ISSN:1424-8832    

DOI:10.1159/000215881

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

Sulfur amino acids have been implicated in the pathogenesis of thromboembolic vascular disease, and observations of patients with several inborn errors of metabolism have led to the ‘homocysteine theory of arteriosclerosis’. Homocysteine is an intermediate in the transsulfuration pathway and it enters into several other reactions, some of which involve transfer of methyl groups. An abnormally high concentration of homocysteine in the blood causes homocystinuria. Deficiency of cystathionine β-synthase is the most frequent cause of homocystinuria. Patients with this disorder are at risk for early vascular occlusions. Treatment with vitamin B6 of patients who are biochemically responsive to this vitamin reduces the risk of thromboembolism. Clinical or pathologic evidence of early vascular disease has also been provided in patients with homocysteinemia due to deficient (re)methylation of homocysteine to methionine. This may be caused by a deficiency of 5,10-methylenetetrahydrofolate reductase or by a deficient synthesis of cobala

ISSN:1424-8832    

DOI:10.1159/000216088

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

124 patients undergoing total hip replacement were randomly allocated to receive Kabi 2165, 2,500 anti-Xa units twice a day (group A); Kabi 2165, 2,500 anti-Xa units twice a day during the first 48 h postoperatively and then 5,000 anti-Xa units once a day (group B), or adjusted-dose standard heparin, monitored by activated partial thromboplastin time (group C). The first dose was given 2 h before surgery in the three groups. Deep-vein thrombosis (DVT) was detected by radiolabelled fibrinogen uptake and bilateral venography was performed in patients who had a positive scan. In patients who had a negative scan, bilateral venography was performed routinely the day before discharge from hospital. The frequency of DVT demonstrated by venography was 4.9% in group A, 7.3% in group B and 10% in group C. The difference between the three groups was not statistically significant. The incidence of proximal DVT was 2.4, 2.4 and 7.5%, respectively, for the three groups. There was no significant difference between the three groups with respect to mean estimated blood loss, the number of blood units transfused, wound hematoma formation, or hemoglobin and hematocrit levels.

ISSN:1424-8832    

DOI:10.1159/000215882

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

Classic homocystinuria is an autosomal recessive metabolic disease due to a cystathionine-β-synthase deficiency with consequent blocking of homocysteine and serine condensation for producing cystathionine. The characteristic biochemical abnormalities in the blood and urine are: abnormal accumulation of methionine, abnormal presence of homocystine and low values of cystathionine, cysteine or cystine (disulfide of the cysteine). The most frequent clinical signs are: subluxation of the lenses, mental retardation of different degrees, long bones excessively lengthened, scoliosis, susceptibility to arterial and venous thromboembolism. The latter is frequent after surgery, and may be life-threatening. This disease must be differentiated from Marfan’s syndrome via laboratory tes

ISSN:1424-8832    

DOI:10.1159/000216090

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

The effects of a normal and a low molecular weight (LMW) heparin fraction were compared by four coagulation methods. Plasma samples of patients were investigated who were treated with normal heparin or with a LMW heparin. The study was undertaken to analyze the interrelationship between the coagulation methods: Heptest, activated partial thromboplastin time, thrombin clotting time, and S 2222 chromogenic anti-factor Xa test. The results showed a high correlation between Heptest and S 2222 anti-factor Xa method for unfractionated and LMW heparin (r = 0.91 and 0.90). Comparing the coagulation times in seconds of Heptest and aPTT, the correlations were r = 0.56 (normal heparin) and 0.15 (LMW heparin). The correlation between the coagulation times of Heptest and thrombin clotting time were r = 0.65 and 0.25, respectively. The correlations between the coagulation methods were higher, when coagulation times rather than transformed values to units per liter of the Heptest and of the S 2222 anti-factor Xa method were employed. Furthermore, the data demonstrate a high sensitivity of the Heptest to conventional and LMW heparin, whereas activated partial thromboplastin time and thrombin clotting time are less sensitive to either heparin. For laboratory control of LMW heparin, Heptest and S 2222 chromogenic method are reliable tests. Therapeutic ranges will have to be established.

ISSN:1424-8832    

DOI:10.1159/000215883

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

Thrombogenesis and accelerated atherogenesis occur in the homocystinurias, both those due to recessively inherited cystathionine β-synthase deficiency and to disorders of remethylation of homocysteine to methionine. The evidence strongly implicates high levels of plasma homocysteine as the mediator. Homocysteine damages cultured human venous and arterial endothelial cells and enhances detachment from their substrate, changes not found with comparable concentrations of other amino acids tested. Homocysteine is oxidized in vitro to homocystine in an oxygen-dependent reaction producing hydrogen peroxide. Since the effects of homocysteine in cell cultures can be prevented by catalase, hydrogen-peroxide-induced injury may be the mechanism responsible. Five different laboratories have documented an association between mild homocysteinaemia and premature vascular disease. The majority of affected patients are heterozygotes for cystathionine β-synthase deficiency whose endothelial cells may have an enhanced susceptibility to injury by homocysteine. Mild homocysteinaemia also occurs in chronic renal failure in which vascular disease is prominent. Mechanisms linking mild homocysteinaemia and possible vascular effects are not yet understood, but could involve prostaglandins and oxidized low-density lipoprotein, and possibly also free radical

ISSN:1424-8832    

DOI:10.1159/000216091

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

In 6 patients on continuous ambulatory peritoneal dialysis we investigated the inhibition of intraperitoneal fibrin formation by heparin. A continuous addition of 500 U of heparin per liter dialysate was used for 52 h. In plasma no heparin activity could be detected, even 52 h after intraperitoneal administration of heparin. The fibrin formation was determined by fibrinopeptide A, a thrombin-induced split product of fibrinogen. In patients under regular continuous ambulatory peritoneal dialysis we determined the fibrinopeptide A concentrations in plasma. The values were comparable with the fibrinopeptide A concentrations measured in disseminated intravascular coagulopathy. They decreased during intraperitoneal administration of heparin from 63.2 ± 11.8 to 4.9 ± 1.7 ng/ml. The fibrinopeptide A concentration in the 4-hour intraperitoneal dialysate (155.8 ± 15.7 ng/ml) decreased after heparin administration to 8.5 ± 2.0 ng/ml and was always higher than in plasma. We conclude that 500 U heparin per liter dialysate prevents the intraperitoneal fibrin formation. The low antithrombin III concentration (0.44 ± 0.13 mg/dl) in protein-poor dialysate seems to be sufficient to inhibit the thrombin activity after acceleration by hep

ISSN:1424-8832    

DOI:10.1159/000215884

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

Few studies have dealt with blood-clotting changes in patients affected by homocystinuria. The aim of this contribution is to briefly review studies published so far on the topic and report the results of our investigation performed in 3 patients. At baseline we found reduced antithrombin III and factor VII levels in all the patients, in line with the results of other authors, and other slight and less constant changes such as lowered factor X activity and protein C antigen, and increased β-thromboglobulin levels. During pyridoxine and folate treatment, antithrombin III activity rapidly returned to normal; factor VII increased and β-thromboglobulin decreased. These blood-clotting abnormalities may play a role in the thrombotic tendency associated with homocystinuria. Their nature is still uncertain, but the improvement observed during active metabolic treatment suggests that the defect in amino acid transsulfuration of homocystinuria may directly affect synthesis or activity of some clotting factor

ISSN:1424-8832    

DOI:10.1159/000216092

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

The activation rate of Glu-plasminogen (Glu-plg) by urokinase (UK) was enhanced in the presence of either tranexamic acid or fibrin with an increase in the catalytic rate contant (kcat). The maximum increase in kcat was obtained at 0.5 mM of tranexamic acid and 0.1 μM of fibrin. Km did not change. The addition of fibrin to 1 mM tranexamic acid resulted in a further increase in kcat of the UK activation of Glu-plg. On the other hand, the addition of tranexamic acid to 0.1 μM fibrin further increased kcat of the UK activation of Glu-plg. Thus, stimulatory effects were observed on the activation of Glu-plg by UK in the simultaneous presence of tranexamic acid and fibrin. Fibrin-binding sites on the kringle 5 of Glu-plg may be involved in the further increase in the activation rate of Glu-plg by UK in the presence of both fibrin and tranexamic acid in comparison to that in the presence of tranexamic acid alone. Possibly, the Glu-plg binding with both tranexamic acid and fibrin (at kringle 5) may be most effectively activated by UK. It is also suggested that two molecules of Glu-plg bind to one molecule of fibrin monome

ISSN:1424-8832    

DOI:10.1159/000215885

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

The frequency of pathological homocysteine accumulation after standardized methionine loading was investigated in 75 patients with clinical signs of ischemic disease before age 50: 25 with occlusive peripheral arterial disease, 25 with occlusive cerebrovascular disease, and 25 with myocardial infarction. On the basis of abnormally high homocysteinemia after methionine loading and cystathionine synthase deficiency in fibroblast cultures, carriership for homocystinuria could be established in 7 patients in each of the first two groups, however in none of the patients in the third group. This high frequency of heterozygosity compared with the frequency of 1 in 70 at the most in the normal population leads to the conclusion that such carriership predisposes to the development of premature occlusive arterial disease.

ISSN:1424-8832    

DOI:10.1159/000216093

出版商:S. Karger AG    

年代:1989

数据来源: Karger