Thanks to advances in medical research and new therapeutic strategies, individuals with cardiovascular diseases have now increased life expectancies and the number of adult patients in therapy with anticoagulants and/or antiplatelets seeking for dental care is significantly increased compared to a few decades ago [16].
Anticoagulant and antiplatelet medication might constitute a challenge for dentists and dental hygienists since possible prolonged bleeding might interfere with dental procedures. The adaptation of the Ivy test in the oral environment has been successful because this method was able to highlight differences among the groups and significant differences compared to the control group.
The outcomes of the present investigation highlighted a different bleeding time among the groups analyzed. VKA patients presented the longest bleeding period. Patients taking VKA had a bleeding time that was more than 2 times higher than that of healthy subjects with a statistically significant difference.
VKA present challenges due to adverse effects and interactions with certain drugs and foods. Additionally, while their antithrombotic effects typically commence 48–72 h post-administration, the reduction of coagulation factors doesn’t manifest until five days into treatment [17]. Consequently, the clinical utilization of these medications is complicated by the necessity for meticulous monitoring of their activity. Anticoagulants necessitate precise monitoring and dosage adjustments to achieve the desired therapeutic outcome while minimizing the risks associated with both excessive anticoagulation (leading to increased risk of bleeding) and inadequate anticoagulation (resulting in increased risk of thrombosis).
The principal used VKA are acenocoumarol and warfarin.
Acenocoumarol is a VKA with a relatively short half-life of 8–10 h, it is typically prescribed once daily and in our research induced the longest bleeding time, followed by warfarin.
Warfarin stands as the most prescribed medication for anticoagulation. It boasts an extended duration of action, characterized by a half-life spanning of 48–72 h.
For VKA, the most invasive therapies (surgical) should be performed when the International Normalized Ratio (INR) is below 2.5, ensuring adherence to the therapeutic cardiologic range and avoiding the need to suspend anticoagulant therapy.
When the intake time was analyzed, VKA seemed not to be influenced. Both groups (intake < 5 h or > 5 h) presented a bleeding time of more than 200 s.
NOAC (DTI and AntiXa) analyzed in this research were apixabam, rivaroxabam and dabigatran.
Rivaroxaban and apixabam are administered orally as selective factor Xa inhibitors, boasting close to 100% absorption rates. Although clinical data remain limited, insights into their metabolism and potential drug interactions are primarily derived from nonclinical studies. Routine monitoring is unnecessary for these medications, similar to dabigatran [18, 19].
Dabigatran serves as a potent inhibitor of free thrombin, thrombin bound to fibrin, and platelet aggregation induced by thrombin, effectively preventing thrombus formation. Its primary indication lies in elective total hip or knee replacement surgery, and also in the prevention of stroke and systemic embolism in adults with non-valvular atrial fibrillation [20]. Notably, it does not necessitate strict monitoring [18, 20, 21]. Administered orally, the recommended dosage consists of two daily doses of 110 mg. Plasma peak concentrations are typically achieved between 30 min and two hours following administration. With a bioavailability of 5–6%, the half-life after single and multiple dosing spans 8 and 17 h, respectively [20]. The majority of the drug (80%) is excreted in urine.
In the present investigation among NOAC, patients assuming rivaroxabam presented the longest bleeding period followed by dabigatran and apixaban.
Even though no statistically significant differences were noted, it is interesting to observe a tendency to reduced bleeding time 5 h after drug intake. This suggests that if a patient undergoes surgery in the early hours after medication intake, there is maximum anticoagulation effect, leading to a heightened risk of bleeding. Conversely, if treated shortly before the next dose, the risk is diminished, if not almost negligible. Authors can speculate that the optimal period for surgical treatment of these patients could be 2–3 h before the next dose, without the need to temporarily suspend the medication.
Regarding antiplatelet, the drugs analyzed were Acetylsalicylic acid and clopidogrel.
Acetylsalicylic acid is absorbed in the stomach and reaches the bloodstream within 10 min, attaining peak plasma concentration between 30 and 40 min [22]. Acetylsalicylic acid functions by deactivating the enzyme cyclo-oxygenase, essential for thromboxane synthesis within platelets, thereby diminishing platelet activation and aggregation [23]. Conversely, clopidogrel serves as an adenosine diphosphate (ADP) antagonist, exerting its effects by irreversibly blocking the ADP receptor on the platelet membrane, leading to alterations in platelet morphology and decreased aggregation [24]. Furthermore, dual antiplatelet therapy (DAPT), comprising Acetylsalicylic acid /clopidogrel or Acetylsalicylic acid /P2Y12 inhibitor, is commonly employed in patients with cardiovascular disease. According to guidelines from the American College of Cardiology Foundation and the American Heart Association, DAPT may be recommended for the secondary prevention of acute coronary events and post-stent placement [25]. Patients taking Acetylsalicylic acid or clopidogrel had almost the same bleeding time, conversely patients taking a combination of the two drugs presented an almost double bleeding time [23].
In the present study, during professional oral hygiene procedures, no significant bleeding episodes have been observed in patients taking antiplatelets, even in cases of dual antiplatelet therapy. However, it is crucial to emphasize that local hemostasis was performed using gauze tamponade (a primary and effective measure). Still, the surgeon can enhance it with the use of sutures, local hemostatic drugs, and, if necessary, defined cauterizations.
Similar results suggesting the continuation of the therapy are present in the recent literature. Sandhu et al. [26] examined the outcomes of dental extractions in patients who continued oral anticoagulants and oral antiplatelets without discontinuation. Local haemostatic measures were employed, and patients were followed up via telephone clinic. Out of 513 surgical episodes involving 1,001 dental extractions, 95.9% of patients experienced no post-operative bleeding. Only 4.1% reported bleeding requiring further intervention, all managed with local measures and without hospital admission. The study underscores the rarity of significant bleeding complications when oral anticoagulants and oral antiplatelets are continued during dental extractions.
López-Galindo [27] in a systematic review compared postoperative bleeding complications in patients undergoing dental extraction under different anticoagulant therapies. Seven studies involving 931 patients on direct oral anticoagulants, vitamin K antagonists, and no anticoagulant therapy were analyzed. Minor bleeding, immediate or delayed, was the most common complication across all groups. These findings suggest that direct oral anticoagulants are safe for dental extractions without requiring therapy alteration. However, further research is needed to assess the necessity of modifying direct oral anticoagulants regimens for dental surgical procedures.
Manfredini et al. [28] employing a comprehensive search methodology following PRISMA-ScR guidelines, suggested that altering drug dosage during surgery is not advisable due to the higher risks of thromboembolism from discontinuation outweighing the hemorrhagic risks. The review underscores the importance of maintaining treatment continuity during oral surgery to prevent adverse outcomes.
Several authors have also looked for ways to mitigate the risk of bleeding after oral surgery. Zaib et al. [29] assessed the efficacy of local tranexamic acid application in reducing postoperative bleeding risk in dental procedures for anticoagulated patients. They highlight the favorable outcomes of local tranexamic acid application in managing postoperative bleeding in dental procedures for anticoagulated patients, offering valuable insights into potential therapeutic interventions in this context.
Other authors analyzed the use of Autologous Platelet Concentrates or leucocyte-and platelet-rich fibrin (L-PRF) as hemostatic agents. Campana et al. [30] in a systematic review aimed to assess the effectiveness of autologous platelet concentrates (APCs) as hemostatic agents following tooth extraction in patients on anticoagulant therapy. The findings suggested that APCs may reduce post-operative bleeding, shorten hemostasis time, alleviate pain, and promote faster wound healing in patients on anticoagulant therapy. Similar results were obtained by Berton et al. [31] that in a clinical study assessed L-PRF’s efficacy as a hemostatic agent in patients on VKAs or DOACs undergoing single tooth extraction suggesting that L-PRF can be safely used in such patients, minimizing bleeding risk and facilitating smooth post-operative outcomes.
Limits of the present research must be acknowledged. First of all, a power analysis was not conducted as no similar studies were found in the scientific literature. Secondarily, periodontal health parameters including bleeding on probing, probing depth or plaque index were not recorded, even if it must be reported that all the patients were included in a strict follow-up recall regimen and were evaluated at the time of their biannual professional oral hygiene session.
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