Key result
Anticoagulation prolonged clot formation lag phase in a concentration-dependent manner for DOACs (r=0.72-0.78), phenprocoumon (r=0.59), and LMWH (r=0.90), and increased susceptibility to fibrinolysis.
Why the study?
How do different classes of anticoagulants affect turbidimetric measurements of plasma clot formation and fibrinolysis in patients with atrial fibrillation?
Observational (n=250)
No
How do different classes of anticoagulants affect turbidimetric measurements of plasma clot formation and fibrinolysis in patients with atrial fibrillation?
Effect estimate: Spearman r = 0.72-0.90
p-value: p=<0.0001
Turbidimetric measurement of plasma clot formation and lysis allows for direct ex vivo comparison of the pharmacodynamic effects of different anticoagulant classes in patients with atrial fibrillation.
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.
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Königsbrügge et al. (2018) conducted an observational in Non-valvular atrial fibrillation (n=250). Anticoagulation treatments (DOACs, VKA, LMWH) vs. No anticoagulation was evaluated on Correlation of clot formation lag phase with anticoagulant concentration or intensity (Spearman r = 0.72-0.90, p=<0.0001). Anticoagulation prolonged clot formation lag phase in a concentration-dependent manner for DOACs (r=0.72-0.78), phenprocoumon (r=0.59), and LMWH (r=0.90), and increased susceptibility to fibrinolysis.
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