TABLE 18.1 Preoperative Medication Instructions
Corticosteroids are typically continued perioperatively, but DMARDs are discontinued. Abrupt discontinuation of corticosteroids can lead to life-threatening adrenal crisis. Historically, DMARDs were thought to significantly impair wound healing, while increasing the risk of surgical site infection. Currently, there is
emerging evidence that DMARDs may not be as detrimental to surgical wound healing and infection as previously thought (3,4,5).
Heparin blocks the intrinsic and common pathways of the coagulation cascade.
UFH has a rapid onset and clearance, allowing for easy titration.
UFH is safe to use in patients with renal insufficiency or failure.
UFH can only be administered parenterally.
A highly variable dose-response relationship necessitates monitoring with frequent measurements of aPTT when using treatment dosing.
UFH has a narrow therapeutic window, with a goal aPTT between 60 and 90.
The main complication of UFH is heparin-induced thrombocytopenia (HIT). HIT is caused by antibodies against platelet factor 4 and heparin complexes, and
is associated with a low or dropping platelet count, with or without thrombosis. Management of HIT entails stopping all heparin products, and using alternative modes of anticoagulation with direct thrombin inhibitors, such as argatroban (2).
The LMWH include: dalteparin (Fragmin), enoxaparin (Lovenox), tinzaparin (Innohep), and nadroparin (Fraxiparine). These medications are manufactured derivatives of UFH that preferentially inhibit factor Xa more than factor IIa.
Fondaparinux (Arixtra) is a synthetic pentasaccharide that selectively inhibits factor Xa mediated via antithrombin III.
LMWH and fondaparinux are administered subcutaneously.
These medications have a more predictable effect than UFH, but dosing is limited by weight and use is limited in renal insufficiency or failure.
These drugs have greater bioavailability than UFH and a longer duration of anticoagulation effect, allowing for once- or twice-daily administration.
Unlike UFH, there is better correlation between LMWH dose and anticoagulant response, thus coagulation monitoring is not necessary.
Checking factor Xa levels may be necessary in obese patients (weight >130 kg) due to the concern for suboptimal absorption (3).
Vitamin K antagonists (VKA), most commonly warfarin, are orally administered.
Warfarin and other VKAs prevent activation of vitamin K-dependent coagulation factors, including factors II (prothrombin), VII, IX, and X.
These medications can be used in patients with renal and liver diseases, and there is no weight limit for dosing (3).
VKAs have several limitations, making their use difficult and cumbersome in the clinical setting:
Warfarin has a slow onset and offset, thus requiring initial bridging therapy with a parenteral anticoagulant (e.g., LMWH) before achieving target therapeutic levels. Its offset of 36 to 42 hours can pose a problem if immediate surgical interventions are required (4).
PT/INR is used to evaluate the target level of anticoagulation. Warfarin has a narrow therapeutic window and exhibits a variable and unpredictable dose response. It is associated with several food and drug interactions, and variable dietary vitamin K intake causes fluctuating levels of anticoagulation with a laboratory control that is very difficult to standardize.
DOACs are newer drugs used in the prevention of VTE or stroke for patients with nonvalvular AF, and are recommended as first-line treatment of deep venous thrombosis (DVT) or pulmonary embolus (PE) in noncancer patients (5). They are not approved for use in patients with prosthetic heart valves (4).
The DOACs include direct thrombin inhibitors (dabigatran) and factor Xa inhibitors (rivaroxaban, apixaban, and edoxaban).
These drugs have favorable qualities compared to other anticoagulants, such as ingestion via oral route, a quick time to peak effect (1 to 3 hours), a simple dosing regimen, and fewer drug and dietary interactions. They are as effective as conventional anticoagulants and are not implicated with HIT.
Renal excretion is the predominant elimination pathway for DOACs, and dosing differs according to a patient’s renal function and the clinical indications for use.
There is an increased risk of bleeding in patients older than 75 years.
There is currently no identified antidote to reverse their anticoagulation effect.
Additional drawbacks include the lack of a routine test to reliably measure their anticoagulant effect.
With direct thrombin inhibitors, such as dabigatran, both PT and aPTT can be prolonged. However these tests should not be used to assess the level of anticoagulation. Better options include the thrombin time. A normal thrombin time indicates that no or only minimal dabigatran is present.
Factor Xa inhibitors, such as rivaroxaban and apixaban can also affect the PT and aPTT. Anti-factor Xa assays are the best option to evaluate the level of anticoagulation with these drugs.
UFH has a biologic half-life of 45 minutes. Therapeutic dose intravenous UFH is continued until 4 to 5 hours before the procedure. If subcutaneous UFH is used, the last dose can be given the evening before the procedure.
LMWH is discontinued 24 hours before procedures, based on a half-life of 3 to 5 hours. One-half of the total dose is given on the morning of the day before surgery (6). Studies have shown a residual anticoagulant effect at 24 hours after stopping therapeutic-dose LMWH so this method ensures that no significant residual anticoagulant is present at the time of surgery (3).
The perioperative management of warfarin and other VKAs is challenging because of their long half-lives. The American College of Chest Physicians (ACCP) recommend stopping VKAs 5 days before surgery to allow clearance of the drug and restoration of functional clotting factors to normal or near-normal levels (3).
The timing of cessation of DOACs before an elective procedure should consider factors such as the type of procedure and its bleeding risk (Table 18.2), the type of anesthetic (general, centroneuraxial, or regional) and the patient’s renal function (6,7).
DOACs are stopped 4 to 5 half-lives before procedures with high bleeding risk, or before centroneuraxial anesthesia to ensure minimal residual anticoagulant effect. These drugs are stopped 2 to 3 half-lives before low bleeding risk procedures.
TABLE 18.2 Surgical Bleed Risk
Surgeries with high bleeding risk (7):
Urologic: Transurethral prostate resection, bladder resection, tumor ablation, nephrectomy, or kidney biopsy; in part due to untreated tissue damage (after prostatectomy) and endogenous urokinase release
Pacemaker or implantable cardioverter-defibrillator device implantation (separation of infraclavicular fascial layers and lack of suturing of unopposed tissues within the device pocket may predispose to hematoma development)
Colonic polyp resection, typically of large (i.e., >1-2 cm) sessile polyps, in which bleeding may occur at the transected stalk following hemostatic plug release
Surgery and procedures in highly vascular organs, such as the kidney, liver, and spleen
Bowel resection in which bleeding may occur at the bowel anastomosis site
Major surgery with extensive tissue injury (e.g., cancer surgery, joint arthroplasty, reconstructive plastic surgery)
Cardiac, intracranial, or spinal surgery
Vascular surgery (aortic aneurysm repair, peripheral artery bypass)
Surgeries with low bleeding risk (6):
Abdominal hernia repair
Arthroscopic surgery lasting <45 minutes
Axillary node dissection
Bronchoscopy with or without biopsy
Carpal tunnel repair
Cataract and noncataract eye surgery
Central venous catheter removal
Cutaneous and bladder/prostate/thyroid/breast/lymph node biopsies
Dilatation and curettage
Gastrointestinal endoscopy ± biopsy, enteroscopy, biliary/pancreatic stent without sphincterotomy, endosonography without fine-needle aspiration
DOACs have a rapid onset of action (1 to 3 hours) and therapeutic levels are reached within a few hours of administration. The risk of bleeding increases if treatment is resumed soon after surgery, especially after major surgeries (e.g., hip or knee replacements). In general, NOAC resumption is delayed at least 24 hours after low bleeding risk procedures. If procedures have a high bleeding risk, therapeutic dosing is delayed 48 to 72 hours once adequate hemostasis is achieved (4).
The most common strategy for the reversal of DOACs is the passage of time. Vitamin K does not reverse the anticoagulant effect of DOACs, and FFP and PCC are of unproven benefit.
Activated charcoal may theoretically reduce absorption of DOACs if recently ingested.
Because dabigatran is approximately 35% protein bound, hemodialysis has been used successfully. Rivaroxaban has no reversal agent and because it is highly protein bound, dialysis is impractical (3).
The concept of bridging in patients on chronic oral anticoagulation is based on the need to stop longer-acting drugs to avoid an increased risk of bleeding during surgery and the desire to use short-acting anticoagulants to minimize time off anticoagulants.
Therapeutic dosing of LMWH or UFH is recommended for bridging. Low or prophylactic dose bridging has not been established as effective in preventing thromboembolism in AF. However, in moderate-risk patients with a history of VTE, prophylactic bridging can be considered, especially postoperatively (1).
The ACCP guidelines from 2012 recommend that patients who have low bleeding risk procedures do not need their anticoagulant discontinued, and bridging is not indicated (grade 2C).7 These recommendations have been validated for procedures such as cataract surgery, pacemaker and dermatologic procedures (1).
The ACCP guidelines categorize patients into low, moderate, and high risk for thromboembolism (Table 18.3). Patients at low thrombotic risk do not require bridging, and those at a high risk should be bridged. The ACCP has no recom-mendations
for patients in the moderate-risk category, and advises that decisions regarding anticoagulation be made after careful consideration of patient and surgery-specific factors (Table 18.3) (7).
TABLE 18.3 Risk of Thromboembolism and Bridging Recommendations (7)