Comparison of the effects of low molecular weight heparin and unfractionated heparin on activation of human platelets in vitro.
An unfractionated heparin (UFH) and a depolymerised derivative of low molecular weight heparin (LMWH) have been compared for their ability to activate platelets suspended in citrated plasma (PRP) or after washing and suspension in hepes buffered tyrode containing fibrinogen. Neither heparin alone induced aggregation of washed platelets, but UFH and to a much lesser extent LMWH, induced aggregation of platelets in PRP. Both heparins caused significant enhancement of a low concentration of ADP-induced activation of PRP and, again, the effect of LMWH was somewhat less than that of UFH. UFH produced a marked potentiation of ADP-induced activation of washed platelets and LMWH was about a third as potent. In addition, UFH induced a potentiation of PAF-induced aggregation and dense-granule release in PRP, a property not shared by LMWH. In PRP, UFH was three times more potent at inhibiting thrombin-induced aggregation and dense-granule release, as might be expected from their specific activities in the KCCT and thrombin time assay. However, with washed platelets, both heparins were equivalent at inhibiting thrombin-induced aggregation, dense-granule release and elevation of cytosolic free calcium ([Ca++]i) as monitored by quin 2 fluorescence. UFH and LMWH alone did not induce a change in [Ca++]i, nor had they any effect on ADP- or PAF-induced elevation of [Ca++]i.
D000244:Adenosine Diphosphate / Q000494:pharmacology / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006493:Heparin / Q000494:pharmacology* / Q000502:physiology; D006801:Humans; D008297:Male; D008970:Molecular Weight; D010972:Platelet Activating Factor / Q000494:pharmacology / Q000502:physiology; D010974:Platelet Aggregation / Q000187:drug effects*; D013917:Thrombin / Q000494:pharmacology / Q000502:physiology
D010972:Platelet Activating Factor; D000244:Adenosine Diphosphate; D006493:Heparin; D013917:Thrombin; D002118:Calcium