Heparin plasma concentration

A more recent study of 18 infants on ECMO life support also reported leaching of di(2-ethylhexyl) phthalate from the PVC circuits at linear rates that were dependent on the surface area of the circuit. For standard 3-10-day treatment courses, the mean peak plasma concentration of di(2-ethylhexyl) phthalate was 8.3 5.7 mg/L, and the estimated exposure over 3-10 days was 10-35 mg/kg bw. No leaching of di(2-ethylhexyl) phthalate from heparin-coated PVC circuits was detected (Karle et al., 1997). 

The indications for the use of heparin are described in the section on clinical pharmacology. A plasma concentration of heparin of 0.2-0.4 unit/mL (by protamine titration) or 0.3-0.7 unit/mL (anti-Xa units) usually prevents pulmonary emboli in patients with established venous thrombosis. This concentration of heparin will prolong the activated partial thromboplastin time (aPTT) to 2-2.5 times that of the control value. This degree of anticoagulant effect should be maintained throughout the course of continuous intravenous heparin therapy. When intermittent heparin administration is used, the aPTT should be measured 6 hours after the administered dose to maintain prolongation of the aPTT to 2-2.5 times that of the control value. 

Plasma is not the site of action of most drugs, so responses will be delayed in relation to pharmacokinetic predictions of plasma concentrations. The only exception is a limited number of drugs (e.g., heparin) whose action directly affects physical components of plasma. 

Prasad R, Maddux MS, Mozes ME, Biskup NS, Maturen A. A significant difference in cyclosporine blood and plasma concentrations with heparin or EDTA anticoagulant. Transplantation 1985 39(6) 667-9. 

For measurement of 5-HIAA in plasma, HPLC methods with electrochemical or fluorescence detection have been described. The latter uses diethyl ether for preliminary extraction of heparinized plasma. The internal standard and 5-HIAA are then separated by gradient elution on a C18 column and detected with a spectrofluorometer (excitation wavelength, 280nm emission wavelength, 345nm). This method is linear to I90ng/L, and the interassay precision, expressed as a coefficient of variation, is less than 6% at a 5-HIAA concentration of 30ng/L. 

Gerhardt W> Nordin G, Herbert AK, Burzell BL, Isaksson A, Gustavsson E, et al. Troponin T and I assays show decreased concentrations in heparin plasma compared to serum lower recoveries in early... 

Serum and heparinized plasma are the preferred specimens for the measurement of phosphate. Concentrations of inorganic phosphate are about 0.2 to 0.3 nig/dL (0.06 to 0.10 mmol/L) lower in heparinized plasma than in serum. Anticoagulants such as citrate, oxalate, and EDTA interfere with formation of the phosphomolybdate complex. 

Serum is the most widely used specimen for the measurement of OC heparinized plasma can be used with some methods. The stability of OC in samples is method-dependent. Decreases in OC immunoreactivity of 50% to 70% after 6 to 24 hours at room temperature and 40% to 80% after 2 weeks at 4 °C have been reported. Trasylol, mixed protease inhibitors, and collection on j ce 9,2i2 improve the stability of OC with some but not all methods. Serum OC concentrations are more stable with methods measuring both intact OC and the N-terminal/midregion fragment (1-43). Concentrations were unchanged after 3 hours at room temperature and after 24 hours at 4... 

Either serum or heparinized plasma is used to measure total or free testosterone. Testosterone is subject to a diurnal variation, reaching a peak concentration between 0400 hours and 0800 hours. Therefore, morning specimens are preferred. Specimens are stable for a week (men) or 3 days (women) refrigerated and for up to 1 year frozen at 20 No steroids, thyroid, ACTH, estradiol, or gonadotropin medications should be given for 48 hours before sample collection. Most assays are standardized for serum or heparinized plasma. Other anticoagulants such as ethylene-diaminetetraacetic acid (EDTA) may give different values. In certain RIA assays, presence of EDTA appears to cause a 10% decrease in total testosterone concentrations. ... 

The brain is perfused with heparinized blood or a suitable subshtute containing plasma concentrations of anesthetic that are sufficient to maintain total anesthesia in vivo. These levels of anesthetics must be maintained throughout the perfusion period. The effluent blood from the internal jugular veins is collected hrst pass or recirculated. 

In 1997, Probst et al modified Furata et al. s method to quantify rocuronium and its 17-desacetyl metabolite in heparinized plasma. This group performed parallel studies of the previously described LLE extraction and an on-column ion pairing using Extrelut solid-phase extraction cartridges. The intra-assay precision (n = 5) at two concentrations (400 and 1052ngmL ) for both parent drug and metabolite showed mean concentrations within... 

Many patients with acute VTE and myocardial infarction have a diminished response to heparin, presumably because of variations in the plasma concentrations of heparin-binding proteins. Some patients have been reported to have acute elevations in factor VIII, preventing the prolongation of the aPTT by UEH. In some cases, antithrombin deficiency may be the culprit. The recommended management of patients with heparin resistance is to adjust the UEH dose based on anti-factor Xa concentrations. Approximately 50% of patients with this heparin resistance have dissociation between aPTT and heparin concentration as a result of an elevated factor VIII concentration. If anti-factor Xa concentrations cannot be measured readily, the dose of UEH should be increased until a therapeutic aPTT is achieved. 

Those which do not inhibit coagulation directly but on being added to plasma produce an inhibitor. Heparin in concentrations sufficient to exert an anticoagulant effect in blood and plasma is the best example. This is a very poor inhibitor when added to purified coagulation systems, but with a special plasma protein, the so-called heparin cofactor , it gives rise to an active anticoagulant. 

In defining anticoagulants above, it was emphasized that heparin in concentrations of 0 1 mg/ml. and over, shows general inhibitory effects and this has led to much confusion in the literature. The important problem is the nature of the action of the heparin-cofactor complex which provides the unique high activity of heparin. In analysing the inhibitory effect of heparin in plasma systems, the essential constituent is the cofactor and its concentration is an unknown limiting variable in many investigations . 

The difficulty in obtaining satisfactory evidence may be due to the fact that thrombosis is a local circulatory problem which will require release of heparin locally for control. Such amounts will not be apparent in gross biochemical tests either as an increase in plasma concentration or a decrease in concentration in tissue. It is probable that heparin will be like other auto-pharmacological agents (e.g. adrenalin, steroids, insulin) in that the amount of heparin in the general circulation at any one time is only a secondary reflection of secretion levels. More important is the determination of rate of urinary excretion of metabolites and still more important the determination of rate of secretion by the glandular tissue (mast cells) itself. 

Figure 6. APTT heparin activity assay curve. Key 9, control heparinized plasma (units mL plasma) calibration APTT and O, derivatized heparin (at known weight concentrations, mg/mL plasma) APTT.

The concentration of potassium in erythrocytes is 25-fold greater than in plasma. The analysis of hem-olyzed samples therefore does not yield clinically meaningful results. Generally, any process that allows potassium to leave erythrocytes or thrombocytes, such as blood storage with or without visible hemolysis (in a refrigerator, no haemolysis), will falsify the potassium concentration. Even clotting of blood will increase potassium concentration hence, its concentration is 0.4 mmol 1 higher in serum (Table 1) than in plasma. Thrombocytosis or chronic myelosis may cause pseudohyperkalemia as well as in vivo haemolysis. For these reasons, heparinized plasma is preferable to serum, as it decreases potassium release from cells. 

Figure 9 shows the application of the hyphenation technique ITP-ITP for the analysis of 5 pi of untreated heparin plasma as a method to follow changes in concentrations of pyruvate, acetoacetate, lactate, and S-hydroxybutyrate in plasma of patients with diabetes mellitus. In the column switching... 

Dugi KA, Schmidt N, Brandauer K, et al. Activity and concentration of lipoprotein lipase in post-heparin plasma and the extent of coronary artery disease. Atherosclerosis 2002 163 127-134. 

In addition to ascorbic acid, uric acid is an important antioxidant in blood plasma (9). To assess the antioxidative capacity of plasma it is useful to determine ascorbic acid and uric acid in a single chromatographic run. Ascorbic acid and uric acid have been measured simultaneously from heparinized plasma by UV detection (64). To optimize the detection during method setup, the sample was dissolved in the mobile phase, pH 5.5, where ascorbic acid had the absorbance maximum at 262 nm and uric acid at 285 nm. The wavelength of 262 nm was chosen because ascorbic acid is present at a lower concentration than uric acid in plasma. The same mobile-phase pH (5.5) and UV detection at 280 nm for... 

---