To The Editor:
The case report entitled "Delayed Onset of Anterior Tibial Compartment
Syndrome in a Patient Receiving Low-Molecular-Weight Heparin. A
Case Report" (80-A: 1789-1790, Dec. 1998), by McLaughlin et al.,
should serve as another reminder that pharmacological prophylaxis
against venous thromboembolism may be associated with serious risks.
Hemorrhagic risks are particularly important to consider as the envelope
of anticoagulation is pushed further by the enthusiasm with which
low-molecular-weight heparins have been embraced in the medical
and surgical community. The introduction of enoxaparin in the United
States at postoperative dosage strengths in excess of those previously
used in Europe has resulted in the emergence of one of the most
important issues now facing anesthesiologists and orthopaedic surgeons
in their routine management of patients who have a joint replacement
procedure - that is, an increased, and probably unacceptable, risk
of epidural hematoma after spinal or epidural anesthesia6.
Since the introduction of enoxaparin in the United States in
1993, more than forty-five cases of spinal epidural hematoma have
been reported to the Food and Drug Administration4,5. Based on these
spontaneous reports, the prevalence of epidural hematoma in patients
receiving enoxaparin after neuraxial anesthesia has been estimated
to be in the range of one per 1000 to one per 10,0004. This represents
an astounding number of patients affected by a very serious complication
of otherwise routine care.
The report by McLaughlin et al. is important and fascinating
but perhaps not surprising. In the most frequently quoted study
on the use of enoxaparin in trauma patients, Geerts et al.2 reported that five
of 129 patients experienced an unusual, delayed episode of major
bleeding after receiving enoxaparin. These complications included
a subdural hematoma, facial soft-tissue bleeding (which required
arterial embolization), and an expanding retroperitoneal hematoma.
In a control group of patients receiving a standard dosage of heparin
(5000 units twice a day), only one patient had a clinical episode
of major bleeding. These adverse outcomes were not mentioned in
the abstract and have been ignored in most citations of the study1,7, probably because
the difference between the heparin and enoxaparin groups did not
reach significance (p = 0.12). Nevertheless, had this trend continued
with a slightly larger group of patients, the message would have
been clear; that is, trauma patients may exhibit delayed bleeding at
sites of minor or otherwise subclinical injury. This delayed bleeding
is likely analogous to the problem seen in patients receiving enoxaparin after
neuraxial anesthesia.
The current standard dosage of enoxaparin, thirty milligrams
every twelve hours, represents a 50 percent increase in the daily
dosage compared with the standard dosage of forty milligrams per
day that is used in many European countries. This postoperative
dosage schedule was designed to alleviate a surgeon's fears of intraoperative
bleeding and to compensate for the omission of a preoperative dose3,8. A direct result
of the 50 percent increase in the daily dosage appears to be, as
one would predict, an increased risk of unusual hemorrhagic complications.
Although enoxaparin and other low-molecular-weight heparins are
effective agents for preventing venous thromboembolism, it is clear
that trauma specialists, neurosurgeons, and orthopaedic surgeons
should continue to carefully consider both the risks and benefits
of aggressive pharmacological prophylaxis.
James M. Hynson, M.D.
Department of Anesthesia
University of California San Francisco
1600 Divisadero Street
San Francisco, California 94143-1605
Dr. McLaughlin, Dr. Paulson, and Dr. Rosenthal reply:
Dr. Hynson's letter serves as an additional reminder of the risks
of prophylaxis against venous thrombosis, which have been well outlined
in the literature. The complications of pharmacological prophylaxis,
although rarely reported, likely affect a large number of patients, given
the widespread use of these medications.
As with any technique or medication, the risks and benefits must
be assessed on an individualized basis. Careful patient selection,
knowledge of the potential complications, and additional research
are all necessary if the use of low-molecular-weight heparin is
going to continue.
John A. McLaughlin, M.D.
Melyssa M. Paulson, M.D.
Ronald E. Rosenthal, M.D.
Corresponding author: John A. McLaughlin, M.D.
Orthopedics and Sports Medicine, P.C.
219 Blooming Grove Turnpike
New Windsor, New York 12553