The following cases and commentary, which focus on management of anticoagulants in the perioperative period, are excerpted from ACP's Medical Knowledge Self-Assessment Program (MKSAP 16).
Case 1: On warfarin before cholecystectomy
A 54-year-old woman is evaluated before an elective cholecystectomy. Medical history is significant for atrial fibrillation, type 2 diabetes mellitus, chronic heart failure, hypertension, and a transient ischemic attack 2 months ago. Medications are warfarin, insulin glargine, insulin lispro, metoprolol, lisinopril, furosemide, and simvastatin.
On physical examination, temperature is normal, blood pressure is 142/88 mm Hg, and pulse rate is 88/min and irregularly irregular. The remainder of the physical examination is normal. INR is 2.5.
Which of the following is the most appropriate treatment?
A. Administer half the usual dose of warfarin for 5 days before surgery
B. Continue warfarin
C. Discontinue warfarin 5 days before surgery
D. Discontinue warfarin 5 days before surgery and administer enoxaparin until the morning of surgery
Case 2: Mechanical valve and hip replacement
A 67-year-old man is seen for preoperative evaluation before elective total hip replacement. He has a mechanical bileaflet aortic valve and takes warfarin. He has no history of stroke.
Physical examination shows normal vital signs. There is a regular rhythm with mechanical S1. There is a grade 2/6 early peaking systolic ejection murmur at the right upper sternal border without radiation. Lungs are clear to auscultation bilaterally.
Which of the following is the most appropriate perioperative recommendation regarding anticoagulation for this patient?
A. Discontinue warfarin 3 days before surgery and bridge with heparin before and after
B. Discontinue warfarin 3 days before surgery and restart on evening of the surgery
C. Do not discontinue warfarin
D. Reverse anticoagulation with fresh frozen plasma transfusion 1 hour before surgery; restart warfarin on evening of surgery
Case 3: Afib and a colonoscopy
A 60-year-old man with paroxysmal atrial fibrillation is scheduled to undergo a screening colonoscopy. Warfarin must be discontinued in case a biopsy is needed. When the patient is in atrial fibrillation, he is asymptomatic. He also has hypertension and type 2 diabetes mellitus. He has never had a stroke, transient ischemic attack, or history of venous thromboembolic disease. Medications are metoprolol, metformin, and warfarin.
On physical examination, pulse rate is 65/min. Other vital signs are normal. Cardiac rhythm is irregularly irregular.
Laboratory studies reveal an INR of 2.3.
In addition to discontinuing warfarin, which of the following is the most appropriate treatment?
A. Switch to aspirin
B. Switch to clopidogrel
C. Switch to intravenous unfractionated heparin
D. Switch to therapeutic doses of low-molecular-weight heparin
E. No bridging agent is needed
Case 4: Cholecystectomy for a patient with a stent
A 60-year-old man with a history of coronary artery disease undergoes a preoperative assessment prior to cholecystectomy following a single episode of biliary colic that occurred 3 weeks ago. Ultrasonography documented cholelithiasis without gallbladder edema. Six months ago, a drug-eluting stent was placed in the left anterior descending coronary artery. He also has hypertension. Medications are lisinopril, aspirin, clopidogrel, and metoprolol. He has modified his diet and has not had any additional abdominal discomfort since the episode 3 weeks ago.
On physical examination, temperature is normal, blood pressure is 125/80 mm Hg, pulse rate is 60/min, and respiration rate is 12/min. BMI is 26. A normal carotid upstroke without carotid bruits is noted, jugular venous pulsations are normal, and normal S1 and S2 are heard without murmurs. Lung fields are clear, distal pulses are normal, and no peripheral edema is present.
Which of the following is the most appropriate management?
A. Postpone surgery for 6 months
B. Stop aspirin and proceed with surgery
C. Stop aspirin and clopidogrel and proceed with surgery
D. Stop aspirin and clopidogrel, begin heparin, and proceed with surgery
Answers and commentary
Correct answer: D. Discontinue warfarin 5 days before surgery and administer enoxaparin until the morning of surgery.
For this patient with a high risk for a perioperative thromboembolic event, the most appropriate treatment is to discontinue warfarin 5 days before surgery and provide bridging anticoagulation with a low-molecular-weight heparin (LMWH), such as enoxaparin, until the morning of surgery. In general, patients using warfarin have three possible preoperative treatment options: stop warfarin, receive bridging therapy with a parenteral anticoagulant, or continue the warfarin. This patient has atrial fibrillation with a high CHADS2 score (1 point each for diabetes mellitus, heart failure, and hypertension, and 2 points for previous stroke or transient ischemic attack [TIA] = 5) and her TIA is recent, placing her at a high risk for thrombosis; such patients should not have anticoagulation withheld for a prolonged period of time. Thus, warfarin should be changed to an agent with a shorter and more predictable half-life, usually LMWH. This agent is then withheld just before surgery and restarted after surgery, thus minimizing the amount of time the patient is not therapeutically anticoagulated.
The effect of dose adjustment of warfarin on INR is hard to predict. Thus, it would be inappropriate to recommend a fixed half dose of warfarin. This may result in an inappropriately high INR level for surgery (as would continuing the current dose of warfarin up to surgery) or a prolonged period of time with an inadequate INR, putting the patient at risk for thromboembolism.
In patients taking warfarin who have a low risk of thromboembolism, including those with a history of venous thromboembolism more than 12 months ago and those with atrial fibrillation with a CHADS2 score of 2 or less, stopping warfarin without providing bridging anticoagulation is acceptable. However, this patient's CHADS2 score is 5, and withholding anticoagulation for 5 days preoperatively is not recommended.
- Patients taking warfarin who are at high risk of postoperative venous thromboembolism and are undergoing intermediate- or high-risk surgery should have warfarin discontinued 5 days before surgery and receive bridging anticoagulation, usually with low-molecular-weight heparin.
Correct answer: B. Discontinue warfarin 3 days before surgery and restart on evening of the surgery.
This patient should discontinue warfarin 3 days before his hip surgery, and restart warfarin on the evening of the surgery, provided hemostasis is maintained. Although the annual risk of a thromboembolic event in a patient with a mechanical heart valve without therapeutic anticoagulation may be as high as 20%, the short-term risk of anticoagulation discontinuation is small. In addition to valve-related characteristics, such as type of mechanical valve and its position (aortic versus mitral), other factors that increase the risk of thromboembolism include atrial fibrillation, more than one mechanical valve, left ventricular systolic dysfunction (ejection fraction <30%), a hypercoagulable state, and previous thromboembolic event, including stroke or transient ischemic attack. The current recommendation is to stop warfarin 48 to 72 hours before the procedure to reduce INR to 1.5, and restart warfarin within 24 hours after the procedure. Bridging with heparin is usually not necessary.
In patients with a mechanical valve and an increased risk of a thromboembolic event, it is recommended that unfractionated heparin is begun intravenously when INR falls below 2.0, stopped 4 to 5 hours before the procedure, and restarted as early after surgery as possible along with warfarin and continued until INR is therapeutic again. This patient does not have an increased risk for a thromboembolic event, so bridging anticoagulation is not needed.
In patients with a mechanical heart valve and therapeutic INR who require emergent surgery, reversal of anticoagulation with transfusion of fresh frozen plasma may be performed. This option is not appropriate for nonemergent surgery, however.
- For patients with a mechanical valve in the aortic position and without additional risk factors, the current recommendation for periprocedural anticoagulation is to stop warfarin 48 to 72 hours before the procedure and restart it within 24 hours after the procedure; bridging with heparin is usually not necessary.
Correct answer: E. No bridging agent is needed.
For this patient with a CHADS2 score of 2 (hypertension and diabetes mellitus), no periprocedural bridging is needed. Periprocedural management of anticoagulation in the setting of atrial fibrillation depends on the patient's risk of developing a thromboembolism and having an adverse bleeding event. The CHADS2 score is one commonly used risk stratification tool for the perioperative period. The assessment of low, moderate, and high risk, however, is different in the perioperative period versus long-term use. For those with CHADS2 scores of 0-2, who are at lowest perioperative risk, it is best to simply discontinue warfarin approximately 5 days before the procedure with no bridging agent. Alternatively, low-dose subcutaneous low-molecular-weight heparin (LMWH) can be used as a “bridge” to provide adequate anticoagulation when the INR is not in the therapeutic range. Therapeutic-dose subcutaneous LMWH or intravenous unfractionated heparin (UFH) is not recommended. Warfarin can then often be restarted 12 to 24 hours after the procedure if there is no active bleeding.
For atrial fibrillation patients with moderate risk features (CHADS2 score of 3 or 4), a history of remote transient ischemic attack or stroke, or a mechanical aortic valve, management is individualized and bridging with therapeutic-dose LMWH or therapeutic dose intravenous UFH may be reasonable.
For those with high-risk features (CHADS2 score of 5 or 6), a recent transient ischemic attack or stroke, a mechanical mitral valve, or rheumatic valvular disease, bridging anticoagulation with therapeutic-dose subcutaneous LMWH or therapeutic-dose intravenous UFH should be provided.
- For atrial fibrillation patients at low perioperative risk for thromboembolism (CHADS2 score ≤2 and no additional risk factors [mechanical valve, history of stroke or transient ischemic attack]), no bridging anticoagulation is needed.
Correct answer: A. Postpone surgery for 6 months.
This patient's elective gallbladder surgery should be postponed for 6 months. Following placement of a drug-eluting coronary stent, aspirin and clopidogrel therapy must be continued without interruption for at least 1 year. For bare metal coronary stents, aspirin and clopidogrel must be continued without interruption for 4 to 6 weeks. Early cessation of antiplatelet therapy can result in stent thrombosis, which usually results in an ST-elevation myocardial infarction and can be catastrophic.
In a patient with a recently placed coronary stent who needs noncardiac surgery, the risk of discontinuing antiplatelet therapy must be weighed against the benefits of proceeding with surgery. The safest solution for this patient is to delay surgery for at least 6 months to allow a full year of dual antiplatelet therapy and complete healing of the drug-eluting stent. Although this approach reduces the probability of stent thrombosis, it does not completely eliminate it, as recent studies have documented late stent thrombosis occurring 1 to 2 years following initial stent placement and 12 months of dual antiplatelet therapy in the setting of noncardiac surgery. This is thought to occur because the perioperative period is associated with a hypercoagulable state caused by shifts in fluid status and hemodynamic alterations, conditions that may predispose to stent thrombosis.
Proceeding to elective surgery while continuing either aspirin or clopidogrel therapy or dual antiplatelet therapy would increase the risk of bleeding complications related to surgery; furthermore, it would not completely eliminate the possibility of stent thrombosis because of the hypercoagulable state associated with the perioperative period.
Use of unfractionated or low-molecular-weight heparin in the perioperative period does not prevent stent thrombosis.
- In a patient with a drug-eluting coronary stent, elective noncardiac surgery should be postponed until completion of a full year of dual antiplatelet therapy.