Associate Professor of Clinical Pharmacy,
Philadelphia College of Pharmacy and Science,
Adjunct Assistant Professor of Pharmacy in Medicine
Cardiovascular Division,
University of Pennsylvania,
Philadelphia, Pa
To the Editor:
In the recent FRIC study,1 the subheading on page
65 states "Anti–Factor Xa Activity and aPTT Values in the Acute
Phase," but no activated partial thromboplastin time (aPTT)
values were provided. Because one of the measures of
performance of unfractionated heparin (UFH) dosing is the aPTT
achieved, the reader cannot interpret the degree of anticoagulation
achieved with UFH if no aPTT values are provided. Because aPTT
measurement was mandated per protocol at 6 and 12 hours as well as
daily through 48 hours, these median aPTT values should be reported as
well as the percentages of patients below and above the target of aPTT
of 1.5 times the control value. If dalteparin at a dose of 120 IU/kg
twice daily is as good as poorly dosed UFH with no safety advantages,
why would one use the more expensive dalteparin?
A separate issue relating to all multicenter studies of anticoagulants
that use one mandated range for aPTT measurement (such as 1.5 times
control) relates to the lack of standardization of the aPTT ranges to
target UFH concentrations as well as variability among reagents used
for aPTT measurement at individual centers when the target range is
only expressed in seconds (eg, 60 to 85 seconds). Both inconsistencies
with aPTT measurement could lead to uninterpretable results with UFH.
If all new, more expensive anticoagulants are to be compared with UFH,
closer scrutiny of dosing is warranted.
References
1.
Klein W, Buchwald A, Hillis SE, Mohiad S, Sanz G, Turpie
AGG, van der Meer J, Olaisson E, Undeland S, Ludwig K. Comparison of
low-molecular-weight heparin with unfractionated heparin acutely and
with placebo for 6 weeks in the management of unstable coronary
artery disease: Fragmin in Unstable Coronary Artery Disease
Study (FRIC). Circulation. 1997;96:61–68.
Medizinische Universitätsklinik Graz,
Graz, Austria
The median aPTT values in the acute phase of the FRIC trial were
as follows (Table 1
Therefore the median aPTT was
In addition, we have calculated how many patients were within (1.5 to
2.0 times the local reference value), below, or above these limits. The
results are shown in Table 2
Approximately 50% of the patients achieved the desired target range
during days 1 to 7. However, during days 1 to 3, 20% were below the
desired range and levels were maintained below an average of 40% for
days 4 to 7.
Finally, it should be mentioned that the use of low-molecular-weight
heparin by the subcutaneous route provides the potential of simple,
effective delivery of anticoagulation with enhanced convenience without
the costs of staff, infusion equipment, and aPTT monitoring associated
with intravenous unfractionated heparin. The simplicity of
dosing and lack of toxicity of subcutaneous low-molecular-weight
heparin allow unstable patients to be treated in a low-cost environment
while infarction is ruled out, such as in accident or emergency holding
wards or general medical wards rather than in a coronary care
unit setting only.
© 1998 American Heart Association, Inc.
Correspondence
Unfractionated Heparin Dosing in the FRIC Study
View this table:
[in a new window]
Table 1. Median aPTT
Values
View this table:
[in a new window]
Table 2. Patients Below, Within, and Above
Limits
Response
): 
60 seconds for days 1 to 3 and
maintained to around 45 seconds for days 4 to 7. The median length of
the heparin infusion was 51 hours and the median total length of
heparin treatment (intravenous only or
intravenous plus subcutaneous) was 6 days. From a clinical
perspective this must be considered sufficient heparin treatment with
aPTT levels as a tool for monitoring. This is also reflected in a
rather low number of ischemic events after 48 hours in the
heparin arm of the FRIC trial.
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