[Dysmegakaryocytopoiesis and thrombopoiesis in autoimmune thrombocytopenias].
Autoimmune thrombocytopenias (or ITP) are due mainly to an increased platelet phagocytosis by macrophages, the platelets being sensitized by the presence of autoantibodies at their surface. However, recent studies have shown, as reported in this review, that a dysmegakaryocytopoiesis possibly occurs concomitantly to the peripheral destruction of platelets. This dysmegakaryocytopoiesis is characterized by an absolute or relative decrease in megakaryocyte proliferation, and an acceleration of megakaryocyte maturation and platelet liberation. Plasma thrombopoietin level is normal or only slightly increased. An increased consumption at the megakaryocyte level has been hypothesized. By in vitro and ex vivo experiments in mice, heparin and other glycosaminoglycans were shown to stimulate megakaryocytopoiesis by acting synergistically with thrombopoietin and interleukin 6, and in the other hand by neutralizing inhibitors of megakaryocytopoiesis such as platelet factor 4 and transforming growth factor beta. A prospective randomized trial was performed in 20 patients with chronic corticoresistant ITP. After randomization, a group received heparin (1,250 IU x 2/SC/day for 30 days). In this group a statistically significant increase in the platelet count was observed with return to the initial value after therapy cessation. Taking together these data suggest that heparin (or analogs more convenient for clinical use), by enhancing megakaryocytopoiesis, may constitute at least a new promising therapeutic strategy for this too often refractory disorder.
Bellucci
S
S
Laboratoire d'Hématologie, Institut des Vaisseaux et du Sang, Hôpital Lariboisière, Paris.
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology / Q000473:pathology*; D001792:Blood Platelets / Q000473:pathology*; D002455:Cell Division; D006410:Hematopoiesis; D006801:Humans; D066298:In Vitro Techniques; D008533:Megakaryocytes / Q000473:pathology*; D051379:Mice; D013921:Thrombocytopenia / Q000276:immunology / Q000473:pathology*
Dysmégacaryocytopoïése et thrombopoïèse au cours des thrombopénies auto-immunes.