● Stroke history. ● Labile INR : Unstable/high INRs, time in therapeutic range <60%. Prior major bleeding or predisposition to bleeding. ● Age >65. ● Medication usage predisposing to bleeding. Aspirin, clopidogrel, NSAIDs. ● Alcohol use : ≥8 drinks/week. The maximum score is 9. 0-1 : Relatively low risk of bleeding. 2-3 : Moderate risk of bleeding. 4-5 : High risk of bleeding Greater than 5 : Very high risk of bleeding. (Hindricks & Potpara, 2020) Despite warfarin being the gold standard for decades, there are advantages to prescribing or receiving DOACs. The advantages of DOACs compared with VKAs include fewer monitoring requirements, less frequent follow-up, more immediate drug onset and offset effects important for periprocedural and acute bleeding management, and fewer drug and food interactions (Frost et al., 2017; Heidenreich et al., 2021; Walsh & Caple, 2018). Regardless of the anticoagulation agent selected, providers must be cognizant of the patient’s current health status, the patient’s adherence to the regimen/follow up appointments, cost of care, access to care, bleeding/ thromboembolic events, adverse side effect profile, medication review for drug interactions, and the reassessment of the appropriateness of therapy as the patient’s clinical status changes (Chen et al., 2020). patients to always update providers on new medications is essential. For supratherapeutic INR, reversal agents are based on the INR and the presence of bleeding. For potentially life-threatening bleeding, the patient would be supported for hemodynamic instability and may be a candidate for 4-factor prothrombin complex concentrate, (Kcentra) which contains Factors II, VII, IX, X, Protein C, and Protein S. This should be administered with Vitamin K and dosing may be institutional dependent. Kcentra is more efficient at normalizing INR than fresh frozen plasma because of the high concentration of coagulation factors in Kcentra (Wigle et al., 2019). If the patient does not have major bleeding, then holding warfarin or giving vitamin K orally can be done outpatient with frequent monitoring of the INR. Risk-benefit of outpatient monitoring needs to be evaluated on a case-by-case basis. Despite some of these aforementioned issues with warfarin, it is the only anticoagulant approved in concomitant AF with valvular heart disease according to the American College of Chest Physicians and American College of Cardiology/American Heart Association guidelines (Chen et al., 2020). Hence, for these patient populations, warfarin’s place within the clinical practice guidelines is important. Continued research is underway to further explore the use of DOAC in valvular heart disease. half-life is approximately 12 hours. Although costly, idarucizumab (Praxbind) is a monoclonal antibody fragment that can be given for life threatening, on-going bleeding or for reversal for emergent procedures (Wigle et al., 2019). Andexanet alfa, a genetically modified variant of factor Xa, has been approved to reverse the anticoagulant effects of rivaroxaban and apixaban in patients with life-threatening or uncontrolled bleeding (Wigle et al., 2019). All DOAC therapies are eliminated by the kidneys to varying degrees, and alterations in renal clearance must be considered when dosing these agents. DOACs are safe and effective in moderate kidney disease (CrCL 30-50mL/
Similarly to a thromboembolism risk scoring of CHA 2 DS 2 ‑VASc, there is a risk scoring for bleeding when taking anticoagulants. This evidence-based risk scoring is HAS-BLED. It was originally developed in 2010 with the intent of determining the one-year risk of bleeding with anticoagulation. The acronym refers to Hypertension, Abnormal liver/renal function, Stroke history, Bleeding predisposition, Labile INR, Elderly, Drug/alcohol usage. Providers calculate the risk scoring by giving one point to each clinical positive indicator: ● Hypertension: Uncontrolled, >160 mmHg systolic. ● Renal disease : Dialysis, transplant, Cr >2.26 mg/dL or >200 µmol/L. ● Liver disease : Cirrhosis or bilirubin >2x normal with AST/ ALT/AP >3x normal (1 point for each). Overview for anticoagulation guidelines A CHA 2 DS 2 ‑VASc score ≥2 warrants the use of oral anticoagulants. Options include warfarin, a vitamin K antagonist (VKA), or one of the direct oral anticoagulants (DOAC). The DOACs are categorized into 2 main classes: oral direct factor Xa inhibitors (i.e., rivaroxaban, apixaban, edoxaban, and betrixaban)
and direct thrombin inhibitors (i.e., dabigatran). Generic Name Trade Name Class of DOAC Dabigatran Pradaxa
Direct thrombin inhibitors
Rivaroxaban Xarelto
Factor Xa inhibitor Factor Xa inhibitor Factor Xa inhibitor Factor Xa inhibitor
Apixaban Edoxaban
Eliquis Savaysa
Betrixaban Bevyxxa
Clinical guidelines for Warfarin Warfarin is classified as a VKA. It inhibits the vitamin K synthesis of factors II, VII, IX and X and decreases proteins C and S. Since it inhibits synthesis, warfarin has a delayed therapeutic onset of action of 3 to 5 days (Wigle et al., 2019). Hence, patients with high-risk scores should be protected from thromboembolism with bridge therapy with heparin (unfractionated or low molecular weight heparin). Once the international normalized ratio (INR) is >/= to 2.0 or within the targeted therapeutic range for 24 hours, heparin can be stopped. The international normalized ratio goal for AF is 2.0 to 3.0. For most patients, the initiation of warfarin is started at 5-10 mg per day with daily INR monitoring starting on day three. Lowered initial doses may be required with the elderly, those with liver disease, poor nutritional status, or heart failure (Wigle et al., 2019). Once the INR is stable, monitoring can be transitioned to weekly, every other week, and then monthly. Stable INR levels may be difficult to achieve and are related to a host of factors such as genetics, patient adherence, female sex, age, two or more comorbidities, and potential drug/food interactions with warfarin (Hindricks & Potpara, 2020). Providers should teach patients to be consistent in the foods that contain vitamin K, rather than avoiding these foods (Wigle et al., 2019). For example, green leafy vegetables have a higher content of vitamin K, yet are included in the heart healthy diet. Providing the patients with written information or online resources can help them maintain consistency in their diet. Drug interactions with warfarin are numerous. Teaching Clinical guidelines for DOAC As noted previously, the DOACs are categorized into two main classes: oral direct factor Xa inhibitors (i.e., rivaroxaban, apixaban, edoxaban, and betrixaban) and direct thrombin inhibitors (i.e., dabigatran). Their utilization in the management of AF anticoagulation continues to grow. Generally, the agents have a quicker onset of action, require less outpatient monitoring, and fewer drug/nutrient interactions as compared to warfarin. However, the provider still needs to be aware of co-morbid conditions that will affect risk of thromboembolism and bleeding. For bleeding with dabigatran, holding a dose leads to a relatively fast decline in active medication, since the
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