Low-molecular-weight heparin inhibits plasma thrombin generation via direct targeting of factor IXa: a reply to rebuttal

Buyue, Yang; Misenheimer, Tina M.; Sheehan, John P.

doi:10.1111/jth.12136

Cited by 2 publications

(2 citation statements)

References 7 publications

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“…Therefore our study is not directly comparable to previous trials using other markers of thrombin generation. Furthermore, the mode of action of heparins in clinical settings is far from clear, still generating a debate whether it is increased thrombin inactivation or decreased prothrombin consumption that is a primary effect [ 20 , 21 ]. While low heparin concentrations facilitate thrombin binding to antithrombin at expense of its binding to other plasma proteins (resulting in increased TAT), it has been suggested that heparin´s primary effect in the setting of higher heparin concentrations is inhibition of prothrombin consumption [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

Heparin and Protamine Titration Does Not Improve Haemostasis after Cardiac Surgery: A Prospective Randomized Study

et al. 2015

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BackgroundBleeding complications are common in cardiac surgery. Perioperative handling of heparin and protamine may influence the haemostasis. We hypothesized that heparin and protamine dosing based on individual titration curves would improve haemostasis in comparison to standard dosing.Subjects and MethodsSixty patients scheduled for first time elective coronary artery bypass grafting or valve surgery were included in a prospective randomized study. The patients were randomized to heparin and protamine dosing with Hepcon HMS Plus device or to standard weight and activated clotting time (ACT) based dosing. Blood samples were collected before and 10 minutes, 2 hours and 4 hours after cardiopulmonary bypass. Primary endpoint was endogenous thrombin potential in plasma 2 hours after surgery as assessed by calibrated automated thrombography. Secondary endpoints included total heparin and protamine doses, whole blood clot formation (thromboelastometry) and post-operative bleeding volume and transfusions. Heparin effect was assessed by measuring anti-Xa activity.ResultsEndogenous thrombin potential and clot formation deteriorated in both groups after surgery without statistically significant intergroup difference. There were no significant differences between the groups in total heparin and protamine doses, heparin effect, or postoperative bleeding and transfusions at any time point. Significant inverse correlations between anti-Xa activity and endogenous thrombin potential were observed 10 min (r = -0.43, p = 0.001), 2 hours (r = -0.66, p<0.001) and 4 hours after surgery (r = -0.58, p<0.001).ConclusionIn conclusion, the results suggest that perioperative heparin and protamine dosing based on individual titration curves does not improve haemostasis after cardiac surgery. Postoperative thrombin generation capacity correlates to residual heparin effect.Trial Registration www.isrctn.com ISRCTN14201041.

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Section: Discussionmentioning

confidence: 99%

Heparin and Protamine Titration Does Not Improve Haemostasis after Cardiac Surgery: A Prospective Randomized Study

et al. 2015

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“…Fluorescence , blood clotting time , circular dichroism , and other analytical methods have also been utilized for the characterization of LMWHs. Due to differences in the processes used in their preparation, AT‐III binding affinities vary among the LMWHs ; however, the amount of 3‐ O ‐sulfo‐ N ‐sulfoglucosamine, which is required for high affinity AT‐III binding, can readily be determined using NMR correlation spectroscopy .…”

Section: Introductionmentioning

confidence: 99%

Affinity capillary electrophoresis for the determination of binding affinities for low molecular weight heparins and antithrombin‐III

2014

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The anticoagulant properties of heparin stem in part from high-affinity binding to antithrombin-III (AT-III) inducing a 300-fold increase in its inhibitory activity against the coagulation protease factor Xa. The minimal structural requirements for AT-III binding are contained in the rare heparin pentasaccharide sequence containing a 3,6-O-sulfated N-sulfoglucosamine residue. ACE is used in this work to measure the relative AT-III binding affinities of the low molecular weight heparins (LWMHs) dalteparin, enoxaparin, and tinzaparin and the synthetic pentasaccharide drug fondaparinux (Arixtra). Determination of the AT-III binding affinities of the LWMHs is complicated by their inherent structural heterogeneity and polydispersity. The fractional composition of 3-O-sulfo-N-sulfoglucosamine residues was determined for each drug substance using 2D NMR and used in the interpretation of the ACE results.

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Low-molecular-weight heparin inhibits plasma thrombin generation via direct targeting of factor IXa: a reply to rebuttal

Cited by 2 publications

References 7 publications

Heparin and Protamine Titration Does Not Improve Haemostasis after Cardiac Surgery: A Prospective Randomized Study

Heparin and Protamine Titration Does Not Improve Haemostasis after Cardiac Surgery: A Prospective Randomized Study

Affinity capillary electrophoresis for the determination of binding affinities for low molecular weight heparins and antithrombin‐III

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