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S Kitchen

Publications and source records attributed to S Kitchen.

At least 37 records · Page 2Linked to original sources
PubMed2000

Monitoring unfractionated heparin therapy: relationship between eight anti-Xa assays and a protamine titration assay.

Several studies have demonstrated that heparin assays, such as anti-activated factor X (anti-Xa) assays, can be successfully substituted for activated partial thromboplastin time for heparin dosage monitoring. A number of different assays are available and the relationship between results with different techniques is largely unknown. The aim of the present study was to assess the relationship between heparin assays by protamine titration and anti-Xa assays. Samples were collected from 43 patients receiving unfractionated heparin (UFH). In each sample, the heparin level was determined using a protamine titration assay and eight commercially available anti-Xa assays. The mean heparin level by protamine titration was 0.31 U/ml. Mean anti-Xa activity results ranged from 0.40 to 0.42 IU/ml for the three clotting-based assays, and from 0.32 to 0.40 IU/ml for five chromogenic assays. Thus mean results of different anti-Xa assays varied by up to 30%. The range of anti-Xa activity equivalent, on average, to 0.2-0.4 U/ml by protamine titration, considered to be the therapeutic range, was approximately 0.25-0.5 IU/ml, depending on the assay. The relationship between results of clotting and chromogenic methods was similar irrespective of whether or not warfarin-induced prolongation of international normalized ratios was present.

Antibodies↗
PubMed1999

Lipid composition of seven APTT reagents in relation to heparin sensitivity.

The phospholipid content of different activated partial thromboplastin time (APTT) reagents was determined and compared to heparin sensitivity. The seven reagents included were those most widely used amongst participants of the U.K. National External Quality Assessment Scheme (NEQAS) at the time of study. Heparin sensitivity was assessed using the APTT ratios obtained by more than 300 NEQAS participants on five plasmas prepared from patients receiving unfractionated heparin. The concentrations of three neutral lipids and six phospholipids present in the seven APTT reagents were determined by high-performance thin-layer chromatography (HPTLC) and densitometry. Both the concentrations and the relative percentages of individual phospholipid components varied markedly between reagents. The total phospholipid concentration included a 12-fold range from 16 to 205 microgram/ml. Phosphatidylserine (PS) was completely lacking from one reagent prepared from vegetable material and ranged from 3 to 22 microgram/ml in the other six reagents containing extracts from animal tissue. The concentration of phosphatidylcholine ranged from 3 to 109 microgram/ml. There was no demonstrable relationship between the concentration of any individual lipid components and heparin sensitivity. However, the relative percentage phospholipid composition was important since a lower % of PS or phosphatidylinositol (PI) correlated with increasing heparin sensitivity.

Anticoagulants↗
PubMed1999

Standardization of prothrombin time for laboratory control of oral anticoagulant therapy.

Laboratory monitoring of oral anticoagulants is mandatory to ensure efficacy and safety of therapy. The test of choice is the prothrombin time (PT), using thromboplastins, which vary markedly in respect of the defect induced by oral anticoagulants. Standardization is improved by the use of the WHO calibration model for thromboplastins. This system defines the International Sensitivity Index (ISI) of a reagent in relation to a reference material. This is then used together with a locally determined mean normal PT to derive the International Normalized Ratio (INR). There is an inverse relationship between sensitivity and ISI, the lower the ISI the greater is the sensitivity of the reagent. There are important practical advantages to using a sensitive reagent with ISI of 1.2 or less. The ISI system was originally designed for manual tests and in some cases the ISI is influenced by the use of coagulometers, which generally have the effect of lowering the ISI. For this reason the ISI should be assigned for the combination of reagent and endpoint detection system. A thromboplastin should not be used with techniques for which the ISI is unknown. In some instances there is variation between instruments of the same type, in which case a local calibration using plasma calibrants with assigned values can be considered. The precise requirements for such local calibrations are presently the subject of research in a number of centers. The INR/ISI system is increasingly being adopted in many countries for anticoagulant therapy. Some past difficulties leading to discrepancies between results with different reagents have now been resolved and the view that this is the best available system for standardization of the PT for monitoring oral anticoagulants is widely held.

Administration, Oral↗
PubMed1999

Anti Xa monitoring during treatment with low molecular weight heparin or danaparoid: inter-assay variability.

If laboratory monitoring of low molecular weight heparin (LMWH) therapy is required the test of choice is the anti Xa activity assay. The relationship between anti Xa results obtained using different techniques is unknown. The aim of the present study was to compare anti Xa results obtained with eight different commercially available anti Xa activity assays (five chromogenic and three clotting based assays) in samples from patients receiving either therapeutic or prophylactic LMWH (enoxaparin or dalteparin) or danaparoid. We have demonstrated that highly significant differences exist between results obtained using different techniques. The mean anti Xa activity in patients receiving treatment or prophylaxis with enoxaparin ranged from 0.28 to 0.64 iu/ml. A similar relationship was present in samples from patients treated with dalteparin, mean anti Xa results ranging from 0.43 to 0.69 iu/ml. The Heptest clotting assay as used here in combination with the Automated Coagulation Laboratory instrument, was associated with lower results than other clotting or chromogenic techniques. In patients receiving danaparoid for heparin induced thrombocytopaenia (HIT) mean results with three clotting based assays were 0.30 to 0.36 u/ml, compared to mean results of 0.47 to 0.65 u/ml for chromogenic assays. Our data clearly indicate that the selection of anti Xa assay method could influence patient management since the dose required to achieve the therapeutic range would differ according to the assay employed. This is particularly important since the frequency of haemorrhagic side effects has been shown by others to be dose dependent, irrespective of the concomitant anti Xa activity results. In danaparoid therapy the clotting assays studied here should not be employed for monitoring without a modified target range, unless it can be demonstrated that the higher doses required to achieve the therapeutic range are safe.

Antibodies↗
PubMed1999

Multicenter evaluation of lyophilized and deep-frozen plasmas for assignment of the International Normalized Ratio.

The interlaboratory variation of the International Normalized Ratio (INR) in various external quality assessment schemes is still relatively high. This is partly caused by inaccuracy of manufacturers' stated International Sensitivity Index (ISI) and/or local instrumentation effects. The interlaboratory variation and accuracy of INR determinations may be improved by a local calibration procedure based on lyophilized plasmas with assigned INRs. The purpose of the present study was to determine INR values for different types of lyophilized plasmas to be used for local calibration. A total of 13 lyophilized plasmas (one normal, six from coumarin-treated patients, six artificially depleted) were analyzed by 10 laboratories, each using five calibrated prothrombin time (PT) systems. INRs were calculated for each plasma using each laboratory's specific ISI and mean normal prothrombin time values. In the same way, five deep-frozen pooled plasmas from coumarin-treated patients were analyzed. There were significant INR differences for the lyophilized plasmas between the prothrombin time systems. The differences were relatively small for the deep-frozen coumarin plasmas (CV 2.6-3.3%) and three lyophilized coumarin plasmas from one manufacturer (CV 3.7-4.8%). Important INR differences were observed for three lyophilized coumarin plasmas from another manufacturer (CV 9.5-14.1%) and several artificially depleted plasmas (CV 5.3-12.8%). The citrate concentrations in the artificially depleted plasmas were lower than those in the normal and coumarin plasmas. These differences should be considered in the selection and certification of plasmas as calibrants for local calibration of PT systems. The lyophilized plasmas' INR values obtained in the present study will be used for a field study of local PT calibration to assess their efficacy.

Animals↗
PubMed1999

Recombinant and tissue extract thromboplastins for determination of international normalised ratio in over-anticoagulated patients.

The international normalised ratio (INR)/international sensitivity index (ISI) system is established for calibration of thromboplastins for laboratory monitoring of oral anticoagulant therapy. The calibration procedure employs patients stabilised on oral anticoagulants, and is therefore validated for patients within the therapeutic range. For practical reasons, the system is used for patients at all levels of therapy, including over-anticoagulated patients with particularly low levels of factors II, VII and X. We studied patients within and above the therapeutic range, using a thromboplastin containing recombinant human tissue factor (Innovin) and two tissue extract thromboplastins. In samples with INRs from 2.0 to 4.0, there was good agreement between results obtained with the three systems (mean INRs within 4% of each other). In patients with INRs > 4.0, results with a human placental extract reagent (Thromborel S) were similar to those obtained with a rabbit brain thromboplastin (IL PT Fib Hs Plus); mean INRs were 6.30 and 6.32 respectively (not significant). Results with Innovin (mean INR: 7.67) were significantly (P < 0.001) greater (on average by 22%) than those obtained with the other two materials. The discrepancy between results with different reagents negatively correlated with factor VII levels. Thus, the lower the factor VII level, the greater was the discrepancy between INRs. Unexpectedly, there was a positive correlation between factor V level and the difference between INRs with different reagents. Thus, the higher the factor V level, the greater was the discrepancy between INRs. The effect of these differences at higher INRs on patient management is unknown, but the recently revised UK guidelines recommend that management of these patients should be influenced by clinical factors, reducing the relative importance of discrepancies between results obtained with different systems.

Anticoagulants↗
PubMed1999

Local calibration of international normalised ratio improves between laboratory agreement: results from the UK National External Quality Assessment Scheme. UK NEQAS (Blood Coagulation) Steering Committee.

In the present study we have performed local calibration of International Normalised Ratio (INR) measurement systems in a large series of laboratories. We assigned INRs to five lyophilised plasma calibrants, one prepared from normal plasma and four using plasma from warfarinised patients, using different International Reference Preparations for Thromboplastin. These five calibrants, and two lyophilised test plasmas were analysed by 349 centres using 60 different thromboplastin instrument combinations. Plasma calibrants were assigned INRs using the WHO reference thromboplastin RBT-90 or the European reference thromboplastin CRM 149R. Each participating centre determined PTs of the calibrants with their local system. These PTs were then used to construct a local calibration graph relating PT to INR. The PTs of test plasmas were converted directly into INR using the local calibration model and into INR using the conventional method. The overall medians of conventionally derived INRs of two test plasmas analysed in 349 centres were 2.50 and 3.10, compared to 2.47 and 3.04 after local calibration where RBT-90 was employed to assign INRs to calibrants. Use of CRM 149R to assign INRs to calibrants led to a significant (p<0.0001) increase in INR to 2.7 and 3.36 respectively. When results were grouped according to the thromboplastin employed, agreement between results with different reagents was improved by local calibration. There was a significant reduction (p<0.01) in the spread of results in different centres as indicated by a reduction in coefficient of variation.

Blood Coagulation↗
PubMed1999

Influence of three types of automated coagulometers on the international sensitivity index (ISI) of rabbit, human, and recombinant human tissue factor preparations--a multicenter study.

Five tissue factor reagents and three types of automated instruments for prothrombin time (PT) determination were studied in an international multicenter collaborative exercise. The purpose of this work was to determine the international sensitivity index (ISI) for each combination of reagent and instrument against the international reference preparation RBT/90. Each type of instrument was used by 3 or 4 centers to assess the interlaboratory variation of the ISI. The interlaboratory variation of the ISI for each combination of reagent and instrument ranged between 0.4% and 7.8% coefficient of variation. For three reagents, the mean ISI values for ACL (nephelometric) and STA (mechanical) were practically identical, but the mean ISI values for MLA (photo-optical) were at least 10% higher. For two other reagents prepared from rabbit tissue, the mean ISI values increased in the order ACL, STA, MLA. The widest range of mean ISI values was noted with one rabbit tissue factor reagent: 1.68 for ACL and 2.00 for MLA. Exclusion of patient specimens with INR <1.5 and INR >4.5 determined by the international reference preparation resulted in a slight decrease of the mean ISI. The interlaboratory variation of the International Normalized Ratio (INR) was assessed from the results obtained with common lyophilized and deep-frozen plasmas. The use of instrument-specific ISI values resulted in reduced interlaboratory variation of the INR. It is recommended that thromboplastin manufacturers provide instrument-specific ISI values.

Animals↗
PubMed1998

Assessment of Actin FS and Actin FSL sensitivity to specific clotting factor deficiencies.

We present a two centre study designed to assess the sensitivity of Actin FS and Actin FSL to deficiencies of factor VIII, IX, XI or XII. The study was undertaken at two centres to avoid bias due to the investigations being undertaken on one analyser. Samples from patients with a factor VIII (n = 36, F VIII = < 1.0-50 iu/dl), factor IX (n = 22, F IX = 2-48 iu/dl), factor XI (n = 23, F XI = 5-50 u/dl) or a factor XII (n = 18, F XII = 1-50 u/dl) deficient state were studied. Activated partial thromboplastin times (APTT) were determined using two batches of Actin FS and of Actin FSL; comparison of APTT results between centres was facilitated by the conversion of clotting times to ratios (test divided by geometric mean normal clotting time). APTT ratios were considered to be elevated if greater than two standard deviations above the mean normal. The factor deficient status of each sample was verified by assaying all samples for factors VIII, IX, XI and XII. Clotting factor assays were performed on a Sysmex CA-1000 fitted with research software, which permitted the auto-dilution and testing of three serial dilution of both a reference preparation and each patient's sample. Assay results were calculated using parallel-line Bioassay principles. This procedure allowed for variation in clotting times due to the effect of temporal drift of any of the reagents within the assay system. Actin FS and Actin FSL demonstrate acceptable sensitivity to factor VIII deficiency, however, both reagents failed to detect a large proportion of factor XI (17.4% and 30.4% of samples, respectively) and factor XII (66.7% and 72.2%, respectively) deficiencies. The detection rate with Actin FSL for factor IX deficiency was also poor (36.4% not detected). As factor IX and XI deficiencies are both associated with haemorrhagic disorders, the inability of these reagents to detect such abnormalities gave cause for concern.

Actins↗
PubMed1998

Laboratory performance of haemophilia centres in developing countries: 3 years' experience of the World Federation of Hemophilia External Quality Assessment Scheme.

A World Federation of Hemophilia External Quality Assessment Scheme has been established to promote high standards of laboratory performance in haemophilia centres worldwide. Results from 21 International Haemophilia Training Centres (IHTCs) provide target values for the prothrombin time (PT), activated partial thromboplastin time (APTT), factor VIII:C, IX:C and von Willebrand factor (VWF) assays, against which the performance of Haemophilia Centres in developing countries (HCs) can be assessed. Eight surveys were distributed over a 3-year period between 1994 and 1997. A higher proportion of HCs failed to identify an abnormal PT or APTT in samples from donors with mild deficiencies of the extrinsic and intrinsic systems, respectively. For factor VIII:C and IX:C assays, agreement between HC results was consistently poorer than between IHTCs. However, improvement in between-centre agreement could be seen for two samples distributed on more than one occasion. A minority of HCs perform assays for VWF, and a questionnaire revealed equipment and reagent costs as limiting the range of assays which could be carried out in several centres. However, agreement was in some cases better between those HCs that did perform VWF assays than between IHTCs. The problems of screening test sensitivity and between-centre agreement for factor assays need to be addressed, together with the limitations which prevent HCs from performing a full range of tests in the diagnosis and treatment of bleeding disorders.

Clinical Laboratory Techniques↗
PubMed1998

Quality control and factor VIII assays.

Quality assurance is a vital prerequisite of good laboratory practice. The application and continuous scrutiny of adequate internal quality control measures are essential to ensure that laboratory performance is consistent from day to day. External quality assessment is particularly important to verify the accuracy and reliability of laboratory results Consequently, without appropriate IQC and EQA, laboratory results can have no true validity.

Biological Assay↗
PubMed1998

DRG reimbursement: geriatric hip fractures in the community hospital trauma center.

BACKGROUND: The purpose of this paper was to determine whether Medicare reimbursement for hip fracture reaches cost in geriatric patients. METHODS: We conducted a retrospective review using the hospital trauma registry. Demographics, operations, length of stay, clinical outcome, discharge disposition, hospital charges, and hospital costs were reviewed and compared with diagnosis-related group (DRG) reimbursement. RESULTS: The study included 153 Medicare patients. Mortality was 3.9%, 71% were discharged to a nursing home or rehabilitation unit, and 25% went directly home. DRG reimbursement constituted 58% of charges. Compared with costs, the DRG amount represented a mean loss of nearly $1,000 per patient. CONCLUSIONS: DRG reimbursement undercompensates the community hospital trauma center for treating a common malady among the geriatric population. A population shift toward the elderly, decreasing Medicare remuneration, and the advance of managed care will make correct identification and control of costs extremely important for the hospital caring for hip fractures in the geriatric population.

Aged↗
PubMed1997

Monitoring oral anticoagulant treatment with the TAS near-patient test system: comparison with conventional thromboplastins.

BACKGROUND: A number of instruments have been developed for determination of prothrombin time (PT) and International Normalised Ratio (INR) at locations not limited to central laboratories. AIM: To evaluate one such portable instrument, the Thrombolytic Assessment System (TAS), which can be used in a near-patient setting. METHODS: Samples from 20 normal subjects and 48 patients treated with warfarin for venous thromboembolic disease were studied. The warfarin group was divided into: initiation phase (n = 10), combined warfarin and heparin (n = 10), stabilised therapy (n = 20), and over anticoagulated patients (n = 8). PTs and INRs were determined in each group using three conventional thromboplastins (Diagen Activated, Manchester Reagent, and Instrumentation Laboratory) and two TAS techniques (whole blood or plasma). An independent International Sensitivity Index (ISI) calibration of the TAS system was performed. RESULTS: Calculated ISIs for the TAS were 1.028 and 0.984 for plasma and whole blood analysis, respectively, compared with manufacturer's values of 0.98 and 0.97. INR results with TAS (whole blood) were 11% less than those obtained with Diagen Activated (p < 0.01) and 16% less than those obtained with Instrumentation Laboratory (p < 0.001) when manufacturers' mean normal PT and ISI were used for TAS INRs. TAS (whole blood) results were similar to TAS plasma or Manchester Reagent results. The use of a locally determined mean normal prothrombin time (MNPT) improved agreement between TAS and the other reagents, abolishing the significant difference between INRs determined with TAS (whole blood) and Diagen Activated techniques. CONCLUSION: The TAS system can be used with whole blood or plasma and produces similar INRs to those obtained with Diagen Activated or Manchester Reagent using manufacturer's ISI and a locally determined MNPT. Results were lower with TAS or Manchester Reagent compared with those obtained with Instrumentation Laboratory thromboplastin.

Anticoagulants↗
PubMed1997

Emergency oral anticoagulant reversal: the relative efficacy of infusions of fresh frozen plasma and clotting factor concentrate on correction of the coagulopathy.

Haemorrhage, including intracranial bleeding, is a common, potentially lethal complication of warfarin therapy and rapid and complete reversal of anticoagulation may be life-saving. Fresh frozen plasma (FFP) and vitamin K are most frequently administered. Because of the variable content of vitamin K-dependent clotting factors in FFP, and the effects of dilution, the efficacy of this approach is open to doubt. We have therefore compared the effects of FFP and clotting factor concentrates on the INRs and clotting factor levels of orally anticoagulated subjects requiring rapid correction of their haemostatic defect. In many, the pre-treatment INR was considered to be dangerously above the target therapeutic range. In the 12 patients given FFP, the INR did not completely correct (range 1.6-3.8, mean 2.3) indicating an ongoing anticoagulated state in all. In contrast, the INR in 29 subjects given clotting factor concentrates was completely corrected in 28 (range 0.9-3.8, mean 1.3). Following treatment, marked differences were observed in clotting factor IX levels between the two groups. The median factor IX level was 19 u/dl (range 10-63) following FFP infusion and 68.5 u/dl (range 31-111) following concentrate. In FFP treated patients, poorer responses were also observed for each of the other vitamin K-dependent clotting factors but these were less marked than for factor IX, which was present in low concentrations in some batches of FFP. Thus, haemostatically effective levels of factor IX cannot be achieved, in most instances, by the conventional use of FFP in patients requiring reversal of their anticoagulant therapy. Clotting factor concentrates are the only effective option where complete and immediate correction of the coagulation defect is indicated in orally anticoagulated patients with life or limb-threatening haemorrhage.

Administration, Oral↗