Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 5 de 5
Filter
Add more filters










Database
Language
Publication year range
1.
Blood Coagul Fibrinolysis ; 6(2): 113-8, 1995 Apr.
Article in English | MEDLINE | ID: mdl-7605875

ABSTRACT

To test whether heparin-induced osteoporosis is influenced by the molecular weight of heparin, 24 male rabbits received single daily subcutaneous injections of either physiological saline (controls, n = 5), low molecular weight heparin (LMWH, n = 7), conventional heparin (UFH, n = 7) or high molecular weight heparin (HMWH, n = 6). Heparin was administered in supratherapeutic daily dosages for 120 days (750 anti-FXa units/kg for 90 days and 1500 anti-FXa units/kg for another 30 days). Studied variables were: serial analysis of serum calcium, albumin, phosphate and alkaline phosphatase, measurement of the cortical thickness of the femur (radiographically), tibial and trabecular bone density (both by cross-sectional analysis) and femoral fragility. Observed changes in blood biochemistry associated with bone metabolism were not correlated to any of the treatments. Compared with the controls, a reduction in cortical and trabecular bone density was seen with UFH (P < 0.05) and HMWH (P < 0.01) but not with LMWH. Femoral fragility was also significantly increased (P < 0.002) by HMWH. In conclusion, LMWH did not cause toxic skeletal effects as opposed to HMWH which clearly did, and UFH which induced some osteoporotic changes.


Subject(s)
Heparin, Low-Molecular-Weight/toxicity , Heparin/toxicity , Osteoporosis/chemically induced , Animals , Bone Density/drug effects , Bone and Bones/drug effects , Bone and Bones/metabolism , Heparin/administration & dosage , Heparin, Low-Molecular-Weight/administration & dosage , Injections, Subcutaneous , Male , Molecular Weight , Rabbits , Spine/drug effects , Time Factors
2.
Br J Haematol ; 89(3): 589-601, 1995 Mar.
Article in English | MEDLINE | ID: mdl-7734359

ABSTRACT

An antithrombin (AT) variant Ala382 to Thr (AT-TRI) was identified by mass spectrometric techniques. The variant behaved as a substrate rather than a thrombin inhibitor, but, contrary to previously described P12 AT variants, AT-TRI, expressed as a heterozygous dominant trait, caused severe thromboembolic tendency beginning in their teens in affected members of an English family. In addition, it underwent the S-to-R conformational state transition as evidenced by an increased resistance to thermal denaturation on active centre cleavage, but did not react with a monoclonal antibody, 4C9, directed against a neoepitope that is present on complexed and cleaved normal AT. Antithrombin-TRI, in plasma, was also associated with an abnormal high molecular weight (M(r)) 194,000) component composed of non-covalently-linked antithrombin molecules. This component (D194) showed low affinity for heparin and was devoid of antithrombin progressive activity. D194, isolated by ammonium sulphate precipitation and three chromatographic steps (heparin Sepharose, ion exchange and immunoaffinity), migrated as a single band of M(r) 60,000 on SDS-PAGE under both reducing and non-reducing conditions and was recognized by monospecific anti-human antithrombin antibodies, but did not immunoreact with antibodies raised against a number of proteins including albumin and thrombin. The above data and the fact that the 15 N-terminal amino acids of this M(r) 60,000 band were identical to that of normal antithrombin indicated that the inactive D194 component was composed of aggregated antithrombin molecules, possibly antithrombin trimers. In conclusion, early adulthood severe thromboembolic tendency, failure to expose the 4C9 epitope, and presence of aggregated AT molecules in the plasma are characteristic features of AT-TRI not previously described in other ALA-382 THR mutations.


Subject(s)
Antithrombins/genetics , Point Mutation , Thrombosis/genetics , Adolescent , Adult , Amino Acid Sequence , Antibodies, Monoclonal , Antithrombins/chemistry , Antithrombins/isolation & purification , Blotting, Western , Cyanogen Bromide , Disease Susceptibility , Electrophoresis, Polyacrylamide Gel , Female , Hot Temperature , Humans , Mass Spectrometry , Middle Aged , Molecular Sequence Data , Molecular Weight , Protein Denaturation , Thrombosis/blood
3.
Br J Haematol ; 89(1): 157-62, 1995 Jan.
Article in English | MEDLINE | ID: mdl-7833256

ABSTRACT

A modified form of antithrombin (AT) cleaved at the active site by thrombin (ATc) has been shown to be generated in vivo, corresponding to 1-4% of the circulating AT. An enzyme immunoassay has been developed for measuring ATc following plasma treatment with ammonium sulphate and heat denaturation of native AT. ATc plasma levels were found to be significantly higher (P = 0.003) in patients developing venous thromboembolism when compared to patients without such events or healthy controls (age and sex matched). In addition, ATc levels correlated with thrombin generation markers: thrombin-AT complex (r2 = 0.66, P = 0.005) and prothrombin fragment 1 + 2 (r2 = 0.58, P = 0.018), but, in contrast to both these markers, elevated ATc levels were detected for at least 2 weeks after the thromboembolic event. In conclusion, ATc appears to be a new marker for thrombin generation and overall activation of the coagulation system, having the advantage of being detected in the circulation for a longer period than other thrombin generation markers.


Subject(s)
Antithrombins/genetics , Biomarkers/blood , Blood Coagulation/physiology , Thrombin/biosynthesis , Thromboembolism/blood , Acute Disease , Adult , Aged , Amino Acid Sequence , Ammonium Sulfate , Antithrombins/chemistry , Antithrombins/metabolism , Blotting, Western , Enzyme-Linked Immunosorbent Assay , Female , Hot Temperature , Humans , Male , Middle Aged , Molecular Sequence Data , Mutation , Prothrombin/metabolism
4.
Blood Coagul Fibrinolysis ; 3(6): 749-58, 1992 Dec.
Article in English | MEDLINE | ID: mdl-1489896

ABSTRACT

During a 3-year period we studied 393 adult patients (382 of whom were unrelated) with a history of acute venous thromboembolism. A congenital deficiency state known to predispose to thrombosis was found in 27.2%. Of these, most were due to deficiencies of protein C (9.2%), protein S (7.6%), antithrombin III (5%) or to increased plasma PAI-1 concentration (3.1%) which, in the absence of any known factor that predisposes towards thrombosis, results in a diminished fibrinolytic activity. There was a characteristic pattern between the age of onset (mean 34 years) of thrombosis and individual protein deficiency. Thrombosis appeared spontaneously in 73% of cases with recurrence in 80%. In contrast, in the remaining unrelated patients, 138 (35.1%) in whom venous thromboembolism was secondary and occurred at a mean age of 43 years, and in the other 140 (35.6%) who suffered thromboembolism spontaneously at a later age (mean age 55), there was no permanent protein deficiency state or alteration in fibrinolytic activity and thrombosis recurrence was lower (53.6% and 20.7% respectively). Of the 393 patients, deep vein thrombosis was the most common manifestation; however, in congenital thrombophilia, thrombosis of visceral vessels and Raynaud's syndrome (6%) were also detected.


Subject(s)
Blood Coagulation Factors/analysis , Pulmonary Embolism/etiology , Thrombophlebitis/etiology , Acute Disease , Adolescent , Adult , Afibrinogenemia/blood , Afibrinogenemia/complications , Aged , Antithrombin III Deficiency , Blood Coagulation Tests , Disease Susceptibility/blood , Disease Susceptibility/congenital , Female , Fibrinolysis , Genetic Predisposition to Disease , Humans , Kininogens/deficiency , Male , Middle Aged , Plasminogen/deficiency , Plasminogen Activator Inhibitor 1/analysis , Postoperative Complications/blood , Prekallikrein/deficiency , Protein C Deficiency , Protein S Deficiency , Pulmonary Embolism/blood , Thrombophlebitis/blood
5.
Blood Coagul Fibrinolysis ; 2(5): 589-93, 1991 Oct.
Article in English | MEDLINE | ID: mdl-1838283

ABSTRACT

In the present study the effect of perturbation of the vessel wall by venous occlusion on protein S release, was evaluated in 10 healthy male volunteers. A 9% (P less than 0.01) increase in free protein S and a 7% (NS) in total protein S over the baseline were observed 7 min after venous occlusion, whereas von Willebrand factor antigen (vWF:Ag)--a known release product of vascular endothelium--increased by 11% (P less than 0.01). In addition, the possibility of free protein S release from unstimulated platelets was investigated in pre- and post-occlusion samples incubated at room temperature for 24 h as whole blood or platelet-rich plasma. An increase in the mean free protein S was observed in the pre-occlusion samples which peaked after 4 h of incubation--121% at time 0 to 130% (P less than 0.05) of the normal pooled plasma whereas total protein S increased by only 4% (NS). In the post-occlusion samples, a similar peak in mean free protein S levels was observed after 12 h of incubation--132% at time 0 increased to 142% (P less than 0.01) of the normal human plasma pooled and the total protein S was increased by 8.55 (P less than 0.05). Small but significant increases in vWF:Ag levels were observed at 2 h and 6 h for the pre- and post-occlusion samples, respectively. No changes in C4b-binding protein were observed throughout the study. We conclude that, firstly, venous occlusion causes release of protein S in addition to vWF:Ag and, secondly, unstimulated platelets release protein S in addition to vWF:Ag.


Subject(s)
Blood Proteins/metabolism , Endothelium, Vascular/metabolism , Glycoproteins/metabolism , Veins/physiology , Adolescent , Adult , Antigens/blood , Blood Platelets/metabolism , Complement C4b/metabolism , Constriction , Female , Humans , Immunoblotting , Male , Middle Aged , Protein S , Thrombosis/blood , von Willebrand Factor/immunology
SELECTION OF CITATIONS
SEARCH DETAIL
...