摘要:

We describe a new congenital dysfibrinogenemia: fibrinogen Barcelona II in 8 members of a family with no major bleeding or thrombotic tendency. Incubation of this fibrinogen with thrombin at low concentration releases half of the expected normal fibrinopeptide A (FPA) and with some delay it releases an abnormal FPA. Abnormal FPA was purified and sequenced and showed a change in the normal amino acid sequence: arginine in position 16 has been substituted by a histidine. This is another case of dysfibrinogenemia in which Aα 16 Arg → His has been identified as the cause of abnormal behavior of the fibrinogen molecu

ISSN:1424-8832    

DOI:10.1159/000216098

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

Heparin was a chance discovery made by a medical student who was searching for a clot-promoting activity in various tissue extracts and found an inhibitor of coagulation. It has taken 20 years from the discovery of heparin in 1916 to its therapeutic use (1937). This long delay was mainly due to problems with the purification and extraction on large scale of the active material. Standard unfractionated heparin is a mixture of mucopolysaccharide chains of various length that may range from 5,000 to 30,000 daltons. Heparin is only effective as an anticoagulant in the presence of a plasma protein, termed antithrombin III, with which it forms a complex. High- and low-affinity heparin are two types that readily bind or do not bind to antithrombin III. The pharmacokinetics of unfractionated heparin are compatible with a model based on the combination of a saturable and a linear mechanism. Low-molecular-weight heparins have been produced by a variety of techniques, and their molecular weights range from 3,000 to 9,000 daltons. These preparations have a ratio of anti-Xa activity to anti-II activity of approximately 4, while it is 1 for unfractionated heparin. After intravenous administration of low-molecular-weight heparins, the half-life of the antifactor Xa activity is considerably longer than for unfractionated heparin, while the anti-factor II half-lives are similar. In contrast to unfractionated heparin, low-molecular-weight heparin is virtually completely absorbed after subcutaneous administration, and its biological half-life is almost twice as long. In spite of certain differences with regard to the ratio between factor Xa and Ila inhibition, the various low-molecular-weight preparations show a rather similar absorption pattern. Low-molecular-weight heparins interact less with platelets than unfractionated heparin; nevertheless, a lower bleeding incidence with low-molecular-weight heparin for equivalent antithrombotic efficacy has yet to be established in man.

ISSN:1424-8832    

DOI:10.1159/000216157

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

Vitamin K1 serum levels were assessed by means of an off-line multidimensional liquid chromatography in 18 mothers, shortly after delivery, and in their healthy term infants. Umbilical cord and venous blood samples were assayed up to 4 weeks of life. Concurrently, levels of coagulation factors II and X, antithrombin III and platelets were established. Although the detection limit of the assay was as low as 22 pg/ml, vitamin K1 concentration appeared to be still beyond that level in cord blood or in newborn serum within 30 min after birth, whereas vitamin-K-dependent coagulation factors are already at a level of 40 %, without evidence for the presence of descarboxy prothrombin, in any of the investigated neonates. After 3 days, breast-fed neonates had lower vitamin K1 levels than formula-fed infants (0.76 and 1.44 ng/ml, respectively). The levels of the vitamin-K-dependent coagulation factors II and X, however, were comparable, regardless of the kind of feeding. After 28 days, breast-fed neonates had even lower vitamin K1 levels (0.49 ng/ml, while the formula-fed infants showed higher vitamin K1 levels (4.45 ng/ml). But even then, the levels of vitamin-K-dependent coagulation factors II and X were comparable, regardless of the kind of feeding. From this we conclude that the serum levels of vitamin K1 in formula-fed neonates exceed those of breast-fed infants from the moment of feeding (24 h and later) without a concomitant rise in vitamin-K-dependent coagulation factors. A relationship between vitamin K1 levels and vitamin-K-dependent coagulation factors could not be established in healthy term breast-fed or formula-fed infants.

ISSN:1424-8832    

DOI:10.1159/000216099

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

Blood coagulation forms part of an integrated series of haemostatic reactions, involving plasma, platelet, and vascular components. Platelets adhere to damaged endothelium or to subendothelium under the influence of adhesive proteins, and when activated they aggregate and expose binding sites for coagulation factors. Platelets, therefore, act as vehicles to concentrate and potentiate coagulation reactions on the damaged vessels. Following interaction of the ‘contact’ factors XII and XI, the coagulation protease zymogens undergo sequential activation, resulting in the generation of thrombin, the conversion of fibrinogen to fibrin, and the formation of a platelet-fibrin haemostatic plug. The fibrinolytic system interacts to regulate fibrin deposition and removal during healing. Central to coagulation is the generation of thrombin. It is involved in promoting haemostatic reactions as well as a number of protective functions. The activities of thrombin and other serine proteases are modulated by the serine potease inhibitors (serpins), including antithrombin III and heparin cofactor II which are important in regulating the physiological anticoagulant action of glycosaminoglycans at the endothelium and the pharmacological action of heparin. Reduction of the formation or function of thrombin and other serine proteases is one of the primary aims of anticoagulant ther

ISSN:1424-8832    

DOI:10.1159/000216159

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

1-Deamino-8-.D-arginine vasopressin (DDAVP) was administered to 3 patients with spontaneous factor VIII inhibitors. In 2 patients with baseline factor VIII levels above 1 %, a marked increase of factor VIII activity after DDAVP infusion could be observed. No rise of factor VIII activity after DDAVP was seen in the 3rd patient with a baseline factor VIII level of less than 1 %. Daily infusion of DDAVP resulted in a reduction of the efficacy, but the full effect could be retained when DDAVP was given at 48-hour intervals. The effect of DDAVP infusion on factor VIII levels in the 2 responding patients was superior to the treatment with 30 U/kg factor VIII concentrate and approximately equivalent to infusion of 45 U/kg factor VIII concentrate. DDAVP may be a useful and less expensive treatment for patients with acquired factor VIII inhibitors and a baseline factor VIII level of more than 1 %.

ISSN:1424-8832    

DOI:10.1159/000216100

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

Data from the start of anticoagulation therapy using the coumarin derivative phenprocoumon were obtained retrospectively for 101 patients, and the correct long-term maintenance dose (MD) of the drug was determined. The average loading dose was 23.2 ± 7.8 mg and the average MD 2.14 ± 0.99 mg. The physician’s prescription on discharge tended to underestimate the true MD by 0.29 ± 0.64 mg. Significant positive correlations with MD were noted for loading dose and weight and negative correlations for age, serum creatinine, initial prothrombin ratio, and length of treatment pause (days) for patients receiving an excessive loading dose. Using stepwise variance analysis, an algorithm was obtained that predicted the MD: MD = -0.7 + loading dose/10 – treatment pause/7 – age/60 + initial prothrombin ratio. The accuracy (0.02 ± 0.54 mg) was similar to that of the discharging physician. The algorithm required an average observation period of 5.4 days and the physician’s estimate 12.4 days. It is suggested that the use of the algorithm would lead to shorter hospitalization without loss of treatme

ISSN:1424-8832    

DOI:10.1159/000216101

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

The intact vessel wall provides diverse anticoagulant mechanisms which, together with circulating components, are actively and dynamically involved in the regulation of the haemostatic system. These mechanisms are able to specifically and co-operatively counteract various procoagulant inducers at localized sites, such that under physiological conditions the endothelium provides a non-thrombogenic surface. Upon activation of the haemostatic system, these different components help to limit the extent of the prothrombotic response of blood coagulation at the site of injury and thereby contribute on different molecular levels to the overall anticoagulant potential of the endothelium. Heparin and possibly vessel wall related glycosaminoglycans may modulate or even enhance some of these anticoagulant mechanisms. A detailed understanding of the molecular architecture of these different processes in vitro may thereby lead to possible new therapeutic regimens.

ISSN:1424-8832    

DOI:10.1159/000216160

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

Tissue plasminogen activator (tPA) antigen levels and plasminogen activator inhibitor (PAI) activity were measured in the plasma from 23 patients with familial amyloidotic polyneuropathy. Both tPA levels and PAI activity were reduced to about half normal, even when the effects of patient age and body mass index were taken into account. There were higher mean tPA levels and PAI activity in patients with mild disability than in those with moderate or severe disability, but these differences were not statistically significant. There were normal tPA levels after venous occlusion of the upper arm, indicating a normal capacity of vascular endothelium to release tPA. This is the first reported disorder with reduced rather than increased basal tPA and PAI levels. The pathogenetic and clinical significances of these disturbances so far remain obscure.

ISSN:1424-8832    

DOI:10.1159/000216102

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

The study of aggregation functions in blood platelets can at present be undertaken in vitro by measuring variations in intensity of transmitted light or electrical impedance change. These two methods allow only a general approach to the aggregation process. The laser rheoaggregometer was constructed to study early morphological modifications induced when the platelets are activated before aggregation. The results obtained are in keeping with the laws of light scattering and allow the measurement of platelet shape change.

ISSN:1424-8832    

DOI:10.1159/000216103

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

The influence of captopril on blood platelet aggregation and on serotonergic mechanisms in blood platelets were studied. In rats pretreated with captopril (10.0 mg/kg p.o.) platelet aggregation induced by ADP and collagen was significantly reduced. In vitro this drug had no inhibitory effect. Besides, captopril did not change the amplifying effect of serotonin on platelet aggregation. Captopril also had no influence on the uptake and storage of 5-hydroxytryptamine by rat blood platelets. These results show that serotonergic mechanisms are not involved in the suppressive effect of captopril on platelet aggregation.

ISSN:1424-8832    

DOI:10.1159/000216104

出版商:S. Karger AG    

年代:1990

数据来源: Karger