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

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.

1977 ◽  
Author(s):  
Jawed Fareed ◽  
Harry L. Messmore ◽  
John U. Balis ◽  
Rogelio Moncada

An earlier report from this laboratory has described the antagonism of the anticoagulant effect of heparin by certain basic polyamino acids. Of the numerous polyamino acids tested, only basic polyarnino acids such as poly-L-lysine (MW 85,000) and poly-L-omithine (MW 120,000) effectively neutralized heparinized plasma (1 u/ml) in concentrations less than 10 μg/ml. Addition of these two polyamino acids in quantities up to 50 μg/ml citrated plasma, significantly shortened the thrombin time. Poly-L-proline (MW 19,000), poly-L-histidine (MW 16,000) and poly-L-lysine (MW 85,000) possessed weak anti-heparin action. These polyamino acids also neutralized the anticoagulant activity of hirudin and polyanetholsulfonic acid in varying degrees. The effects of polyamino acids on platelet aggregation was also tested. Of the 15 basic polyamino acids tested, only poly-L-α-omithine was found to induce aggregation of platelets. Polyornithine in the amounts of 50.0, 25.0 and 12.5 μg/ml to platelet rich plasma caused a 65, 45 and 30% change in transmittance, respectively. The polyornithine induced aggregation (PIA) of platelets was only partially blocked by acetylsalicylic acid. Contrast media (6.0 mg/ml) used in diagnostic radiology and meglumine (5 mg/ml) totally blocked the PIA. The PIA of platelets was found to be a biphasic process, an initial lag time of 30 seconds, after which irreversible aggregation was observed. These studies suggest that basic polyamino acids may be used clinically to antagonize overheparinization; in addition, polyornithine may prove useful in the diagnosis of platelet function defects.


1979 ◽  
Author(s):  
R. Moncada ◽  
H. L. Messmore ◽  
J. Fareed ◽  
P. J. Scanlon ◽  
Z. Parvez

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.


1981 ◽  
Author(s):  
Z Parvez ◽  
H L Messmore ◽  
R Moncada ◽  
A C Anderson ◽  
J Fareed

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.


1982 ◽  
Vol 23 (4) ◽  
pp. 401-404 ◽  
Author(s):  
Z. Parvez ◽  
R. Moncada ◽  
H. L. Messmore ◽  
J. Fareed

1981 ◽  
Author(s):  
M Yamamoto ◽  
K Watanabe ◽  
Y Ando ◽  
H Iri ◽  
N Fujiyama ◽  
...  

It has been suggested that heparin caused potentiation of aggregation induced by ADP or epinephrine. The exact mechanism of heparin-induced platelet activation, however, remained unknown. In this paper, we have investigated the role of anti-thrombin III ( AT ) in heparin-induced platelet activation using purified AT and AT depleted plasma. When ADP or epinephrine was added to citrated PRP one minute after addition of heparin ( 1 u/ml, porcine intestinal mucosal heparin, Sigma Co. USA ), marked enhancement of platelet aggregation was observed, compared with the degree of aggregation in the absence of heparin. However, in platelet suspensions prepared in modified Tyrode’s solution, heparin exhibited no potentiating effect on platelet aggregation induced by epinephrine or ADP. Potentiation of epinephrine- or ADP-induced platelet aggregation by heparin was demonstrated when purified AT was added to platelet suspensions at a concentration of 20 μg/ml. AT depleted plasma, which was prepared by immunosorption using matrix-bound antibodies to AT, retained no AT, while determination of α1-antitrypsinα2- macroglobulin and fibrinogen in AT depleted plasma produced values which corresponded to those of the original plasma when dilution factor was taken into account. The activities of coagulation factors were also comparable to those of the original plasma. Heparin exhibited potentiating effect on ADP- or epinephrine-induced aggregation of platelets in original plasma, but no effect in AT depleted plasma. When purified AT was added back to AT depleted plasma at a concentration of 20 μg/ml, potentiation of platelet aggregation by heparin was clearly demonstrated.Our results suggest that effect of heparin on platelet aggregation is also mediated by anti-thrombin III.


1997 ◽  
Vol 77 (02) ◽  
pp. 343-349 ◽  
Author(s):  
Vibhuti D Chouhan ◽  
Raul A De La Cadena ◽  
Chandrasekaran Nagaswami ◽  
John W Weisel ◽  
Mehdi Kajani ◽  
...  

SummaryWe describe a patient with severe epistaxis, prolonged coagulation tests and decreased plasma factor V following exposure to bovine topical thrombin. Patient IgG, but not normal IgG, showed binding to immobilized thrombin (bovine > human) and fibrinogen, and to factor V by Western blotting; the binding to thrombin was inhibited by hirudin fragment 54-65. Electron microscopy of rotary shadowed preparations showed complexes with IgG molecules attached near the ends of trinodular fibrinogen molecules. Patient IgG inhibited procoagulant, anticoagulant and cell-stimulating functions of thrombin demonstrated by inhibition of fibrinogen clotting, protein C activation and platelet aggregation; thrombin hydrolysis of S-2238 was not inhibited. The results suggest that the antibody is targeted against anion-binding exosite and not catalytic site of thrombin. Antifibrinogen antibodies have not been reported in patients exposed to bovine thrombin. There is a pressing need to re-evaluate the role of bovine thrombin as a therapeutic agent.


1983 ◽  
Vol 50 (03) ◽  
pp. 652-655 ◽  
Author(s):  
F Bauer ◽  
P Schulz ◽  
G Reber ◽  
C A Bouvier

SummaryThree mucopolysaccharides (MPS) used in the treatment of degenerative joint disease were compared to heparin to establish their relative potencies on 3 coagulation tests, the aPTT, the antifactor X a activity and the dilute thrombin time. One of the compounds, Arteparon®, was one fourth as potent as heparin on the aPTT, but had little or no influence on the 2 other tests. Further in vitro studies suggested that Arteparon® acted at a higher level than factor Xa generation in the intrinsic amplification system and that its effect was independent of antithrombin III. In vivo administration of Arteparon® confirmed its anticoagulant properties, which raises the question of the clinical use of this MPS.


2021 ◽  
pp. 028418512110198
Author(s):  
Frank Mosler ◽  
Johannes K Richter ◽  
Marc Schindewolf ◽  
Nando Mertineit ◽  
Hendrik von Tengg-Kobligk ◽  
...  

X-ray contrast media have been reported to have inhibitory effects on bacterial growth. Despite its potentially beneficial effect on patients, these features of contrast media have received relatively little attention in the medical literature in the past decades. The aim of this review is to evaluate the literature concerning the bactericidal and bacteriostatic effects of X-ray contrast media, specifically if there is a known difference concerning these effects between ionic and non-ionic contrast media. Systematic literature review was performed for the years of publication between 1911 and 2019. Since the publication of Grossich in 1911, the effect of iodine on the treatment of superficial infections in surgical procedures has been established clinical knowledge. Bacteriostatic and bactericidal effects of ionic X-ray contrast media are well established. However, non-ionic contrast agents have been the subject of little research in this respect. In past decades, the hypothesis emerged in the literature that mainly the concentration of free iodine might be responsible for any bacteriostatic or bactericidal effect of ionic X-ray contrast media. Nowadays, however, only non-ionic contrast media are used. The question regarding the mechanism and magnitude of bacteriostatic or bactericidal effects of these, non-ionic contrast media, could not be answered conclusively from this review. Non-ionic contrast media could be used intentionally when a local antibacterial effect is intended (e.g. in percutaneous abscess drainage), as well as to reduce the overall dose of antibiotics administered to a patient. Thus, this question remains relevant and might constitute the area of future research.


1994 ◽  
Vol 22 (1) ◽  
pp. 63-66
Author(s):  
M Matsumoto ◽  
H Murakami ◽  
T Matsushima ◽  
J Tamura ◽  
H Sadakata ◽  
...  

An investigation was carried out on two patients with infective endocarditis associated with reduction of ristocetin-induced aggregation of platelets. The plasma of these patients reduced the aggregability with ristocetin of normal platelets. It is suggested that the patients had certain plasma factors which disturbed platelet aggregation with ristocetin.


1997 ◽  
Vol 78 (2) ◽  
pp. 244
Author(s):  
Sujatha Ramesh ◽  
Robert E. Reisman

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