Anna D. Garrett, PharmD, BCPS, CPP
Dr. Garrett is manager of the Health Education Center at Mission Hospitals in Asheville, North Carolina.
Laxatives May Interfere with Warfarin
Excessive use of stimulant laxatives,
such as senna, may interfere with
warfarin therapy. A case was recently
reported of a patient who
used excessive senna. The
patient presented with
bloody stools and an international
normalized ratio
(INR) of 11.9. The interaction
may be due to diarrhea,
which can develop
if laxatives are overused.
Diarrhea is known to decrease the
absorption of vitamin K, which can lead
to elevated INRs and bleeding. Patients
should be counseled to
use herbal laxatives with
care. Natural products that
are promoted for weight
loss and detoxification may
contain ingredients such as
aloe, cascara, or European
buckthorn, all of which
have laxative properties.
Alteplase Effective for Stroke up to 4.5 Hours After
the Event
Intravenous thrombolysis with alteplase
is the only approved treatment for acute
ischemic stroke, but its efficacy and
safety when administered > 3 hours after
the onset of symptoms have not been
established. A recent study of patients
with ischemic stroke, confirmed by
computed tomography showed a benefit
of the drug when given beyond the
typical 3-hour limit. Researchers studied
a total of 821 patients given alteplase or
placebo 3 to 4.5 hours after the onset of
stroke symptoms. The major end point
studied was disability at 90 days.
The median time for the administration
of alteplase was 3 hours 59 minutes.
More patients had a favorable
outcome with alteplase (52.4%) than
with placebo (45.2%). The incidence
of intracranial hemorrhage was higher
with alteplase. Mortality did not differ
between the groups. The authors concluded
that alteplase may offer significant
benefit to patients beyond the time
that is specified by the manufacturer;
however, further study is needed.
Protein C and S Deficiency Increase TE Risk
Protein C, protein S, and antithrombin
deficiencies are associated with
increased risk of thromboembolism (TE).
Dutch researchers recently conducted
a retrospective study of 552 subjects
representing 84 families to determine if
a history of venous TE predisposed the
subjects to arterial TE (ATE). Detailed
information on previous venous TE, ATE,
anticoagulant use, and atherosclerosis
risk factors was collected.
Of 552 subjects, 35% had protein S,
39% had protein C, and 26% had antithrombin
deficiency. Overall, annual incidences
of ATE were 0.34% in deficient
subjects versus 0.17% in nondeficient
subjects; the hazard ratio was 2.3. After
adjusting for atherosclerosis risk factors
and clustering within families, deficient
subjects had a 4.7-fold higher risk for ATE
before 55 years of age versus 1.1 thereafter,
compared with nondeficient family
members. For separate deficiencies, the
risks were 4.6-, 6.9-, and 1.1-fold higher in
protein S?, protein C?, and antithrombindeficient
subjects, respectively, before 55
years of age. History of venous TE was
not related to subsequent ATE.
The researchers concluded that subjects
with protein S or protein C deficiency,
but not antithrombin deficiency,
have a higher risk for ATE before 55
years of age that is independent of prior
venous TE.
Cigarette Smoking
Decreases Platelet
Aggregation
Researchers have discovered that cigarette
smoking is an independent predictor
of the level of platelet aggregation a
patient exhibits. This finding may help
explain the variability in response to
clopidogrel therapy. Cigarette smoking
induces the CYP1A2 isoenzyme of the
cytochrome P450 system and enhances
the antiplatelet effect of clopidogrel,
researchers reported in a recent issue
of the
Journal of the American College
of Cardiology.
Earlier work in this area of study
showed that responders to clopidogrel
therapy were more often smokers. The
current paper expands on that initial
observation and demonstrates how an
external factor, smoking, can influence
platelet reactivity in patients treated
with a prodrug that is metabolized by
the hepatic cytochrome P450 pathway.
The researchers studied 104 current
smokers and
155 nonsmokers
who were
undergoing
elective coronary
stenting.
They were
either already
on clopidogrel
or received a
600-mg loading
dose. Current
smokers
on chronic clopidogrel showed significantly
greater platelet inhibition and
significantly lower platelet aggregation
than their nonsmoking counterparts.
This also was true of smokers who
received the loading dose, compared
with nonsmokers who received the
loading dose. Smoking was a highly
significant independent predictor of low
platelet aggregation.
Inside the Issue
