Clinical And Experimental Studies On The Ionic And Nonionic Contrast Media Interactions With Anticoagulant Drugs

1981 ◽  
Author(s):  
Z Parvez ◽  
H L Messmore ◽  
R Moncada ◽  
A C Anderson ◽  
J Fareed
Keyword(s):  
Contrast Media ◽  
Partial Thromboplastin Time ◽  
Experimental Studies ◽  
Thrombin Time ◽  
Dextran 40 ◽  
Sodium Heparin ◽  
In Vivo Experiments ◽  
Anticoagulant Action ◽  
Anticoagulant Drugs

Interactions of ionic and non-ionic radiologic contrast media (CM) with anticoagulant drugs like heparin and Dex- tran-40 have been investigated. Renografin-60 (Squibb and Sons, Princeton, New Jersey), P-297, ioxigalic acid and iothalamic acid (Laboratoire Guerbet, Paris, France) were used. Human, monkey, dog and rabbit plasmas were incubated with CM, CM + heparin, CM + Dextran-40 and saline; prothrombin time (PT), partial thromboplastin time (PTT), and thrombin time (TT) were determined. In human plasma, Renografin-60 (final cone. 30 mg/ml) produced a strong anticoagulant effect and clotting times PT, PTT, and TT were prolonged by 1-1.5X their base value. When Renografin-60 was supplemented with 0.2u/ml heparin, the TT was greatly elevated, >100 secs, (control < 20 secs). No such prolongation of TT was noted when Dextran-40 was mixed into CM + plasma mixture. Iothalamic acid also showed potent anticoagulant action. P-297, which is a .non-ionic CM, showed the least anticoagulant action by itself, but did manifest some synergistic reaction with 0.2 - 0.4u/ml heparin (TT >100 secs, with 10 NIH u/ml thrombin). Similar results were obtained with monkey, dog and rabbit plasmas. In the in vivo experiments, dogs weighing 11-18kg were injected intravenously with 100-150 u sodium heparin/kg body weight, along with 50-100 ml Renografin-60. Blood samples were drawn at 1 hr., 3 hrs., 4 hrs., and 6 hrs., post injection and assayed for clotting times. 5 ml/kg CM injected with 25 u/kg heparin prolonged the activated partial thromboplastin time (APPT) and TT for upto 6 hours, while sodium heparin along produced anticoagulant effects for shorter duration (< 4 hours). Our studies indicate that ionic forms of CM produce relatively stronger antithrombotic response in animals as compared to non-ionic ones and utmost care should be exercised in their usage in patients on anticoagulant drugs.

Clinical and Experimental Evaluation of the Interaction of Anticoagulant Drugs with Radiologic Contrast Media

1979 ◽  
Author(s):  
R. Moncada ◽  
H. L. Messmore ◽  
J. Fareed ◽  
P. J. Scanlon ◽  
Z. Parvez
Keyword(s):  
Contrast Media ◽  
Media Studies ◽  
Oral Anticoagulants ◽  
Thrombin Time ◽  
Clotting Time ◽  
Activated Clotting Time ◽  
Anticoagulant Action ◽  
Human Volunteers ◽  
Anticoagulant Drugs ◽  
Vascular Angiography

Although clinical incompatibilities of antihistamines and protamine with radiologic contrast media are well recognized, no report is available on the interaction of heparin, Coumadin, dextrans and other anticoagulants with these agents. We have employed the automated activated clotting time (ACT), prothrombin time (FT), partial thromboplastin time (PTT) and the thrombin time (TT) methods to monitor the anticoagulant actions of contrast media and its interaction with various anticoagulant drugs in patients undergoing angiography, A strong synergism of the anticoagulant action of heparin was observed in patients given heparin along with contrast media. Studies conducted in human volunteers revealed that contrast media at a 1-5 mg/ml level (clinical, 0.5-0.6 mg/ml) produce a strong synergistic effect on the anticoagulant action of heparin, oral anticoagulants, dextrans, and antiplatelet drugs. When blood obtained from patients undergoing angiography was supplemented with 0.25 u/ml heparin, the ACT, PTT and TT were equal to 1.5-2.0 units of heparin. Conventional amounts of protamine are incapable of neutralizing this synergistic interaction. These studies show that contrast media temporarily augments the degree of anticoagulation in patients undergoing angiography, which should be taken into consideration in patients undergoing vascular angiography.

Anticoagulant And Antithrombotic Properties Of D-PHE-PRO-ARG-H /1/, BOC-D-PHE-PRO-ARG-H /2/, BZ-D-ALE-PRO-ARG-H /3/ And β-D-Phenyl-Lactyl-PRO-ARG-H /4/

1981 ◽  
Author(s):  
D Bagdy ◽  
É Barabás ◽  
S Banusz ◽  
E Széll ◽  
I Boaor
Keyword(s):  
Blood Clotting ◽  
Competitive Inhibitor ◽  
Thrombin Time ◽  
In Vivo Experiments ◽  
Anticoagulant Action ◽  
Antithrombotic Effects ◽  
Conscious Rabbits ◽  
Dose Dependent

A series of tripeptide derivatives was synthetized and studied for blood clotting inhibition in vitro and in vivo experiments. Whole blood clotting time /WBCT/, activated partial thromboplastin time /APTT/, thrombin time /TT/ and prothrombin time /PT/ were measured in Thrombelastograph and Coagulometer, resp. using heparin and hirudin as reference substances. The inhibition by /1-4/ of platelet aggregation /PA/ was tested in Chrono-Log Aggregometer. The anticoagulant action of /1-4/ in vivo was investigated in mice, rats, rabbits, dogs and monkeys, resp. by different ways of administration. /1/ was found to be a non competitive inhibitor of thrombin according to Dixon plots /Ki = 7.5 × l0-8 M /. /1-4/ inhibited the thrombin induced PA specifically. By giving to animals i.v.,i.m.,s.c. and orally, resp. /1-4/ proved to be effective in all species and the anticoagulant action was dose dependent. In the course of continuous i.v.infusions to conscious rabbits and narcotized dogs, resp. /3-4 mg pro kg/hr for 3 to 6 hrs / WBCT, APTT and TT prolonged to 3-5 times of the starting values. The anticoagulant effect appeared 15 min after starting and returned to normal within 1-2 hrs after stop the infusions. No change either in blood pressure or in respiration could be observed during the infusions. ED50 and LD50 of i.v. infusion in conscious rabbits was found to be 1.3 and 58 mg, resp.. Our results suggest that /1-4/ represent powerful anticoagulant and antithrombotic effects and can be regarded as a new tyoe of anticoagulants.

scholarly journals Effect of Angiography on Blood Coagulation

1977 ◽  
Author(s):  
W. H. Krause ◽  
A. Lang
Keyword(s):  
Contrast Media ◽  
Prothrombin Time ◽  
Antithrombin Iii ◽  
Degradation Products ◽  
Anticoagulant Activity ◽  
Thromboembolic Complication ◽  
Thrombin Time ◽  
Media Concentration

It is known, that angiographic contrast media have an anticoagulant activity in vitro. The purpose of the present study was, to investigate this effect in vivo. The catheter was introduced percutaneously according to Seldinger into the femoral artery. The prothrombin time, activated thromboplastin time (APTT), thrombin time, reptilase time, fibrinogen, plasminogen, antithrombin III, platelets, fibrin/fibrinogen degradation products (FDP), haematocrit and contrast media concentration were studied in a series of 50 patients before and following abdominal aorto-arteriographic procedures up to 6 hours. Thrombin time and reptilase time were prolonged significantly 30 and 60 minutes after angiography. There was a correlation between clotting tiies and contrast media concentrations. Prothrombin time, APTT, and platelet counts remained unchanged. Fibrinogen, plasminogen,and antithrombin III levels showed a significant reduction after 30 minutes. FDP concentrations were increased significantly up to 6 hours, there was no correlation between contrast media concentrations and split products. The results were corrected for contrast media dilution according to the haematocrit. No thromboembolic complication was observed. The results suggest that angiographic procedure may initiate an intravascular coagulation with an activation of the fibrinolytic system. In addition the contrast media showed an inhibition of fibrin polymerization in vivo.

In Vivo Fluorescence Microscopy of Microcirculation in the Renal Cortex of Mice

1993 ◽  
Vol 34 (2) ◽  
pp. 174-178 ◽  
Author(s):  
B. Högstrωm ◽  
P. Rooth ◽  
O. Sunnegårdh ◽  
S.-O. Hietala
Keyword(s):  
Blood Flow ◽  
Fluorescence Microscopy ◽  
Contrast Media ◽  
Renal Cortex ◽  
Experimental Studies ◽  
Cortical Blood Flow ◽  
In Vivo Fluorescence ◽  
Renal Cortical Blood Flow ◽  
Increased Blood Flow

In vivo fluorescence microscopy was used for experimental studies of renal cortical microcirculation in 46 mice. The cortical circulation was studied after i.v. infusions of mannitol of various osmolalities as well as nonionic low osmolar (iohexol) and ionic high osmolar (metrizoate) contrast media. All infusions produced an increase in the number of capillaries with increased blood flow, significantly more pronounced after the infusion of iohexol, metrizoate and mannitol 1.46 mol/l than after the infusion of mannitol 0.3 mol/l. However, the renal cortical blood flow was inhomogeneous with respect to different capillaries. While the blood flow was increased in some capillaries it was to some extent simultaneously decreased in others, significantly more after infusion of metrizoate than after infusion of mannitol 0.3 mol/l.

Effect Of Ionic And Non-Ionic Contrast Media On Components Of Coagulation And Complement Pathways

1981 ◽  
Author(s):  
R Moncada ◽  
Z Parvez ◽  
J Fareed ◽  
P Agrawal ◽  
H L Messmore
Keyword(s):  
Contrast Media ◽  
Protein C ◽  
Thrombin Time ◽  
Complement Protein ◽  
Ionic Contrast ◽  
Anticoagulant Drugs ◽  
Coagulation Tests ◽  
Induced Aggregation ◽  
Aggregation Of Platelets ◽  
Ionic Forms

The effects of a recently developed non-ionic contrast media (CM) P-297 and two ionic forms Ioxigalic acid and Iothalamic acid (Laboratoire Guerbet, Paris, France) were studied on coagulation and complement systems, and their interactions with anticoagulant drugs. In coagulation studies, a 1:10 mixture of P-297 (10%) in human plasma (both normal and abnormal) was prepared and prothrombin time (PT), partial thromboplastin time (PTT), and thrombin time (TT) were determined. Similar studies were performed with Ioxigalic acid (10%), and Iothalamic acid (10%). Separate pools of (10) individual plasmas representing disorders of intrinsic and extrinsic pathways of coagulation were similarly mixed with CM and the clotting times were determined. In all of these experiments, there was only a slight increase in TT whereas PTs and PTTs were not affected. Of the three CM tested, P-297 (10%) showed considerably less anticoagulant action than ioxigalic and iothalamic acids. All the CM exhibited a synergistic effect with 0.2u/ml heparin and greatly prolonged (>100 secs.) all coagulation tests. All of the three CM at (10 mg/ml) failed to produce any significant blockade of thrombin-induced aggregation of platelets, however at 40-80mg/ ml level did block thrombin-induced aggregation. In complement activation studies, serum C-3 levels in pre-and post-CM incubation samples were determined by a rocket technique. No consumption of the complement protein C-3 or split products of C-3 were seen in counter immunoelectrophoresis. These studies indicate that P-297 possesses mild anticoagulant and complement activating actions, and seems relatively safer than other ionic forms of CM. Furthermore, our studies suggest that non-ionic contrast agents produce minimal effects on coagulation and complement systems and can be used without much risk to patients with pre-existing coagulation and/or complement disorders.

scholarly journals A Comparison of the Anticoagulant Actions of Commercially Available Contrast Media (CM)

1977 ◽  
Author(s):  
Rogelio Moneada ◽  
Jawed Fareed ◽  
Harry Messmore ◽  
Terrence Demos
Keyword(s):  
Sodium Chloride ◽  
Contrast Media ◽  
Toluidine Blue ◽  
Partial Thromboplastin Time ◽  
Antithrombin Iii ◽  
Thrombin Time ◽  
Clotting Factors ◽  
Antithrombin Activity ◽  
Viii And Ix

Previous studies have reported on the anticoagulant effect of commercially available contrast media used in diagnostic radiology. The purpose of this study is to compare the anticoagulant actions of these agents in vitro. Eight commercially available contrast medias were supplemented to citrated human plasma (CNP) in 1:10, 1:20 and 1:50 proportions; isomolar sucrose, glucose, sodium chloride, and saline supplemented CNP were used as controls. Prothrombin time (FT) , partial thromboplastin time (PTT), thrombin time (TT), antithrombin-III, plasminogenplasnun and factor assays were performed at 0 time, 30 minutes and 2 hours after incubation at 37°C. No significant alteration of the coagulation parameters were observed at 1:50 dilution, however at 1:10 and 1:20 dilution, most contrast media produced aberration of clotting parameters. The antithrombin potency of these contrast media at a 1:10 dilution ranged from 0.3-1.3 u/ml heparin. In addition, this antithrombin activity was synergistic with heparin. The antithrombin activity of these agents was not neutralized by protamine sulfate, polybrene or toluidine blue in the amounts which neutralized 1 u/ml heparin. Analysis of various clotting factors revealed that factors II, V, VII and XII were not affected by contrast media. Factors VIII and IX were depressed significantly. These changes were mainly dependent on the concentration of meglumine in the contrast media. Similar studies on the blood obtained from patients infused with contrast media for diagnostic purposes are in progress in our laboratory.

Effects of Isosmolar Contrast Media on the Renal Cortical Blood Flow in Mice

1996 ◽  
Vol 37 (3P2) ◽  
pp. 587-590 ◽  
Author(s):  
B. Högström ◽  
S.-O. Hietala ◽  
P. Rooth
Keyword(s):  
Blood Flow ◽  
Contrast Media ◽  
Contrast Medium ◽  
Experimental Studies ◽  
Initial Increase ◽  
Cortical Blood Flow ◽  
Renal Cortical Blood Flow ◽  
The Difference ◽  
Increased Blood Flow

Purpose: In vivo fluorescence microscopy was used in experimental studies of renal cortical microcirculation in mice. The effects of i.v. infusion of a nonionic monomeric contrast medium (iohexol), a nonionic dimeric contrast medium (iodixanol), and mannitol of corresponding osmolalities were studied. Results: All infusions produced marked effects on the distribution and velocity of renal cortical blood flow. Renal cortical blood flow was inhomogeneous as regards the different capillaries. There was an initial rapid rise in the blood flow in some capillaries after all infusions, while decreased flow was seen in other capillaries. The initial increase in renal cortical blood flow (RCBF) was significantly (p<0.05) more pronounced after infusion of iohexol than after infusion of mannitol 0.69 mol/l. In all other respects, the effects of contrast media on RCBF were the same as the effects of mannitol solutions with a corresponding osmolality. The effects of each contrast medium were the same as those of mannitol of corresponding osmolality. In the capillaries showing increased blood flow, the peak value was encountered slightly later after the infusion of iodixanol than after the infusion of iohexol. This was considered to be related to differences in viscosity rather than osmolality. Conclusion: The difference in osmolality between iodixanol and iohexol is of no significance with regard to their effects on RCBF.

Anticoagulant and Antithrombotic Action of Novel Specific Inhibitors of Thrombin

1980 ◽  
Vol 43 (02) ◽  
pp. 118-123 ◽  
Author(s):  
J Hauptmann ◽  
B Kaiser ◽  
F Markwardt ◽  
G Nowak
Keyword(s):  
Time Course ◽  
Anticoagulant Effect ◽  
Thrombin Time ◽  
Anticoagulant Action ◽  
Derivatives Of ◽  
Specific Inhibitors

SummaryA series of new specific inhibitors of thrombin, cyclic amides of Nα-arylsulfonyl-amidinophenylalanine, was studied for anticoagulant action in vitro and in vivo. The inhibitors showed strong anticoagulant effects in vitro. The time course of the anticoagulant effect of the inhibitors in rabbits and rats was monitored using plasma thrombin time determinations. In rats, the inhibitors prevented the formation of experimental venous thrombi and of thrombin-induced microthrombosis. The new derivatives of benz-amidine presented may be useful as immediately acting anticoagulants.

Release of Platelet Factor 4 in Vivo during Intravascular Coagulation and in Thrombotic States

1968 ◽  
Vol 19 (03/04) ◽  
pp. 578-583 ◽  
Author(s):  
R Farbiszewski ◽  
S Niewiarowski ◽  
K Worowski ◽  
B Lipiński
Keyword(s):  
Coronary Thrombosis ◽  
Laboratory Diagnosis ◽  
Tolerance Test ◽  
Platelet Factor 4 ◽  
Thrombin Time ◽  
Significant Elevation ◽  
Platelet Factor ◽  
Thrombotic Diseases ◽  
Disseminated Intravascular Clotting

SummaryPlatelet factor 4 released from platelets into the circulating blood was determined using both the heparin thrombin time and paracoagulation methods. It has been found that thrombin injected intravenously into rabbits releases large amounts of this factor. Infusion of plasmin does not release this factor and this finding may be of importance for the differential diagnosis between disseminated intravascular clotting and primary fibrinolysis. PF4 is not released during the hyper coagulable condition induced by HgCl2 intoxication. Only small amounts of this factor are released after contact factor infusion.A significant elevation of extraplatelet PF4 was found in 23 patients with fresh coronary thrombosis and in 9 patients with thrombophlebitis and thromboembolic complications.The significance of the above findings for the pathogenesis, treatment and laboratory diagnosis of thrombotic diseases with particular reference to heparin tolerance test is discussed.

Consumption of Hageman Factor Activity in the Generalized Shwartzman Reaction Induced by Liquoid

1970 ◽  
Vol 23 (02) ◽  
pp. 386-404 ◽  
Author(s):  
G Müller-Berghaus ◽  
H. G Lasch
Keyword(s):  
Partial Thromboplastin Time ◽  
Lethal Dose ◽  
Control Group ◽  
Factor V ◽  
Consumption Coagulopathy ◽  
Factor Activity ◽  
Hageman Factor ◽  
Intravascular Coagulation ◽  
Shwartzman Reaction

SummaryThe role of Hageman factor in triggering intravascular coagulation has been studied in rabbits injected intravenously with Liquoid. Besides changes of coagulation parameters characteristic of consumption coagulopathy (e.g. decrease in platelet counts, fibrinogen levels, factor V activity), a pronounced drop in Hageman factor activity was observed after injection of Liquoid. Likewise, the partial thromboplastin time became prolonged.The activation of Hageman factor in vivo could be prevented by intravenous infusion of lysozyme. Twenty min after starting the lysozyme infusion, the partial thromboplastin time became prolonged from a mean of 29 sec to 108 sec. Animals infused with lysozyme and injected with a lethal dose of Liquoid did not develop a consumption coagulopathy. In the same manner, none of 10 animals treated with lysozyme developed the generalized Shwartzman reaction, whereas in the control group 19 out of 20 animals showed fibrin thrombi in the glomerular capillaries.From the present study it may be concluded that the intravascular coagulation process after intravenous injection of Liquoid is triggered by Hageman factor activation.

Sign in / Sign up

Export Citation Format

Share Document