Circulation 60,475 • Volume 13, No. 1 • Spring 1998

Low Molecular Weight Heparin and Epidurals

James C. Crews, M.D.

[Editor’s note: The recently issued FDA Advisory regarding the risk associated with peridural anesthesia and anticoagulation has generated significant discussion.]

On December 15, 1997, the Food and Drug Administration (FDA) published a public health advisory concerning reports of epidural or spinal hematomas with the concurrent use of low molecular weight heparin and spinal/epidural anesthesia or spinal puncture.1 The purpose of this advisory was to notify patients and health care professionals of a series of more than 30 spontaneous post-marketing reports of patients who have developed epidural or spinal hematomas with the concurrent use of low molecular weight heparin and spinal/epidural anesthesia or spinal puncture. The FDA felt that this public advisory was warranted due to the number and potential seriousness of this complication in this patient population. All reports received to date involved patients who were treated with Lovenox® (enoxaparin sodium) Injection. The FDA suggested that the complication may also be expected to occur if other drugs with similar pharmacological activity (dalteparin sodium, ardeparin sodium, danaparoid sodium) were used in the same manner. Additionally the report cautioned that the risk of spinal/epidural hematomas may be increased by the use of indwelling epidural catheters for administration of analgesia; by the concomitant use of drugs affecting hemostasis such as non-steroidal anti-inflammatory drugs (NSAIDs), platelet inhibitors, or other anticoagulants; or by traumatic or repeated epidural or spinal puncture. All manufacturers of low molecular weight heparins and heparinoids have been asked to revise their package inserts to provide further information for the safe and effective use of these drugs.

Since publication of this advisory by the FDA, many anesthesiologists have had cause to consider a reevaluation of the potential benefits of the use of neuraxial anesthetic and analgesic procedures versus the potential risk of spinal/epidural hematoma in patients concurrently receiving low molecular weight heparin or heparinoid products specifically and other types of anticoagulant agents in general. The benefits of neuraxial blockade anesthetic and analgesic techniques as compared to general anesthesia and systemic opioid analgesia in terms of superior analgesia, reduced perioperative blood loss and need for transfusion, and a decreased incidence of perioperative thromboembolic complications are well documented.2-4 The risk of development of venous thrombosis may exceed 70% in the major orthopedic surgery patient population with 2–16% of these patients having clinical or laboratory evidence of pulmonary embolism.5-7 Therefore it has become common clinical practice to use thromboprophylaxis in patients with major trauma or patients undergoing major surgical procedures, especially major orthopaedic and abdominal procedures. Several excellent reviews of the use of regional anesthesia and analgesia in patients receiving concurrent antiplatelet therapy or thromboprophylaxis have been recently published in the anesthesiology literature.8-11

Striking a Balance

So, how does the anesthesiologist balance the relative clinical benefits of regional anesthesia and analgesia techniques versus the risks of the complication of spinal epidural hematoma, spinal cord compression, and permanent neurologic injury in the perioperative management of these patients? As a group of anesthesiologists with a special interest in regional anesthesia, postoperative pain management, and perioperative patient care, we have reviewed the literature and current clinical practice of the various surgeons and surgical subspecialties within our institution with respect to perioperative thromboprophylaxis and have adopted the following clinical guidelines for our practice at Wake Forest University Baptist Medical Center:

1. Patients with no clinical evidence of coagulopathy or concurrent anticoagulant therapy are routinely offered regional anesthetic and analgesic techniques for appropriate surgical procedures;

2. Patients receiving chronic anticoagulant therapy prior to surgery are evaluated on an individual basis with respect to the therapeutic effect of the anticoagulant therapy, the risk/benefit assessment regarding regional versus general anesthesia, and the risks of withdrawing anticoagulant therapy prior to elective surgical procedures. Patients with therapeutic levels of anticoagulant therapy (INR or PTT > 1.5 times normal) in which anticoagulant therapy cannot be withheld prior to elective surgery are evaluated with respect to a risk/benefit assessment of general anesthesia or peripheral neural blockade techniques versus neuraxial blockade techniques;

3. Postoperatively patients may be started on coumadin 2.5 – 5.0 mg orally or heparin 5000 units subcutaneously on the day of surgery as thromboprophylactic therapy;

4. Patients with epidural catheters for continuous postoperative epidural analgesia have a PT, INR, and PTT measured every morning postoperatively while receiving coumadin thromboprophylaxis;

5. Epidural catheters are removed on postoperative day 1 in patients receiving coumadin after confirming an INR < 1.5. For patients with an INR > 1.5 on the morning of postoperative day one, the epidural catheter is left in place and subsequent coumadin doses are withheld until the INR is

< 1.5, and then the catheter is removed; following removal of epidural catheters, analgesia is maintained through the use of peripheral neural blockade techniques, and/or systemic opioid and non-opioid analgesics;

6. Patients receiving subcutaneous heparin thromboprophylaxis have the heparin dose held for at least one hour following placement of spinal or epidural neuraxial blocks and following removal of epidural catheters. Additionally, epidural catheters are removed late in the heparin dosing interval (6 – 10 hours following the dose);

7. Epidural analgesia is not routinely continued into the postoperative period for patients anticipated to receive low molecular weight heparin thromboprophylaxis. Patients with continuous epidural catheters who receive concurrent LMVH therapy have epidural analgesia discontinued and catheters removed 10 – 12 hours following the dose of LMWH, and the next dose is held for at least 1 – 2 hours following catheter removal;

8. Patients with major traumatic injury or other hospitalized patients receiving LMWH prophylaxis are evaluated on an individual basis with respect to the benefits of neuraxial regional anesthetic techniques or continuous epidural analgesia versus the risk of spinal epidural hematoma. If epidural analgesia is judged to be medically indicated, consideration is given to changing the thromboprophylaxis therapy and avoiding placement of or removal of epidural catheters near the dosing interval of the LMWH.

Despite what is known about the benefits of regional anesthesia and analgesia and the risks of perioperative deep vein thrombosis, pulmonary embolism, and the potential bleeding complications of spinal epidural hematoma in patients receiving concurrent thromboprophylactic therapy, some important pieces of information remain unknown. Studies of the incidence of thromboembolic complications in patients receiving regional versus general anesthesia involved patients receiving no postoperative thromboprophylactic therapy. What is the relative risk of development of perioperative thromboembolic complications in patients receiving regional anesthesia and continuous postoperative epidural analgesia versus patients receiving general anesthesia and systemic opioid analgesia plus thromboprophylaxis? What is the relative efficacy of the various thromboprophylactic medications and what should be considered the target clinically therapeutic endpoint for the various agents?

Some may consider the practice guidelines adopted at WFUBMC to be conservative or overly cautious. However, with respect to what is known and unknown regarding the issues surrounding postoperative thromboprophylactic therapy and in light of the seriousness of the complication of spinal epidural hematoma and permanent neurologic injury in these patients, the guidelines adopted as outlined above were felt to be justified in the interest of patient safety. It will be essential to continue to investigate the unknown aspects surrounding the relative risks and benefits of neuraxial regional anesthetic and analgesic techniques with respect to postoperative thromboembolic complications and effective thromboprophylactic therapies. We must continue to evaluate these issues as anesthesiologists and perioperative physicians in association with our medical and surgical colleagues to determine the most safe and efficacious approach to the postoperative rehabilitation management of these patients.

Dr. Crews is Associate Professor and Director, Acute Pain Service, Department of Anesthesiology, Wake Forest University School of Medicine, Winston-Salem, NC.


1. Lumpkin MM. Reports of epidural or spinal hematomas with the concurrent use of low molecular weight heparin and spinal/epidural anesthesia or spinal puncture. FDA Public Health Advisory. U.S. Department of Health and Human Services B Public Health Service. 15 December 1997.

2. Modig J, Maripuu E, Sahlstedt B. Thromboembolism following total hip replacement: A prospective investigation of 94 patients with emphasis on the efficacy of lumbar epidural analgesia in prophylaxis. Reg Anesth 1986;11:72.79.

3. Modig J, Borg T, Bagge T, Saldeen T. Role of extradural and of general anesthesia in fibrinolysis and coagulation after total hip replacement. Br J Anaesth 1983;55:625-629.

4. Modig J, Borg T, Karlstrom G, Maripuu E, Sahlstedt B. Thromboembolism after total hip replacment: Role of epidural and general anesthesia. Anesth Analg 1983;62:174-180.

5. O’Meara PM, Kaufmann EE. Prophylaxis of venous thromboembolism in total hip arthroplasty: a review. Orthopedics 1990;13:173-178.

6. Hirsh J, Levine M. Prevention of venous thrombosis in patients undergoing orthopaedic surgical procedures. Br J Clin Pract 1989;65:2-8.

7. Sculco TP. Establishing a universal protocol for deep vein thrombosis following orthopedic surgery: total knee arthroplasty. Orthopedics 1996:19 Suppl:6-8.

8. Horlocker TT, Wedel DJ, Schlichting JL. Postoperative epidural analgesia and oral anticoagulant therapy. Anesth Analg 1994;79:89-93.

9. Vandermeulen EP, Van Aken H, Vermylen J. Anticoagulants and spinal-epidural anesthesia. Anesth Analg 1994;79:1165-1177.

10. Horlocker TT, Wedel DJ, Schroeder DR, et al. Preoperative antiplatelet therapy does not increase the risk of spinal hematoma associated with regional anesthesia. Anesth Analg 1995;80,303-309.

11. Horlocker TT. Regional anesthesia and analgesia in the patient receiving thromboprophylaxis. Editorial. Reg Anesth 1996;21:505-507.