Antithrombin III, Heparin Cofactor and Antifactor Xa in Relation to Age, sex And Pathological Conditions

1979 ◽  
Author(s):  
F. Panicucci ◽  
A. Sacripanti ◽  
E. Pinori ◽  
M. Vispi ◽  
B. Conte ◽  
...  

Determinations of AT-III activity, heparin cofactor activity, antifactor Xa activity and AT-III protein were carried out in 200 healthy adults, evenly distributed within age and sex groups, in 60 patients with cerebral thrombosis and in 20 oral contraceptive users. There was a positive correlation between AT-III protein and its activitiesin normal subjects and in patients with cerebral thrombosis. In oral contraceptive users the positive correlation was between AT-III protein and its activities, antifactor Xa activity excepted. The mean AT-III protein and heparin cofactor activity values decreased in males with age and were significantly lower in the groups between 50 and 70 years. The mean AT-III protein and heparin cofactor activity values decreased slightly in women in fertile age and were lower in the 40 to 50 age-group. The mean AT-III protein and its activities values did not show any variation in the patients with cerebral thrombosis. The mean antifactor Xa activity value in the women, taking the pill for 3 months, decreased, whereas the other AT-III activities and AT-III protein were unchanged.

1979 ◽  
Author(s):  
F. Panicucci ◽  
A. Sacrioanti ◽  
E. Pinori ◽  
M. Vispi ◽  
B. Conte ◽  
...  

Determinations of AT-III activity, heparin cofactor activity, antifactor Xa activity and AT-III protein were carried out in 200 healthy adults, evenly distributed within age and sex groups, in 60 patients with cerebral thrombosis and in 20 oral contraceptive users. There was a positive correlation between AT-III protein and its activities in normal subjects and in patients with cerebral thrombosis. in oral contraceptive users the positive correlation was between AT-III protein and its activities, antifactor Xa activity excepted. The mean AT-III protein and heparin cofactor activity values decreased in males with age and were significantly lower in the groups between 50 and 70 years. The mean AT-III protein and heparin cofactor activity values decreased slightly in women in fertile age and were lower in the 40 to 50 age-group. The mean AT-III protein and its activities values did not show any variation in the patients with cerebral thrombosis. The mean antifactor Xa activity value in the women, taking the pill for 3 months, decreased, whereas the other AT-III activities and AT-III protein were unchanged.


1989 ◽  
Vol 61 (01) ◽  
pp. 020-024 ◽  
Author(s):  
Kenji Okajima ◽  
Hidetsugu Ueyama ◽  
Youichiro Hashimoto ◽  
Yasuto Sasaki ◽  
Keiko Matsumoto ◽  
...  

SummaryAbnormal antithrombin III (AT III) was found in the plasma of a 31-year-old female who suffered from recurrent thrombotic episodes. Heparin cofactor activity was 28% of normal and undetectable when measured by inhibition of thrombin and factor Xa (F. Xa), while both progressive antithrombin and antifactor Xa activities were normal. The concentration of plasma AT III antigen was 37 mg/dl. Analysis by crossed-immunoelec- trophoresis (CIE) in the presence of heparin and affinity chromatography on heparin-Sepharose revealed that the propositus’ AT III did not bind to heparin. When heparin cofactor II (HC II) was removed from propositus’ plasma, heparin cofactor activity of AT III was not detected. Thus, HC II seemed to account for the plasma heparin cofactor activity found in the presence of thrombin. The patient’s parents and three of her brothers demonstrated qualitative abnormality of AT III; heparin cofactor activity was 30-50% of normal levels in the presence of both thrombin and F. Xa. These findings indicate that the propositus’ AT III lacks affinity for heparin and the mode of its inheritance seems to be autosomal dominant and, hence, the propositus would be a homozygote. For this variant, the name of AT III Kumamoto is proposed.


1981 ◽  
Vol 45 (01) ◽  
pp. 051-054 ◽  
Author(s):  
A M Fischer ◽  
J Tapon-Bretaudiere ◽  
A Bros ◽  
F Josso

SummaryIn order to investigate the mechanism of thrombin inactivation in the presence of both antithrombin III (AT III) and α 2-macroglobulin (α 2 M), thrombin and the inhibitors have been purified from human material and thrombin inactivation studied using purified reagents either alone or added to defibrinated plasma. Comparison of clotting and amidolytic activities of residual thrombin allowed to measure the amount of thrombin bound to α 2 M. In a purified reagent system as well as in plasma, part of exogenous thrombin is bound to α 2 M. The amount of bound thrombin is related to α 2 M concentration. Conversely, previous plasma α 2 M depletion by immunoabsorption increases the consumption of heparin-cofactor activity by exogenous thrombin. Thus AT III and α 2 M compete for thrombin inactivation. This finding could be of practical interest in clinical situations associating high plasma α 2 M levels and a decrease of AT III concentration.


1986 ◽  
Vol 55 (02) ◽  
pp. 218-221 ◽  
Author(s):  
A M Fischer ◽  
P Cornu ◽  
C Sternberg ◽  
F Mériane ◽  
M D Dautzenberg ◽  
...  

SummaryA qualitative abnormality of antithrombin III (AT III) was found in the plasma of a 41-year old patient. The plasmatic AT III antigen concentration was 130% and the progressive anti-F IIa and anti-F Xa activities were normal (105% and 137%). The plasma heparin cofactor activity was less than 10%, when measured by F Ila or F Xa inhibition. Crossed immunoelectrophoresis of AT III in the presence of heparin revealed in the plasma an abnormal slow-moving peak. When tested by affinity chromatography on heparin Sepharose, this abnormal AT III did not bind to heparin. Among the investigated relatives, 5 subjects had normal AT III levels, whatever the test used, the nine others having reduced levels of antithrombin heparin cofactor activity (45-61%) but normal levels of immunoreactive AT III (97-122%). Consanguinity was found in the family history. We therefore considered our patient as homozygous for an AT III molecular abnormality affecting the binding site for heparin.


1966 ◽  
Vol 53 (2) ◽  
pp. 177-188 ◽  
Author(s):  
P. Lund-Johansen ◽  
T. Thorsen ◽  
K. F. Støa

ABSTRACT A comparison has been made between (A), a relatively simple method for the measurement of aldosterone secretion rate, based on paper chromatography and direct densitometry of the aldosterone spot and (B) a more elaborate isotope derivative method. The mean secretion rate in 9 normal subjects was 112 ± 26 μg per 24 hours (method A) and 135 ± 35 μg per 24 hours (method B). The »secretion rate« in one adrenalectomized subject after the intravenous injection of 250 μg of aldosterone was 230 μg per 24 hours (method A) and 294 μg per 24 hours (method B). There was no significant difference in the mean values, and correlation between the two methods was good (r = 0.80). It is concluded that the densitometric method is suitable for clinical purposes as well as research, being more rapid and less expensive than the isotope derivative method. Method A also measures the urinary excretion of the aldosterone 3-oxo-conjugate, which is of interest in many pathological conditions. The densitometric method is obviously the less sensitive and a prerequisite for its use is an aldosterone secretion of 20—30 μg per 24 hours. Lower values are, however, rare in adults.


Blood ◽  
1986 ◽  
Vol 67 (1) ◽  
pp. 93-98
Author(s):  
EA Knot ◽  
E de Jong ◽  
JW ten Cate ◽  
AH Iburg ◽  
CP Henny ◽  
...  

Purified human radioiodinated antithrombin III (125I-AT III) was used to study its metabolism in six members from three different families with a known hereditary AT III deficiency. Six healthy volunteers served as a control group. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and crossed immunoelectrophoresis (CIE) showed the purified AT III to be homogeneous. Amino acid analysis of the protein revealed a composition identical to a highly purified internal standard. The specific activity was 5.6 U/mg. Analysis of plasma radioactivity data was performed, using a three-compartment model. Neither plasma disappearance half-times nor fractional catabolic rate constants differed significantly between patients and control subjects. The mean absolute catabolic rate in the patient group was significantly lower than that of the control group at 2.57 +/- 0.44 and 4.46 +/- 0.80 mg/kg/day, respectively. In addition, the mean patient alpha 1-phase, flux ratio (k1,2 and k2,1) of the second compartment alpha 2-phase and influx (k3,1) of the third compartment were significantly reduced as compared with control values. It has been tentatively concluded that the observed reduction in the second compartment may be caused by a decrease in endothelial cell surface binding.


1981 ◽  
Author(s):  
S Kondo ◽  
T Matsuo ◽  
Y Ohoki ◽  
O Matsuo

In the familial AT III deficiency of a Japanese family, the propositus (a-39-yr old female) and her mother had episodes of recurrent thrombosis and their AT III levels as measured immunologically and biologically were below the normal value. In the plasma of her brother, the AT III concentration as measured immunologically was half of the normal value, but his biological antithrombin activity was within the normal range. The progressive antithrombin activity and antifactor Xa activity of plasma samples in this familial AT III deficiency were within the normal range. Measurements of the rate of thrombin neutralization activity revealed that the brother’s plasma was in the normal range, but the plasma of the propositus and of her mother showed rates of thrombin neutralization activity which were somewhat below the normal value. The rate of thrombin neutralization activity per mg protein of AT III was highest in the plasma of the brother, and became slower in the mother, propositus, and pooled normal plasma in that order. In the plasma of this familial AT III deficiency, the rate of Xa neutralization activity was much slower than the normal value. It is postulated that since the antithrombin of the brother of the propositus was found to react as normal in the neutralization of thrombin, he does not have episodes of thrombosis. Such characteristic hyperfunction of antithrombin in the plasma of the brother may be due to some molecular abnormality of AT III within this hereditary deficient family.


1975 ◽  
Author(s):  
O. R. Ødegård ◽  
U. Abildgaard

Heparin cofactor activity and antithrombin III (At-III) activity measured with amidolytic methods; antifactor Xa by a clotting method (Biggs et al., Brit. J. Haemat. 19, 287, 1970) and immunoassay of At-III (Fagerhol & Abildgaard, Scand. J. Haemat. 7, 10, 1970) in plasma and serum showed:1) There was a close correlation between the plasma values as measured by all these methods (r = 0.84–0.93).2) The difference between plasma and serum values (“consumption”) was lower in warfarin treated and in haemophiliacs than in the other groups.3) The difference between plasma and serum was greater when measured by the heparin cofactor activity method than by the other methods. The reason for this discrepancy will be discussed. The results in different patient groups will be reported.4) As the heparin cofactor activity assay can be completed within 10 minutes after blood sampling, and has a higher precision than clotting assay and immuno assay, it is preferable for clinical use.


1987 ◽  
Author(s):  
K Takahashi ◽  
M Niwa ◽  
N Sakuragawa

Purpose: Low molecular weight(LMW) heparin shows stronger antifactor Xa(F-Xa) and weaker anti-thrombin(TH) activities compared with unfractionated(UF) heparin, and shows less bleeding tendency in the cases of clinical use. Platelet factor 4(Pf-4) and histidine-rich glycoprotein(HRG) neutralize heparin. We investigated on the heparin neutralizing effects of them to both kinds of heparinMaterials and methods: LMW heparin(Kabi and Pharmuka) and UF heparin(Novo) were used. Antithrombin III(AT-III), HRG(human origin ) and pf-4( bovine origin ) were purified by our methodsTH(Green-Cross) and F-Xa(Sigma) were used. Reaction mixtures for anti-TH or anti-F-Xa were as follows: 1 vol of AT-III( 0.1 U/ml)+ 1 vol of heparin( 10 ug/ml)+l vol of pf-4 or HRG(varied)→incubated for 5 min→+l vol of TH(5 U/ml) or F-Xa( 7 nKat/ml)→incubated for 5 min→ + S-2238 or S-2222→ recorded at 405 nm.Results: (1) Pf-4 showed the equivalent anti-TH effect on both kinds of heparin, and 3 ug of pf-4 neutralized 1 ug of heparinOn F-Xa neutralizing effect, 13 ug of pf-4 neutralized 1 ug of UF heparin, but could not neutralize LMW heparin. (2) HRG showed the same results on anti-TH effect of both kinds of heparin, but could not neutralize the anti-F-Xa effect of LMW heparin on the same amount of HRG which neutralized that of UF heparin. Conclusion: Anti-F-Xa effect of. LMW heparin could not be easily neutralized by pf-4 or HRG compared with that of UF heparin.


1985 ◽  
Vol 108 (2) ◽  
pp. 277-283 ◽  
Author(s):  
S. Andò ◽  
C. Giacchetto ◽  
G. M. Colpi ◽  
E. Beraldi ◽  
M. L. Panno ◽  
...  

Abstract. In the present study we determined progesterone (p), 17-OH-progesterone (17-OH-P), androstenedione (Δ4), dehydroepiandrosterone (DHEA) and testosterone (T) in spermatic venous blood of 34 varicocele patients and of 13 normal subjects. We also used the DHEA/Δ4 ratio as an index of the Δ5/Δ4 pathway ratio in testosterone biosynthesis. The mean of T and Δ4 in the spermatic blood of varicocele (V) patients appeared to be significantly lower with respect to that of normal (N) subjects (T:N = 1718.2 ± 202.4 (sem) nmol/l, No. 11; V = 1243.7 ± 97 (sem) nmol/l, No. 34; P < 0.03. Δ4: N = 56.4 ± 5.6 (sem) nmol/l, No. 12; V = 38.1 ± 4 (sem) nmol/l, No. 27, 0.02> P>0.01). A negative correlation was observed between the individual age of varicocele patients and 17-OH-P (No. 34, y = −30.66x + 1300, r = −0.57, P < 0.01) Δ4 values (No. 27, y = −1.981x + 96.52, r = −0.67, P< 0.01). When the ratio of T precursors was evaluated, we observed a positive correlation between the P/17-OH-P ratio and age of varicocele (No. 33, y = 0.0065x–0.092, r = 0.45, P < 0.03). The 17-OH-P/Δ4 ratio was greatly increased with respect to that of normal subjects (N = 5.12 ± (sem), No. 12; V= 10.77 ± 1.31 (sem), No. 27; P<0.01). These data suggest that the reduced T levels in spermatic venous blood of varicocele patients were due firstly to the enzymatic deficiency of 17-20-lyase and secondly to that of 17α-hydroxylase activity as the patients grow relatively older. The negative correlation between the DHEA/Δ4 ratio and Δ4/T ratio was observed in normal subjects (No. 10, y = −0.00432x + 0.0542, r = −0.67, P < 0.03) as well as in varicocele patients (No. 27, y = −0.00399x + 0.0587, r = −0.48, 0.02 > P > 0.01). This indicates that in the testis of varicocele patients the testosterone remains prevalently supplied by the Δ5 pathway of biosynthesis.


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