摘要:

The anticoagulant and antithrombotic effect of heparin has been known for many decades. Nevertheless, the knowledge of structure-activity relationships and its mechanisms of action has been rather limited. However, in recent years important progress has been made and our understanding of how heparin works has increased significantly. Based on this information, attempts have been made to modify heparin to get improved pharmacological properties. The present communication summarizes the recent development. It is shown that certain heparin derivatives of low molecular weight are highly interesting compounds from a clinical point of view. Biochemical and pharmacological properties of such a preparation named Fragmin are presented.

ISSN:1424-8832    

DOI:10.1159/000215348

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

Studies in 8 healthy volunteers showed that the low molecular weight heparin Fragmin KabiVitrum is eliminated according to first order kinetics without dose dependency after intravenous injection of doses between 40 and 120 anti-Xa U/kg. Fragmin remains in the circulation more than twice as long as unfractionated heparin (UFH). Fragmin administered subcutaneously has a bioavailability which is much greater than that of UFH. Fragmin administered subcutaneously twice a day results in a significant anti-Xa activity and provides an alternative to intravenous infusions.

ISSN:1424-8832    

DOI:10.1159/000215349

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

In a randomized, prospective, double-blind multicenter trial, the effect of low-dose conventional heparin (5,000 IU/12 h) was compared to a low molecular weight (LMW) heparin fragment (5,000 antifactor Xa U/24 h). 432 patients 40 years or older undergoing elective abdominal surgery were included, 382 correctly treated. 45% had malignant diseases. The groups did not differ in risk factors. Analysis was made both on the basis of intention to treat and correct prophylaxis. No difference in results between these 2 groups was seen. Deep vein thrombosis (125I-fibrinogen) occurred in 4.3% of the low-dose heparin group and in 6.4 of the LMW heparin group. There was a significant delay in the onset of deep vein thrombosis in the LMW heparin group. Mortality, peroperative blood loss, transfusions or infectious complications did not differ. Hemorrhagic complications occurred significantly more often in the LMW heparin group (11.6%) than in the low-dose heparin group (4.6%). Significantly fewer patients experienced local injection pain in the LMW heparin group. APTT and AT III were similar in both groups, but anti-Xa activity was significantly higher in the LMW heparin group. Single daily LMW heparin injection reduced the frequency of deep vein thrombosis to the same level as low-dose heparin twice daily. The dose or administration interval of LMW heparin in this study caused significantly more bleeding complications.

ISSN:1424-8832    

DOI:10.1159/000215351

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

The efficacy and safety of 2 regimens of Fragmin in preventing postoperative venous thromboembolism was compared on 206 consecutive patients, aged 40 years or more, undergoing major abdominal surgery. Ninety-four patients received a single daily injection of 2,500 U of Fragmin for at least 6 postoperative days (group I), while 112 received 5000 U per day in 2 injections of 2,500 U each (group II). In group I 7.4% of patients and in group II 2.6% of patients developed postoperative deep venous thrombosis (DVT); the difference was not statistically significant (p& < 0.05). There was no significant difference between the 2 groups in terms of numbers of patients having excessive postoperative blood loss, requiring prophylaxis to be discontinued, or measured postoperative drainage. None of the patients in group I, and 2 out of 112 in group II developed wound haematoma. These findings suggest that a single daily injection of 2,500 U of Fragmin may provide an effective prophylaxis against postoperative venous thromboembolism.

ISSN:1424-8832    

DOI:10.1159/000215353

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

54 patients with venographically verified deep venous thrombosis (DVT) were randomized to treatment with either intravenous infusions of 240 anti-Xa U/kg/l2h unfractionated heparin (UFH) or 240 or 120 anti-Xa U/kg/l2 h of the low molecular weight heparin Fragmin. Repeated venographies showed improvement in 48% of the UFH-treated patients and 50 and 77%, respectively, in the Fragmin-treated patients. Progression was seen only in the UFH-treated patients and was observed in 11 %. Two bleeding complications were seen in the Fragmin group in 2 patients receiving the very high dose of 240 anti-Xa U/kg/l2h. Anti-Xa activity in plasma and activated partial thromboplastin time (APTT) does not correlate in the Fragmin-treated patients. Fragmin was as effective as UFH in preventing the progress of thrombosis in DVT.In another study 120 anti-Xa U/kg Fragmin given subcutaneously 2 times daily to 13 patients with DVT resulted in adequate anti-Xa activity but with a tendency for accumulation of the Fragmin-induced activity. Subcutaneous injections of Fragmin 2 times daily also appears to prevent the progression of thrombosis effectively.

ISSN:1424-8832    

DOI:10.1159/000215354

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

In a double-blind study, patients with phlebographically proven deep venous thrombosis (DVT) were treated with subcutanous injections twice a day of either unfractionated heparin (UH; n = 27) or low molecular weight heparin (LH; n = 29) for 7 days, and the dose was adjusted until therapeutic range was reached, according to a chromogenic substrate anti-Xa assay. Forty-eight percent of the LH group did not need dose adjustment as compared to 24% of the UH group. During the course of heparin administration, deviation from initial heparin activity was frequent in both groups, but mean activity did not indicate a cumulative effect in either group. There was 1 incidence of pulmonary embolism (LH) and only 1 minor bleeding episode (UH). Half of the patients in both groups were phlebographically improved. We conclude that subcutaneous heparin treatment with UH or LH appears safe and convenient.

ISSN:1424-8832    

DOI:10.1159/000215355

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

Anticoagulation during haemodialysis for chronic renal failure can be assessed by measurement of plasma fibrinopeptide A (FPA) levels as an objective method of monitoring the initial step in fibrin formation, in conjunction with visual inspection of the dialyser circuit for fibrin clot deposition. Employing this approach, unfractionated commercial heparin administered as an intravenous bolus followed by an intravenous maintenance dose (5,000 IU + 1,500 IU/h) was found to suppress almost completely fibrin formation and deposition during prolonged dialysis. Comparison of a low molecular weight heparin, Kabi 2165, revealed that it can inhibit fibrin formation in the extracorporeal circulation, that this property is largely reflected in its anti-factor Xa activity in plasma, and that a useful and effective dose of Kabi 2165 for haemodialysis may be 4,000 anti-factor Xa U intravenous bolus + 750 anti-factor Xa U/h intravenous maintenance infusion. This dose only minimally alters the KCCT and corresponds to approximately 60% of that of unfractionated heparin, which may be important in the long-term use of heparin in these patients.

ISSN:1424-8832    

DOI:10.1159/000215356

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

Antithrombotic activity, necessary doses and effects on coagulation and lipid variables of the low molecular weight heparin derivative Fragmin were compared to unfractionated (UF) heparin in long-term multicentre trials. Results of more than 10,000 dialyses are reported. On the basis of preliminary studies, UF heparin and Fragmin doses were used that lead to anti-Xa activities of more than 0.5 U/ml. With this dose, sufficient antithrombotic activity was achieved with both heparins. Bleeding complications were not noticed. Partial thromboplastin time (PTT) and thrombin time were only marginally increased by Fragmin (5–8 s) in contrast to UF heparin (PTT 90–120 s, thrombin time 230–260 s). Surprisingly, the elevated levels of factor VIII strongly decreased during the 6-month treatment period with Fragmin and increased again during the following 6-month treatment period with UF heparin. Creatinine, urea, haemoglobin and transaminases did not change in both heparin groups: this excluded reduced dialysis efficiency or occult blood loss. Additionally, 15 patients with acute renal failure and high bleeding risk were dialysed with low doses of Fragmin (anti-FXa: 0.2–0.3 U/ml). No severe bleeding occurred. A continuous ambulant peritoneal dialysis patient with deep vein thrombosis was treated effectively with intraperitoneal application of Fragmin for 6 months without any p

ISSN:1424-8832    

DOI:10.1159/000215357

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

Ten patients on chronic intermittent hemodialysis treatment received either unfractionated heparin or low molecular weight (LMW) heparin K 2165 in a single-blinded randomized cross-over study to assess: (1) effects on hemostasis and ex vivo platelet functions, and (2) effectiveness, i.e. prevention of fibrin formation in the extracorporeal circuit. The 20 dialysis treatments were without untoward side effects, for both drugs used. The variation in the plasma anti-Xa activities was significantly less during K 2165 treatment than during heparinization. No differences between the drugs were observed regarding the Ivy bleeding time, platelet count and platelet aggregation (spontaneous, and induced by ADP and collagen). Plasma platelet factor 4 levels did not increase under K 2165 to such an extent as under heparin. Both drugs did not influence the plasma levels of β-thromboglobulin, thromboxane B2 and platelet serotonin content. K 2165 did not affect platelet adhesion to collagen, in contrast to heparin which substantially inhibited platelet adhesion. Under both treatments, 4 minor clots were observed in 4 artificial kidneys, despite plasma anti-Xa levels in between 0.19 and 0.46 U/ml. K 2165 may therefore be considered as effective an anticoagulant as heparin, with less effects on ex vivo platelet functions

ISSN:1424-8832    

DOI:10.1159/000215582

出版商:S. Karger AG    

年代:1986

数据来源: Karger

ISSN:1424-8832    

DOI:10.1159/000215273

出版商:S. Karger AG    

年代:1986

数据来源: Karger