HemOnc Today recently convened its well-respected Section
Editors to present on ‘hot’ or controversial topics they deemed
important to their subspecialty area. Presented here is Joel Moake,
MD’s, discussion of his hit list of topics that he believed fulfilled
this qualification. HemOnc Today will continue to follow and
expand coverage of these topics in the ensuing months. We hope you find these
executive overviews informative.
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Joel
Moake
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There are several topics in hemostasis and thrombosis that are creating
great enthusiasm among physicians in the specialty. Although most of these
therapies and concepts are still in early development, more data are expected
on them in 2010.
Here I will discuss the top seven topics of interest for 2010.
1) First is the use of oral anti-Factor Xa and antithrombin
anticoagulants as possible replacements for warfarin. The two drugs in these
classes that have advanced furthest in clinical trials process are dabigatran,
which is an antithrombin oral agent, and rivaroxaban, an anti-Factor Xa oral
agent. There is considerable interest and enthusiasm for the use of these
agents in prophylactic, and possibly therapeutic, anticoagulation in venous
thromboembolic disorders.
2) Also on the subject of anticoagulation in venous thromboembolism,
fondaparinux (Arixtra, GlaxoSmithKline) may become the preferred heparin type
of parenteral, immediate-use anticoagulant for therapeutic and prophylactic
antithrombotic therapy. Fondaparinux does not, or almost never, causes
heparin-induced thrombocytopenia. The potential cost associated with expanded
use of fondaparinux is not yet known.
3) Also of interest is the development of new antiplatelet agents for
use in various arterial thrombotic diseases. For example, the drug prasugrel
(Effient, Eli Lilly) is a possible replacement for clopidogrel.
Prasugrel is more effectively converted to its active metabolite and has
the potential of being more effective than clopidogrel for arterial thrombotic
problems. It is unknown if prasugrel, which is the same class of compound as
ticlopidine and clopidogrel, might also occasionally cause thrombotic
thrombocytopenic purpura. It also must be determined, with maximum confidence,
if prasugrel, at effective antiarterial thrombotic doses, is associated with
unacceptable incidence of bleeding complications.
4) The pathophysiology of thrombotic microangiopathies (TMAs) other
than those caused by familial and autoantibody-mediated ADAMTS-13 deficiency
remains obscure. TMAs associated with transplantation, particularly
hematopoietic stem cell transplantation, is a deadly complication that may be
related to immunosuppression with cyclosporine and tacrolimus. The basic
pathophysiologic process is unknown, except for a few clues that have surfaced
recently. In 2010, there may be more precise information about the
pathophysiology of transplantation-associated TMAs.
5) Other new drugs of interest include ARC-1779 and a
“nanobody” that have similar effects. ARC-1779 is an oligonucleotide
aptamer (Archimex) that blocks platelet adherence to von Willebrand factor and
may be of use in ADAMTS-13 deficient types of TTP. It may also be useful in
other types of TMAs, and possibly even in myocardial infarction and stroke.
Further information on this agent will likely be forthcoming in 2010.
In addition to ARC-1779, there is another compound, a nanobody fragment
of an antibody (Ablynx) that also blocks platelet adherence to von Willebrand
factor. This latter compound is also far along in development but not into
clinical trials. It may also be useful for TTP, possibly other TMAs, and maybe
even the common arterial thrombotic entities, heart attack and stroke.
6) Also in development is a recombinant ADAMTS-13 for possible use in
familial and autoantibody-mediated ADAMTS-13 deficient types of TTP, and
possibly in other types of TMAs. This agent is far along in development and may
enter into clinical trials in 2010. It also has the possibility of being useful
in MI and stroke.
7). Finally, the postmarketing results of thrombopoietin-mimetics in the
treatment of idiopathic thrombocytopenic purpura will be of interest in 2010.
These compounds are romiplostim (NPlate, Amgen), which is given subcutaneously,
and eltrombopag (Promacta, GlaxoSmithKline), which is taken orally. These
agents are extremely promising in the therapy of ITP, but it remains to be
known exactly how they should be combined with prednisone, IVIg and anti-CD20
monoclonal antibody inhibitors in the treatment of ITP. This will probably be
progressively clarified during 2010.
Joel Moake, MD, is a Senior Research Scientist at Rice University and
is Section Editor of the Platelet Disorders & Physiology Section of
the HemOnc Today Editorial Board.