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Measurement of the activated partial thromboplastin time from a capillary (fingerstick) sample of whole blood. A new method for monitoring heparin therapy.

The monitoring of heparin anticoagulation is fraught with difficulties because of the need for repetitive venipunctures and the vagaries of sample handling and processing. The authors evaluated a new aPTT monitoring system with the potential to eliminate many of these difficulties. The Ciba Corning Diagnostics 512 Coagulation Monitor (CCD monitor) is a hand-held portable instrument that can measure an aPTT from a fingerstick sample of capillary whole blood. Fingerstick aPTTs from 319 subjects (including controls and individuals on heparin and/or warfarin) were compared to venipuncture-derived standard laboratory plasma aPTTs using different aPTT reagents on conventional instruments. The correlation coefficients between fingerstick and standard aPTTs (0.79-0.83) were the same as the correlation coefficient between standard laboratory aPTTs using different reagents (0.79). When venipuncture-derived whole blood was compared to fingerstick samples on the new instrument, the correlation coefficient was excellent (0.93). A high degree of precision, as demonstrated by low coefficients of variations, was shown for within-day and between-day testing using the CCD monitor and normal controls. This capillary whole blood, aPTT system is the first to provide the clinician with a means of rapidly and reliably assessing the anticoagulant response to heparin therapy at the bedside, and its use may ultimately lead to more efficient and effective therapy overall.

Blood Coagulation Tests↗

Enzymatic elimination of heparin from plasma for activated partial thromboplastin time and prothrombin time testing.

The prolongation of the APTT and PT by heparin can be neutralized by treating the plasma with heparinase or with certain anion-exchangers. The purpose of the present study was to assess the effectiveness of a new commercial heparinase reagent. Heparinase (Hepzyme) for the removal of heparin from plasma was compared with ECTEOLA-cellulose treatment. In ex vivo heparin samples, shorter APTT values were obtained with heparinase than with ECTEOLA-cellulose, suggesting that the former treatment is more effective for the removal of heparin from plasma. Heparinase (Hepzyme) treatment may be used to improve INR assessment in patients treated with heparin and oral anticoagulants concomitantly.

Cellulose↗

Usefulness of lyophilized calibration plasmas for International Normalized Ratio determination with the bovine combined thromboplastin (Thrombotest): results of a collaborative study.

The logical solution to account for the influence of coagulometers on the International Sensitivity Index (ISI) is local calibration with freeze-dried plasmas. However, because of their unpredictable behavior these plasmas must be validated before large-scale implementation. We report on a collaborative exercise designed to evaluate the suitability of a set of such plasmas used with Thrombotest in combination with a coagulometer provided by the manufacturer to be used with that reagent. This was a two-step study. First, one lot of reagent was calibrated against the international standard OBT/79 in two expert laboratories. The calibrated lot was then used as an intermediate standard to calibrate two additional lots of the same reagent in four field laboratories where the ISI was determined for both plasma and native blood. The International Normalized Ratio (INR) for the patient plasmas tested in each laboratory were calculated using two algorithms: the World Health Organization-recommended ISI mode (gold standard), and the simplified calibration plasma mode. In the latter, the INR was derived from the local calibration curve constructed by plotting the certified INR versus local coagulation times obtained with calibration plasmas. The between-algorithm INR differences indicate that this set of calibration plasmas may be employed for local INR calibration of the investigated reagent/instrument combination, especially when plasma is used for INR determination where the average INR (range) difference is 5% (3-13%) or 2% (3-8%) according to whether the INRs to calibration plasmas were assigned by the manufacturer or by the two expert laboratories. A slight but measurable difference of the INR may be predicted [9% (6-20%) or 6% (8-15%)] if this set of calibration plasmas is used for local calibration when native blood is employed for INR determination. Whether this bias is of practical significance is to be determined.

Animals↗

A 2-year retrospective analysis of laboratory testing for activated protein C resistance with a factor V-corrected activated partial thromboplastin time-based method.

The factor V-corrected activated protein C resistance assay is the test of choice to screen for the factor V Leiden mutation. During the past 2 years, local test results with the frequently used Coatest APCR kit were evaluated and compared with the results of DNA analysis, the 'gold standard'. Samples of 278 patients were analysed by both techniques. We were unable to confirm that factor V Leiden carriers can clearly be delineated from normal individuals with the Coatest APCR test. A ratio of 2.0 as the cut-off provides 99.0% sensitivity and 95.4% specificity.To evaluate the lupus anticoagulant interference, we retrospectively analysed 16 lupus anticoagulant-positive patients. In this study, two (12.5%) showed a false-positive activated protein C resistance result. Six out of 16 (37.5%) lupus anticoagulant-positive patients were also carriers of the factor V Leiden mutation. Four out of eight (50%) false-positive activated protein C resistance results presented with an abnormal baseline clotting time. In order to prevent reporting false-positive results, a maximum baseline clotting time (65.8 s) was calculated. A new scheme for interpreting activated protein C resistance ratios was proposed.

Activated Protein C Resistance↗