Comparison of High-Dose Thrombin Time with Activated Clotting Time for Monitoring of Anticoagulant Effects of Heparin in Cardiac Surgical Patients

1994 ◽  
Vol 79 (1) ◽  
pp. 9???13 ◽  
Author(s):  
Jian-Sheng Wang ◽  
Chung-Yuan Lin ◽  
Robert B. Karp
Keyword(s):  
Surgical Patients ◽  
High Dose ◽  
Thrombin Time ◽  
Clotting Time ◽  
Activated Clotting Time

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.

In vitro effect of hemodilution on activated clotting time and high-dose thrombin time during cardiopulmonary bypass

1996 ◽  
Vol 62 (2) ◽  
pp. 533-537 ◽  
Author(s):  
Robert J. Huyzen ◽  
Willem van Oeveren ◽  
Feiyan Wei ◽  
Pieter Stellingwerf ◽  
Piet W. Boonstra ◽  
...  
Keyword(s):  
Cardiopulmonary Bypass ◽  
High Dose ◽  
Thrombin Time ◽  
Clotting Time ◽  
Activated Clotting Time ◽  
Vitro Effect

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.

The Effects of MDCO-2010, a Serine Protease Inhibitor, on Activated Clotting Time in Blood Obtained from Volunteers and Cardiac Surgical Patients

2012 ◽  
Vol 115 (2) ◽  
pp. 244-252 ◽  
Author(s):  
Heezoo Kim ◽  
Fania Szlam ◽  
Kenichi A. Tanaka ◽  
Andreas van de Locht ◽  
Satoru Ogawa ◽  
...  
Keyword(s):  
Protease Inhibitor ◽  
Serine Protease ◽  
Serine Protease Inhibitor ◽  
Surgical Patients ◽  
Clotting Time ◽  
Activated Clotting Time

Anticoagulation Monitoring

2004 ◽  
Vol 17 (5) ◽  
pp. 317-326 ◽  
Author(s):  
Maureen A. Smythe ◽  
Anne Caffee
Keyword(s):  
Therapeutic Range ◽  
Gold Standard ◽  
Point Of Care ◽  
International Normalized Ratio ◽  
Heparin Therapy ◽  
Thrombin Inhibitor ◽  
High Dose ◽  
Specific Procedure ◽  
Clotting Time ◽  
Activated Clotting Time

Optimal management of anticoagulant therapy requires an understanding of the laboratory tests often employed to guide therapy. The activated partial thromboplastin time (aPTT) can detect abnormalities in the intrinsic and common clotting pathways. Despite numerous limitations in the aPTT test, it remains the gold standard for monitoring unfractionated heparin and direct thrombin inhibitor therapy. The aPTT can be performed in the central laboratory or at the bedside (point of care [POC] testing). The activated clotting time (ACT) is a POC test that is routinely employed to monitor high-dose heparin during invasive and surgical procedures. The ACT therapeutic range will depend on the specific procedure or surgery being performed. Heparin levels are becoming more routinely available and are used to establish the aPTT therapeutic range for heparin therapy as well as for direct monitoring of heparin and low-molecular-weight heparin therapy. The international normalized ratio (INR) is the gold standard for monitoring warfarin patients. The target INR depends on the indication for anticoagulation. POC monitoring for warfarin is becoming increasingly used. Clinicians should have a thorough understanding of the benefits as well as the limitations of warfarin POC monitoring.

Influence of High-dose Aprotinin on Anticoagulation, Heparin Requirement, and Celite- and Kaolin-Activated Clotting Time in Heparin-pretreated Patients Undergoing Open-Heart Surgery

1995 ◽  
Vol 83 (4) ◽  
pp. 679-689. ◽  
Author(s):  
W. Dietrich ◽  
G. Dilthey ◽  
M. Spannagl ◽  
M. Jochum ◽  
S. L. Braun ◽  
...  
Keyword(s):  
Blood Loss ◽  
Thrombin Generation ◽  
Plasma Concentrations ◽  
Postoperative Blood Loss ◽  
High Dose ◽  
Clotting Time ◽  
Activated Clotting Time ◽  
High Dose Aprotinin ◽  
Group A ◽  
Fibrin Monomers

Background Aprotinin causes a prolongation of the celite-activated clotting time (CACT), but not of the kaolin-activated clotting time (KACT). Therefore, concern has been raised regarding the reliability of CACT to monitor anticoagulation in the presence of aprotinin. The current study was designed to test the efficacy of aprotinin to improve anticoagulation, and to investigate whether the prolongation of CACT reflects true anticoagulation or is an in vitro artifact. To elucidate this antithrombotic effect of aprotinin, this study was done in patients prone to reduced intraoperative heparin sensitivity. Methods In a prospective, randomized, double-blind clinical trial, 30 male patients scheduled for elective primary coronary revascularization and treated with heparin for at least 10 days preoperatively, received either high-dose aprotinin (group A) or placebo (group C). The CACT and KACT were determined, but only CACT was used to control anticoagulation with heparin. Parameters of coagulation that are indicators of thrombin generation and activity (F1+2 prothrombin fragments, thrombin-antithrombin III complex, and fibrin monomers), parameters of fibrinolysis (D-dimers), aprotinin, and heparin plasma concentrations were measured. Postoperative blood loss and allogeneic blood transfused were recorded. Results Total heparin administered was 36,200 units (95% confidence interval: 31,400-41,000; group C) compared with 27,700 (25,500-29,800) units (group A; P < 0.05). Hemostatic activation during cardiopulmonary bypass (CPB) was significantly reduced in group A compared with group C. After 60 min of CPB, all parameters were significantly different (P < 0.05) between the groups (group C vs. group A): F1+2 prothrombin fragments, 9.7 (8.9-11.7) ng/ml versus 7.5 (6.2-8.6) ng/ml; thrombin-anti-thrombin III complex (TAT), 53 (42-68) ng/ml versus 29 (23-38) ng/ml; and fibrin monomers, 23 (12-43) ng/ml versus 8 (3-17) ng/ml. Fibrinolysis was also attenuated; D-dimers at the end of operation were 656 (396-1,089) and 2,710 (1,811-4,055) ng/ml for groups A and C, respectively (P < 0.05). The CACT 5 min after the onset of CPB was 552 (485-627) versus 869 (793-955) s for groups C and A, respectively (P < 0.05), whereas the KACT showed no differences between the groups (569 [481-675] vs. 614 [541-697] s for groups C and A, respectively; P = NS). The 24-h blood loss was 1,496 (1,125-1,995) versus 597 (448-794) ml for groups C and A, respectively (P < 0.05). Conclusions Aprotinin treatment in combination with heparin leads to less thrombin generation during CPB. Aprotinin has anticoagulant properties. Celite-activated ACT is reliable for monitoring anticoagulation in the presence of aprotinin, because the prolonged CACT in the aprotinin group reflects improved anticoagulation. Kaolin-activated ACT does not reflect this effect of aprotinin.

scholarly journals Assay-Based Differentiation in the Neutralization Profile of Unfractionated Heparin, Enoxaparin, and Fondaparinux by Andexanet Alfa

2020 ◽  
Vol 26 ◽  
pp. 107602961989512
Author(s):  
Fakiha Siddiqui ◽  
Alfonso Tafur ◽  
Emily Bontekoe ◽  
Omer Iqbal ◽  
Walter Jeske ◽  
...  
Keyword(s):  
Unfractionated Heparin ◽  
Thrombin Generation ◽  
Factor Xa ◽  
Dependent Manner ◽  
Thrombin Time ◽  
Clotting Time ◽  
Activated Clotting Time ◽  
Complete Reversal ◽  
Andexanet Alfa ◽  
Partial Neutralization

Andexanet alfa is a recombinant factor Xa decoy protein, designed to reverse bleeding associated with oral anti-Xa agents. Andexanet alfa is also reported to neutralize the effects of heparin-related drugs. This study focused on the neutralization profiles of unfractionated heparin (UFH), enoxaparin, and, a chemically synthetic pentasaccharide, fondaparinux by andexanet alfa. Whole blood clotting studies were carried out using thromboelastography (TEG) and activated clotting time (ACT). The anticoagulant profile of UFH, enoxaparin, and fondaparinux was studied using the activated partial thromboplastin time (aPTT), thrombin time (TT), and amidolytic anti-Xa, and anti-IIa methods. Thrombin generation inhibition was studied using the calibrated automated thrombogram system. Reversal of each of these agents was studied by supplementing andexanet alfa at 100 µg/mL. In the TEG, andexanet alfa produced almost a complete reversal of the anticoagulant effects of UFH and enoxaparin; however, it augmented the effects of fondaparinux. In the ACT, aPTT, and TT, UFH produced strong anticoagulant effects that were almost completely neutralized by andexanet alfa. Enoxaparin produced milder anticoagulant responses that were partially neutralized, whereas fondaparinux did not produce any sizeable effects. In the anti-Xa and anti-IIa assays, UFH exhibited partial neutralization whereas enoxaparin and fondaparinux did not show any neutralization. All agents produced varying degrees of the inhibition of thrombin generation, which were differentially neutralized by andexanet alfa. These results indicate that andexanet alfa is capable of differentially neutralizing anticoagulant and antiprotease effects of UFH and enoxaparin in an assay-dependent manner. However, andexanet alfa is incapable of neutralizing the anti-Xa effects of fondaparinux.

Potency Adjusted Generic Versions of Argatroban Can Be Differentiated from Branded Argatroban in Thrombin Generation and Platelet Activation Assays.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4007-4007
Author(s):  
Cafer Adiguzel ◽  
Omer Iqbal ◽  
Michael Sammikannu ◽  
Josephine Cunanan ◽  
Walter Jeske ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Platelet Activation ◽  
Thrombin Generation ◽  
Generic Product ◽  
Cellular Systems ◽  
Thrombin Time ◽  
Clotting Time ◽  
Activated Clotting Time ◽  
Branded Product ◽  
Generic Products

Abstract Argatroban represents a widely used direct parenteral thrombin inhibitor for the anticoagulation management of patients with heparin-induced thrombocytopenia. Several generic versions of argatroban namely Slovastan, Gartban and Argaran have also become available in Japan. Although the antithrombin potency of the generic products of argatroban is adjusted to be comparable to the branded product, apparent differences in the pharmacodynamic effects have been noted in thrombin generation and platelet activation assays. To further investigate the bioequivalence of the three generic products with the branded argatroban, these agents were compared in whole blood (WB), platelet rich plasma (PRP) platelet poor plasma (PPP) and isolated biochemical systems. In the WB assays, the activated clotting time (ACT) studies were carried out mimicking the anticoagulant dosing (0–5 ug/ml). In the citrated WB, PRP and PPP various clotting tests such as the prothrombin time/INR (PT/INR), activated partial thromboplastin time (APTT), Heptest, prothrombinase activated clotting time (PICT) and thrombin time were carried out. To test the effect of these agents on tissue factor mediated activation of blood cells, flow cytometric studies were carried out. In addition, thrombin generation markers such as the fibrinopeptide A, thrombin/antithrombin complex and prothrombin fragment 1.2 were also measured. The effect of different forms of argatroban were also investigated on Xa and thrombin generation inhibition. While there was no difference in the anticoagulant effects of the branded and generic products in the clotting assays such as the PT, APTT, Heptest, PICT and thrombin time, matrix based differences were apparent. In the ACT assay, the anticoagulant effect of the branded and generic product were approximately the same, however, upon supplementation of the tissue factor the relative anticoagulant effects of these agents differed. All of the agents also produced a concentration dependent inhibition of the generation of microparticles in the WB studies where each of these agents were differentiated. Argaran produce weaker responses than the other agents. All of the agents also blocked p-selectin expression induced by tissue factor with an IC50 ranging from 1.8–2.3 ug/ml. There were obvious differences among the generic and branded products. In the thrombin and Xa generation assays differences were also noted between the generic and branded product. The relative ability of the generic and the branded argatroban in inhibiting the activation of thrombin activatable fibrinolysis inhibitor (TAFI) showed noticeable differences. These studies clearly indicated that while in the antithrombin titration and global anticoagulant assays the generic brands of argatroban exhibit comparable effects, in cellular systems and other assays differences between the generic product and branded versions can be noted. These obvious differences may be related to the solution matrix and the relative proportion of different forms of argatroban. These observations warrant additional pharmacoequivalent studies on the generic product to assure clinical equivalence of these products.

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