Evaluation of the activated partial thromboplastin time (APTT) sensitivity to heparin using five commercial reagents: implications for therapeutic monitoring

Heparin is an effective drug for prevention and treatment of thromboembolic conditions. Although several biological assays have been proposed for monitoring unfractionated heparin therapy, the measurement of the activated partial thromboplastin time (APTT) is the most widely employed test, and the overall risk of thromboembolic episodes was markedly reduced by maintaining APTT ratios above 1.5. However, the adjustment of the heparin therapy on the basis of APTT presents several questions which are still unresolved. Major discrepancies were found in APTTs performed using different reagents in both ex vivo and in vitro heparinized samples and occasionally with different lots of the same reagents; poor correlation was observed between APTT values and plasma heparin concentrations. In order to gain further insights into this phenomenon, we analysed the sensitivity to heparin of five commercial reagents for APTT measurement in 19 ex vivo heparinized samples. Differences were observed; correlation coefficients ranged from 0.820 to 0.985 and slopes of linear regressions from 0.26 to 1.14. Moreover, unsatisfactory correlations were obtained when APTT ratios were compared with heparin plasma concentrations in the same patients' samples. In the heparin therapeutic range of 0.35 - 0.70 U/ml, reagent-dependent differences were observed in the corresponding APTT values. These results point out a critical role of the assay methodology in monitoring heparin therapy by APTT. We suggest that reference materials and methods should be urgently identified, a universally agreed scale for reporting results should be established and reference ranges for the unfractionated heparin therapy should be reconsidered taking on account the reagent employed.     

Effect of warfarin on activated partial thromboplastin time in patients receiving heparin

BACKGROUND: The activated partial thromboplastin time (APTT) is used to adjust heparin sodium dosage. However, warfarin sodium is often administered concomitantly with heparin and may also affect the APTT and, therefore, heparin dose. We performed a prospective cohort study to quantify the effect of warfarin on the APTT in patients who are being treated with heparin. METHODS: Serial assays of APTT, international normalized ratio, heparin levels, and functional levels of prothrombin (factor II) and factors VII and X were performed in 24 patients with acute venous thromboembolism who were treated with concomitant continuous intravenous heparin and warfarin. The effects of warfarin, as expressed by international normalized ratio and coagulation factor levels, on APTT were determined. RESULTS: Warfarin markedly affected APTT; for each increase of 1.0 in the international normalized ratio, the APTT increased 16 seconds (95% confidence interval, 10-22 seconds). The effects of warfarin and heparin on APTT were additive. Consequently, warfarin markedly altered the relationship between APTT and heparin levels; of the 29 blood samples with supratherapeutic APTT, 13 had a therapeutic heparin level and 10 had a subtherapeutic heparin level. CONCLUSIONS: In patients receiving concomitant heparin and warfarin therapy, APTT reflects the combined effects of both drugs. Because of the marked effect of warfarin on the APTT, decreasing heparin dose in response to a high APTT frequently results in subtherapeutic heparin levels.     

Accuracy of coagulation values obtained from a heparinized central venous catheter

PURPOSE/OBJECTIVES: To compare coagulation values of blood samples drawn from heparinized central venous catheters (CVCs) and peripheral veins. DESIGN: Correlational. SETTING: Adult, acute-care hematology/oncology unit in a 1,000-bed teaching hospital. SAMPLE: Twelve adult patients with cancer who had varied diagnoses and patent CVCs. METHODS: Simultaneous blood samples were drawn from the CVC and a peripheral vein and were tested for prothrombin time (PT) and activated partial thromboplastin time (aPTT). MAIN RESEARCH VARIABLES: PT and aPTT values. FINDINGS: PT and aPTT values were significantly prolonged in samples drawn from CVCs when compared to peripherally drawn samples. CONCLUSIONS: Accurate coagulation values cannot be obtained from a heparinized CVC. IMPLICATIONS FOR NURSING PRACTICE: Blood for coagulation values should be obtained from peripheral veni-puncture. Further research should explore the effects of various catheters, heparin dwell time, and systemic anticoagulation on coagulation values.     

Removal of heparin and protamine from plasma

A simple chromatographic technique for rapid adsorption of heparin and protamine from plasma samples is described, allowing accurate interpretation of coagulation screening tests and specific clotting factor assays. With the use of columns of ECTEOLA-cellulose, up to 300 U. of heparin could be completely adsorbed from a 1 ml. plasma sample. When citrated nonheparinized plasma was passed over the ECTEOLA-cellulose columns, the thrombin, prothrombin, and partial thromboplastin times were unaffected. Levels of fibrinogen, prothrombin, and factors V, VII, VIII, IX, and XI average within 90 per cent of control, nonchromatographed samples. When heparinized plasma samples (0.1 and 1.0 U. per milliliter) were passed over columns, heparin was completely removed and the results of the screening tests and the specific factor assays were the same as for the chromatographed nonheparinized samples. In addition, heparinized samples with decreased factor VIII activity maintained their pretreatment factor VII activities after heparin removal. Blood samples containing heparin were obtained from two patients during open-heart surgery. Following heparin adsorption on ECTEOLA-cellulose columns, factor VIII activity levels remained above 60 per cent during cardiopulmonary by-pass. The presence of protamine sulfate in plasma samples prolonged the prothrombin and partial thromboplastin times while slightly shortening the thrombin time. The protamine effect persisted after ECTEOLA-cellulose, but could be removed by a similar column of carboxymethyl-cellulose. The latter resin had no effect on screening tests or on assays of factors VIII or IX activity. The combination of the two resins was then used to remove the separate inhibitory effects from heparinized plasma samples to which protamine had been added.     

Preparation of lyophilized partial thromboplastin time reagent composed of synthetic phospholipids: usefulness for monitoring heparin therapy

To contribute to the development of a reference reagent for monitoring heparin therapy, a lyophilized partial thromboplastin time (PTT) reagent was prepared from synthetic dioleoylphosphatidylcholine, dioleoylphosphatidylserine, and dioleoylphosphatidylethanolamine, with colloidal silica as activator. The reagent, coded 91/558, was contained in sealed glass ampoules; it deteriorated in a heat degradation experiment, but its activity remained constant for at least 4 years when stored at -70 degrees C. Within- and between-run precision with this reagent complied with the requirements proposed by the International Committee for Standardization in Haematology (ICSH) Panel on PTT. The response of this reagent and of two other reagents to heparin added to pooled normal plasma was nonlinear. Citrated samples from 58 patients receiving intravenous heparin and from 24 apparently healthy volunteers were tested with reagent 91/558, with Automated APTT (Organon Teknika), with Manchester APTT reagent, with an antifactor Xa assay, and with an anti-factor IIa assay. The correlation of APTT with anti-Xa and anti-IIa activity was poor. The best correlation was observed between reagent 91/558 and the Organon Teknika reagent. Correlations were improved when individual patients' samples were replaced by pooled plasmas from heparinized patients, in whom the effect of oral anticoagulation was minimal. These results suggest that preparation of a lyophilized synthetic phospholipid reagent is feasible for use in monitoring heparin therapy.     

Establishing an institution-specific therapeutic range for heparin

The relationship between heparin concentration and activated partial thromboplastin time (aPTT) in pooled plasma was compared with that in patient samples to assess the feasibility of using heparin-spiked pooled plasma in determining a therapeutic range for aPTT. Blood samples were taken from 32 patients who had been receiving intravenous unfractionated heparin sodium for more than 24 hours. The samples were stored at -70 degrees C until anti-Xa assay within three months of collection. Pooled normal plasma was spiked with unfractionated heparin sodium to produce nominal anti-Xa concentrations of 0, 0.05, 0.1, 0.2, and 0.5 unit/mL. Heparin concentrations and a aPTT values were measured, and the relationship between the two was determined by linear regression. For the ex vivo samples, the range of aPTT values corresponding to therapeutic heparin concentrations of 0.3-0.7 anti-Xa unit/mL was 64-106 seconds, which corresponds to an aPTT range of 2.3-3.9 times the mean of the normal range (compared with the traditionally defined therapeutic range of 1.5-2.5 times the control value). For the in vitro samples, the aPTT range corresponding to heparin concentrations of 0.3-0.7 unit/mL was 121-256 seconds, which corresponds to an aPTT range of 4.4-9.4 times the mean of the normal range. Each institution should establish a therapeutic aPTT range by calibrating aPTT values against heparin concentrations from blood samples of patients receiving intravenous heparin.     

On the value of the activated partial thrombo-plastin time (aptt) in monitoring heparin therapy

Of 1068 blood samples referred for evaluation of the haemostatic mechanism 135 contained heparin as judged by the polybrene titration method. Of the 57 samples with a heparin concentration in the defined therapeutic range, 65 per cent had APTT values in the "therapeutic range". Of the samples from patients who had not received any anticoagulant, 213 (24 per cent) had prolonged APTT, and 48 of these samples had APTT values in the "therapeutic range" for heparin therapy. It is suggested that the APTT test is of limited value in monitoring heparin therapy.     

Species-specific odor in closely related species: period of development in ontogenesis of house (Mus musculus musculus) and mound-building (Mus spicilegus) mice

Underfilling of specimen tubes containing 129 mmol/L (3.8%) buffered citrate prolongs prothrombin time (PT) and activated partial thromboplastin time (APTT) values. We studied this phenomenon by using 109 mmol/L (3.2%) buffered citrate as the anticoagulant, anticipating some increase in tolerance to underfilling. Venous blood drawn from 12 healthy subjects and 30 patients receiving long-term oral warfarin therapy was mixed with 109 mmol/L buffered citrate solution in proportions equivalent to filling the collection tubes from 52% to 100% of capacity. Accurate PT values were obtained from normal specimens if the tubes were filled to 65% or more of capacity. Accurate PT results in the therapeutic range were obtained only with filling to 80% or more of capacity (using a "moderately sensitive" thromboplastin reagent, International Sensitivity Index [ISI] = 2.06) or 90% or more of capacity (using a "highly sensitive" thromboplastin reagent, ISI = 1.01). In contrast, APTT was much less tolerant to underfilling, with prolonged values observed in most specimens filled to less than 90% of capacity. No false low values were observed. Specimen tubes should be filled to at least 90% of capacity to avoid falsely elevated PT or APTT results, but values within the reference range may be acceptable even from underfilled tubes.     

Comparison of the antithrombotic effects of low molecular weight heparinoid KB-101 and heparin in a rat experimental model

1. We compared the low molecular weight heparinoid KB-101 and heparin with regard to suppression of experimental thrombus formation and effects on bleeding time, prothrombin time (PT), and activated partial thromboplastin time (APTT) in rats. 2. KB-101 exerted a similar antithrombotic activity as that of heparin. 3. Heparin prolonged bleeding time, PT, and APTT more than KB-101 did. 4. These results suggested that KB-101 is superior to heparin as an anticoagulant.     

The effect of N-alkyloxycarbonyl group on the anticonvulsant activities of N-alkyloxycarbonyl-alpha-aminoglutarimides

The aim of this study was to determine the effect of heparin therapy on the international normalized ratio (INR). In vitro heparin sensitivity curves were created using normal and warfarinized plasma samples from patients. The INR results were measured with each of two reagents. In addition, a comparison of INR values with these two reagents was performed on plasma from patients receiving therapeutic heparin and warfarin. The INR values were measured before and after heparin removal with a heparin adsorbent system. While one of the reagents was found to be sensitive to even low levels of therapeutic heparin, the other thromboplastin was resistant up to at least 0.9 U/mL. The INR values determined for patients with one of the reagents were found to be erroneously elevated by an average of 16%. The error ranged from 2% to 55% depending on the in vivo heparin concentration. With the other reagent, the INR values were not substantially affected by heparin. Previous studies have described the effect or lack thereof of heparin on the prothrombin time. The present study demonstrates that the degree to which INR results are prolonged by heparin therapy depends on the reagent formulation. As the therapeutic index for monitoring warfarin is relatively narrow (2.0-3.0), an INR value that is falsely elevated due to reagent sensitivity may precipitate premature cessation of heparin therapy and place certain patients at risk for recurrent thrombosis in the short term.     

The hemostatic effect of packed red cell transfusion in patients with anemia

BACKGROUND: The hemostatic effect of platelets has been well established, but the possible role of red cells in hemostasis has not yet been well studied. An evaluation of the hemostatic effect of packed red cell transfusion in patients with chronic anemia was the purpose of this study. STUDY DESIGN AND METHODS: In a prospective study, bleeding time (BT), activated partial thromboplastin time (APTT), and prothrombin time (PT) were measured before and after the transfusion of allogeneic packed red cells in 42 patients with chronic anemia. The results were compared and analyzed. RESULTS: APTT and BT decreased significantly after transfusion, by a mean of 1.3 seconds (p = 0.01) and 2.6 minutes (p < 0.01), respectively. PT did not change significantly after transfusion (p = 0.65). Factors studied (patient's age, sex, and renal function measurements; pretransfusion and posttransfusion hemoglobin levels, platelet counts, and PTs; change in platelet count [delta platelet count] and PT [delta PT] after transfusion) did not independently affect the change in BT (delta BT) or in APTT (delta APTT). The delta BT was not affected by the pretransfusion or posttransfusion levels of APTT or by the delta APTT. The delta APTT was not affected by the pretransfusion or posttransfusion levels of BT or by the delta BT. Diagnosis of malignant or benign diseases was found to affect delta APTT, but not delta BT. Patients with pretransfusion hemoglobin < or = 60 g per L had a 4.07 times greater chance of posttranfusion increase in BT than the patients with hemoglobin > 60 g per L (p = 0.04). CONCLUSION: Red cell transfusion might decrease the APTT and BT in some anemic patients, though the actual cause of the decrease was not determined in the present study.     

Thrombophilia in patients with hypercholesterolemia

To investigate a possible interrelationship between hypercholesterolemia and the coagulation and fibrinolytic system, the Cardiovascular Disease Risk Factor Two-Township Study in Taiwan was undertaken as a longitudinal prospective study focusing on the evolution of cardiovascular disease risk factors, with an emphasis on hemostatic factors. Hemostatic parameters measured in this study included prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, factor VIIc, factor VIIIc, antithrombin III, and plasminogen. Subjects of both sexes with hypercholesterolemia (> 6.2 mmol/L) also had significant elevations of diastolic blood pressure, plasma glucose, triglycerides, fibrinogen, and factor VIIc and reduced PT and APTT compared with subjects with lower cholesterol. The hypercholesterolemic women additionally had significant elevations of systolic blood pressure and factor VIIc. Levels of the anticoagulant factors, antithrombin III and plasminogen, were also higher in both hypercholesterolemic men and women. In men, only factor VIIIc had no statistically significant elevation. In women, only PT showed no statistical difference. Established coronary risk factors such as fibrinogen and factor VIIc showed remarkable elevations in patients of both sexes. Using Pearson correlation and multiple regression, the most significant parameter related to cholesterol level was factor VIIc. The present results show that hemostatic abnormalities do exist in patients with hypercholesterolemia, and this thrombophilic phenomenon sheds further light on the study of higher cardiovascular mortality in these subjects.     

The effects of heparinase 1 and protamine on platelet reactivity

BACKGROUND: Protamine is currently the most widely used drug for the reversal of heparin anticoagulation. Heparinase 1 (heparinase) is being evaluated as a possible alternative to protamine for the reversal of heparin anticoagulation. The authors evaluated the effects of equivalent doses of heparinase and protamine on platelet reactivity by measuring agonist-induced P-selectin expression. METHODS: After Institutional Review Board (IRB) approval, informed consent was obtained from 12 healthy volunteers and 8 patients undergoing surgery requiring cardiopulmonary bypass (CPB). Twenty-four ml of blood was obtained from each volunteer; 10 ml of blood was obtained from each patient before the CPB, and another 10 ml was obtained after CPB. Heparin was neutralized using heparinase or protamine. Platelet reactivity was assessed by measuring the expression of P-selectin after stimulation of platelets with increasing concentrations of a thrombin receptor agonist peptide (TRAP). Data were analyzed using analysis of variance. P < 0.05 was considered significant. RESULTS: For the healthy volunteers, the activated coagulation times (ACTs) of the heparinized samples returned to baseline values with heparinase (12.5 U/ml) or protamine (32.5 microg/ml). For the 8 patients, the ACTs returned to baseline with heparinase (20 U/ml) or protamine (50 microg/ml). The authors found no difference in the expression of P-selectin in samples neutralized with heparinase, but samples neutralized with protamine showed a significant decrease in the expression of P-selectin when compared with heparinized samples. CONCLUSIONS: At dosages that reverse the anticoagulant effects of heparin, heparinase has minimal effects on platelets, whereas platelet reactivity was markedly inhibited by protamine.     

Automated heparin-delivery system to control activated partial thromboplastin time: evaluation in normal volunteers

BACKGROUND: Unfractionated heparin is used widely; however, control of the level of anticoagulation remains its greatest problem, with fewer than 35% of patients having activated partial thromboplastin times (aPTTs) within a range of 55 to 85 seconds in recent trials. METHODS AND RESULTS: We developed and tested a prototype of an automated heparin control system (AutoHep) in which a computer-based titration algorithm adjusted the heparin infusion to reach a target aPTT. In 1 study, 12 healthy male subjects received an intravenous infusion of heparin with the rate determined by AutoHep and were randomized to receive an initial bolus or no bolus of heparin preceding the infusion. A second study evaluated the automated blood sampling system in 12 subjects. Of the 344 end-point aPTT measurements, 78% were within +/-10 seconds of the target (prespecified primary end point), and 89% were within a +/-15-second range. The time to achieve a target aPTT was 93 minutes without and 150 minutes with an initial heparin bolus. The total percentage of time within the target range +/-15 seconds was 46 of 48 hours (96%). The automatic blood sampling system successfully obtained 96% of all scheduled samples. CONCLUSIONS: These results suggest that the AutoHep system has the potential to significantly improve aPTT control of intravenous heparin compared with current clinical practice.     

The effects of hepes buffer on clotting tests, assay of factors V and VIII and on the hydrolysis of esters by thrombin and thrombokinase

Shorter clotting times were found in the presence of 50 mM Hepes (N-2-hydroxyethylpiperazine-N1-2-ethanesulfonic acid) buffer than of 50mM Imidazole buffer in one-stage assays of factors V and VIII, in modified APTT and PT tests and in tests of the clotting of human plasma by purified human thrombin. All tests were performed at ionic strength 0.155 in the presence of either Hepes. NaOH or Imidazole. HCl buffer, pH 7.4 at 37 degrees. The faster clotting in the presence of Hepes buffer, therefore, is probably due, at least in part, to acceleration by Hepes of thrombin's enzymatic action on fibrinogen and/or of the polymerization of the fibrin monomers. Hepes may also have effects of other blood clotting reactions. Rates of hydrolysis of TAME or BAME (p-toluenesulfonyl- or benzoyl-L-arginine methyl ester) at pH 7.4 37 degrees by purified human bovine thrombin were essentially the same in 200 mM Hepes as in 250 mM Tris. HCl buffer (rates in Hepes. NaOH or Hepes. KOH buffers were compared with those in Tris. HCl plus NaCl for KCl). However, with purified bovine thrombokinase, rates of TAME hydrolysis in Hepes buffer were accelerated and rates of BAME hydrolysis slightly inhibited. Hepes, therefore, reacts with thrombokinase but whether this accelerates (or inhibits) the rate of converting prothrombin to thrombin remains to be determined. In addition, Hepes has an inhibitory effect on clotting since increasing the concentration of Hepes from 50 mM to 200 mM inhibits clotting in the PT, APTT and bovine thrombin-human plasma tests. Hepes buffer is being added to some plasmas and to some reagents used in clotting tests. It is, therefore, important to realize that its concentration must be monitored closely or erroneous results may be obtained in clotting tests and assays of clotting factors. The clotting times were the same in the presence of 50 mM Tris. HCl as in Imidazole. HCl buffers in APTT tests at three ionic strengths but they differed slightly in plasma-thrombin tests. Depending upon the ionic strength, 17 mM Barbital Sodium. HCl buffer inhibited APTT tests but accelerated plasma-thrombin tests. All the buffers tested, therefore, have individual effects on the clotting tests.     

Evaluation of a modified APTT-based method for determination of APC resistance in plasma from patients on heparin or oral anticoagulant therapy

An APTT-based kit method (Coatest APC Resistance), modified by predilution 1+4 of sample plasma in a plasma diluent containing a heparin antagonist (V-DEF plasma), has been evaluated on plasmas from patients treated with unfractionated (n = 110) or either of three different low molecular heparins (n=44), or with oral anticoagulants (n=147). Irrespective of treatment, no difference was observed in the APC response as compared to untreated individuals (n=62), and a complete discrimination was obtained between individuals with a normal factor V genotype and those carrying the FV:Q506 mutation. Furthermore, in contrast to the original, APTT-based kit method, where anticoagulant therapy results in a prolongation of the APTT, the modified kit provided APTT values within the normal range for orally anticoagulated (INR< or =6) and for all heparin treated (< or =1 IU/mL) patients except for one with a suspected presence of phospholipid antibodies. Due to the predilution in V-DEF plasma, contamination with platelets up to 1.5 x 10(4)/microL had a negligible effect on analysis of frozen plasmas regarding their classification as normal or abnormal. Analyses of fresh plasmas show no influence at platelet counts up to 6x10(4)/microL. Consequently, negligible differences in APC ratios were obtained between fresh and frozen plasmas. In conclusion, the modified kit method is applicable to plasmas from anticoagulated patients as well as from untreated individuals, allowing a safe assignment regarding the presence or absence of the FV:Q506 genotype.     

Blood collection technique: no effect on in vitro protein binding of prednisolone

The effect of the blood collection vessel and systemic heparin administration on in vitro protein binding of prednisolone was examined in blood collected from human subjects. No differences in the fractional binding of prednisolone were found in plasma from plain glass culture tubes, heparinized culture tubes, and two types of red- and green-top commercial vacuum tubes. Thus, these blood collection techniques do not alter serum or plasma albumin and transcortin binding of prednisolone.     

Pharmacokinetics of heparin and its pharmacodynamic effect on plasma lipoprotein lipase activity and coagulation in healthy horses

We evaluated the pharmacokinetics of IV administered sodium heparin and the pharmacodynamic effect of heparin on lipoprotein lipase (LPL) activity. Horses were allotted to 3 groups. Plasma samples were obtained from each horse before and at various times for 6 hours after heparin administration for determination of heparin concentration, LPL activity, and activated partial thromboplastin time (APTT). The disposition of heparin was dose dependent. The area under the plasma heparin concentration vs time curve (AUC) increased more than proportionally with dose, indicating that heparin elimination was nonlinear. Total clearance of heparin was similar after the 40 and 80 IU/kg of body weight dosages, averaging 0.45 and 0.36 IU/kg/min, respectively. However, after administration of the 120 IU/kg dose, clearance was significantly less than that after the 40 IU/kg dose. The half-life of heparin averaged 53, 70, and 136 minutes after 40, 80, and 120 IU/kg, respectively, with significant differences observed between the low and high doses. In contrast to heparin, the area under the plasma concentration vs time curve for LPL activity increased less than proportionally with dose. Maximal LPL activity observed was independent of dose, averaging 4.8 mumol of free fatty acids/ml/h. The APTT was significantly prolonged for 120 minutes after administration of the 40 IU/kg dose. Correlation coefficients for LPL activity vs either plasma heparin concentration or APTT were less than 0.7, indicating that neither laboratory measure can be used to accurately predict plasma LPL activity.     

An open trial of bupropion for ADHD in adolescents with substance use disorders and conduct disorder

The objective of the study was to evaluate the performance of an amperometric enzyme based lactate sensor and to investigate the possibility of replacing a double lumen catheter based blood withdrawal system with a heparin coated single lumen system. The inner lumen of a double lumen catheter which was placed in a peripheral vein was perfused with heparin solution. The outer lumen was used to collect heparinized blood samples at a defined flow rate. The single lumen system was attached to a heparinized catheter which was also placed in a peripheral vein. The undiluted blood samples were collected at a specified flow rate. A sensor flow chamber incorporating an amperometric thin-film lactate microbiosensor was placed in the sampling line for real-time lactate monitoring. Plasma lactate concentrations were measured during frequently performed hyperlactatemia bicycle ergometer experiments in six healthy volunteers (age 25.8 +/- 2.8 years, BMI 22.7 +/- 1 kg/m2). Additionally, plasma lactate was measured in real-time using the lactate sensors. The first three experiments were performed with a double lumen based catheter system whereas the following three experiments were performed with a heparin coated catheter system. The correlation coefficients of sensor readings and laboratory analyzer results in all six experiments were between 0.93 and 0.99, respectively (P < 0.001). The miniaturized lactate sensors showed a linear range up to 25 mmol/l lactate concentration and 95% response times < 30 s in undiluted serum. During the experiments maximum lactate concentrations of 14 mmol/l were achieved. Improvements of system performance using heparin coated catheter systems could be shown. The overall SD of the sensor readings compared to laboratory results using three double lumen catheter based systems was 0.91 mmol/l whereas the SD using three heparin coated systems was 0.65 mmol/l. In summary, real-time monitoring of lactate in human whole blood is feasible with such a device and can be improved by using heparin coated catheter systems.     

Comparison of mean normal prothrombin time (PT) with PT of fresh normal pooled plasma or of a lyophilized control plasma (R82A) as denominator to express PT results: collaborative study of the International Federation of Clinical Chemistry. IFCC Working Group Standardization of Coagulation Tests

The mean normal prothrombin time (MNPT) is currently recommended as the denominator term in the expression of PT ratio or International Normalized Ratio (INR) values. The PT of lyophilized normal control plasmas might also be used in calculating PT ratios, but the overall accuracy of this approach and its dependence on reagents and endpoint detectors have not been evaluated in detail. In an IFCC collaborative study involving 15 expert laboratories and 58 PT systems, the PT ratios of 30 apparently healthy subjects were expressed with the use of the MNPT, the PT of fresh normal pooled plasma (FNPP) obtained from the same apparently healthy subjects, or the PT of plasma R82A--a lyophilized normal pooled plasma prepared by the Verband der Deutschen Ger?te-Hersteller for in-house calibration of a large amount of control plasma--as the denominator term. The total imprecision of the PT of plasma R82A averaged 2.16%. Mean PT ratios did not differ from 1.00 (mean 1.00, range 1.00-1.01) with the use of the MNPT as the denominator term. Mean PT ratios were > 1.00 with the FNPP-PT as the denominator term (1.02, 0.96-1.05), and differed according to endpoint detectors (P = 0.024). Mean PT ratios with plasma R82A-PT as the denominator term averaged 0.98 (range 0.91-1.06) with plain thromboplastins (n = 11), 1.02 (0.98-1.06) with combined thromboplastins (n = 3), and 0.93 (0.87-0.97) with recombinant thromboplastins (n = 2), but they differed according to the brand of plain or recombinant reagents (P = 0.00001), the endpoint detector (P < 0.0025), and the plasma citrate concentration (P < 0.0025). These findings underline the differences in the PT of lyophilized plasma R82A and the MNPT and PT of FNPP obtained from the same individuals and support the recommendation that the system-specific MNPT should be used as the ideal index of the normal PT in the calculation of INR values.