Heparin effects on superoxide production by neutrophils.

Heparin is widely used in the treatment of various diseases, but the mechanisms of its biologic actions remain largely obscure. Recently, oxygen radicals, which are produced in a variety of conditions and cause tissue damage, have been implicated in the pathophysiology of various diseases. To investigate the relationship between heparin and oxygen radical production by neutrophils, we compared the effects of standard heparin (heparin sodium), which has been widely used, and a recently developed low molecular weight heparin (LMWH) which has potent anti-Xa activity, on neutrophil oxygen radical production in vitro. Standard heparin increased neutrophil oxygen radical production slightly at the low concentrations used clinically but reduced it at high concentrations, so that the effect of heparin on neutrophil oxygen radical production was biphasic. The effects of LMWH on neutrophil oxygen radical production were slight at both low and high concentrations. In disseminated intravascular coagulation (DIC) locally activated neutrophils produce oxygen radicals and have toxic effects in vivo. Thus we concluded that LMWH should be indicated for the treatment of DIC.