FRAXIPARIN, A LOW-MOLECULAR-WEIGHT HEPARIN, STIMULATES MEGAKARYOCYTOPOIESIS IN-VITRO AND IN-VIVO IN MICE

The effect of a low-molecular-weight heparin, faxiparin (Nadroparin(R) ), on murine megakaryocytopoiesis in vitro and in vivo was studied in comparison with unfractionated heparin. The addition of fraxiparin at 1-20 IU/ml into plasma clot cultures but not serum-free agar culture s ignificantly enhanced MK colony growth. Furthermore, fraxiparin was fo und to potentiate the stimulating activity of aplastic anaemia serum ( AAS) but not stem cell factor (SCF), interleukin-3 (IL-3), granulocyte -macrophage colony-stimulating factor (GM-CSF) and erythropoietin (Epo ), on MK colony growth in vitro, and to neutralize the inhibitory effe ct of platelet factor 4 (PF4) in vitro and in vivo. Fraxiparin also ac ted synergistically with heparin cofactor II and antithrombin III to p romote megakaryocyte colony formation. Intraperitoneal administration of fraxiparin twice daily for 4d at 0.1-25IU/injection increased in mi ce the level of blood platelet counts and the number of single MKs and CFU-MK in bone marrow. These data demonstrate that fraxiparin is able to positively regulate megakaryocytopoiesis.