Increased Anti-Xa Bioavailability Of Heparin By Jet Injection

1981 ◽  
Author(s):  
D Arleth ◽  
J Harenberg ◽  
K Mattes ◽  
R Zimmermann

To improve the standardisation and to diminish the time requirement of the subcutaneous (s.c.) application of low dose heparin a semiautomatic injection pistol was compared to the commonly used one way syringe.The precision of the injected amount of heparin was significantly higher by jet injection (VK 1% vs 4%). The time required for one injection was 110 sec by jet injection and 215 sec by the one way syringe including all preparation times.7500 USP heparin were injected into 10 volunteers by both techniques at weekly intervals randomly. The pharmacodynamic effects were controlled on the factor Ila activity (thrombin clotting time), aPTT and factor Xa activity (chromogenic substrate S2222) for 10 hrs by 12 blood samples. No differences were observed on the factor IIa activity and aPTT between the two injection techniques. The anti- Xa-activity of the heparin applicated by jet injection was significantly higher (maximal effect after 3 hrs: 0.24 vs 0.20 USP heparin/ml plasma, p < 0.01, area under the time related curve p < 0.01).The data indicate, that the bioavailability of heparin for factor Xa is even higher after the s.c. application by the jet injection method than after the one way syringe technique. These differences should be considered, when an improvement of the prophylaxis of thromboembolic diseases is discussed.

1981 ◽  
Author(s):  
P B Lundquist ◽  
J Swedenborg

The purpose of the study was to demonstrate postoperative hypercoagulability and its possible prevention by low dose heparin (LDH). Healthy volunteers (with LDH), patients undergoing cholecystectomy (with & without LDH) and patients undergoing arterial reconstructive surgery with synthetic grafts (with LDH), were tested. All were tested 1, 3 & 5 hrs after LDH.Overall coagulability was determined by using platelet free plasma and a modified recalcification time system with a nefelometer to detect first fibrin formation. Recalcification times were measured before (T0) and after (TA) plasma activation against glass, in vitro. Heparin levels were determined with the Factor Xa inhibition test using a chromogenic substrate (CoatestR, Kabi).T0 and TA were prolonged after LDH in healthy volunteers. Cholecystectomy caused shortening of T0 and TA. This could be prevented by LDH, raising T0 to level recorded after LDH in normals. Patients receiving synthetic arterial grafts showed no prolongation of T0 and TA after surgery with LDH, but rather a shortening. These patients showed hypercoagulability in spite of LDH.It is concluded that postoperative hypercoagulability can be traced with the presented method and counteracted by LDH in patients undergoing cholecystectomy but not in patients receiving synthetic arterial grafts. All patients on LDH had similar heparin levels, determined with the Factor Xa inhibition test. Vascular surgery with synthetic grafting and Cholecystectomy seem to induce two different kinds of hypercoagulability, where the former is thought to be induced by the foreign surface. Subcutaneous heparin therapy (LDH) results in poor inhibition of surface induced coagulation, in vivo.


1979 ◽  
Author(s):  
V. Tilsner ◽  
U. Müller

The antithrombotic effect of low-dose heparin has been ascertained clinically. The postoperative activation of the coagulation factors must be decreased, without increasing any bleeding tendencies. In order to determine the optimal dosage in low-dose heparin prophylaxis we examined the RCT, PTT, TT, Factor Xa, AT III and heparin concentrations in 400 patients prior to and following emergency surgery. Any thrombotic or haemorrhagic complication was registered. All 100 cases received one of the following treatment plans: 1) 5000 U heparin s.c. TID, 2) 7500 U heparin s.c. TID, 3) 100 U heparin/kg s.c. BID, 4) 150 U heparin/kg s.c. BID. Only plans 2 and 4 achieved a measureable heparin effect without increasing the risk of bleeding. The PTT did not shorten in either of these 2 groups and the thrombin time rose only occasionally to the upper normal limits. All other values remained within normal limits. The thrombo-embolic incidence amounted to 1% in groups 2 and 4, 2% in groups 3 and 5% in the first group.


1987 ◽  
Author(s):  
D Bergqvist ◽  
J Frisel ◽  
T Hallböök ◽  
A Horn ◽  
A Lindhagen ◽  
...  

Bergen, Halmstad, Goteborg and KabiVitrum AB Stockholm, Sweden and Norway. At the Xth Int. Congress on Thrombosis and Haemostasis in San Diego results from a multicenter trial on 432 patients were presented, comparing a low molecular weight heparin (LMWH) fragment (Fragmin, Kabi) once daily with low dose heparin twice daily. Prophylaxis started 2 hours preoperatively. The frequency of postoperative DVT did notdiffer (6.4 % v. 4.3 %) but the onset of thrombosis was delayed in the LMWH group. Haemorrhagic complications occurred significantly more often in the LMWH group (11.6 % v. 4.6 ?o). The results were similar independent whether the analysis was made according to the intention to treat principle or based on patients with correct prophylaxis. On the basis of these data and newer knowledge regarding the pharmacokinetics of LMWH a second prospective randomized double-blind multicenter trial on patients.older than 40 years undergoing elective abdominal surgery was started. The only difference was that the first dose of 5000 ariti-factor Xa units of LMWH was given on the evening before surgery. Only conventional low dose heparin was given 2 h before surgery. The study is designed to include 1000patients, a number which will be obtained during the spring 1987. At the time of abstract deadline 799 patients have been included. The over-all frequency of DVT (fibrinogen uptake test) is 6.8 %, the frequency of haemorrhagic complications 3.6 % and mortality 1.8 % (one fatal pulmonary embolism). These frequencies remained unaltered after inclusion of 336, 576, 655 and 799 patients. Although the code has not been broken yet, it can be concluded that the new regimen with start of prophylaxis the evening before surgery has not altered the frequency of DVT or mortality whereas the frequency of haemorrhagic side effects has decreased considerably.


BMJ ◽  
1978 ◽  
Vol 2 (6130) ◽  
pp. 95-95 ◽  
Author(s):  
J Black ◽  
C J Nagle ◽  
C J Strachan

2020 ◽  
Vol 26 ◽  
pp. 107602962097549
Author(s):  
Johannes E. Wehner ◽  
Martin Boehne ◽  
Sascha David ◽  
Korbinian Brand ◽  
Andreas Tiede ◽  
...  

Dose adjustment of unfractionated heparin (UFH) anticoagulation is an important factor to reduce hemorrhagic events. High doses of heparin can be monitored by Activated Clotting Time (ACT). Because of limited information about the monitoring of low-dose heparin we assessed monitoring by ACT, aPTT and anti-Xa. Blood samples from healthy volunteers (n = 54) were treated ex vivo with increasing UFH doses (0-0.4 IU/ml). Samples from ICU-patients (n = 60), were drawn during continuous UFH infusion. Simultaneous ACT measurements were performed using iSTAT and Hemochron. In UFH treated blood, iSTAT and Hemochron showed a significant change of ACT at ≥0.075 IU/ml and ≥0.1 IU/ml UFH, respectively. In ICU-patients no relationship between ACT and either UFH dose, aPTT and anti-Xa was observed. Hemochron was affected by antithrombin and platelet count. iSTAT was sensitive to CRP and hematocrit. A moderate correlation was identified between UFH dose and aPTT (R2 = 0.196) or anti-Xa (R2 = 0.162). In heparin-spiked blood, ACT is sensitive to heparin at levels of ≥0.1 IU/ml heparin. In ICU-patients, ACT did not correlate with UFH dose or other established methods. Both systems were differently influenced by certain parameters.


1981 ◽  
Author(s):  
W Salzmann ◽  
K Andrassy ◽  
E Ritz ◽  
J Koderisch

It is often necessary to treat uremic patients with low dose heparin therapy,e.g. for prophylaxis of Cimino-fistula thrombosis. However, little information is available on heparin pharmacokinetics and heparin action in uremic patients. In the present study, plasma activity time profiles during low dose heparin therapy were investigated in control individuals (CO) and in uremic patients (UP). Patients and methods: Heparin levels 0;3;8;10;12;24;27;32;34 and 36 h after s.c. injection of various doses of heparin (2×7.500 IU/day for 2 days; 3×5.000 IU and 2×5.000 IU each for 2 days) were measured in 9 control individuals and in 11 uremic patients (Ccr < 10 ml/min.). Heparin activity was determined by measurements of (1) neutralisation of factor Xa-activity (Denson and Bonnar); (2) neutralisation of Xa measuring amidolytic activity (Teien and Lie); (3) PTT and thrombin time. Heparin cofactor concentrations were measured with immuno-diffusion and by measuring amidolytic activity. Results: With the dose of 2×5.000 IU heparin s.c. no difference between CO and UP was found; in contrast, peak concentrations of heparin were significantly lower in UP after 7.500 IU heparin s.c. With the dose of 3×5.000 IU heparin s.c.there was a significant (p<0.05) difference of heparin levels between CO and UP. This difference was even more pronounced after repeated administration of heparin; heparin levels in UP were markedly lower than in controls. The antithrombin III levels did not change significantly during the study. Conclusion : The results show that in order to reach a given profile of heparin activity, higher s.c. doses of heparin must be administered in uremic patients than in non-uremic controls.


Anaesthesia ◽  
2009 ◽  
Vol 64 (4) ◽  
pp. 430-434 ◽  
Author(s):  
L. Racioppi ◽  
A. Quinart ◽  
M. Biais ◽  
K. Nouette-Gaulain ◽  
P. Revel ◽  
...  

1981 ◽  
Author(s):  
R C Briel

Administration of low-dose heparin by jet injection is regarded as most suitable for both patient and staff. The present study deals with the comparison of plasma heparin levels and various coagulation parameters after s.c. and jet injection (K3-pistol Sandoz) of 5000 IU calcium heparin in 0.2 ml and 5000 IU sodium heparin + 0.5 mg dihydroergotamin (DHE) in 0.7 ml. The injection sites were upper arm, abdcmen or upper leg. Estimations were performed in 10 healthy volunteers each receiving 12 different injections. Heparin level profiles (chromogenic substrate S-2222), AT III activity (S-2238) and concentration (Mancini technique), antifactor Xa (S-2222), antiheparin activity (S-2222), antiplasmin (S-2251), TT, aPTT and TEG r+k were measured.There was a positive and significant correlation between postinjection heparin levels and body weight, preinjection “endogenous heparin”, AT III activity and concentration, and a negative correlation to the antiheparin activity found before injection. Heparin levels were slightly higher after heparin/DHE than after heparin alone, but the differences were not significant. 30 min after jet injection heparin levels were slightly higher than after s.c. injection, while after 1 hr they were similar. After 2 to 3 hrs the highest levels were found, being significantly higher after s.c. injection. After 4 and 6 hrs there were no differences between s.c. and jet injection. TT, aPTT and TEG showed similar behavior patterns. The values were independant of the injection site, upper arm or abdomen with both s.c. and jet injection. They were lower, however, if heparin jet injection was done in the upper leg.Thus, the pretreatment measurement of AT III, endogenous heparin and antiheparin activity with chromogenic substrates may be helpful in the management of an inividualized heparin prophylaxis. After heparin jet injection, altered heparin kinetic has to be considered: a more rapid initial absorption is followed by lower peak heparin levels. The upper leg can not be recommended as injection site for heparin jet injection.


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