摘要:

The measurement of fibrinogen (Fg) plasma levels is one of the more frequently performed tests in clinical practice, usually by clotting assay. However, for the diagnosis of dysfibrinogenemia the use of an immunological assay is necessary to compare total and clottable protein. Little information is available on the range of the ratio clottable (C) Fg/immunological (I) Fg levels in normal population. This study aimed at evaluating the CFg/IFg ratio in 70 control subjects (age range 17-74 years – group A), in 57 acute patients (age range 17-79 years – group B) and in 14 pregnant women (age range 27-41 years, pregnancy weeks 30-40 – group C), as a physiologic model of hyperfibrinogenemia. CFg was assayed on citrated plasma by the Clauss clotting method and IFg was assayed by radial immunodiffusion technique. In the three groups, CFg/IFg ratios were not significantly different (respectively group A 0.98 ± 0.17, group B 1.02 ± 0.18 and group C 1.01 ± 0.11), whereas both CFg (310 ± 45 mg/dl) and IFg (326 ± 70mg/dl) levels were lower (p < 0.001) in control subjects than in patients (CFg 556 ± 92 mg/dl; IFg 561 ± 121 mg/dl) and in pregnant women (CFg 530 ± 65 mg/dl; IFg 530 ± 77 mg/dl). The analysis of the relationship between CFg and IFg in the three groups (group A: y = 11.53 + 1.01x, r = 0.64, p < 0.001; group B: y = 68.72 + 0.88x, r = 0.67, p < 0.001; group C: y = 71.59 + 0.87x, r = 0.73, p < 0.01) indicates that a good correlation exists (p < 0.001) for values of fibrinogenemia ranging from 180 to over 700 mg/dl. A reference range of CFg/IFg (mean ± 2 SD in group A) was 0.64-1.32. These data could be of practical importance for a rapid screening of dys

ISSN:1424-8832    

DOI:10.1159/000217170

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Intron 40 of the human von Willebrand factor gene contains a region with variable-number tandem repeats (VNTR), type (ATCT)n, showing length polymorphism. In order to carry out family studies of von Willebrand’s disease, we performed PCR procedures to analyze 3 previously described microsatellites from that region, both in normal individuals and in von WiUebrand disease patients. Three pairs of primers were used to amplify independently nucleotides 1890-1991 (VNTR 1), 2215-2380 (VNTR 2) and 1640-1794 (VNTR 3) from intron 40. The observed heterozygosities (0.75, 0.73 and 0.86 for VNTRs 1, 2 and 3, respectively) were in good agreement with the expected heterozygosities derived from the allele frequencies (0.70,0.73 and 0.79, respectively). Furthermore, the combination of the 3 VNTRs showed 96% of heterozygosity, which correspond with the 98% expected value under linkage equilibrium. Therefore, our conclusion is that the use of these 3 markers, especially VNTR 3, constitutes a rapid and reliable method for performing segregation studies in von WiUebrand disease familie

ISSN:1424-8832    

DOI:10.1159/000217171

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

The fibrinolytic activity of the new plasminogen activator, recombinant staphylokinase, was compared to that of streptokinase and tissue-type plasminogen activator in the fibrin plate assay. The pattern of fibrinolysis by staphylokinase on fibrin plates differs from the other plasminogen activators. A number of mutants of staphylokinase with various amino acids in position 26 substituted for methionine in wild-type staphylokinase were compared with respect to their fibrinolytic potencies. Only the mutants with cysteine or leucine in this position have a fibrinolytic activity comparable to wild-type staphylokinase. The results on the fibrinolytic activities in the fibrin plate assay correlate with those of a plasmin generation assay, the latter is, however, less sensitive.

ISSN:1424-8832    

DOI:10.1159/000217172

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

In order to investigate a possible relationship between serotonergic and fibrinolytic systems, serotonin (5-hydroxytryptamine, 5-HT) metabolism was modified by the use of a monoamine oxidase inhibitor (tranylcypromine: 10 mg/kg body weight) and its effect on the fibrinolytic system was analyzed. Tranylcypromine caused a rise in whole blood 5-HT with a simultaneous fall in 5-hydroxyindoleacetic acid. Euglobulin clot lysis time was significantly prolonged 1 and 4 h after injection and tissue plasminogen activator (tPA) activity declined 4 h following administration with a simultaneous increase in its inhibitor (PAI) activity. Blood 5-HT was negatively related to tPA (r = -0.48; p < 0.05) and positively to PAI activities (r = 0.43; p < 0.05) in tranylcypromino-treated rats, whereas there were no such correlations in solvent-treated rats.

ISSN:1424-8832    

DOI:10.1159/000217173

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Beside the anticoagulant and antithrombotic activity, heparin also exerts a lipolytic activity. In a prospective study on patients with venous thromboembolism and some contraindications to coumarin therapy, a low-molecular-weight heparin (Fragmin®) was compared to unfractioned (UF) heparin in terms of both efficacy and safety. A secondary aim was to study the influence of both types of heparin on serum lipid levels. Sixty-six consecutive patients who were not taking concomitant treatment with lipid-lowering drugs entered the study. Patients received treatment with either UF heparin, 10,000 IU s.c, b.d., or Fragmin 5,000 IU anti-factor Xa s.c, b.d. for a period of 3 or 6 months, according to whether the initial diagnosis was deep venous thrombosis or pulmonary embolism. Each patient was followed up at 6-weekly intervals, and blood samples were obtained at discharge, and then 6 and 12 weeks after discharge. Finally, a further sample was obtained 3 months after therapy was discontinued. Total cholesterol levels increased significantly in both groups of patients: levels increased from 193 ± 56 to 246 ± 63 mg/dl in the UF heparin group (p < 0.001), and from 189 ± 53 to 222 ± 47 mg/dl in the Fragmin group (p < 0.05). The increase was mostly due to a very strong increase in HDL cholesterol levels in patients receiving UF heparin (from 46 ± 12 to 71 ± 23 mg/dl; p < 0.000005). Three months after discharge, HDL cholesterol levels were significantly higher in patients taking UF heparin than in patients in Fragmin (p = 0.006). By contrast, patients on Fragmin exhibited a significant increase in LDL cholesterol levels: from 112 ± 39 to 139 ± 37 mg/dl;

ISSN:1424-8832    

DOI:10.1159/000217174

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

The relationship between the inhibition of venous thrombosis and antifactor Xa (AXa) plasma levels, measured as ex vivo AXa activity at the moment of experimental thrombosis induction, was evaluated in rats treated by different administration routes with different doses of heparins of various molecular masses: unfractionated heparin (UH, 13 kDa), low-molecular-mass heparin (LMM-H, 5kD) and oligo-heparin (OL-H, 2 kD). The AXa activity levels of plasma samples were measured by an amidolytic method and expressed in AXa U/ ml. The antithrombotic effect was determined by a vena cava ligature model and expressed as the percent inhibition of thrombus weight. A correlation between the two parameters was determined, regardless of the administration route used. Every heparin requires different AXa plasma levels to develop the same antithrombotic activity: the plasma concentration inducing a 50% protection was 0.09,0.12 and 0.15 AXa U/ml, for UH, LMM-H and OL-H, respectively. Oligo-H has a significant antithrombotic activity when delivered by the intraileal route and the time course pharmacodynamics showed two phases for the parameters considered: in the second phase, a dissociation between AXa plasma level and antithrombotic effect was observed.

ISSN:1424-8832    

DOI:10.1159/000217175

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Recombinant human erythropoietin (rHuEpo) is now well established in the management of the anaemia associated with chronic renal failure. The aim of this study was to assess the efficacy and safety of low doses of subcutaneous (s.c.) erythropoietin in continuous ambulatory peritoneal dialysis (CAPD) patients and particularly its effects on haemostasis. Seven CAPD patients were given s.c. erythropoietin for more than 1 year. Their mean age was 36.2 ± 9.2 years and their mean pretreatment haemoglobin (Hb) was 7.05 ± 0.53 g/dl. All patients were started on 20 U/kg, 3 times/week, to be doubled every 4 weeks if no response was obtained. Five patients had a good response and attained the target Hb of 10-12 g/dl and were maintained on low doses of rHuEpo (20 U/kg s.c, twice a week). A marked improvement in haemostatic function was noted when comparing the pre- with the post-treatment measurements. There was a significant reduction in the bleeding time, significant increases in fibrinogen and factor VIII clotting activity but not in von Willebrand factor antigen or risto-cetin cofactor. There was also simultaneous enhancement of the platelet aggregation responses to adrenalin, collagen, arachidonic acid and ADP. In conclusion, long-term treatment with small doses of s.c. rHuEpo is safe, convenient and effective in correcting anaemia in patients on CAPD, rHuEpo caused significant improvement of bleeding time which can be explained partly through the correction of anaemia and in part by the improvement in haemostatic functio

ISSN:1424-8832    

DOI:10.1159/000217176

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Abnormal cytokine levels have been described in patients with chronic liver disease, but studies correlating cytokine homeostasis with abnormalities in coagulation and fibrinolysis are lacking. In order to establish a link between cytokines and the hemostatic changes the following parameters were determined in 44 patients with cirrhosis (alcoholic =15, postnecrotic = 22, others = 7): TNF-α, IL·6, thrombin-antithrombin (TAT) complexes, prothrombin fragment 1 + 2 (F1 + 2) and t-PA by using enzyme-linked immunosorbent assays, and PAI-1, plasminogen and α2-antiplasmin (α2-AP) by using chromogenic substrates. All patients were at stages B and C of Child’s classification when entering the study. Mean cytokine concentrations were significantly higher in cirrhotic patients as compared to age- and sex-matched controls (p < 0.009). There was a significant increase of TAT (p < 0.02) and F1 + 2 (p < 0.001) in the patients groups, suggesting a grade of intravascular coagulation. A hyperfibrinolytic state as demonstrated by an increase of t-PA and decrease of plasminogen and α2-AP was also observed (p < 0.001). We could define a subgroup of patients with cytokine values higher than 20 pg/ml. Interestingly, in this group there was a significant increase of TAT (p < 0.04) and t-PA (p < 0.02) levels and a decrease of plasminogen and α2-AP (p < 0.02) as compared to values observed in patients with cytokines lower than 20 pg/ml. We conclude that high levels of TNF-α and IL-6 may contribute to hyperfibrinolysis and intravascular coagulation in patients with liver cirrhosis, as assessed by the increase of TAT and t-PA levels and the reduction of plasminogen and α2

ISSN:1424-8832    

DOI:10.1159/000217177

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Protein Z is a vitamin K-dependent plasma protein, which promotes the association of thrombin with phospholipid surfaces. Deficiency states of protein Z have recently been showr in patients with a bleeding tendency of an otherwise unknowr origin. In the present study severe diminutions of blood plasma protein Z were found in patients with chronic liver diseases. Protein Z levels decreased with increasing severity of liver disease. Strong correlations between protein Z and other plasma proteins of liver origin indicate that protein Z primarily originates from the liver. The cutaneous bleeding tendency in cirrhosis may in part be due to protein Z deficiency.

ISSN:1424-8832    

DOI:10.1159/000217178

出版商:S. Karger AG    

年代:1995

数据来源: Karger

ISSN:1424-8832    

DOI:10.1159/000217179

出版商:S. Karger AG    

年代:1995

数据来源: Karger