Platelet interaction with heparin

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... 

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 . 

Chemical synthesis of heparin fragments and analogues has been used for biological studies and to define structure-activity relationships [46]. For example, the heparin-antithrombin m interaction [47,48,49,50,51,52,53], which is responsible for the anticoagulant activity of heparin, has been studied in detail by using synthetic fragments. The interaction of heparin with FGF-1, FGF-2, platelets [54,55,56,57,58,59,60,61,62,63,64], and the Herpes Simplex virus, has also been studied by using synthetic specimens. 

In two of the five spontaneous bleeding episodes described in Heading 4, medications that can affect platelet function or prothrombin time (PT) (i.e., aspirin and warfarin) were involved. Because GB is known to be an inhibitor of PAF (41), in theory GB could interact with antiplatelet drugs (e.g., aspirin, nonsteroidal anti-inflammatory drugs, clopidogrel, ticlopidine, dipyridamole) or anticoagulants (e.g., warfarin, heparin). EGb 761 was shown to potentiate the antiplatelet effect of ticlopidine in rats (42). However, in two studies in humans, the coadministration of GB with warfarin had no effect on either international normalized ratio or warfarin metabolism (43,44). 

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... 

The drug most commonly used in clinical practice that can produce immune thrombocytopenic purpura is heparin. Other examples are sulfonamides, thiazide diuretics, chlorpropamide, quinidine, and gold. These types of immune thrombocytopenic purpura are reversed when the drug is withdrawn. Molecular mechanisms for the formation of specific drug-dependent antibodies appear to be very similar. The glycoproteins on the platelet surface interact with the drugs to form neo-epitopes. Subsequent... 

Heparin, a natural mannallan mucopolysaccharide, has attracted the attention of biologists because of Its specific Interaction with various physiological entitles Including antlthronibln M, platelets, and lipoprotein lipase (16). 

Other concerns regarding the practicality of surface bound heparin for the preparation of materials with long-term thromboresistance remain. Because the interaction of heparin with platelets is unclear (31), whether the immobilized heparin causes greater thrombosis under conditions where platelet deposition is more important than fibrin formation remains to be shown. The passivating effect of antithrombin III on platelet consumption caused by surface-bound heparin is a significant observation in this context (32, 33). 

Heparin can affect various steps of the coagulation cascade. It is now generally recognized that heparin acts as an anticoagulant of blood mainly by dramatically potentiating the inhibitory eflfect of antithrombin on the proteinases. However, heparin can also interact directly with some of the proteinases, modulate most of the reactions in the cascade by interaction with such co-factors as Ca ions and phospholipids, and significantly affect other functions (such as the platelet function) or processes (such as fibrinolysis) associated with formation and lysis of... 

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. 

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