The online version of this article (https://doi.org/10.1007/s10238-018-0490-9) contains supplementary material, which is available to authorized users.
The effect of direct oral anticoagulants (DOACs) on turbidimetric measurements of plasma clot formation and susceptibility to fibrinolysis may facilitate a comparison between different classes of anticoagulants in plasma samples. We obtained 424 citrate plasma samples from 226 atrial fibrillation patients on anticoagulation and 24 samples without anticoagulation serving as controls. As comparators, we measured the international normalized ratio (INR) for phenprocoumon samples (N = 166), anti-Xa for low molecular weight heparin (LMWH) samples (N = 42), and DOAC levels with mass spectrometry (dabigatran N = 40, rivaroxaban N = 110, apixaban N = 42). Plasma clot formation and lysis were recorded continuously on a photometer after addition of an activation mix (tissue factor 2 pmol/l and tissue plasminogen activator 333 ng/ml). We used linear regression and ANCOVA for correlation analysis. Clot formation lag phase was prolonged in the presence of anticoagulants in a concentration-dependent manner for DOACs (dabigatran Spearman r = 0.74; rivaroxaban r = 0.78; apixaban r = 0.72, all p < 0.0001), INR dependent for phenprocoumon (r = 0.59, p < 0.0001), anti-Xa level dependent in LMWH samples (r = 0.90, p < 0.0001). Maximum rate of clot formation and peak clot turbidity were reduced in the presence of anticoagulants, but correlated only moderately with the comparator measures of anticoagulation. The clot lysis time was inversely correlated with DOAC concentrations in the presence of recombinant thrombomodulin. A direct ex vivo comparison between the effects of different classes of anticoagulants is possible with turbidimetric measurement of plasma clot formation and lysis. Anticoagulation inhibited clot formation in a plasma concentration manner for DOACs, INR dependent for phenprocoumon, and anti-Xa dependent for LMWH. Susceptibility to fibrinolysis increased with increasing DOAC concentrations.
Bridge KI, Philippou H, Ariëns RAS. Clot properties and cardiovascular disease. Thromb Haemost. 2014;112:1–8. CrossRef
Bajzar L, Fredenburgh JC, Nesheim M. The activated protein C-mediated enhancement of tissue-type plasminogen activator-induced fibrinolysis in a cell-free system. J Biol Chem. 1990;265:16948–54. PubMed
Ruff CT, Giugliano RP, Braunwald E, et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: A meta-analysis of randomised trials. Lancet. 2014;383:2288–95. CrossRef
He S, Johnsson H, Zabczyk M, et al. A fibrinogen concentrate Haemocomplettan ® (Riastap ®) or a Factor XIII concentrate Fibrogammin ® combined with a mini dose of tranexamic acid can reverse the fibrin instability to fibrinolysis induced by thrombin- or FXa-inhibitor. Br J Haematol. 2013;160:806–16. CrossRefPubMed
- Plasma clot formation and clot lysis to compare effects of different anticoagulation treatments on hemostasis in patients with atrial fibrillation
- Springer International Publishing
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