Values for ADAMTS-13 Activity, Antigen and Autoantibodies in Normal European Controls.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4199-4199
Author(s):  
Sabine Geiter ◽  
Markus Graf ◽  
Elin Tschokert ◽  
Agnes Veyradier ◽  
Martine Wolf ◽  
...  

Abstract Abstract 4199 INTRODUCTION In recent years, diagnostic tests for ADAMTS-13 and respective autoantibodies became available and are routinely used to support thrombotic thrombocytopenic purpura (TTP) diagnosis and therapy. ADAMTS-13 abnormalities have also been described in other pathological situations such as liver cirrhosis (Uemura, 2008), sepsis- induced DIC (Ono, 2006) or inflammatory bowel disease (Feys, 2009), where the relationship between ADAMTS13 parameters and state of disease is less clear than in TTP. A clear-cut distinction between normal and pathologic levels of ADAMTS-13 parameters (activity, antigen and autoantibodies) is only available in most TTP, with ADAMTS-13 activity levels < 10% and antibody titers well above normal levels. Pathological ranges for other diseases are not yet well defined. As normal ranges for ADAMTS-13 levels seem to be very broad, differentiation between normal and pathologic levels in cases other than TTP will depend on the size of the population used to establish the normal range and presumably also on age, gender, and likely also on other parameters present in this population. AIM The aim of this study was therefore to establish normal values for ADAMTS-13 parameters by analyzing normal populations in five different European laboratories using the same commercial assays. Material and Methods ADAMTS-13 autoantibodies were measured using the TECHNOZYM®ADAMTS-13 INH ELISA (anti-IgG). ADAMTS-13 activity and antigen concentrations were measured using TECHNOZYM®ADAMTS-13 ELISA, a combined assay for activity and antigen. Samples were frozen citrated plasma samples used in the respective laboratories as normal controls (approximately 40 in each laboratory; all together 193 normal controls). RESULTS The normal range for anti-ADAMTS-13 IgG was compared between the 5 different labs. For ADAMTS-13 INH, the median in these different populations varied between 6 and 9 U/ml which is well below the previously defined borderline value of 12 – 15 U/ml in this assay. The median for all samples was 6.7 U/ml; the number of “false-positives” (>15U/ml) varied from 5 to 10%. To analyze a possible age dependency, three groups were considered : <30 y.o., 31-50 y.o. and >50 y.o. No age dependent differences between these groups could be found (p>0.6). No significant differences were either found between male and female controls (p=0.55). For ADAMTS-13 activity and antigen only data from 140 normal subjects and 60 TTP patients are currently available. For normal subjects, the median for ADAMTS-13 activity was 103%, for antigen 101%. Both parameters showed a wide distribution of values between 53% and 205% for activity and 34% and 217% for antigen. In comparison, the median values in TTP patients were significantly lower (activity 12%, antigen 49%). Conclusion We can show that a substantial variation in normal values for ADAMTS-13 activity and antigen exists in normal subjects, while the range for ADAMTS-13 autoantibodies is rather narrow. All values in normal subjects are well separated from those obtained in TTP patients. The broad range of ADAMTS-13 activity and antigen in normal subjects has to be considered when these parameters are measured in diseases other than TTP. Disclosures: Geiter: Technoclone GmbH: Employment. Graf:Technoclone GmbH: Employment. Tschokert:Technoclone GmbH: Employment. Vetr:Technoclone GmbH: Employment.

1974 ◽  
Vol 20 (12) ◽  
pp. 1535-1542 ◽  
Author(s):  
Eugene K Harris

Abstract Normal ranges based on the distribution of single samples from a large number of individuals reflect both intra- and interindividual variation. If the average ratio of these two sources of variation is small, then, assuming gaussian distributions, the conventional normal range will usually include a larger than expected proportion of an individual's distribution of values. When the average ratio exceeds 1.4, the normal range will include a proportion either larger or smaller than expected, depending on whether the individual's variability is less than or greater than average intra-individual variation. Investigation of multivariate normal regions in certain cases where calculations are feasible produced similar results. With these numerical guidelines, data from recent blood-chemistry studies indicate that conventional normal ranges are likely to be less sensitive than desired to significant changes in an individual's biochemical state. This analysis supports the continued development and use of cumulative (in time) systems for reporting laboratory test results for individuals.


1987 ◽  
Author(s):  
G Castaman ◽  
F Rodeghiero ◽  
M Ruggeri

Sporadic cases of thromboembolic events have been reported in patients with congenital factor XII deficiency and a relationship with a reduced intrinsic fibrinolysis has been suggested.We report here the results of clinical and laboratory investigations in 10 new families comprising 15 homozygotes (age 16-72) and 14 heterozygotes (age 18-65).In homozygotes, kaolin-activated-PTT was indefinitely prolonged and F XII activity and antigen were undetectable, whereas functional assays . of high molecular weight kininogen ahd kallikrein yielded normal values. Intrinsic fibrinolytic activity - assayed on fibrin plate by measuring lysis zones determined i. by euglobulin fraction, obtained in presence of dextran sulphate and flufenamate (Blood activator inventory test, Kluft 1979) - was reduced in all homozygous pts. to about 50% of normal (range 15-70%; normal range 80-120%); normal values were observed in all heterozygotes. Basal extrinsic fibrinolytic activity (measured after addition of Cl-inhibitor) was absent or minimal as in normal controls. None of our patients showed evidence of thrombotic diathesis.In conclusion, our study demonstrates that a reduced intrinsic fibrinolysis, as assayed by blood activator inventory test, is a common finding in F XII deficiency. The absence of thrombotic diathesis in our cases suggests that, this defect is probably devoid of any clinical significance.


2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
MohammadBagher Shamsi ◽  
Korosh Veisi ◽  
Loghman Karimi ◽  
Javad Sarrafzadeh ◽  
Farid Najafi

Background. Although there are frequent studies about normal range of thoracic kyphosis, there is still a controversy about the exact values of this curve. In nine reported studies on 10 to 20 years of age boys, the value ranged from 25.1° to 53.3°. Objective for the Study. The aim of the present research was investigation of normal ranges of thoracic kyphosis in school children in Kermanshah, western Iran. Methods. 582 male students aged 13 to 18 years old using cluster random sampling were recruited from schools in Kermanshah city, 97 students for each age. Thoracic curves were measured using the flexicurve method. Results. Mean thoracic kyphosis for whole population was 35.49° SD 7.83 and plus or minus two standard deviations ranged from 19.83° to 51.15°. It increased gradually from 13 to 16 and then there was a little decrease to 18 years. Mean values for each age (13–16) were 13 (34.41 SD 7.47°), 14 (34.86 SD 8.29°), 15 (35.79 SD 7.93°), 16 (36.49 SD 7.85°), 17 (35.84 SD 8.33°), and 18 (35.55 SD 7.07°). Conclusions. Our results are in agreement with previous reports and can be used as normal values for local and regional purposes.


1977 ◽  
Author(s):  
Z.M. Ruggeri ◽  
R. Bader ◽  
T. Barbui ◽  
P.M. Mannucci

In 10 normal subjects washed human platelets (Pl)contained FVIII related antigen(VIIIR:AG) as measured by immunoradiometric assay (iRMA)and electroimmunodif fusion (EID);and ristocetin co-factor (VIIIR:RCo)as assayed by a washed platelet method. The observed values were: AG(IRMA) 0.11-0.24u/mg Pl protein; VIIIR:AG (EID)0.11-0.30u/mg; VIIIR:RCo 0.06-0.21u/mg, In 10pts with seve re homozygous VWD, VIIIR:AG was unmeasurable in 7 and extremely low (1x10-3-0.6x10-3u/mg) in 3 u-sing the very sensitive IRMA; VIII RCo was always unmeasurable. In 12 pts with “classical” dominant VWD characterized by very low plasma levels of VIIIR:AG(0.03-0.09u/ml)and VIIIR:RCo(<0.03u/ml), FVIII related properties were normal in Pl and the mobility of PI VIIIR:AG on bidimensional immunolectrophoresis was not different from that of normal controls. In 7 pts showing a faster mo bility of plasma VIIIR:AG, the same abnormality was found in Pl.Pl VIIIR:AG level was within the normal range when assayed by EID whereas IRMA gave lower values both in plasma and in PI.PI VIII R:RCo was lower than in normal subjects and pts with “classical”VWD without electrophoretic variant. These findings show that severe VWD is the expression of a marked reduction of VIII synthesis fully expressed both in PI and in plasma. In “classical” VWD the plasma defects are not reflected in PI, which show normal levels of FVIII-related properties accompanied by normal electro, phoretic mobility of VTIIR:AG; this suggests a defective transfer from PI to plasma. Patients with abnormal mobility are the expression of a qualitative alteration of the FVIII molecole functionally defective both in Pl and in plasma.


1975 ◽  
Vol 79 (3) ◽  
pp. 451-458 ◽  
Author(s):  
J. C. Davis ◽  
L. J. Hipkin ◽  
V. K. Summers ◽  
T. M. D. Gimlette

ABSTRACT Bioassays of long-acting thyroid stimulator (LATS) were performed in three groups of subjects: in normal controls, in thyrotoxic patients before and serially after 131I treatment, and in patients with hypopituitarism. Of the untreated thyrotoxic patients, 27.7 % had raised serum LATS levels initially. There was no correlation between the relapse rate after 131I therapy and the initial or subsequent LATS titres: in particular, thyrotoxicosis sometimes recurred after an initially high LATS titre had fallen into the normal range. The distribution of the results of LATS assays in the hypopituitary patients was significantly different from that in the normal subjects; 4 out of 27 hypopituitary patients had LATS levels above the normal range, although they had no thyroxicosis. On the other hand, the majority of the patients with hypopituitarism, 19 out of 27, had LATS titres below the mean normal level, possibly due to deficiency of a substance we have termed pseudo LATS. These results raise doubts about a direct causative role for LATS in most cases of thyrotoxicosis.


2012 ◽  
Vol 126 (6) ◽  
pp. 563-569 ◽  
Author(s):  
M Moore ◽  
R Eccles

AbstractThis review examines why there is no normal range of nasal patency available to the surgeon when assessing nasal obstruction, and discusses the factors that influence nasal patency. Current normal ranges are examined and criticised because of the variability of normal values and the poor sampling methods used. Instability of physiological nasal patency is related to factors such as the nasal cycle and the nose's direct exposure to the external environment. Decongestion of the nose is proposed as a way of stabilising anatomical nasal patency, and measurements of patency in this state may be more useful to the surgeon. Population studies are needed to establish a normal range, but these studies must control for factors such as age, height, sex, and nasal shape and size related to climatic adaptation. Rather than classify populations according to unscientific categories such as race, anthropometric measures such as the nasal index are proposed.


1986 ◽  
Vol 32 (5) ◽  
pp. 808-810 ◽  
Author(s):  
M Schöneshöfer ◽  
B Weber ◽  
W Oelkers ◽  
K Nahoul ◽  
F Mantero

Abstract Using liquid chromatography, we estimated the urinary excretion of 20 alpha-dihydrocortisol (20-DH) and urinary free cortisol (UFC) in normal subjects and in 40 patients with Cushing's syndrome of different etiologies. The median normal excretion rate (nmol/24 h) was 174 for 20-DH and 68 for UFC, the 20-DH/UFC ratio thus being 2.55. For patients with Cushing's syndrome, the excretion rate was 1798 for 20-DH and 298 for UFC, the ratio 6.03. We evaluated the effect of acute stimulation of adrenal secretion on 20-DH and UFC by administering corticotropin to six normal subjects. After such stimulation, the excretion rate was 566 for 20-DH and 1238 for UFC (ratio 0.45). Whereas 20-DH excretion rate exceeded the normal range in all patients, six patients had normal or even below-normal values for UFC excretion. Evidently, measurement of urinary 20-DH is a better test for chronic hypercorticoidism than is measurement of urinary UFC, and chronic hypercorticoidism can be differentiated from the acute state by the 20-DH/UFC ratio.


1981 ◽  
Author(s):  
A Duncan ◽  
P Didisheim

The variability of normal ranges in different laboratories and the occurrence of occasional elevated values of β-TG and PF-4 in normal subjects are well established. We examined the influence of factors such as age, sex, smoking, exercise, oral contraceptives and day-to-day variation in 148 healthy subjects. The β-TG and PF-4 assays were performed by commercial RIA’s modified by utilizing an EDTA- PGE1 -theophylline mixture as anticoagulant.The statistical method used to compare our groups was a student t-test after log transformation of the data. Our baseline control group (N=63) were non smokers and not taking oral contraceptives (O/C) or any medications. There was no difference between sexes or a significant change with increasing age, although the mean β-TG and PF-4 does increase in cohosts of 20 years. [<30 years (21.65±8.35)(SD), 30-50 years (24.32±10.94) >50 years (27.88±14.3)-β-TG data].Women on O/C were significantly different from those not on O/C for β-TG [35.06±22.45 (O/C) and 23.67±9.38 (N)] but not for PF-4 values [3.79±1.77 (O/C) and 3.91±1.63 (N)].Strenuous exercise was the parameter that influenced both β-TG and PF-4 significantly, showing an elevated value after exercise for both β-TG [81.9±31.4 v 26.73±10.91] and PF-4 [7.08±1.71 v 3.73±1.91].Day-to-day variations in β-TG and PF-4 were examined in 10 subjects for 7-10 days. The coefficient of variation (CV) amongst these subjects was 21-51%. In athletes day-today variation was the same unless a change in pattern of exercise occurred [CV-49-132%].Our results confirm that parameters such as above do influence normal values and should be taken into consideration in establishing a normal range.It also indicates the β-TG is a more sensitive parameter for delineating differences in physiological parameters in normal subjects than PF-4, and this may be applicable to clinical studies.


Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1107-1107
Author(s):  
Malak Elbatarny ◽  
Shamim Mollah ◽  
Julie Grabell ◽  
Margaret L. Rand ◽  
Dewi S. Clark ◽  
...  

Abstract Background Challenges in reporting subjective hemorrhagic symptoms consistently has led to the need for standardized, quantitative Bleeding Assessment Tools (BATs), some of which assign Bleeding Scores (BSs). The ISTH-BAT (International Society on Thrombosis and Hemostasis – Bleeding Assessment Tool (Rodeghiero et al JTH 2010; 8:2063)) aimed to consolidate and optimize advances made by its predecessors, which were based on the 2005 “Vicenza Bleeding Questionnaire”. It is important to note, however, that the scoring systems differ among the BATs, with each bleeding symptom scored from 0 to +3 for the original Vicenza, -1 to +4 for the MCMDM-1VWD and Condensed MCMDM-1VWD Bleeding Questionnaires and the PBQ (Pediatric Bleeding Questionnaire), and 0 to +4 for the ISTH-BAT. As a result, the normal ranges of BSs vary among questionnaires. To date, the normal range for the ISTH-BAT has not been established; the objective of this study was to determine the normal range of bleeding scores for the ISTH-BAT for both adults and pediatric patients. Patients and Methods BS data from different studies, originally generated using 4 different Vicenza-based BATs, were compiled using a bioinformatics system created to facilitate the collation and analysis using different scoring systems. Demographic and BS data, along with blood group, VWF:Ag/VWF:RCo/FVIII:C (when available) were collected from all enrolled subjects. Data were derived from multiple studies; all defined normal subjects as those without a known problem with bleeding or bruising. All BATs were expert-administered. The normal range for both adults and pediatrics was determined by: 1) removing outliers > 3 SD away from the mean and then, 2) selecting the mid-95th %ile. Results 1,422 normal subjects were included (adult: n=1,079, pediatric: n=343). Adult data were collected using MCMDM-1VWD (n=294), Condensed MCMDM-1VWD (n=660), and ISTH-BAT (n=125), while pediatric data were collected using PBQ (n=324) and ISTH-BAT (n=19). 48 adults were removed from the analysis because they had BSs > 6.3, (i.e., >3 SD away from the mean), leaving n=1,031 for determination of the normal range. For children, BSs > 3.5 were judged to be outliers and therefore 18 children were removed, leaving n=325 children for determination of the normal range. The remaining adults had a mean age of 43 yrs (range 18 – 88) with 695 females and 336 males. The remaining children had a mean age of 9 yrs (range 0.4 – 17 yrs), with 169 females and 156 males. The relationship between BSs and demographic and lab data are given in Table 1. For the ISTH-BAT, the normal range of BSs was 0 - 4 in adults (meaning that for individuals 18 yrs or older, a BS 5 or greater is positive or abnormal) and 0 - 2 in children (meaning that for individuals < 18 yrs, a BS 3 or greater is positive or abnormal). Conclusion The newly established normal BS ranges can now be used to objectively assess the bleeding symptoms of individuals by administration of the ISTH-BAT. They also highlight the strength of merging existing datasets to generate meaningful results. By making these data accessible to all investigators using the web-based ISTH-BAT system housed at Rockefeller University we hope to aid investigators initiating new studies and facilitate correlating bleeding symptoms with genotypic, molecular, and environmental data. Disclosures: Mauer: CSL Behring: Honoraria. James:CSL Behring: Honoraria, Research Funding; Octapharma: Honoraria, Research Funding; Baxter: Honoraria; Bayer: Honoraria.


Hand Surgery ◽  
2004 ◽  
Vol 09 (02) ◽  
pp. 137-143 ◽  
Author(s):  
R. K. Pratt ◽  
G. A. Hoy ◽  
C. Bass Franzcr

Dislocation or subluxation of the extensor carpi ulnaris (ECU) tendon is one of the differential diagnoses of ulnar-sided wrist pain. No data exists on the degree of subluxation occurring in normal wrists. Retrospective review of surgical cases revealed two patients with dorsal and four with volar instability. Magnetic resonance imaging and ultrasound were not always predictive of the direction of instability. A standardised ultrasound technique was used to evaluate ECU subluxation in 20 asymptomatic wrists. In normal subjects, as a percentage of the width of the osseous groove, the volar edge of extensor carpi ulnaris may displace by up to 40% beyond the volar lip of the osseous groove with wrist flexion and the dorsal edge by 33% beyond the dorsal lip with wrist extension. The effect of gender on normal range and the diagnostic use of the standardised ultrasound technique need further evaluation.


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