Heparin assessment

RM Marks, H Lu, R Sundaresan, T Toida, A Suzuki, T Imanari, MJ Hernaiz, RJ Linhardt. Probing the interaction of dengue virus envelope protein with heparin assessment of glycosaminoglycan-derived inhibitors. J Med Chem 44 2178-2187, 2001. 

Before administering the first dose of heparin, the nurse obtains the patients vital signs. The most commonly used test to monitor heparin is activated partial thromboplastin time (APTT). Blood is drawn for laboratory studies before giving the first dose of heparin to obtain baseline data (See the discussion on preadministration assessment for the oral anticoagulants.)... 

The ongoing assessment of a patient receiving heparin requires close observation and careful monitoring. The nurse assesses vital signs every 2 to 4 hours or more frequently during administration. 

The PRO ACT-11 trial was designed to assess the clinical efficacy and safety of lA r-pro-UK. In this study, 180 patients were enrolled in a 2 1 randomization scheme to receive either 9 mg lA r-pro-UK plus 4 hours of low-dose IV heparin, or low-dose IV heparin alone. The primary clinical outcome, the proportion of patients with slight or no disability at 90 days (mRS of < 2), was achieved in 40% of the 121 patients in the r-pro-UK treatment group, compared to 25% of the 59 patients in the control group (absolute benefit 15%, relative benefit 58%, number need to treat = 7 p = 0.04). The recanalization rate (TlMl 2 and 3) was 66% for the r-pro-UK group and 18% for the control group (p < 0.001). Symptomatic ICH within 24 hours occurred in 10% of r-pro-UK patients and 2% of control patients (p = 0.06). All symptomatic ICHs occurred in patients with a baseline NIHSS... 

A specific immunoassay for measuring two-chain factor VIIa levels in plasma has been developed to identify activation of factor VII in patients with acute coronary syndromes suchs as myocardial infarction and unstable angina (12). Because regulation of factor VIIa is believed to be mediated by tissue factor pathway inhibitor (TFPI), its measurement is also useful in assessing thombotic and cardio-vasular disorders. Because TFPI is released by heparin, its measurement is also useful in assessing the efficacy of heparin and endothelial cell function (93). 

Tyler-Cross, R., M. Sobel, L.E. McAdory, and R.B. Harris. 1996. Structure-function relations of antithrombin Ill-heparin interactions as assessed by biophysical and biological assays and molecular modeling of peptide-pentasaccharide-docked complexes. Arch Biochem Biophys 334 206-213. 

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. 

Special rules 13-18 govern several hazardous characteristics that may be found in certain devices and require a certain level of control and conformity assessment. Rule 13 deals with devices incorporating a medicinal substance whose action is ancillary to that of the device -Class 111, for example, antibiotic bone cements, condoms with spermicides, heparin-coated catheters. 

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. ... 

In a placebo-controlled randomized supplementation trial (approved by the ethic commission of Ethiopia) in the rural area (AZOZO) district of Gondar Ethiopia from 220 households, 161 children (2-5 years of age) were selected at random for the study at a first visit to the local clinic, nutritional assessment, and stool examination (parasites or ova) were performed (Biesalski et ah, 1999). 141 children with parasites were treated with mebendazole. Heparin blood was obtained for assessment of vitamin A, RBP, and TTR (transthyretine) concentrations. 

Zidar I, Jackman J, Gmmon R, et al. Serial assessment of heparin coating on vascular response to a new tantalum stent [abstr]. Circulation 1992 89 1-185,... 

Kedev S, Guagliumi G, Valsechi O, Tespili M. Heparin-coated versus uncoated Palmaz-Schatz stent in native coronary circulation. A randomized study with blind angioscopic assessment. Int J Artif Organs 2002 25(5) 461 -469. 

Initially, plasma and oral fluid specimens from patients (n = 21) on different antidepressant treatment were collected twice to assess if any of the studied analytes was likely to show a good correlation. The best results were obtained for venlafaxine (%CV for plasma/oral fluid concentrations ratio (f OF/PL) <21%). Therefore, the study was extended for this antidepressant by analysis of oral fluid and plasma specimens from five patients on venlafaxine treatment collected on four occasions. Daily doses of venlafaxine retard formulations were 75 mg for two patients, and 150 mg for the remaining participants. Collection of oral fluid (direct spitting into polypropylene tubes) and plasma (heparinized tubes) specimens was performed, when possible, before the next dose to ensure the drug was in the elimination phase. The dose and the time of collection was the same on the four different occasions for each patient. For the analysis, oral fluid and plasma specimens were centrifuged at 14 x 103 rpm, and 0.2 mL of the supernatant were extracted. In addition, correlation between the concentrations in the plasmatic free fraction and in oral fluid was also evaluated. Plasmatic proteins were eliminated by filtering 0.5 mL of plasma samples using Microcon filter devices Ultracel YM-3 (Millipore Corp., Billerica, MA, USA). 

Rivera TM, Leone-Bay A, Paton DR, Leipold H, Baughman RA (1997) Oral delivery of heparin in combination with sodium N-[8-(2-hydroxybenzoyl) aminojcaprylate pharmacological considerations. Pharm Res 14 1830-1834 Sakai K, Kutsuna TM, Nishino T, Fujihara Y, Yata N (1986) Contribution of calcium ion sequestration by polyoxyethylated nonionic surfactants to the enhanced colonic absorption of p-aminobenzoic acid. J Pharm Sci 75 387-390 Sakai M, Imai T, Ohtake H, Azuma H, Otagiri M (1997) Effects of absorption enhancers on the transport of model compounds in Caco-2 cell monolayers assessment by confocal laser scanning microscopy. J Pharm Sci 86 779-785... 

Aldurazyme polymorphic variation of human a-L-iduronidase lysosomal hydrolase hydrolysis of terminal a-L-iduronic acid residues of dermatan sulfate and heparin sulfate No genotoxicity studies clinical trials Studies to assess mutagenic and carcinogenic potential have not been conducted No warnings or precautions regarding carcinogenic risk... 

CRITICAL ASSESSMENT OF THE METHOD Breddin (1989) described the Wessler model because of its static character as the retransformation of an in vitro experiment into a very artificial test situation. One of the major drawbacks is the relative independence of platelet function and hemodynamic changes that largely influence thrombus formation in vivo. However, the model has been shown to be very useful for evaluation of the antithrombotic effect of compounds like heparin and hirudin. 

The general drawback of the Wessler model is the static nature of the venous thrombus development. To overcome this problem some investigators have developed more dynamic models with reperfusion of the occluded vessel segments after clot development. Depending on the time of test compound administration (pre- or post-thrombus initiation), the effect on thrombus growth and fibrinolysis can be evaluated. Levi et al. (1992) have used this model to assess the effects of a murine monoclonal anti-human PAI-1 antibody and Biemond et al. (1996) compared the effect of thrombin and factor Xa inhibitors with a low molecular weight heparin. 

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