Heparin, consider heparins

Fic. 6.—Proposed Distribution of Disaccharide Units Along an Average Heparin Chain.151 [For simplicity, possible linkage regions and antithrombin-binding sequences are not considered. For notations, see legend and footnote to Scheme 1. Arrows indicate possible insertion of units G-Ana.]... 

Howell88 considered it to be a derivative of D-glucuronic acid, but this view was not confirmed by Charles and Scott,89 who isolated a crystalline barium heparinate from beef lung and detected the presence in it of an amino sugar. 

It is of interest to note that the crystalline barium heparinate, which is an acid salt, tends to lose its anticoagulant powers very readily and that the authors consider that sulfur content gives no indication of heparin activity.93 Some polysaccharide sulfuric esters from marine algae possess anticoagulant activity. 

The binding of cations to heparin derivatives was also investigated by NOE and T2 relaxation analysis.21,22 The detailed effect of the presence of different cations was analysed, by differentiating the sulphation pattern of the several GAGs under analysis. NMR along with other techniques allowed concluding that the sequence alone does not define the conformation and flexibility for this class of molecules. Indeed, the associated cations must also be considered. Interestingly, the presence of particular cations... 

Specihc poly anions such as dextran sulfate (DS) appear to exhibit strong anti-HIV activity in vitro [36,37]. Human oral administration of DS is poorly absorbed, but intravaneous administration does result in increased plasma lipolytic activity [38]. Poly anions that have been considered for intravaginal anti-HIV activity include DS, carrageenan, heparin, heparan sulfate, dermatan sulfate, pentosan polysulfate, fucoidan chondroitin sulfate, keratan sulfate, and PAVAS [21,22,39,40],... 

Where a device incorporates, as an integral part, a substance which, if used separately, may be considered to be a medicinal product and which is liable to act upon the body with action ancillary to that of the device (e.g. a heparin-coated catheter), the product is classed as a medical device. However, the medicinal product is to be assessed in accordance with the requirements of Directive 75/318/EEC (replaced by 2001/83/EC and updated by 2003/63/EC). A notified body undertaking conformity assessment on a medical device which incorporates a medicinal substance having ancillary action has a responsibility to consult a national medicines agency about the medicinal substance, to verify its safety, quality and usefulness by analogy with the appropriate methods specified in Directive 75/318/EEC. 

Cost-minimisation analysis are performed when the clinical outcomes (e.g. efficacy and safety) of the comparator groups are virtually identical and for all practical purposes can be considered to be equal. Because no decision can be made based on differences in the clinical endpoints, decisions are based on the incremental costs of the treatment pathways. Such was the case in a study that assessed the cost-effectiveness of treating proximal deep vein thromboses (DVT) at home with low molecular weight heparin versus standard heparin in hospital therapy. A cost-minimisation approach was chosen for this analysis because the results from a comparative clinical trial confirmed that there were no statistically significant differences in safety or efficacy between the two treatment groups. The study authors concluded that for patients with acute proximal DVTs, treatment at home with low molecular weight heparin was less costly than hospital treatment with standard heparin. ... 

Danaparoid although sometimes considered as a low molecular weight heparin is chemically distinct from heparin and thus has little cross-reactivity in heparin-intolerant patients. 

The following points should be considered in all patients receiving heparin Platelet counts should be performed frequently thrombocytopenia appearing in a time frame consistent with an immune response to heparin should be considered suspicious for HIT and any new thrombus occurring in a patient receiving heparin therapy should raise suspicion of HIT. Patients who develop HIT are treated by discontinuance of heparin and administration of a direct thrombin inhibitor or fondaparinux (see below). 

Heparin is considered a hazardous drug, Heparin may be the leading cause of drug-related deaths in hospitalized patients who are relatively... 

In present times, because of early mobilization and shorter stays in hospital, venous thrombosis in the legs and resulting pulmonary embolism has declined to a large degree. In persons with acute myocardial infarction, prophylactic low-dose heparin has reduced the incidence of venous thrombosis in the legs. It is considered as a reasonable alternative to warfarin in selected patients. Preventive anlicoagulalion may be indicated in some cases to prevent strokes due to left ventricular mitral thrombi embolizing in tire brain. 

The authors of the above-discussed results consider the constant rate of heparin elution to be absolutely necessary for a successful functioning of the implant. Catheters made of these copolymers are much better, in respect of their thromboresistant properties, than the commercially available poly(tetrafluoroethylene) polyethylene, and plasticized polyvinyl chloride catheters (Table 8). The tested catheters were clotted in 9 cases of 81 (11 %), whereas usual silicone rubber catheters were clotted in 5 cases of 8 (63 %)70). 

In summary, it must be noted that in spite of the wide-spread utility of the methods of ionic immobilization of heparin it is difficult to consider a long-term use of the resultant HCP. All of the reported results indicate that after the contact of HCPs with blood and other physiological media, heparin is qurite rapidly desorbed from the polymeric surface. This does not restrict the use of such heparin-containing polymers for the purposes of a short-term contact with blood. Today such materials are already used to manufacture catheters for perito-venous shunting in Japan, USA, France, and Sweden85 87). 

Heparinization, as is seen from Table 12, results not only in the increase in blood clotting time, but also in an increase of the platelet adhesion the increase in both cases being more intensive the higher the content of the immobilized heparin. It should be noted that there is a complete agreement between the scientists concerning the effect of heparin on the blood clotting time the result of the contact of blood with HCP is considered analogous to that of the direct injection of soluble heparin into the bloodstream, whereas the data on platelet adhesion is quite contradictory. 

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