Drawing First Blood
We invite two experts to debate controversial
topics in hematology and health care
For Anticoagulation in CancerAssociated Thrombosis, Is Less More?
David A. Garcia, MD
Cancer-associated thrombosis
is a major cause of morbidity
and mortality in patients with
cancer. While low-molecularweight heparin (LMWH) anticoagulation therapy is a standard
regimen for treating acute
thrombotic events in these patients, questions remain about
its optimal use, including the
duration of anticoagulation.
ASH Clinical News invited David
A. Garcia, MD, and Agnes
Y. Lee, MD, to debate the
question: “What is the optimal
duration of LMWH treatment in
patients with cancer-associated
thrombosis – shorter (6 months)
or longer?” Dr. Garcia will be
arguing “shorter,” while Dr. Lee
will be arguing “longer.”
Agnes Y. Lee, MD
Disclaimer:
The following positions were assigned
to the participants and do not
necessarily reflect ASH’s opinion, the
participants’ opinions, or what they
do in daily practice.
Agree? Disagree? We want to hear
from you! Send your thoughts and
opinions on this controversial
issue to ashclinicalnews@
hematology.org.
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ASH Clinical News
David A. Garcia, MD: As we know, the risk
of recurrent thrombosis in cancer patients
is very high. Historical studies, especially
the one you authored more than a decade
ago, Dr. Lee, suggested that it might be
as high as 8 or 9 percent after six months
– even with aggressive LMWH therapy.1
More recent studies suggest that, with
optimal therapy, this risk may be lower;
however, it is still higher than patients
without cancer.
There is high-quality evidence that
administering a LMWH for six months to
treat acute deep-vein thrombosis (DVT)
and/or pulmonary embolism (PE) in the
setting of cancer is the standard of care,
and there are strong recommendations
from different consensus, evidence-based
guidelines to that effect.2,3 I think we can
both agree that a LMWH is the treatment
of choice, at least for the initial six months
after a thrombosis occurs.
Agnes Y. Lee, MD: Yes, I agree that LMWH
is the treatment of choice for at least the
initial six months. After six months, some
form of anticoagulation is needed in the
majority of patients in order to reduce
the risk of thrombosis recurrence. It’s a
simple concept: Anticoagulants reduce
the risk of thrombosis. If our goal is to
reduce recurrence, we can all agree that
– even in the absence of a clinical trial –
anticoagulation would be the choice over
no anticoagulation at the six-month point.
The million-dollar question is, though,
after those six months, how should we treat
these patients? Unfortunately, we don’t yet
have a definitive answer to that question.
The recently published DALTECAN
trial did provide some data on the risk
of recurrent VTE and major bleeding in
patients who continue using LMWH for
up to 12 months, showing that the risks
of recurrent thrombosis and of major
bleeding are both 0.7% per patient-month
during months seven to 12 of therapy.4
However, the lack of a comparative group
in this study still leaves us in the dark about
how LMWH would compare with other
anticoagulants beyond six months.
Dr. Garcia: There is uncertainty in this area.
For instance, at the most recent European
Hematology Association (EHA) Congress,
a group from McMaster University led by
Chatree Chai-Adisaksopha, MD, presented
an analysis of the RIETE registry in which
they found an association between extended
LMWH use beyond six months and lower
risk of VTE recurrence.5 But, again, there
are no prospective, randomized controlled
trials that prove that extended LMWH
therapy is better than any of the alternatives
currently available.
Dr. Lee: True, but if we accept that LMWH
is superior to warfarin over the first six
months – and we do have strong evidence
to support that recommendation – there
is no reason to assume that the improved
efficacy of LMWH over warfarin would
suddenly stop at six months. Then, at the
six-month mark, it is important to ask
if the same risk factors are still present
that produced the procoagulant state that
resulted in thrombosis.
Dr. Garcia: I totally agree. There are so
many factors that define cancer patients’
thrombotic risk, including: whether they
have an indwelling catheter, whether they
are receiving active chemotherapy, whether
that chemotherapy is a type known to
be strongly associated with thrombosis,
and whether or not they have evidence of
disease. The patient’s age, sex, and cancer
type also affect the clotting risk. Some of
these factors may change after six months
of therapy and take a different form than
when the cancer and/or thrombosis was
initially di agnosed.
Without a doubt, we need better riskprediction methods to identify patients
who would benefit from an extension of
more aggressive antithrombotic therapy
like LMWH – rather than exposing all
patients to extended LMWH.
Dr. Lee: Yes, a validated risk-prediction
model would be very helpful in identifying
those who would benefit from continuing
LMWH and those who might be able
to switch to an oral agent or even stop
anticoagulation altogether. Unfortunately,
such a model is not available; we barely
have data to show what happens after the
first six months of treatment.
Dr. Garcia: Given that we do not currently
have a reliable method for stratifying
patients into different risk groups for
August 2015