Half Life 2: Episode One ( Pc Highly Compressed Full ) | 680 MB
Carlota Sproul
The periprocedural management of patients receiving long-term oral anticoagulant therapy remains a common but difficult clinical problem, with a lack of high-quality evidence to inform best practices. It is a patient's thromboembolic risk that drives the need for an aggressive periprocedural strategy, including the use of heparin bridging therapy, to minimize time off anticoagulant therapy, while the procedural bleed risk determines how and when postprocedural anticoagulant therapy should be resumed. Warfarin should be continued in patients undergoing selected minor procedures, whereas in major procedures that necessitate warfarin interruption, heparin bridging therapy should be considered in patients at high thromboembolic risk and in a minority of patients at moderate risk. Periprocedural data with the novel oral anticoagulants, such as dabigatran, rivaroxaban, and apixaban, are emerging, but their relatively short half-life, rapid onset of action, and predictable pharmacokinetics should simplify periprocedural use. This review aims to provide a practical, clinician-focused approach to periprocedural anticoagulant management.
The periprocedural management of patients who are receiving long-term oral anticoagulant therapy, usually with a vitamin K antagonist (VKA), such as warfarin, is a common but complex clinical problem, affecting an estimated 250 000 patients per year in North America alone or approximately 1 in 10 patients on chronic VKA.1 It is well established that continuing oral anticoagulation is associated with an increased risk of bleeding in the periprocedural period and that the absence of anticoagulant therapy postoperatively confers a marked increased risk for venous thromboembolism (VTE), especially after major surgery.2,3 Emerging data suggest that interruption of warfarin in patients with arterial indications, especially in the immediate postoperative period, confers a higher risk of arterial thromboembolism (ATE) than predicted by mathematical modeling assumptions.4,5 The accumulating clinical data relating to periprocedural antithrombotic therapy has necessitated the development of new chapters and recommendations in clinical practice guidelines that are dedicated to periprocedural antithrombotic management.1,6,7
The emergence and anticipated routine clinical use of novel oral anticoagulants (NOACs), such as the direct factor IIa (thrombin) inhibitor dabigatran and the direct factor Xa inhibitors rivaroxaban and apixaban, have the potential to greatly simplify periprocedural anticoagulant management because of their relatively short elimination half-lives, rapid onset of action, predictable pharmacokinetic properties, and few drug-drug interactions.10 There is emerging guidance for NOAC-treated patients who may require anticoagulant reversal and measurement of hemostatic function.10,11 Although periprocedural protocols for the use of the NOACs in the absence of robust clinical data are emerging,12,13 early reports as to their use and clinical outcomes in the immediate periprocedural period using large databases from phase 3 clinical trials will be forthcoming in constructing evidence-based periprocedural guideline recommendations.14
This review will use a case-based approach to illustrate the periprocedural management of patients on chronic oral anticoagulant therapy in clinical practice. Our aims are to address: (1) patients on VKA undergoing minor procedures; (2) patients on VKA needing temporary anticoagulant interruption for an elective surgery or procedure; (3) the use of heparin bridging therapy; and (4) the periprocedural management of patients receiving a NOAC. Our clinical guidance discussed herein will incorporate the best available evidence, acknowledging that this evidence can be weak or based solely on expert opinion.
In patients with VTE indications for VKA therapy, it is estimated that the risk of recurrence is 40% in the first month after discontinuing a VKA and 10% during the subsequent 2 months.2 The overall risk of recurrence is much lower after 3 months of VKA therapy, estimated at 15% for the first year.2 Acquired hypercoagulable states, such as the antiphospholipid syndrome, active malignancy and certain congenital thrombophilias (eg, homozygous factor V Leiden), are independent risk factors for VTE recurrence.15,16
In patients with arterial indications for VKA therapy, patients with nonvalvular atrial fibrillation (NVAF) or mechanical heart valves (MHV) are at increased risk of stroke in the absence of warfarin therapy or with subtherapeutic levels of anticoagulation.5,17 For patients with NVAF, the CHADS2 score is a validated clinical prediction score that uses congestive heart failure, hypertension, age > 75 years, diabetes, and history of stroke or transient ischemic attack in a cumulative manner to estimate expected stroke rate per 100-patient years in nonsurgical settings.18 Recently, preliminary data suggest that the CHADS2 score may also be used to predict risk for postsurgical stroke.19 Thus, patients with CHADS2 scores of 5 or 6 would be considered at high risk of thrombosis.
Patients with MHVs are at increased risk of systemic embolization and occlusive thrombus of the orifice of the prosthetic valve during subtherapeutic levels of warfarin, especially when the international normalized ratio (INR) falls below 2.0.20 Older, caged-ball valves (ie, Starr-Edwards) are the most thrombogenic, followed by tilting disc valves (ie, Bjork-Shiley), and with bileaflet valves (ie, St Jude) being the least thrombogenic.21 In the absence of anticoagulant therapy, mitral position valves have an annualized risk of thrombosis of 22% compared with aortic position valves, with an annualized risk of approximately 10%-12%,21 Similarly, patients with caged-ball valves, mitral position valves, and prosthetic valves with other risk factors for embolization (such as prior embolic event, severe left ventricular dysfunction, and an underlying hypercoagulable state) are considered at high risk for thrombosis.22
The American College of Chest Physicians (ACCP), as part of their most recent 9th Edition Evidence-Based Clinical Practice Guidelines on Antithrombotic Therapy, suggest a clinically useful thromboembolic risk stratification in the periprocedural period as shown in Table 1.7 The 3 most common groups of patients receiving VKAs (those with VTE, MHV, and NVAF indications) are divided into a 3-tier low-, intermediate-, and high-risk scheme for periprocedural thromboembolic risk. It is a patient's thromboembolic risk that should drive the need for a conservative or aggressive strategy (such as bridging therapy) with respect to periprocedural antithrombotic management.
Lastly, in addition to patient-related factors for thrombosis, there is a well-described prothrombotic effect of major surgery and laparoscopic procedures where the presence of pneumoperitoneum and reverse Trendelenburg position may introduce additional thrombotic risk.23 Although it is estimated that surgery will theoretically increase the postoperative VTE risk 100-fold,2,23,24 there is emerging evidence that surgery may also increase the risk of ATE in the postoperative period, with recent estimates suggesting a 10-fold higher than expected risk of stroke in the periprocedural period in warfarin-treated patients compared with mathematical modeling assumptions.4,25
An overall periprocedural antithrombotic strategy for a patient on chronic oral anticoagulation should be conceptualized in the scheme shown in Figure 1 within 5 categories (A-E) based on a 3-tier thromboembolic risk scheme and a 2-tier bleed risk scheme. It is a patients' estimated thromboembolic risk that determines whether a conservative or aggressive periprocedural antithrombotic strategy is used (such as bridging therapy). It is the procedural bleed risk that determines how that strategy is used in the postoperative period (such as stepwise increase in anticoagulant intensity). Lastly, because of the more severe clinical consequences with ATE than major bleeding, a strategy that incurs 3-10 more major bleeds to prevent one stroke would be, in theory, clinically acceptable based on the trade-off between the clinical consequences of a stroke as compared with a bleed.
Suggested periprocedural heparin bridging strategies for patients on chronic VKA based on patient thromboembolic and procedural bleed risk. Data from the 9th edition ACCP Guidelines: all grade 2C, except intermediate TE risk.7 *For high-bleed risk procedures: wait a full 48-72 hours before reinitiating postprocedural heparin (LMWH) bridging (especially treatment dose); stepwise increase in postprocedural heparin (LMWH) dose from prophylactic dose first 24-48 hours to intermediate/treatment dose; no postprocedural heparin (LMWH) bridging in very high bleed risk procedures (ie, major neurosurgical or cardiovascular surgeries) but use of mechanical prophylaxis. **Based on individual patient- and procedural-related risk factors for thrombosis and bleeding.
This patient is at high thromboembolic risk (older generation prosthetic heart valve in the mitral position) and is undergoing a minor procedure (multiple dental extractions). Approximately 15%-20% of patients receiving a VKA who are assessed for perioperative anticoagulant management require minor dental, dermatologic, or ophthalmologic procedures.26 The majority of these procedures are associated with little or self-limiting blood loss that can be controlled with local hemostatic measures.
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