Interaction heparin-platelets

The increased bioavailability of LMWHs together with their limited interactions with platelets and other plasma proteins lends itself to once-a-day dosing, in contrast to two or more injections needed with conventional heparin. Thus, unlike conventional heparin, which needs frequent monitoring with the activated partial... 

The second type of heparin-induced thrombocytopenia is severe and may be associated with a platelet count below 100,000/mm and thrombosis. ° ° The platelet count generally begins to decline 5 to 10 days after the start of heparin therapy (sooner in patients previously treated with heparin). Thrombocytopenia and thrombosis may develop with low-dose heparin, heparin-coated catheters, or even heparin flushes. Historically, the reaction was thought to be mediated by the formation of antibodies to the platelet-heparin complex. However, evidence suggests a complex interaction between heparin, platelet factor 4 (PF4), platelet membrane Fc receptors, and possibly heparin-like molecules on the surface of endothehal cells (Fig. 102-6). Circulating heparin reacts with PF4 to produce a... 

A similar series of experiments concerned a blend of a terpolymer of PVC with a cationic elastomer, containing or not ionically bound heparin. Perfusion with washed platelet suspensions, under conditions excluding thrombin generation from plasma, demonstrated the activation of platelets by heparin 3U), as reflected in a parallel increase in platelet deposition and RTG secretion (Table V). The perfusion system thus offers a simple means of in vitro screening of biomaterials for short term interactions with platelets and plasma proteins. 

Therapy, in the short term, is with intravenous unfractionated or subcutaneous low molecular weight heparin. Aspirin, given in low doses between 50 and 100 mg per day, is sufficient to diminish platelet-vessel interaction. Alternatives include 100-200 mg of sulphinpyrazone once or twice a day or dipyridamole where 100 mg four times a day can be used on its own or between 25 and 75 mg combined with aspirin three times a day. More recently thiopy-ridines, as a class, has been shown to have equivalence at 250 mg twice a day. In hyperhomocysteinaemia the risk is reduced by 5 mg of folate and 100 mg of vitamin Bg daily, with addition of oral vitamin Bi2 of less clearly defined benefit. The effect of this intervention requires re-assay at 3-monthly intervals, following standard methionine challenge, to ensure that suitable suppression has been achieved in the plasma amino acid level (Table 5). 

There is further data confirming the results compiled in Table 12. Figure 5 shows the results of the studies on the interaction of heparinized silicone rubber with blood 4). The surface is seen to adhere the platelets up to its complete saturation, which then prevents further interaction. 

Quite significant is the fact that the amount of platelets adhered depends on the synthesis procedure for HCP. For example, the platelet adhesion onto silicone rubbers heparinized via the TDMAC procedure was 150000 platelets/cm2, while the very same rubbers that were heparinized via y-aminopropyltriethoxysilane adhered only 90000 platelets/cm2 88). The platelets are to a greater extent adhered by the polymers containing covalently immobilized heparin than by those that elute heparin into the bloodstream n3) although the immobilized heparin itself does not interact with the platelets 21 . 

The reasons for the increased platelet adhesion onto covalently-immobilized heparin-containing polymers were disclosed in the studies of the protein adsorption onto HCP i.e., as stated above, the first step of the complicated blood-polymer interaction. 

Thus, the increased platelet adhesion observed upon heparinization is a consequence of the enrichment of the surface of a HCP by fibrinogen 108,. Fibrinogen, as was already stated above, may specifically interact via its oligosaccharide fragments with the enzymes of the platelet membrane. 

All interactions between UFH and platelets are complex and only partially elucidated, but it is known that heparin itself stimulates platelets via a platelet-binding domain of heparin (14). In the therapeutic range, UFH induces the release of P-selectin and activates GPIIb/llla receptors when adenosine diphosphate (ADP) or thrombin receptor agonist peptide stimulates platelet responsibility, and then enhances platelet aggregation (15,16). Even in healthy individuals, agonist-induced platelet aggregation is often enhanced when heparin is added. 

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