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Hot topics in hemostasis-thrombosis for 2010
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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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.