Four Heparin Preparations: Anti-Xa Potentiating Effect of Heparin after Subcutaneous Injection

1976 ◽  
Vol 35 (03) ◽  
pp. 586-591 ◽  
Author(s):  
E. A Johnson ◽  
T. B. L Kirkwood ◽  
Yvonne Stirling ◽  
J. L Perez-Requejo ◽  
G. I. C Ingram ◽  
...  

SummaryFour different heparin preparations - sodium and calcium salts of the same batch of heparin (mean molecular weight 15,000), low molecular weight sodium heparin (mean m. w. 9,000) and high molecular weight sodium heparin (mean m. w. 22,000) were injected subcutaneously on different days each into 6 healthy young volunteers in a randomized trial. Plasma heparin levels were measured using the anti-Xa assay at 1 hour, 3-4 hours and 6-7 hours after the injection. The highest anti-Xa potentiating effect was obtained after the injection of the low molecular weight sodium heparin (mean 0.381 i. u./ml) at 3-4 hours after the injection. With sodium heparin (m. w. 15,000) the highest values (0.135 i. u./ml) were found at 1 hour. Significantly lower anti-Xa potentiating effect was obtained 1 hour after the injection of calcium heparin and in particular after the injection of high molecular weight heparin (mean values 0. 072 i. u./ml and 0.043 i. u./ml respectively). Both these preparations showed an increase from 1 hour after injection to 3-4 hours after injection (mean values 0.082 i. u./ml and 0.057 1. u./ml at 3-4 hours after injection).These results indicate that the salt and the molecular weight of the preparation may strongly influence the degree of anticoagulation achieved after subcutaneous injection.

1999 ◽  
Vol 81 (03) ◽  
pp. 391-395 ◽  
Author(s):  
S. Colliec Jouault ◽  
S. Mauray ◽  
J. Theveniaux ◽  
C. Sternberg ◽  
Boisson Vidal ◽  
...  

SummaryFucoidans (high-molecular-weight sulfated polysaccharides extracted from brown seaweeds) have anticoagulant and antithrombotic effects. They inhibit thrombin by catalyzing both serpins (antithrombin and heparin cofactor II) according to their chemical structures and origins. In this study, a low-molecular-weight (LMW) fucoidan of 8 kDa was obtained by chemical degradation of a high-molecular-weight fraction. The antithrombotic and anticoagulant activities of this new compound were compared to those of a low-molecular-weight heparin (LMWH), dalteparin, following subcutaneous administration to rabbits. This LMW fucoidan exhibited dose-related venous antithrombotic activity, with an ED80 of about 20 mg/kg, 2 h after a single subcutaneous injection. Its activity was comparable to that of dalteparin (close to 200 anti-Xa IU/kg) and was maximal 30 min after a single subcutaneous injection. The activity remained stable (about 70%) from 1 to 4 h after injection, but disappeared by 8 h. The antithrombotic activity was not associated with either a prolongation of the thrombin clotting time (TCT) or an increase in anti-Xa activity, contrary to dalteparin. A slight prolongation of APTT occurred with both compounds. This venous antithrombotic activity was associated with a decrease in ex vivo thrombin generation and with a significant increase in the lag phase in a thrombin generation test. LMW fucoidan thus has potent antithrombotic activity and a potentially weaker haemorrhagic effect (i.e. a smaller effect on coagulation tests and a smaller prolongation of the bleeding time) than dalteparin.


1978 ◽  
Vol 40 (02) ◽  
pp. 397-406 ◽  
Author(s):  
Joyce Low ◽  
J C Biggs

SummaryComparative plasma heparin levels were measured in normal subjects injected subcutaneously with 5,000 units of the sodium and calcium salts of heparin. Plasma heparin levels were measured up to 7 hr post-injection by an anti-factor Xa assay (Denson and Bonnar 1973). Preliminary studies indicated that heparin levels were reproducible in subjects who received two injections of the same heparin. Peak plasma concentrations (Cmax) and the time at which peak concentration was reached (Tmax) varied greatly from subject to subject. In one group of subjects (15) two commonly used heparins, a sodium heparin (Evans) and a calcium heparin (Choay) were compared. Peak heparin concentrations were not significantly different. However the Tmax for the sodium heparin (1.5 hr) was significantly earlier than the Tmax for the calcium heparin (3 hr) and this was not due to a difference in the volume of the two heparin injections. No significant difference could be detected in the plasma clearance rate and the molecular weight distribution of the two heparins.In two other groups of subjects, sodium and calcium preparations from two manufacturers were compared. In general, the sodium salts gave rise to significantly higher plasma concentrations, which could be interpreted as a greater bioavailability of sodium salts. These results indicate that the salt of the heparin can influence the plasma concentration achieved after subcutaneous injection.


1961 ◽  
Vol 06 (01) ◽  
pp. 015-024 ◽  
Author(s):  
Sven Erik Bergentz ◽  
Oddvar Eiken ◽  
Inga Marie Nilsson

Summary1. Infusions of low molecular weight dextran (Mw = 42 000) to dogs in doses of 1—1.5 g per kg body weight did not produce any significant changes in the coagulation mechanism.2. Infusions of high molecular weight dextran (Mw = 1 000 000) to dogs in doses of 1—1.5 g per kg body weight produced severe defects in the coagulation mechanism, namely prolongation of bleeding time and coagulation time, thrombocytopenia, pathological prothrombin consumption, decrease of fibrinogen, prothrombin and factor VII, factor V and AHG.3. Heparin treatment of the dogs was found to prevent the decrease of fibrinogen, prothrombin and factor VII, and factor V otherwise occurring after injection of high molecular weight dextran. Thrombocytopenia was not prevented.4. In in vitro experiments an interaction between fibrinogen and dextran of high and low molecular weight was found to take place in systems comprising pure fibrinogen. No such interaction occurred in the presence of plasma.5. It is concluded that the coagulation defects induced by infusions of high molecular weight dextran are due to intravascular coagulation.


2013 ◽  
Vol 71 (8) ◽  
pp. 512-515 ◽  
Author(s):  
Fabiana Cruz Gomes da Fonseca-Papavero ◽  
Dagoberto Callegaro ◽  
Paulo Diniz da Gama ◽  
Jose Antonio Livramento ◽  
Adelaide Jose Vaz ◽  
...  

The "hygiene hypothesis" postulates an inverse relationship between the prevalence of parasitic infections and the frequency of multiple sclerosis (MS). Objective: It was to study whether antibodies against parasites could be demonstrated more frequently in blood serum from MS patients with oligoclonal bands (OCB) than from MS patients without OCB. Methods: We studied serum samples from 164 patients who had previously been analyzed to investigate OCB. Parasitic antibodies were studied through unidimensional electrophoresis of proteins on polyacrylamide gel against Taenia antigens, searching for antiparasitic specific low molecular weight antibodies and also for antiparasitic nonspecific high molecular weight antibodies. Results: Two of the 103 patients with no evidence of OCB had antibodies of low molecular weight and 59 of them had antibodies of high molecular weight. Of the 61 patients with evidence of OCB, one showed antibodies of low molecular weight and 16 showed antibodies of high molecular weight. Conclusion: Antiparasitic antibodies are detected with similar frequency in MS patients with OCB and in MS patients without OCB.


1998 ◽  
Vol 28 (1) ◽  
pp. 25-32 ◽  
Author(s):  
I.M. Verbruggen ◽  
W.S. Veraverbeke ◽  
A. Vandamme ◽  
J.A. Delcour

1980 ◽  
Vol 189 (1) ◽  
pp. 9-15 ◽  
Author(s):  
Yoav Ben-Yoseph ◽  
Melinda Hungerford ◽  
Henry L. Nadler

Galactocerebrosidase (β-d-galactosyl-N-acylsphingosine galactohydrolase; EC 3.2.1.46) activity of brain and liver preparations from normal individuals and patients with Krabbe disease (globoid-cell leukodystrophy) have been separated by gel filtration into four different molecular-weight forms. The apparent mol.wts. were 760000±34000 and 121000±10000 for the high- and low-molecular-weight forms (peaks I and IV respectively) and 499000±22000 (mean±s.d.) and 256000±12000 for the intermediate forms (peaks II and III respectively). On examination by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis, the high- and low-molecular-weight forms revealed a single protein band with a similar mobility corresponding to a mol.wt. of about 125000. Antigenic identity was demonstrated between the various molecular-weight forms of the normal and the mutant galactocerebrosidases by using antisera against either the high- or the low-molecular-weight enzymes. The high-molecular-weight form of galactocerebrosidase was found to possess higher specific activity toward natural substrates when compared with the low-molecular-weight form. It is suggested that the high-molecular-weight enzyme is the active form in vivo and an aggregation process that proceeds from a monomer (mol.wt. approx. 125000) to a dimer (mol.wt. approx. 250000) and from the dimer to either a tetramer (mol.wt. approx. 500000) or a hexamer (mol.wt. approx. 750000) takes place in normal as well as in Krabbe-disease tissues.


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