Year: 2021
Type: article
Abstract: This guideline is an update; some sections have been adopted from the previous guideline issued in 2014 [1]. More detailed information on the methods can be found in the long version of this guideline at www.awmf.org. This article does not include a comprehensive presentation of all contents of the guideline and serves only as an overview (Figures 1, 2). In the perioperative management of surgical patients, medication with oral anticoagulants (OAC) and platelet aggregation inhibitors (PAI) remains a challenge. In dermatology, but also in other specialties, there are large differences in the perioperative management of antithrombotic drugs [2-4]. The first version of this guideline has already led to a more unified approach in managing aspirin (acetylsalicylic acid, ASA) and vitamin K antagonists (VKA) [1, 5, 6]. Within the context of a repeated cross-sectional study in Germany on the management of anticoagulants and platelet aggregation inhibitors, a strong heterogeneity in care was still apparent, most recently in 2017, in particular with regard to the perioperative management of direct oral anticoagulants (DOAC) [4, 5]. The aim of this guideline is to update the recommendations of the previous guideline, taking into account new study data, newly gained experience within the expert panel, and data from the health services research study. In the last few years, prescriptions of antithrombotic drugs have shifted significantly in Germany, with an increase in the prescriptions of DOAC by 360 % between 2013 and 2018 [7]. Figure 3 offers an overview on available antithrombotic drugs. In patients receiving treatment with vitamin K antagonists (VKA), the coagulation status must be monitored by measuring thromboplastin time (‘Quick test’). Its results are usually reported in percent. Since thromboplastin reagents may show varying sensitivity, the INR value (International Normalized Ratio) has been recommended since 1986 to improve comparability. A standardized method comparing the marketed measuring methods with a standard reagent and applying a formula for calculation ensures that the result is independent of the reagent used, and coagulation values can be compared. “Normal” plasmatic coagulation corresponds to an INR of 1.0. Table 1 offers an overview of the therapeutic goals in various indications. As opposed to VKA, monitoring of the anticoagulant effect is usually unnecessary in patients treated with DOAC. Anticoagulants For dermatological surgery with an increased risk of postoperative bleeding requiring intervention (see risk classification) and a positive history of bleeding episodes*, it is suggested that preoperative INR assessment be performed. *Spontaneous bleeding (nosebleeds, bruises), medications that affect bleeding, previous bleeding events associated with surgery on phenprocoumon [7]. Dermatological surgery should not be performed in patients with a positive history of bleeding episodes if the surgery entails an increased risk of postoperative bleeding that itself would require intervention* (see Table on risk classification) and the INR is above the therapeutic range. *Spontaneous bleeding (nosebleeds, bruises), medications that affect bleeding, previous bleeding events associated with surgery on phenprocoumon [7]. Strong Consensus (100 %) Evidence “Management of VKA” The review by Scherer et al. [8] reported on a prospective study on phenprocoumon versus no phenprocoumon, with the outcome of “significant postoperative bleeding” be, see Table 2. Evidence “Switching from VKA to heparin” Additional evidence from two other systematic reviews [10, 11] was included for the comparison of bridging VKA with heparin versus continued VKA. The thromboembolic event rates of the two management strategies did not differ. Bridging was, however, associated with an increased risk of perioperative bleeding. The studies included in the systematic reviews were mostly performed with the VKA acenocoumarol and warfarin. The systematic search did not reveal any relevant data on bleeding risk with apixaban, dabigatran, rivaroxaban, or edoxaban (Scherer et al. [8]). Thus, the recommendations could be developed and agreed upon solely based on expert opinion, as well as on the guidelines issued by other medical specialties. The cross-sectional study to evaluate current management strategies found significant heterogeneity in the perioperative management of DOAC during skin surgeries [5]. This heterogeneity was also reflected within the guideline panel. Our recommendations therefore represent a corridor for action. More research is needed. The highest concentrations of apixaban, dabigatran, edoxaban, or rivaroxaban are reached between 30 minutes and 4 hours after intake. It is therefore prudent to avoid surgery during this period since the bleeding risk for surgical procedures is at its highest [12-15]. Differences in the biological half-life of the various substances and altered pharmacokinetics in patients with renal insufficiency need to be considered [12]. Aspirin (acetylsalicylic acid, ASA) Evidence on aspirin The systematic review included data on six different outcomes extracted from ten cohort studies and one RCT, comparing “aspirin” with “no aspirin” (Table 5). Clopidogrel Evidence on clopidogrel versus no clopidogrel Relevant outcomes were extracted from four cohort studies (Table 6). Combination treatment (aspirin + P2Y12 receptor antagonist [clopidogrel, ticagrelor, prasugrel]) Evidence on combination therapy The systematic review combined the results of two cohort studies comparing aspirin plus clopidogrel combination therapy with “no aspirin” or with “no clopidogrel” (Table 7). The identified studies on the risk of bleeding associated with skin surgery in patients on treatment with anticoagulants or platelet aggregation inhibitors remain quite limited in terms of quality and quantity. Therefore, this guideline cannot offer clear recommendations especially not on management of DOAC. In comparison with the previous version of the guideline, our recommendations have been opened up based on expert experience and will need to be re-evaluated after a few years. The evidence on thromboembolic events is even worse, so again the available evidence limited the possibilities of an evidence-based consensus. The evidence we found on all questions addressed in this guideline was of low quality, there is an urgent need for large studies comparing perioperative discontinuation of DOAC with continued treatment [8]. Guidelines represent systematically developed tools for clinically relevant counseling and decision settings. The development of a guideline can only reflect a limited number of standardized clinical situations. The recommendations in clinical guidelines are not legally binding; deviations from the recommendations may and should occur in specific circumstances. Implementation of guideline recommendations in any given clinical situation must always be analyzed in view of all relevant conditions (such as comorbidities, co-medications, contraindications). Medical science is in constant flux. Users of the guideline need to be aware of new developments occurring after publication of the guideline. Users of this guideline are also urged to verify, by carefully examining the information and taking into account the product information provided by the manufacturers, whether the recommendations given are complete and up to date with regard to the way in which the interventions are carried out, contraindications to be considered, drug interactions, etc., as well as with regard to the approval and reimbursement situation. Users of this guideline are dermatologists/dermatosurgeons, plastic surgeons, oro-maxillofacial surgeons, and other physicians from related or interested specialties. The target group of this guideline covers patients treated with anticoagulants and/or platelet aggregation inhibitors who undergo dermatological surgery in an in-patient or out-patient setting. How high is the risk of complications during dermatological surgery in patients receiving anticoagulants/platelet aggregation inhibitors? Does the perioperative interruption of direct oral anticoagulants, as compared to their continued use, reduce perioperative complications associated with dermatological surgery? Does the perioperative interruption of vitamin K antagonists with a switch to heparin, as compared to continued use, reduce perioperative complications associated with dermatological surgery? A list of various endpoints was generated via a systematic review, see Scherer et al. [8]. To better evaluate study results or meta-analyses, all experts were asked to assess the relevance of individual endpoints on a scale of 1 to 9, employing the recommendations of the GRADE working group [16]. This was performed separately for all six outcomes via an anonymous online survey. All experts participated. Table 8 shows the results of this assessment. The PICO model was used for systematic research of the abovementioned key questions (KQ). Inclusion and exclusion criteria were also developed; see below. Step 1 was the specific search for guidelines addressing the key questions. We focused our search on dermatological and cardiological guidelines, We searched the websites of theAssociation of the Scientific Medical Societies in Germany (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e.V., AWMF), the Guidelines International Network (GIN), the National Institute of Clinical Excellence (NICE), and the websites of cardiological associations in Germany, Europe, and the USA. The search was performed in January 2020. No guidelines specifically addressing dermatological surgery were identified. We therefore widened our search to include other types of surgery. Ultimately, e.g. the 2018 European Heart Rhythm Association Practical Guide was used [12]. KQ 1: KQ 2: KQ 3: Since no guidelines could be found, a systematic review was performed to update an existing review [6] that had been prepared in 2014 during the development of the first guideline “Management of anticoagulants in dermatological surgery”. Detailed reporting on the procedure can be found in Scherer et al. [8]. The protocol of this systematic review was published on PROSPERO: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=167337 The review identified data on all three key questions. Two “Evidence to Decision” frameworks describing the results of the systematic review were prepared (see online supplement). Both frameworks were made available to the members of the expert panel. The most important GRADE-Summary-of-Findings-Tables [17] were then incorporated into this guideline (permission received). Since our search for key question 3 returned very few hits, an additional search for systematic reviews was conducted that was no longer limited to dermatological surgery. The search was performed on February 13, 2020. A total of 882 hits were generated: 199 in CENTRAL, 0 in CDSR 0, 254 in MEDLINE Ovid, and 429 in Embase Ovid. Selection was performed according to the abovementioned criteria. 13 hits were included from the title/abstract screening. Seven systematic reviews were included in the final selection and subsequently evaluated via the SIGN checklist [18]. Reviews that did not assess the included primary studies were excluded. Ultimately, two systemic reviews were included. These were summarized for the group with regard to the relevant outcomes [10, 11]. During an online consensus conference on 7th October 2020, agreement on the proposed recommendations was achieved utilizing the nominal group technique. The structured consensus finding process was facilitated by Professor Alexander Nast. After presentation of the recommendations which needed to be agreed upon, each group member commented on the draft. Dissenting suggestions were noted. This was followed by discussion, preliminary voting, debate/discussion, and final voting. Every member of the expert panel had one vote. Strong consensus (> 95 % agreement) was the general goal. If this was not achieved even after discussion, a “consensus” decision (> 75 % agreement) was an option. In our case, all recommendations were agreed upon with strong consensus. The strength of consensus was documented in each case. An overview of wording, symbols, and notes regarding the interpretation of the strength of recommendations can be found in Table 9. Open access funding enabled and organized by Projekt DEAL. Please refer to the long version of this guideline at www.awmf.org for our declaration on conflicts of interest.
DOI: 10.1111/ddg.14522
Institutions: Humboldt-Universität zu Berlin, Freie Universität Berlin, Charité – Universitätsmedizin Berlin, Universitätsklinikum Tübingen, Innsbruck Medical University, Universität Innsbruck, University Hospital Innsbruck, Ludwig-Maximilians-Universität München, Klinikum Ludwigshafen, University Hospital Frankfurt, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Asklepios Klinik Weißenfels, Asklepios
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,300
OpenAlex ID: W3206197852