Sabtu, 13 Juni 2009

Thorax Haemarhogic

Perioperative Anticoagulation Management

Author: Brian James Daley, MD, MBA, FACS, Associate Program Director, Professor, Department of Surgery, Division of Trauma and Critical Care, University of Tennessee School of Medicine
Coauthor(s): Dana Taylor, MD, FACS, Assistant Professor of Surgery, Graduate School of Medicine, University of Tennessee; Consulting Surgeon, University General Surgeons, PC; Jose Fernando Aycinena, MD, Staff Physician, Department of General Surgery, University of Tennessee Graduate School of Medicine

Definition of Problem

In performing noncardiac surgery on patients on anticoagulation, the major concern is when it is safe to perform surgery without increasing the risk of hemorrhage or increasing the risk of thromboembolism (eg, venous, arterial) after discontinuing treatment. In treating patients on long-term coumadin perioperatively, consider the risks of hemorrhage or thromboembolism versus the benefit from the operation. When considering noncardiac surgery, these factors and the need to weigh the risk of hemorrhage against that of thromboembolism must analyzed on an individual patient basis. Certain procedures (eg, oncologic procedures, threats to limb or life) are easy analyses. More complex discussions must be had for such cases as hernia repair of other elective nonurgent operations.

The approach options for these patients can be one of the following: continue warfarin therapy, withhold warfarin therapy for a period of time before and after the procedure, or temporarily withhold warfarin therapy and also provide a “heparin bridge” during the perioperative period. Which management option to follow is primarily determined by the characteristics of the patient and by the nature of the procedure.

Patients with prosthetic heart valves pose a particular problem. Arterial thromboembolism from the heart often results in death (40% of events) or major disability (20% of events). The greatest problem encountered is that no consensus exists regarding the optimal perioperative management of anticoagulation for patients who have been receiving long-term warfarin therapy. Some prospective studies have suggested that patients on long-term warfarin therapy who undergo minor invasive procedures and are taken off their oral anticoagulation for up to 5 days have a less than 1% risk of experiencing a thromboembolic event.

The American College of Chest Physicians have proposed guidelines for antithrombotic prophylaxis in patients with different risk factors, and it recommends that if the annual risk for thromboembolism is low, warfarin therapy can be withheld for 4-5 days before the procedure without bridging.

It has been suggested that patients on long-term warfarin therapy (including those with mechanical heart valves or atrial fibrillation) who are undergoing minor elective invasive outpatient procedures (eg, colonoscopy, dental procedures) may have a slightly increased risk of perioperative bleeding if placed in some form of heparin therapy (eg, heparin bridge) than those who have their oral anticoagulation withheld for 4-5 days (major hemorrhage 3.7% vs 0.2% and significant nonmajor hemorrhage 9% vs 0.6%, respectively). The perioperative risk of bleeding when using a heparin bridge appears to be higher and the risk of thromboembolic events appears to be lower when coumadin is stopped than what is reported elsewhere in the literature.

For excellent patient education resources, visit eMedicine’s Circulatory Problems Center. Also, see eMedicine’s patient education article Blood Clot in the Legs

Indications for Perioperative Management

Any patient who is on long-term anticoagulation and is to undergo a major surgery needs proactive management. Some authors believe that patients can be maintained on oral anticoagulation for minor procedures, such as dental extractions, biopsies, ureterorenoscopy, Ho:YAG lithotripsy, and ophthalmic operations, as long as the therapeutic range of the prothrombin time (PT) value is not greater than 2.5.1 A recently published study revealed a higher rate of hemorrhagic complications after glaucoma surgery in patients on anticoagulation or antiplatelet therapy. Patients who continued anticoagulation during glaucoma surgery had a hemorrhagic complication rate of 31.8% compared to 3.7% of patients with no anticoagulation or antiplatelet therapy.2 Local bleeding with dental surgery may be controlled with tranexamic acid mouthwash or epsilon amino caproic acid mouthwash.

The American Society of Gastrointestinal Endoscopy divided endoscopic procedures into low and high risk for bleeding in its 2002 guidelines on anticoagulation. Low bleeding-risk endoscopic procedures do not require a change in anticoagulation.

Low bleeding-risk endoscopic procedures are as follows:

* Upper endoscopy with or without biopsy
* Flexible sigmoidoscopy with or without biopsy
* Colonoscopy with or without biopsy
* Endoscopic retrograde cannulation of the pancreatic duct without sphincterotomy
* Biliary stent insertion without sphincterotomy
* Endosonography without fine-needle aspiration
* Push enteroscopy of the small bowel

High bleeding-risk endoscopic procedures are as follows:

* Polypectomy
* Laser ablation and coagulation
* Endoscopic sphincterotomy
* Pneumatic or bougie dilation
* Percutaneous endoscopic gastrostomy tube placement
* Treatment of varices

In general, antithrombotic therapy is indicated for venous thromboembolic disease (ie, deep venous thrombosis [DVT]; pulmonary embolism [PE]; primary prophylaxis of DVT or PE; antithrombin III [ATIII], protein C, and protein S deficiency); arterial thromboembolic disease (ie, prosthetic heart valves, atrial fibrillation, congestive cardiomyopathies, mural cardiac thrombus, acute myocardial infarction, mitral valve disease); disseminated intravascular coagulation; and maintaining patency of vascular grafts, shunts, and bypasses.

Currently, it is generally recommended that patients with the highest risk of arterial or venous thromboembolism, who require interruption of oral anticoagulant therapy for surgery, should receive therapeutic-dose heparin therapy (eg, unfractionated heparin [UFH], low molecular weight heparin [LMWH]) during much of the interval when the international normalized ratio (INR) is subtherapeutic.

Usually, unless accompanied by significant cardiomyopathy or recent arterial embolus, patients with atrial fibrillation can have their coumadin stopped 4 days prior to surgery, then resumed at the usual dose the night of surgery.

Patients with prosthetic heart valves usually are treated with perioperative LMWH, although randomized controlled trials validating this method are lacking. Coumadin can be stopped 4-5 days preoperatively, with LMWH started the next day at a therapeutic dose (see Media file 1). The last dose should be 12 hours preoperatively. LMWH and coumadin can be retitrated the evening of the operative day. LMWH is stopped when the coumadin reaches the target range. For patients at higher risk of valve thrombosis (ie, patients with 2 prosthetic valves or with caged-ball type of valves), whether LMWH provides adequate anticoagulant protection is unclear. For these patients, consider use of perioperative UFH instead of LMWH. Preoperatively, the heparin should be stopped 6 hours before the procedure. Postoperatively, the heparin can be restarted when the surgeon agrees that it is safe, usually 6-12 hours postoperatively.

Contraindications to antithrombotic therapy are relative, and the risks and benefits need to be weighed. Relative contraindications are bleeding abnormality (eg, thrombocytopenia, platelet defect, peptic ulcer disease), CNS lesion (eg, stroke, surgery, trauma), spinal anesthesia or lumbar puncture, malignant hypertension, and advanced retinopathy. Contraindications specific to warfarin are early or late pregnancy, poor patient cooperation, and occupational risk. LMWH should be avoided in patients with renal insufficiency, because it is cleared primarily by the kidney. If used, the anticoagulant effect of LMWH should be measured with an antifactor Xa level done 4 hours after the LMWH dose. The targeted therapeutic antifactor Xa level is 0.5-1.5 U/mL.

Preoperative Treatment

Several protocols have been developed to care for patients taking oral anticoagulants. Regardless of the protocol used, the period of subtherapeutic oral anticoagulation should be kept to a minimum in patients with previous embolism and in others who are at highest risk for embolism. Kearon formulated a preoperative and postoperative strategy divided into sites of embolic disease.3 His recommendations are summarized below.

Arterial thromboembolism

In patients with previous arterial embolism, only 4 daily doses of warfarin should be withheld preoperatively and the INR should be measured the day before surgery to determine if a small dose of vitamin K is needed to accelerate the reversal of anticoagulation. If the INR is more than 1.7 on the day before surgery, administer 1 mg of vitamin K subcutaneously and repeat the INR the morning of the surgery. If on the day of surgery the INR is 1.3-1.7, administer 1 unit of frozen plasma; administer 2 units of frozen plasma if the INR is 1.7-2. The active reversal of oral anticoagulants should be discouraged in patients with mechanical valves, especially with the use of fresh frozen plasma.

For a patient who has had an arterial thromboembolism within a month of surgery, start intravenous UFH when the INR drops to less than 2 to minimize the risk of recurrent embolism. Discontinue the intravenous heparin 6 hours before surgery.

Venous thromboembolism

After an acute episode of venous thromboembolism (VTE), defer surgery, if feasible, until patients have received at least 1 month, and preferably 3 months, of anticoagulation. If surgery must be performed within 1 month of an acute VTE, intravenous UFH should be administered while the INR is less than 2. If surgery must be performed within 2 weeks after an acute episode, intravenous heparin may be withheld 6 hours preoperatively and 12 hours postoperatively, if the surgery is short. If the acute event was within 2 weeks of major surgery and/or patients have a higher risk of postoperative bleeding, a vena caval filter should be inserted preoperatively or intraoperatively.

Warfarin should be withheld for only 4 doses if the most recent episode of VTE occurred 1-3 months before surgery. If the patient has been anticoagulated for 3 or more months, 5 doses of warfarin can be withheld before surgery. Preoperatively, subcutaneous UFH or LMWH is needed only for immobilized inpatients with an INR of less than 1.8.

Jaffer formulated the Cleveland Clinic Anticoagulation Clinic Protocol and defined the following 3 risk categories for thromboembolism (see Media files 2-3):4

* High – 1-year risk of arterial embolism greater than 10%, or 1-month risk of venous thromboembolism greater than 10%
* Intermediate – 1-year risk of arterial embolism greater than 5-10%, or 1-month risk of venous thromboembolism at 2-10%
* Low – 1-year risk of arterial embolism less than 5%, or 1-month risk of venous thromboembolism less than 2%

Postoperative Management

Arterial thromboembolism

If surgery is performed within 1 month after an episode of arterial thromboembolism, intravenous heparin is warranted until the INR reaches 2 if the risk of bleeding is not very high. Administer intravenous UFH without a loading dose 12 hours after surgery at a rate of no more than 18 U/kg/h. Defer the first activated partial thromboplastin time (aPTT) for 12 hours to attain a stable anticoagulant response. Postoperative intravenous heparin is not recommended for patients who undergo major surgery and who are at high risk for anticoagulant-induced bleeding, even if an episode of arterial embolism has occurred within 1 month before surgery. Instead, administer subcutaneous UFH or LMWH (3000 U bid) until the INR reaches 1.8.

Venous thromboembolism

If the patient had an episode of VTE within 3 months before surgery, intravenous UFH is recommended until the INR is greater than or equal to 2. Patients who have a vena caval filter are protected from pulmonary embolism, and intravenous heparin can be avoided in their early postoperative period. If no previous episodes of VTE occurred within 3 months, postoperative intravenous heparin is not indicated. Subcutaneous heparin is recommended.

Madura et al recommend discontinuing coumadin 5 days before surgery and beginning intravenous heparin at 1000 U/h, while adjusting to maintain the aPTT at therapeutic levels.5 Heparin is discontinued 6-12 hours before surgery and restarted at 200-400 U/h at 4-6 hours after surgery. Coumadin is restarted as soon as tolerated by the patient.

Stop oral anticoagulants at least 5 days preoperatively, and do not perform the procedure until the PT is in the reference range. Substitute intravenous heparin infusion for oral anticoagulant therapy preoperatively to prevent thromboembolic complications in the perioperative period. Stop the intravenous heparin infusion 6-12 hours preoperatively to allow the aPTT to return to normal for adequate intraoperative hemostasis. Restart the intravenous heparin infusion within 6 hours of completion of the surgical procedure to prevent postoperative thromboembolism. Resume oral coumadin therapy as soon as the patient is able to tolerate oral liquids. Do not release the patient until the PT is once again in the therapeutic range.
Consensus Conference on Antithrombotic Therapy

Perioperative management of anticoagulation entails an understanding of all thromboembolic events, indications for treatment, and duration of treatment. The AmericanCollege of Chest Physicians for Prevention of Thromboembolism published the following guidelines.6 A full listing is available at American College of Chest Physicians.

* Low-risk general surgery patients – Early ambulation
* Moderate-risk general surgery patients – Low-dose unfractionated heparin (LDUH), LMWH, intermittent pneumatic compression (IPC), or elastic stockings (ES)
* Higher-risk general surgery patients – LDUH or higher-dose LMWH
* Higher-risk general surgery patients prone to wound complications (eg, hematomas, infection) – IPC is an alternative.
* Very high-risk general surgery patients with multiple risk factors – LDUH or LMWH combined with IPC
* Selected very high-risk general surgery patients – Perioperative warfarin (goal INR 2.5, range 2-3)
* Patients undergoing total hip replacement surgery – LMWH started 12-24 hours after surgery or warfarin started before or immediately after surgery (goal INR 2.5, range 2-3) if adjusted-dose heparin is started preoperatively; possible adjuvant use of ES or IPC
* Patients undergoing total knee replacement surgery – LMWH, warfarin, or IPC
* Patients undergoing hip fracture surgery – LMWH or warfarin (goal INR 2.5, range 2-3) started preoperatively or immediately after surgery
* High-risk patients undergoing orthopedic surgery – Inferior vena cava (IVC) filter placement only if other forms of anticoagulant-based prophylaxis are not feasible because of active bleeding (should rarely be necessary)
* Patients undergoing intracranial neurosurgery – IPC with or without ES; LMWH and LDUH may be acceptable alternatives; consider IPC or ES, with LMWH or LDUH, for high-risk patients
* Patients with acute spinal cord injury – LMWH; although ES and IPC appear ineffective when used alone, ES and IPC may have benefit when used with LMWH or if anticoagulants are contraindicated; during rehabilitation, consider continuation of LMWH or conversion to full-dose oral anticoagulation
* Trauma patients with an identifiable risk factor for thromboembolism – LMWH, as soon as considered safe; consider initial prophylaxis with IPC if administration of LMWH is delayed or is contraindicated; in high-risk patients with suboptimal prophylaxis, consider screening with duplex ultrasonography or filter placement in the IVC
* Patients with myocardial infarction – LDUH or full-dose anticoagulation; IPC and possibly ES may be useful when heparin is contraindicated
* Patients with ischemic stroke and lower extremity paralysis – LDUH or LMWH; IPC with ES also probably is effective
* General medical patients with clinical risk factors for VTE, particularly those with congestive heart failure (CHF) or chest infections – LDUH or LMWH
* Patients with long-term indwelling central vein catheters – Warfarin (1 mg/d) or daily LMWH to prevent axillary-subclavian venous thrombosis
* Patients having spinal puncture or epidural catheters placed for regional anesthesia or analgesia – LMWH should be used with caution (additional data are now reported on timing of catheter removal), ES, LDUH


perioperative anticoagulation management, anticoagulation medication, coumadin therapy, warfarin therapy, deep venous thrombosis, DVT, pulmonary embolism, PE, antithrombin III deficiency, ATIII deficiency, protein C deficiency, protein S deficiency, thromboembolism, venous thromboembolic disease, arterial thromboembolic disease, prosthetic heart valves, atrial fibrillation, congestive cardiomyopathies, mural cardiac thrombus, acute myocardial infarction, mitral valve disease, disseminated intravascular coagulation, vascular grafts, vascular shunts, vascular bypasses

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