Lipoprotein-Associated Coagulation Inhibitor

2015 ◽  
pp. 22-25 ◽  
Author(s):  
George J. Broze ◽  
Thomas J. Girard ◽  
William F. Novotny
Keyword(s):  
Coagulation Inhibitor

Heparin Cofactor II Deficiency in Patients Infected with the Human Immunodeficiency Virus

1993 ◽  
Vol 70 (05) ◽  
pp. 730-735 ◽  
Author(s):  
P Toulon ◽  
M Lamine ◽  
I Ledjev ◽  
T Guez ◽  
M E Holleman ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Absolute Number ◽  
Thrombin Inhibitor ◽  
Unusual Complication ◽  
Healthy Individuals ◽  
Heparin Cofactor Ii ◽  
Immunodeficiency Virus ◽  
Coagulation Inhibitor ◽  
The Mean ◽  
Cd4 Lymphocytes

SummaryIn human plasma, heparin cofactor II (HCII) is a thrombin inhibitor, whose deficiency has been reported to be associated with recurrent thrombosis. The finding of two cases of low plasma HCII activity in two patients infected with the human immunodeficiency virus (HIV) led us to investigate this coagulation inhibitor in the plasma of a larger population of HIV-infected patients. The mean plasma HCII activity was significantly lower in 96 HIV-infected patients than in 96 age- and sex-matched healthy individuals (0.75 ± 0.24 vs 0.99 ± 0.17 U/ml, p <0.0001). HCII antigen concentration was decreased to the same extent as the activity. The proportion of subjects with HCII deficiency was significantly higher in the HIV-infected group than in healthy individuals (38.5% vs 2.1%). In addition, HCII was significantly lower in AIDS patients than in other HIV-infected patients, classified according to the Centers for Disease Control (CDC) on the basis of an absolute number of circulating CD4+ lymphocytes below 200 x 106/1. The link between HCII and immunodeficiency is further suggested by significant correlations between HCII activity and both the absolute number of CD4+ lymphocytes and the CD4+ to CD8+ lymphocyte ratio. Nevertheless, the mean HCII level was not different in the various groups of patients classified according to clinical criteria, except in CDC IVD patients in whom HCII levels were significantly lower. In addition, no correlation could be demonstrated between HCII and protein S activities, another coagulation inhibitor whose plasma level was also found to be decreased in HIV-infected patients. A similar prevalence of HCII deficiency was also found in a small series of 7 HIV-infected patients who developed thrombotic episodes, an unusual complication of the infection. This suggests that, in HIV-infected patients, HCII deficiency is not in itself the causative factor for the development of thrombosis.

On the Natural Blood Coagulation Inhibitor System Investigations of Inhibitor Factors Based on Antithrombin Deficient Blood

1965 ◽  
Vol 14 (03/04) ◽  
pp. 473-489 ◽  
Author(s):  
O Egeberg
Keyword(s):  
Normal Level ◽  
Antithrombin Iii ◽  
Strong Support ◽  
Blood Protein ◽  
Coagulation Inhibitor ◽  
Inhibitor System ◽  
Normal Human ◽  
Partial Deficiency ◽  
Antithrombin Iii Activity ◽  
Prothrombinase Activity

SummaryNatural coagulation inhibitor factors were studied in sera, or in fractions of sera, from patients with congenital partial deficiency of antithrombin and from normal persons. In the patients’ sera the progressive antithrombin (antithrombin III) and heparin cofactor (antithrombin II) had both been measured around 50 per cent of normal level.No decreased activity could be demonstrated in the patients’ sera as to antiprothrombinase, the inhibitor against blood intrinsic prothrombinase activity.For anticonvertin, the inhibitor against the tissue convertin complex, the activity was found decreased to about the same level as that demonstrated for antithrombin III and II. The results lend strong support to the hypothesis that the activities measured as anticonvertin, antithrombin III and antithrombin II represent functions of the same blood protein, which on the other side appears to be distinct from antiprothrombinase. In accordance with this explanation, an antithrombin III concentrate had also antithrombin II and anticonvertin activity, and further, adsorption of a normal human serum with convertin appeared to specifically reduce its antithrombin III activity.The inhibitor against activated antihemophilic C factor (AHC’ = activated f. XI) was studied in sera adsorbed with BaS04 and celite. The inhibitor activity was found at normal level in the patients’ sera, consistent with the view that anti-AHC’ is distinct from antithrombin III, II and from anticonvertin. No acceleration of the anti-AHC’ activity could be demonstrated after addition to the inhibition mixture of weak solutions of heparin.The results are discussed.

scholarly journals Plasma antigen levels of the lipoprotein-associated coagulation inhibitor in patient samples

Blood ◽  
1991 ◽  
Vol 78 (2) ◽  
pp. 387-393 ◽  
Author(s):  
WF Novotny ◽  
SG Brown ◽  
JP Miletich ◽  
DJ Rader ◽  
GJ Jr Broze
Keyword(s):  
Mean Value ◽  
Tissue Type ◽  
Extrinsic Pathway ◽  
Type Plasminogen Activator ◽  
Intravenous Heparin ◽  
Normal Individuals ◽  
Coagulation Inhibitor ◽  
Gram Negative Bacteremia ◽  
Heparin Plasma ◽  
Low Levels

Abstract Human plasma contains an inhibitor of tissue factor-initiated coagulation known as the lipoprotein-associated coagulation inhibitor (LACI) or also known as the extrinsic pathway inhibitor (EPI). A competitive fluorescent immunoassay was developed to measure the plasma concentration of LACI in samples from normal individuals and patients with a variety of diseases. The LACI concentration in an adult control population varied from 60% to 160% of the mean with a mean value corresponding to 89 ng/mL or 2.25 nmol/L. Plasma LACI levels were not decreased in patients with severe chronic hepatic failure, warfarin therapy, primary pulmonary hypertension, thrombosis, or the lupus anticoagulant. Plasma LACI antigen was decreased in some, but not all patients with gram-negative bacteremia and evidence for disseminated intravascular coagulation. Plasma LACI levels were elevated in women undergoing the early stages of labor (29%), in patients receiving intravenous tissue-type plasminogen activator (45%), and in patients receiving intravenous heparin (375%). A radioligand blot of the pre- and post-heparin plasma samples shows the increase to be in a 40-Kd form of LACI. Very low levels of plasma LACI antigen were found in patients with homozygous abetalipoproteinemia and hypobetalipoproteinemia, diseases associated with low plasma levels of apolipoprotein B containing lipoproteins. Following the injection of heparin into one patient with homozygous abetalipoproteinemia, the plasma LACI antigen level increased to a level comparable with that in normal individuals after heparin treatment.

scholarly journals The lipoprotein-associated coagulation inhibitor that inhibits the factor VII-tissue factor complex also inhibits factor Xa: insight into its possible mechanism of action

Blood ◽  
1988 ◽  
Vol 71 (2) ◽  
pp. 335-343 ◽  
Author(s):  
GJ Jr Broze ◽  
LA Warren ◽  
WF Novotny ◽  
DA Higuchi ◽  
JJ Girard ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Antithrombin Iii ◽  
Polyacrylamide Gel Electrophoresis ◽  
Sodium Dodecyl ◽  
Factor Xa ◽  
Factor Vii ◽  
Diisopropyl Fluorophosphate ◽  
Plasma Factor ◽  
Coagulation Inhibitor ◽  
Catalytically Active

Abstract Blood coagulation is initiated when plasma factor VII(a) binds to its essential cofactor tissue factor (TF) and proteolytically activates factors X and IX. Progressive inhibition of TF activity occurs upon its addition to plasma. This process is reversible and requires the presence of VII(a), catalytically active Xa, Ca2+, and another component that appears to be associated with the lipoproteins in plasma, a lipoprotein-associated coagulation inhibitor (LACI). A protein, LACI(HG2), possessing the same inhibitory properties as LACI, has recently been isolated from the conditioned media of cultured human liver cells (HepG2). Rabbit antisera raised against a synthetic peptide based on the N-terminal sequence of LACI(HG2) and purified IgG from a rabbit immunized with intact LACI(HG2) inhibit the LACI activity in human serum. In a reaction mixture containing VIIa, Xa, Ca2+, and purified LACI(HG2), the apparent half-life (t1/2) for TF activity was 20 seconds. The presence of heparin accelerated the initial rate of inhibition threefold. Antithrombin III alpha alone had no effect, but antithrombin III alpha with heparin abrogated the TF inhibition. LACI(HG2) also inhibited Xa with an apparent t1/2 of 50 seconds. Heparin enhanced the rate of Xa inhibition 2.5-fold, whereas phospholipids and Ca2+ slowed the reaction 2.5-fold. Xa inhibition was demonstrable with both chromogenic substrate (S-2222) and bioassays, but no complex between Xa and LACI(HG2) could be visualized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Nondenaturing PAGE, however, showed that LACI(HG2) bound to Xa but not to X or Xa inactivated by diisopropyl fluorophosphate. Thus, LACI(HG2) appears to bind to Xa at or near its active site. Bovine factor Xa lacking its gamma-carboxyglutamic acid-containing domain, BXa(-GD), through treatment with alpha-chymotrypsin, was used to further investigate the Xa requirement for VIIa/TF inhibition by LACI(HG2). LACI(HG2) bound to BXa(-GD) and inhibited its catalytic activity against a small molecular substrate (Spectrozyme Xa), though at a rate approximately sevenfold slower than native BXa. Preincubation of LACI(HG2) with saturating concentrations of BXa(-GD) markedly retarded the subsequent inhibition of BXa. The VII(a)/TF complex was not inhibited by LACI(HG2) in the presence of BXa(-GD), and further, preincubation of LACI(HG2) with BXa(-GD) slowed the inhibition of VIIa/TF after the addition of native Xa. The results are consistent with the hypothesis that inhibition of VII(a)/TF involves the formation of a VIIa-TF-XA-LACI complex that requires the GD of XA.(ABSTRACT TRUNCATED AT 400 WORDS).

Intracranial hemorrhage and circulating coagulation inhibitor in β-thalassemia major

1981 ◽  
Vol 99 (5) ◽  
pp. 700-703 ◽  
Author(s):  
D. Sinniah ◽  
H. Ekert ◽  
J. Bosco ◽  
L. Nathan ◽  
S.L. Koe
Keyword(s):  
Intracranial Hemorrhage ◽  
Thalassemia Major ◽  
Coagulation Inhibitor

scholarly journals Identification of Coagulation Inhibitor Proteins from Microcystis aeruginosa

2010 ◽  
Vol 33 (6) ◽  
pp. 73-79 ◽  
Author(s):  
Shingo ISHIFUJI ◽  
Yuichi SATO ◽  
Hirotaka IMAE ◽  
Tomoko TAKAARA ◽  
Daisuke SANO ◽  
...  
Keyword(s):  
Microcystis Aeruginosa ◽  
Coagulation Inhibitor

An Unusual Coagulation Inhibitor Encountered in Refractory Hemophilia

1956 ◽  
Vol 26 (5) ◽  
pp. 477-486 ◽  
Author(s):  
Robert J. Speer ◽  
Joseph M. Hill ◽  
Margaret Malonev ◽  
Ammarette Roberts ◽  
Morton D. Prager
Keyword(s):  
Coagulation Inhibitor

Characterization of Bothrops jararaca coagulation inhibitor (BjI) and presence of similar protein in plasma of other animals

Toxicon ◽  
2004 ◽  
Vol 44 (3) ◽  
pp. 289-294 ◽  
Author(s):  
Anita M Tanaka-Azevedo ◽  
Ricardo J.S Torquato ◽  
Aparecida S Tanaka ◽  
Ida S Sano-Martins
Keyword(s):  
Similar Protein ◽  
Bothrops Jararaca ◽  
Coagulation Inhibitor
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