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.

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.

Development of Prothrombinase Induced Clotting Time (Pefakit ®, PiCT) Assay and its Validation in the Monitoring of Anti-Xa and Anti-FIIa Drugs.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1858-1858
Author(s):  
Debra A. Hoppensteadt ◽  
Josephine Cunanan ◽  
Jeanine M. Walenga ◽  
Jawed Fareed
Keyword(s):  
Dose Range ◽  
Fibrin Clot ◽  
Thrombin Time ◽  
Plasma Samples ◽  
Clotting Time ◽  
Prothrombinase Complex ◽  
Anticoagulant Drugs ◽  
Normal Human ◽  
Ecarin Clotting Time ◽  
Direct Acting

Abstract Unfractionated heparin (UFH), low molecular weight heparin (LMWH), fondaparinux, danaparoid, direct and indirect (via a cofactor) acting anti-FIIa and anti-Xa anticoagulant drugs are being used in patients for the prophylaxis and treatment of thrombosis. The aPTT does not reliably measure the effects of these drugs. Therefore, there is no simple/reliable method for monitoring patients administered these drugs, particularly those with renal insufficiency and obesity. The newly developed Prothrombinase Induced Clotting Time (PiCT) assay (Pefakit®; Pentapharm, Ltd.; Basel, Switzerland) was developed for monitoring heparins. The PiCT is based on the activation of plasma coagulation by a defined amount of activated FXa, phospholipid and Russell’s viper venom (RVV). The prothrombinase complex formed following recalcification is independent of endogenous thrombin mediated FV activation because the RVV directly activates FV. In this study, the PiCT was used to determine the relative anticoagulant actions of UFH, LMWH, anti-FIIa and anti-FXa drugs. Drugs were supplemented to normal human pooled plasma in a concentration range of 10- 0.08 μg/ml. Plasma samples were analyzed using the PiCT, aPTT, Heptest, thrombin time (TT), ecarin clotting time (ECT), chromogenic anti-FIIa, chromogenic anti-FXa and fibrinopeptide A (FPA) generation assays. In addition, plasma samples from patients treated with these drugs were also tested. The UFH, LMWH, anti-FIIa drugs and the indirect acting anti-FXa drugs produced a concentration-dependent prolongation of the PiCT. Different responses were obtained for each drug. The anti-FIIa drugs gave the strongest dose-response response followed by UFH, LMWH and fondaparinux, in that order. The direct acting anti-FXa agents showed a weak response in the PiCT. Compared to the other assays, the PiCT response showed better sensitivity, reproducibility and linearity over a broader dose range than the aPTT, Heptest, TT, ECT, anti-FIIa and anti-FXa assays. Samples from patients treated with enoxaparin (0.5 mg/kg IV) gave peak concentrations of 0.92± 0.11 U/ml by the PiCT, compared to 0.95± 0.24 U/ml by the anti-FXa assay. Samples from patients treated with bivalirudin, lepirudin or argatroban gave comparable values by the PiCT, aPTT and ECT. The relative prolongation of the PiCT was proportional to the inhibition of thrombin generation as measured by FPA. The PiCT is as simple to perform as the aPTT and can be adapted to any instrument capable of detecting a fibrin clot. Unlike other clot-based tests, the PiCT is sensitive to most old and new anticoagulant drugs and the results are linear through both the therapeutic and interventional dosing ranges. The PiCT may offer the first available single assay that can be universally used for monitoring most of the new anticoagulant drugs regardless of their mechanism of action.

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 Safety of a single bolus administration of heparin without the measurement of activated clotting time during cryoballoon ablation: a prospective randomized controlled trial

2021 ◽  
Author(s):  
Dong Geum Shin ◽  
Jinhee Ahn ◽  
Sang-Jin Han ◽  
Hong Euy Lim
Keyword(s):  
Controlled Trial ◽  
Oral Anticoagulants ◽  
Bleeding Complications ◽  
Cryoballoon Ablation ◽  
Bolus Administration ◽  
Single Shot ◽  
Clotting Time ◽  
Single Bolus ◽  
Activated Clotting Time ◽  
Group A

Introduction: Single-shot ablation has emerged as an effective technique for index atrial fibrillation (AF) ablation, with an advantage of short procedure time. Although recent guidelines recommend peri-procedural uninterrupted oral anticoagulants (OACs), the intra-procedural anticoagulation strategy remains uncertain under non-vitamin K OACs (NOACs). We investigated procedural safety of a single bolus administration of heparin without activated clotting time (ACT) measurement during cryoballoon ablation (CBA). Methods: Two hundred patients (64.2±10.0years, 70% with non-paroxysmal AF) who underwent CBA with uninterrupted NOACs were randomly assigned to No-ACT group and ACT group. A bolus of heparin (100 U/kg) was routinely administered immediately after transseptal puncture. In the ACT group, an additional injection of heparin (30 U/kg) was administered if ACT at 30-min after the initial bolus was <300 s. Results: There were no differences in baseline characteristics including CHA2DS2-VASc score between two groups. The left atrium indwelling and procedure times were 60.4±13.1 min and 78.9±13.9 min, respectively and not significantly different between two groups. The mean ACT was 335.2±59.9 s in the ACT group. Any bleeding rate was 3.2% in all patients and there was no statistically difference in bleeding complications between two groups. In the ACT group, groin hematoma, laryngopharyngeal bleeding, and hemoptysis occurred in 3, 1, and 1 patient, respectively. Cardiac tamponade occurred in 1 patient in the No-ACT group. No thromboembolic events occurred during the 30-day follow-up after CBA. Conclusion: Single bolus administration of heparin without ACT measurement is a feasible anticoagulation strategy for CBA in patients with uninterrupted NOACs intake.

Factor XII deficiency and cardiopulmonary bypass

Perfusion ◽  
1995 ◽  
Vol 10 (1) ◽  
pp. 13-16 ◽  
Author(s):  
M. Wallock ◽  
C. Arentzen ◽  
J. Perkins
Keyword(s):  
Cardiopulmonary Bypass ◽  
Coagulation Cascade ◽  
High Dose ◽  
Factor Xii ◽  
Thrombin Time ◽  
Clotting Time ◽  
Activated Clotting Time ◽  
Coagulation Tests ◽  
Deficient Patient ◽  
Routine Coagulation

Factor XII initiates the intrinsic coagulation cascade and may affect the fibrinolytic system. Routine coagulation tests used during cardiopulmonary bypass (CPB) are abnormal in factor-XII-deficient patients and are useless for monitoring anticoagulation in these patients. A factor-XII-deficient patient requiring CPB is described. The baseline celite activated clotting time (ACT) was greater than 1400 seconds and the thrombin time was 12.4 seconds (control, 11.9 seconds). Two units of plasma were given resulting in an ACT of 173 seconds. Following 300 units/kg of heparin and during CPB, the ACT ranged from 670-596 seconds with the thrombin time greater than 200 seconds. Plasma provides exogenous factor XII allowing an endpoint on the ACT test and may protect against possible postoperative hypofibrinolytic complications. A commercially available modified thrombin time may also be useful and provide an endpoint during high-dose heparinization.

Variability of three activated clotting time point-of-care systems in cardiac surgery: reinforcing available evidence

Perfusion ◽  
2021 ◽  
pp. 026765912110236
Author(s):  
Diego Solís Clavijo ◽  
Abel Ortega Cotano ◽  
Nuria Alonso Peña ◽  
Sergio Caballero Gálvez ◽  
Fernando Arellano Núñez ◽  
...  
Keyword(s):  
Cardiac Surgery ◽  
Point Of Care ◽  
Clotting Time ◽  
Mean Values ◽  
Activated Clotting Time ◽  
Bland Altman Method ◽  
Anticoagulant Drugs ◽  
Care Systems ◽  
Point Of Care Systems ◽  
The Mean

Background: Cardiac surgery with extracorporeal circulation (ECC) requires the administration of anticoagulant drugs to maintain ACT ranges 400–600 seconds, which requires exhaustive coagulation monitoring for which various point-of-care devices are available. However, there is variability between them, so we aimed to compare the values in ACT measurement. Methods: Simultaneous ACT measurements were performed with the Hemochron Response®, Hemostasis Management System Plus® (HMS Plus®) and Hemochron Signature® systems. Results: A total of 255 simultaneous measurements were taken, the mean and standard deviation (SD) of each device were: Hemochron Signature® 361.1 seconds (SD: 156.9), HMS Plus® 412.8 seconds (SD: 180.9) and Hemochron Response® 422.8 seconds (SD: 187.9), being these differences statistically significant (Fridman’s test p < 0.01). For comparisons the Bland–Altman method was used, resulting the Hemochron Response® has 61.7 seconds higher mean values than the Hemochron Signature®, the Hemochron Response® 10 seconds higher than the HMS Plus® and the HMS Plus® 51.7 seconds higher than the Hemochron Signature®. Conclusion: The differences found in comparisons are considered to be clinically relevant, which is why it is considered important to make the variability of the different monitoring systems known and to take them into account for optimal control of this parameter and its clinical repercussions.

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