Biological Activrty and Safety of the Subcutaneous Administration of High Doses of Low Molecular Weight Heparin for 8 Days in Human Volunteers

1989 ◽  
Vol 61 (03) ◽  
pp. 357-362 ◽  
Author(s):  
J Harenberg ◽  
Ch Giese ◽  
C E Dempfle ◽  
G Stehle ◽  
D L Heene
Keyword(s):  
Molecular Weight ◽  
Factor Xa ◽  
Low Molecular Weight ◽  
Chromogenic Substrate ◽  
Clotting Time ◽  
Human Volunteers ◽  
Factor Xa Inhibition ◽  
Group 2 ◽  
High Doses ◽  
Group 1

SummaryThis study reports on the biological activity and safety of high dose low molecular weight (LMW) heparin therapy administered by two subcutaneous (s.C.) injections daily for 8 days in healthy human volunteers. Group 1 received 2 × 30 aPTT units LMW heparin/kg bodyweight, and group 2 received 2 × 50 aPTT units/kg per day.In group 1, activated partial thromboplastin time (aPTT) and thrombin clotting time (TCT) were uniformly prolonged by 3-5 sec 4 hrs after s.c. administration of heparin. Heptest coagulation time values were prolonged consistently as well by 57 sec on day 1 to 68 sec on day 8. Factor Xa inhibition measured by the S 2222 chromogenic substrate method continuously increased from 0.16 units/ml on day 1 to 0.28 units/ml on day 8.In group 2 prolongation of a aPTT and TCT values increased from 6 sec on day 1 to 15 sec on day 8 and of Heptest time from 70 sec on day 1 to 110 sec on day 8. S 2222 method showed factor Xa inhibitory activity which increased from 0.5 units/ml on day 1 to 0.75 units/ml on day 8. The clinical tolerance of the treatment was good. No changes in clinical chemistry parameters were detected, except for a reversible increase of serum transaminases.The coagulation studies demonstrate accumulation of LMW heparin when high doses are given twice daily. The half life of LMW heparin of factor Xa inhibition increases with increasing doses.Heptest coagulation values were prolonged to 4-6 times the normal values during administration of heparin. S 2222 chromogenic substrate values were in the same range as upon application of high doses of unfractionated heparin. aPTT and thrombin clotting time values ranged from 1.2 to 1.5 times the starting values.

A NEW ONE STAGE CLOTTING ASSAY FOR HEPARIN AND LOW MOLECULAR WEIGHT HEPARINS

1987 ◽  
Author(s):  
Ch Giese ◽  
A Knodler ◽  
R Zimmermann ◽  
J Harenberg
Keyword(s):  
Molecular Weight ◽  
Factor Xa ◽  
Low Molecular Weight ◽  
Chromogenic Substrate ◽  
Clotting Time ◽  
Low Molecular Weight Heparins ◽  
One Stage ◽  
High Preference ◽  
Coagulation Tests ◽  
Plasma Assay

Heparin and its low molecular weight (LMW) derivatives are usually measured by chromogenic or fluorogenic synthetic substrate assays and by coagulation tests. Since the activated partial thromboplastin time (aPTT) and thrombin clotting time (TCT) are insensitive to LMW heparins, we report here of data obtained with heptest, a new one stage modification of the original heparin in plasma assay of Yin. The assay was compared with the antifactor Xa chromogenic substrate S2222 method, the TCT and aPTT tests in 100 patients receiving unfractionated pig intestinal mucosa heparin and 100 patients treated with low molecular weight heparin Kabi 2165. The results indicate a high correlation between the heptest and the anti Xa chromogenic substrate method, whereas the correlations were lower for the aPTT and TCT. correlations with LMW heparinThe lowest detection limit of the heptest is 0,005 heparin units per ml plasma. The test is very sensitive, simple, highly reproducable and reliable clotting assay for unfractionated and low molecular weight heparins in human plasma. The test detects with high preference the inhibition on factor Xa but also the other anticoagulant effects on die coagulation tractors.

Effects of an Enzymatically Depolymerized Heparin as Compared with Conventional Heparin in Healthy Volunteers

1987 ◽  
Vol 57 (01) ◽  
pp. 097-101 ◽  
Author(s):  
Thomas Mätzsch ◽  
David Bergqvist ◽  
Ulla Hedner ◽  
Per Østergaard
Keyword(s):  
Molecular Weight ◽  
Body Weight ◽  
Healthy Volunteers ◽  
Factor Xa ◽  
Low Molecular Weight ◽  
Normal Range ◽  
Factor Xa Inhibition ◽  
At Iii ◽  
Mean Molecular Weight ◽  
Enzymatic Depolymerization

SummaryA low molecular weight heparin (LMW-heparin) with a mean molecular weight of 4900 dalton was prepared by controlled enzymatic depolymerization of conventional porcine mucosal heparin. The effects of 2,500, 5,000 and 10,000 U (Xal; 29,58 and 116 mg) on factor Xa inhibition (Xal), factor Ila inhibition (Hal), APTT, AT III and platelet count were compared to those of 5,000 U (Xal; 26 mg) of conventional heparin given s. c. to 6 healthy volunteers. 5,000 U (Xal; 58 mg) of LMW-heparin was given i. v. A dose related response with regard to the Xal and the Ila-inhibitory activities with peak values at 4 hours after the s. c. injections was obtained. An increase of the Xal/IIal ratio over the time after injection was seen only after i. v. administration of the LMW-heparin. The APTT was only slightly prolonged and remained within normal range after s. c. injection. AT III and platelet counts were unaffected. The biological half life of the LMW-heparin was 111 minutes if assayed by Xa inhibition, 76 minutes if assayed by Ila inhibition and 40 minutes if assayed by APTT. A strong correlation between the Xal activities obtained and body weight was seen, indicating that LMW-heparin should be administered individually according to body weight.

Anti-Xa Potentiating Effect Of Low Molecular Weight Heparin

1981 ◽  
Author(s):  
W Junker ◽  
J Harenberg ◽  
F Fussi ◽  
K Mattes ◽  
R Zimmermann ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Intestinal Mucosa ◽  
Low Molecular Weight Heparin ◽  
Bleeding Complications ◽  
Low Molecular Weight ◽  
Chromogenic Substrate ◽  
Clotting Time ◽  
Blood Samples ◽  
Increased Risk

Recently special attention has been drawn to bleeding complications of commercial heparins in patients with increased risk for haemorrhages. Alternative heparin preparations with high antithrombotic and low haemostaseological properties have been developed. We now report on a new low molecular weight (LMW) heaprin (mean MW 5000, 85 USP/mg), which has been obtained by depolymerisation of a heparin from pig intestinal mucosa (mean MW 15000, 154 USP/mg).In vitro the anti-Xa-activity (chromogenic substrate S2222) was 15% higher for the LMW heparin in a range of 0.01-2.0 USP/ml plasma. No difference was seen on the anti-IIa-activity (thrombin clotting time)and the aPTT for both heparins in the same range. Both Heparins were injected s.c. in a dose of 100, 50 and 25 USP/kg bodyweight into each of six volunteers randomly at weekly intervalIs. The pharmacodynamic effects were controlled for 6-10 hrs by 8-12 blood samples in relation to the dose applied. Increasing dosis the effects of each heparin increased in all test systems. The anti- Xa-activity of LMW heparin was somewhat higher at 100 and 25 USP/kg. At 50 USP/kg the effect of LMW heaprin was in the same range as 100 USP/kg of the original preparation (MW 15000). The factor Ila activity and aPTT were not influenced differently by the two heparins at each dose.The data indicate, that the LMW heparin presented here may have a more pronounced antithrombotic property by a specific anti-Xa-activity than the compaired commercial heparin. This effect is most pronounced at doses, which have only small haemostaseological effects.

COMPARATIVE CLINICAL PHARMACOLOGY OF LOW MOLECULAR WEIGHT HEPARINS IN MAN

1987 ◽  
Author(s):  
Y Ordu ◽  
J Augustin ◽  
E V Hodenberg ◽  
V Bode ◽  
J Harenberg
Keyword(s):  
Molecular Weight ◽  
Clinical Pharmacology ◽  
Ex Vivo ◽  
Average Molecular Weight ◽  
Factor Xa ◽  
Low Molecular Weight ◽  
Pharmacological Properties ◽  
Clotting Time ◽  
Activity Time ◽  
Low Molecular Weight Heparins

Low molecular weight (LMW) heparins are obtained by diffent chemical procedures from conventional pig intestinal mucosa heparin. The LMW heparins differ in their molecular weight distribution and physicochemical properties. Therefore, we report of comparative studies on the anticoagulant and lipolytic effects of low molecular weight heparins in man.The following LMW heparins were used: BM 21-23 (Braun, Melsungen, FRG), CY 216 (Choay Laboratories, Paris, France), Heparin NM (Sandoz, Niimberg, FRG), Kabi 2165 (Kabi Vitrum AB, Stockholm, Sweden), RD Heparin (Hepar Industries, Franklin, US A), normal heparin (Braun). All heparins were administered intravenously and subcutaneously to six volunteers each.The data show considerable differences in the anticoagulant and lipolytic effects between the different low molecular weight heparins. From the area under the activity time curves (AUC) of the clotting assays for factor Xa (heptest), aPTT and thrombin clotting time the aXa/aPTT ratio ex vivo and aXa/alla ratio ex vivo were determined (table, average values)It can be seen that there are clear differences in the ex vivo ratios of the LMW heparins. There is a good correlation between the average molecular weight of the LMW heparins and the aXa/aPTT ratio after s.c. administration and of the aXa/alla ratio ex vivo after s.c. administration. Therefore, LMW heparins differ significantly in their clinical pharmacological properties.

Peculiarities of Fibrinolytic and Proteolytic Activity of Blood Plasma in Patients with Chronic Pancreatitis Combined with Hypothyroidism

2021 ◽  
Vol 6 (5) ◽  
pp. 233-238
Author(s):  
V. V. Ratsa ◽  
◽  
O. I. Fediv
Keyword(s):  
Molecular Weight ◽  
Chronic Pancreatitis ◽  
Blood Plasma ◽  
Fibrinolytic Activity ◽  
The State ◽  
Low Molecular Weight ◽  
Healthy Individuals ◽  
Group 2 ◽  
Low Molecular Weight Proteins ◽  
Group 1

The purpose of the study is to analyze the state of proteolytic and fibrinolytic activities of blood plasma in patients with chronic pancreatitis combined with hypothyroidism. Materials and methods. 105 people participated in our study, of which group 1 consisted of patients with chronic pancreatitis (n = 27), group 2 – patients with hypothyroidism (n = 30), group 3 – patients with chronic pancreatitis combined with hypothyroidism (n = 28), group 4 – almost healthy individuals (n = 20). The state of fibrinolytic activity of blood plasma was studied by lysis of azofibrin, followed by determination of total fibrinolytic activity, non-enzymatic fibrinolytic activity and enzymatic fibrinolytic activity. Assessment of the state of the proteolysis system was studied by lysis of azoalbumin (breakdown of low molecular weight proteins), azocasein (breakdown of high molecular weight proteins) and azocol (breakdown of collagen). Results. When analyzing the results of the study, we observe a probable increase in lysis of azoalbumin by 1.89, 1.96 and 2.16 times (p <0.05) in groups 1, 2, 3 compared with the group of almost healthy individuals. In patients with chronic pancreatitis and hypothyroidism, the most pronounced degradation of low molecular weight proteins was observed, which was 13.86% and 9.75% (p <0.05) higher than in the first and second groups. Indicators of azocasein lysis by 52.48%, 56.35% and 95.03% (p <0.05) were found in groups 1, 2, 3 compared with almost healthy individuals. Azocasein lysis was higher by 27.89% and 24.73% (p <0.05) in patients with chronic pancreatitis combined with hypothyroidism than in patients in groups 1 and 2. Azocol lysis was significantly higher by 10.85%, 12.05%, 16.87% (p <0.05) in groups 1, 2, 3 compared with almost healthy individuals. In addition, in patients with comorbid pathology there was an increase in lysis of azocol by 5.3% and 4.3% (p <0.05) compared with the first and second groups. The total fibrinolytic activity of blood plasma was 8.3%, 6.7%, 16.26% (p <0.05) lower in patients of groups 1, 2, 3 compared with almost healthy individuals. Non-enzymatic fibrinolytic activity of blood plasma was 44.89%, 49.64%, 66.27% higher in groups 1, 2 and 3 than in almost healthy individuals. Enzymatic fibrinolytic activity of blood plasma was 44.28%, 42.25%, 90.57% (p <0.05) lower in group 1, 2, 3 compared with the group of almost healthy individuals (p <0,05). There was a decrease in the level of enzymatic fibrinolytic activity of blood plasma by 32.07% and 33.96% (p <0.05) in patients with chronic pancreatitis associated with hypothyroidism compared with participants in groups 1 and 2 without comorbid pathology. Conclusion. The most pronounced changes in proteolytic (increased lysis of azoalbumin, azocasein, azocol) and fibrinolytic (decrease in total, non-enzymatic and enzymatic) activities of blood plasma in patients with chronic pancreatitis associated with hypothyroidism were determined

Measurement of whole blood factor Xa-activated clotting time during hemodialysis with low-molecular-weight heparin

1998 ◽  
Vol 12 (3) ◽  
Author(s):  
Masakazu Mori ◽  
Shigenori Yoshitake ◽  
Takaaki Kitano ◽  
Shunsuke Oda ◽  
Takayuki Noguchi
Keyword(s):  
Molecular Weight ◽  
Whole Blood ◽  
Low Molecular Weight Heparin ◽  
Factor Xa ◽  
Low Molecular Weight ◽  
Clotting Time ◽  
Activated Clotting Time

Pharmacological Properties of a Low Molecular Weight Butyryl Heparin Derivative (C4-CY 216) with Long Lasting Effects

1992 ◽  
Vol 67 (03) ◽  
pp. 346-351 ◽  
Author(s):  
S Saivin ◽  
M Petitou ◽  
J C Lormeau ◽  
D Dupouy ◽  
P Sié ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Low Molecular Weight Heparin ◽  
Specific Activity ◽  
Parent Compound ◽  
Factor Xa ◽  
Low Molecular Weight ◽  
Pharmacological Properties ◽  
Factor Xa Inhibition ◽  
Antifactor Xa ◽  
Heparin Derivative

SummaryWe have investigated the pharmacological properties of an O-acylated butyryl derivative of the low molecular weight heparin CY 216 (C4-CY 216). In a purified system the ability of C4-CY 216 to catalyze thrombin and factor Xa inhibition was comparable to that of CY 216. The antithrombin and antifactor Xa catalytic efficiencies of C4-CY 216 were reduced 217 and 12 times respectively when albumin (10 mg ml-1) was added to the reagents, while those of CY 216 were essentially unchanged. In plasma, the antifactor Xa specific activity of C4-CY 216 was close to that of CY 216 but the antithrombin specific activity was 2 times lower. After bolus and continuous intravenous injection to rabbits, the clearances of the two activities of C4-CY 216 were on average half the corresponding values of CY 216. After subcutaneous injection, the bioavailability of C4-CY 216 was comparable to that of CY 216. C4-CY 216 was as potent as CY 216 in preventing venous thrombosis in the thromboplastin-Wessler model and the duration of the antithrombotic effect was longer than that of the parent compound. The chemical alteration of CY 216 did not enhance the prohaemorrhagic effect in the rat tail transection model. Therefore, the new concept of heparin derivative having a low clearance and long lasting effects that we have recently reported for unfractionated heparin may also be applied to a low molecular weight heparin.

scholarly journals A Comparative Study of the Effects of Heparin and a Low Molecular Weight Semi-Synthetic Heparin Analogue Upon Platelet Function

1977 ◽  
Author(s):  
R. Michalski ◽  
D. A. Lane ◽  
V. V. Kakkar
Keyword(s):  
Molecular Weight ◽  
Intravenous Injection ◽  
Platelet Function ◽  
Factor Xa ◽  
In Vitro Tests ◽  
Low Molecular Weight ◽  
Clotting Time ◽  
Induced Aggregation

We have already reported O) some in vitro and in vivo properties of a low molecular weight glycosaminoglycan polysulphate. It was found that while this semi-synthetic heparin analogue (SSHA) was virtually inactive in a number of in vitro clotting assays, following intravenous or subcutaneous injection it has a more specific anti-Xa potentiating effect than heparin. In the present communication a comparison has been made of some effects of SSHA and heparin upon platelet function. In several of the in vitro tests performed, such as their potentiating effect on ADP and adrenaline induced aggregation and their effects on the aggregation of washed platelets by Factor Xa, heparin proved to be far more potent than SSHA. It was found that after intravenous injection of both drugs, PRP samples containing comparable anti-Factor Xa activities responded differently to the addition of thrombin as SSHA barely inhibited thrombin induced aggregation. Similarly, SSHA had little effect on the dilute thrombin clotting time of plasma, following intravenous injection. Heparin and analogue were neutralised to approximately the same degree by a crude PF4 preparation, and similar transient thrombocytopenia effects were observed with both drugs.

scholarly journals Evaluation of Anticoagulant Activity for Low Molecular-Weight Heparin by Chromogenic Substrate. Measurement of Factor Xa and Thrombin Activities

1994 ◽  
Vol 114 (8) ◽  
pp. 611-617
Author(s):  
Susumu ISHIMITSU ◽  
Takayuki SUGIYAMA ◽  
Mari ITOH ◽  
Tohru NATSUGA ◽  
Hiroaki KOMATSU ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Low Molecular Weight Heparin ◽  
Anticoagulant Activity ◽  
Factor Xa ◽  
Low Molecular Weight ◽  
Chromogenic Substrate

Comparative Evaluation of Low-Molecular Weight Hyaluronic Acid and Autologous Conditioned Serum in Coxarthrosis

2011 ◽  
Vol 18 (4) ◽  
pp. 38-41
Author(s):  
S M Noskov ◽  
Larisa Yur'evna Shirokova ◽  
T I Bakhtiarova ◽  
K Yu Shirokova ◽  
O M Parulya ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Hyaluronic Acid ◽  
Comparative Evaluation ◽  
Local Therapy ◽  
Low Molecular Weight ◽  
Clinical Effects ◽  
Autologous Conditioned Serum ◽  
Group 2 ◽  
First Time ◽  
Group 1

For the first time the results of a comparative evaluation of low-molecular weight hyaluronic acid (synocrom forte) and autologous conditioned serum (ACS) in coxarthrosis (CA) are presented. Throughout the 12-month monitoring we examined 54 patients with CA who were divided into 2 groups of comparable age and sex composition and the duration of the disease. Group №1 had a 3-week course of local therapy of synocrom forte and group №2 - of ACS. It is concluded that the use of ACS at CA to achieve favorable clinical effects is almost as good as hyaluronic acid, but it characterized by a greater duration of their conservation (from six to twelve months).

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