Normal and low molecular weight heparins: interaction with human platelets

Abstract

Porcine mucosal heparin was chemically depolymerized. The depolymerization was stopped at different steps to obtain two low molecular weight (LMW) heparins with a molecular weight of 10 000 and 6000, respectively. The LMW heparins were tested in vitro for anti-clotting activities and for platelet serotonin release in different systems in comparison with normal heparins, dermatan and heparan sulphate. After addition of various amounts of heparin preparations to washed platelets, no significant release was observed for all tested heparins. On the contrary, different heparins showed an inhibition of serotonin-release induced by collagen in platelet rich plasma, whereas the ADP-induced release was increased. The effect on the platelet release appears related to the molecular weight. In fact, it is significant only for normal heparins whereas it is not for LMW heparins. A good relation was observed, also, between anti-activated factor X activity/antiglobal clotting activity (Xa/APTT) ratio of different heparins and the effect on platelet release.

Effects of low-molecular-weight heparin on platelets as compared with commercial heparin

“…It has been shown that the different molecular weights each have a different effect on the clotting assay systems [1,2]. On the platelet function assayed in vitro, low-molecular-weight (LMW) heparin seems to determine a lesser activation than that produced by high-molecular-weight heparin [3,4]. When heparin is injected in vivo as a bolus, it determines an immediate release of platelet factor 4 (PF4) measured by radioimmunoassay [5].…”

Heparin and its derivatives in the treatment of arterial thrombosis: a review

“…In these models, LMWH's are slightly less effective than UFH; however, they cause significantly less systemic bleeding under standardized conditions (Esquivel et al, 1982;Ockelford et al, 1982;Hobbelen et al, 1987). Whenever these sulphated polysaccharides are compared to each other, their effect on platelets (Fabris et al, 1983;Fernandez et al, 1986;Sobel et al, 1991), as well as on blood vessel permeability (Blajchman et al, 1989) should be kept in mind.…”

Heparin-induced thrombocytopenia

“…The origin of non-immune heparin associated thrombocytopenia is not yet completely understood, though it is thought to be caused by heparin-induced platelet clumping (Fabris et al, 1983;. Thrombocytopenia of this type is mild (platelet count, >100 x 10 9 cells/L), not progressive, nor associated with bleeding or thrombosis (Salzman et al, 1980), and is independent of any immune reaction (Chong et al, 1993a;Burgess & Chong, 1997;Shantsila et al, 2009).…”

“…This phenomenon gradually resolves without interruption of heparin administration, and platelet counts gradually rises to pre-treatment levels within a few days without special treatment. Non-immune heparin associated thrombocytopenia may be related to the direct binding of heparin to platelet membranes (Salzman et al, 1980;Fabris et al, 1983;.…”