HDCN Ask the
Professor:
Coumadin to maintain vascular access patency
Question:
I am a practicing nephrologist, and like all nephrologists, I find maintaing
the patency of vascular access, especially of PTFE grafts, difficult. I am
aware of the abnormalities related to protein C in hemodialysis patients and
their implications if coumadin is used in such patients.
A review of the literature reveals various therapeutic measures which could be
taken to lengthn the lifespan of the vascular access. These include heparin,
gene therapy, dipyridamole, ASA, etc. But I am not aware on any studies
evaluating the role of coumadin for this purpose.
Are there any nephrologists using coumadin prophylactically to prevent
thrombosis of the vessel access, or are there any ongoing studies?
M. Babu, MD (Santa Maria, CA)
The expert consulted in this question was:
Steve Fishbane, M.D.
SUNY Stonybrook School of Medicine
As you are aware from your review of the literature, there is not much in the
way of clinical studies evaluating warfarin's safety or efficacy for
preventing graft thrombosis. As is so often the case in clinical medicine, we
must base our approach on theoretical considerations, while weighing risk,
reward, and cost.
Our approach to preventing graft thrombosis is two pronged: Since most
thrombotic episodes are related to venous stenotic lesions, we do monthly
venous pressure screening on all patients (Beathard et al 1989). We primarily
use venous drip chamber readings for this purpose, although we are looking at
a method for obtaning intragraft pressures (Besareb et al 1995). Our second
component to the prevention of graft thrombosis is the selective use of
antithrombotic agents. In patients we believe to be at high risk for
thrombosis (history of recurrent previous thromboses, positive
antiphospholipid antibodies, or knowledge of a structural defect which cannot
be corrected etc.), we often treat with warfarin on a chronic basis. We
believe that we decrease significantly the risk of thrombosis with this
regimen, but because we are not doing it as part of a controlled trial, I
would not use our experience to suggest the efficacy of warfarin. You should
of course be aware that any potential effectiveness must be weighed against
1) safety concerns, up to a 3% per year risk of a major bleeding episode, 2)
the direct cost of the medication, 3) the direct cost of prothrombin time
screening, 4) the indirect cost of nurse/physician monitoring of PT results.
As with warfarin, the efficacy of antiplatelet agents is unclear. I would
refer you to a recent, well designed study by Sreedhara et al (cited below),
which demonstrated a beneficial effect of dipyridamole in new grafts, but no
benefit of aspirin or dipyridamole for the secondary prevention of graft
thrombosis. Interestingly, the incidence of thrombotic episodes appeared to
be increased when aspirin was used alone.
We are currently engaged in a prospective study of a low molecular weight
heparin formulation for the prevention of graft thromboses. Low molecular
weight heparins have recently gained interest in clinical medicine due to a
reasonable safety profile, consistent pharmacokinetics which eliminates the
need for monitoring, an antiproliferative effect, and a lower incidence of
heparin induced thrombocytopenia compared to unfractionated heparin. I would
hope that we will have meaningful data at some point in the next year.
References
Beathard GA. Percutaneous transvenous angioplasty in the treatment of
vascular access stenosis. Kidney Int 42:1390, 1992
Besarab A, Sullivan KL, Ross RP, Moritz MJ. Utility of intra-access pressure
monitoring in detecting and correcting venous outlet stenoses prior to
thrombosis. Kidney Int 47:1364, 1995
Sreedhara R, Himmelfarb J, Lazarus JM, Hakim RM. Anti-platelet therapy in
graft thrombosis: results of a prospective, randomized, double-blind study.
Kidney Int 45:1477, 1994
(May, 1996)