Emerging treatments for thrombocytopenia: increasing platelet production.
Thrombocytopenia is a common medical problem. The first generation thrombopoietic agents, recombinant THPO and 'megakaryocyte growth and development factor' (PEG-rHuMGDF) entered clinical trials, but their development was discontinued owing to neutralizing auto-antibodies cross-reacting with endogenous THPO, causing thrombocytopenia in healthy volunteers. Although an approved drug for prevention of severe thrombocytopenia following myelosuppressive chemotherapy (human Interleukin-11) exists, the search for new thrombopoietic agents continued because its use is limited by side effects. Several second generation thrombopoietic factors have entered clinical trials and some new negative regulators of megakaryopoiesis have been found, such as platelet factor 4 (PF4) and the pituitary adenylate cyclase activating polypeptide (PACAP). Their inhibition may be useful in the treatment of thrombocytopenia. This article reviews second generation thrombopoietic factors and those recently discovered regulators of megakaryopoiesis.
Peeters
Karen
K
Center for Molecular and Vascular Biology, University of Leuven, Herestraat 49, Leuven, Belgium.
Stassen
Jean-Marie
JM
Collen
Désiré
D
Van Geet
Chris
C
Freson
Kathleen
K
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D008533:Megakaryocytes / Q000187:drug effects; D010982:Platelet-Derived Growth Factor / Q000627:therapeutic use; D013921:Thrombocytopenia / Q000188:drug therapy*
D010982:Platelet-Derived Growth Factor