also been observed (4). The most famous classification of the disease distinguishes three inherited types: classes 1 and 3 include quantitative factor deficits, while class 2 includes qualitative defects [1,2].

The second most common congenital bleeding disorder is haemophilia, a class of hereditary diseases whose etiopathogenetic mechanism is based on defects of the proteins involved in the coagulation process. It was once called "the royal disease" due to its presence in European royal families in the 19th and 20th centuries. Queen Victoria of England (1818-1901) was an asymptomatic carrier and her descendants in turn transmitted the mutation in various royal houses across Europe [3,4,5].

Anti-platelet drugs, also called "antiaggregant", interfere with the platelet plug formation. Acetylsalicylic acid (aspirin) and clopidogrel are the most commonly prescribed. They are used both in acute treatment and in the prevention of coronary artery disorders and stroke; they are also used for prevention of venous thromboembolism after orthopedic surgery, in generic vascular diseases, unstable angina and in patients who have undergone percutaneous coronary artery surgery and cardiac surgery [6].

Coagulation inhibitors selectively act on certain clotting factors, hindering the clot formation process. These drugs are indicated for deep venous thrombosis, venous and arterial thromboembolic disease, pulmonary embolism, atrial fibrillation with risk of embolization, mechanical heart valve prostheses (to prevent thrombus formation on valves), myocardial infarction, recent heart attack to prevent the onset of new cardiovascular events (another heart attack, stroke, etc.), unstable angina, acute peripheral arterial occlusion and unstable coronary syndromes.[7] Anticoagulant medicines that have been most used over the years are vitamin K-dependent inhibitor drugs Warfarin[8] and Acenocumarol [9]. Recently, to overcome the limits of these kind of anticoagulants, direct thrombin inhibitors and activated Factor X inhibitors have been proposed [10].

Another anticoagulant worth mentioning is heparin, although most often used as short-term therapy or to overlap a long-term therapy when a suspension is required [11]. Thrombocytopenia goes beyond the boundaries of the above classification, as it can be due to a congenital disorder or medically induced. By definition, thrombocytopenia is observed when the platelet count is below 150,000 / μL. The reasons why a platelet count may be below the normal range can be many and varied (4).

Nowadays, clinicians are reluctant to perform dental implants in this type of patients with bleeding disorders and prefer to send the patient to hospital facilities or choose other prosthetic solutions. Moreover, randomized controlled clinical trials cannot be conducted for security and ethical reasons. Therefore, the management of these patients are often demanded to expert opinions and practical guidelines that differs between countries. The aim of this paper is to perform a literature review about dental implants inserted in patients with bleeding disorders and to provide indications for clinicians to help them dealing with these patients.

2. Materials and Methods

Bibliographic electronic search was performed on Pubmed/MEDLINE, Scopus, Web of Science and Cochrane Library databases. The latest research was performed in July 2022. Only article in English were considered.

The keywords “oral implant”, “dental implant(s)”, implantology and implant(s) were searched in combination with the following terms: haemophilia, von Willebrand Desease, thrombocytopenia, bleeding disorder(s), aspirin, clopidogrel, prasugrel, ticagrelor, anti-platelet, antiaggregant, warfarin, sintrom, heparin, dabigatran, rivaroxaban, apixaban, edoxaban, anticoagulant, NOAC, DOAC, novel anticoagulant, direct anticoagulant.

Randomized controlled trials, , cohort studies, cross-sectional studies, case-control studies, review, case series, case reports and animal studies were included in the analysis. Letters to the Editor, expert opinion and article evaluations were excluded.

3. Results

Among the articles found on PubMed and Scopus seventeen were selected for the first section, fourteen for the second one and twenty-six for the third.

Six articles considered both patients with either anticoagulant or anti-platelet therapy. Therefore, they were considered for analysis in both the second and the third categories. Articles retrieved from the electronic search are reported in Table 1, 2 and 3. Literature reviews were not reported. Results are divided into three sections, one for each of the different bleeding disorder.

3.1. Congenital Coagulation Disorders (CCDs)

Among seventeen articles, twelve were case reports and five reviews. Seven articles considered patients with haemophilia [12,13,14,15,16,17,18], seven considered patients with Von Willebrand Disease [19,20,21,22], one considered patients with Idiopatic Trombocitopenic Purpura [23]. Five articles performed the surgery flapless [12,18,19,20,21], three articles did not [13,14,17] and four articles did not specify [15,16,22,23]. One article did not report on post-operative complications [22], one article reported mild post-operative bleeding complication [18] and one article reported a severe bleeding complication, which required an emergency tracheotomy and hospitalization of the patient [23]. The remaining articles reported no complications [12,13,14,15,16,17,19,20,21].

Literature reviews considered the safety of oral surgery in general and not specifically the implant surgery. Four out of five reviews concluded that there is no contraindication to implant surgery in this type of patient [24,25,26,27]. The remaining article recommended not to perform implant surgery in all patients with coagulation disorders [28].

3.2. Antiplatelet induced bleeding disorders (APBDs)

Among fourteen articles included: one case report [29], one case-cross-over study [30], two cohort studies [31,32], four case-control studies [33,34,35,36] , two animal studies [37,38] and four reviews [39,40,41,42]. In almost all clinical studies related to this section, implant surgeries took place without interruption of the anti-aggregative therapy [29,31,32,33,34,35,36]. Only two studies reported a change in drug therapy [30,31]. This occurred in patient with dual antiaggregant therapy or when an anticoagulant was used in addition. Few hemorrhagic complications were observed, with a range between 1% and 15% of the surgeries. Most of the studies agreed on compressive hemostasis after surgery, with or without the association of tranexamic acid. Literature reviews agree on not suspending the antiaggregant therapy before implant surgery [39,40,41,42].

3.3. Anticoagulant induced bleeding disorders (ACBD).

Among twenty-six articles: four were case reports [43,44,45,46], one was a case series [47], six were cohort studies[8,31,48,49,50,51], eight were case control studies [33,34,35,36,52,53,54,55], six were reviews [40,56,57,58,59,60] and one was an animal study.

Considering the clinical studies, five authors treated patients undergoing conventional anticoagulant drugs [8,44,45,48,53]; six treated patients using DOAC [43,47,49,51,54,55] and in the remaining articles the sample considered used both medications [31,33,34,35,36,52].

Case-control studies showed no significant differences in hemorrhagic complications after implant surgery between patients in the test and in the control group.

However, in every clinical study, where a haemorrhagic complication occurred, it was always solved with the only help of local hemostatic measurements [33,34,36,43,48,49,51,52,53,54,55]. The only animal study investigated the effects of Rivaroxaban on osteointegration and it showed that it did not effect it. The results emerged from the evaluation of the clinical studies are in accordance with the evidence found in the reviews [56,57,58,59,60].

4. Discussion

The present review addressed implant rehabilitation of patients with bleeding disorders. The information obtained from the analysis of the clinical studies was rather heterogeneous, and thus difficult to compare with each other.

As regard the Section I, in almost all the Case Reports local hemostatic measures and pre-medication with missing factor or desmopressin were implemented. It didn’t happen in the Case Report concerning the patient with idiopathic thrombocytopenic purpura. It may not be a coincidence that this Case Report is the only one in which the patient developed complication not manageable by only local hemostatic measures or the simple administration of tranexamic acid.

In the II and III Sections, the trend observed is to not interrupt the anticoagulant therapy before the implant surgery, as recommended by the European Guidelines.

5. Clinical indications

The following clinical indications should be considered when treating patients with bleeding disorders. The evidence cannot be considered strong, since these recommendations are based on case reports, case series, few cohort studies, some reviews. Stronger scientific evidence is not available now.

• Consulting the physician who treat the patient for his bleeding disorder before implant surgery;
• Administer deficiency factor or desmopressin before the surgery in patients with congenital hemostasis disease;
• Do not withdraw anti-aggregative therapy for implant surgery, even if dual;
• Do not interrupt therapy with dicumarolics. On the contrary, clinicians should check the INR value before implant surgery;
• When dealing with direct anticoagulants (DAOC) skip only one dose of the drug, the day before;
• Choose the minimally invasive or even a flapless approach, if reasonable. A thorough clinical and radiographic evaluation should be performed, respecting bone thickness and the lingual cortical wall;
• Adopt local hemostatic measures at the end of the procedure and in case of postoperative bleeding: compressive hemostasis with gauze soaked in Tranexamic Acid showed excellent results in both situations;
• Instruct the patient about the appropriate post-operative measures: soft and cold diet for 2-3 days, avoiding vigorous rinses, physical effort and supine position, applying a gauze for 5 minutes in case of bleeding. If not enough, repeat the application of the gauze soaking with tranexamic acid.