ristocetin and Atrial-Fibrillation

Atrial fibrillation (AF) comes along with high risk of stroke. This risk continues even after re-establishing sinus rhythm with cardioversion. Aim of this study is to evaluate the contribution of electric cardioversion (EC) to platelet activation and procoagulatory tendency.. Extent of platelet activation before and after electric cardioversion was quantified using flow cytometry, impedance aggregation measurements with Multiplate®, and quantification of serum levels of platelet factor 4 (PF4) and ß-thromboglobulin (ß-TG) in patients with AF (N = 10).. No significant differences were observed in any of the measured parameters comparing the values from before and after cardioversion. Geometric means of P-selectin expression and integrin αIIbβ3 activation were 0.27 (+/- 0.07) and 2.30 (+/- 2.61) before EC and 0.28 (+/- 0.17) and 1.67 (+/- 1.82) after EC. Levels of ß-TG were 110.11 ng/ml (+/- 3.78) before and 110.51 ng/ml (+/- 2.56) after EC, levels of PF4 were 35.64 ng/ml (+/- 12.94) before and 32.40 ng/ml (+/- 4.95) after EC. Platelet aggregation triggered with adenosine diphosphate (ADP), arachidonic acid, collagen, Ristocetin, or thrombin receptor activating peptide (TRAP) revealed results within the normally expected ranges without significant changes before and after EC.. Electric cardioversion has no influence on platelet activation markers which is in agreement with other studies reporting electrical cardioversion to be safe.

Topics: Adenosine Diphosphate; Adult; Aged; Arachidonic Acid; Atrial Fibrillation; Blood Coagulation; Collagen; Electric Countershock; Female; Humans; Male; Middle Aged; Peptide Fragments; Platelet Activation; Platelet Aggregation; Platelet Factor 4; Platelet Function Tests; Ristocetin; Treatment Outcome

The direct thrombin inhibitor (DTI) dabigatran is a non-vitamin K antagonist oral anticoagulant for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation. In addition to its anti-thrombotic efficacy, dabigatran has been suggested to exert some pro-thrombotic effect due to fostering the ligation of thrombin to its high affinity platelet receptor glycoprotein (GP) Ibα in patients with atrial fibrillation. On the other hand, we provided evidence that a member of another class of DTIs, lepirudin, stimulates the inhibitory cyclic guanosine monophosphate (cGMP)/soluble guanylate cyclase pathway in human platelets. Here, we investigated the effect of lepirudin and dabigatran spiked to platelets from healthy volunteers on GPIbα-mediated platelet aggregation and agglutination. Ristocetin/von Willebrand factor (vWF)-induced aggregation of platelets in the presence or absence of plasma was significantly inhibited by lepirudin, dabigatran and D-phenylalanyl-L-prolyl-L-arginine chloromethyl ketone (PPACK). However, ristocetin/vWF-mediated platelet agglutination and binding of vWF to platelets were not affected by the DTIs. The anti-aggregatory effect was confirmed by using the GPIbα-specific agonist echicetin beads for human and murine platelets. DTIs diminished echicetin beads-induced Syk Y352 phosphorylation (used here as readout for an early signal occurring during echicetin-induced platelet aggregation), but did not inhibit adenosine diphosphate- or thromboxane A2-induced platelet aggregation. Thrombin was not generated in response to ristocetin/vWF or echicetin beads and therefore did not explain the inhibitory effect of the DTIs. Therapeutic concentration of lepirudin and dabigatran did not affect significantly platelet vasodilator-stimulated phosphoprotein S239 phosphorylation or cGMP and cyclic adenosine monophosphate levels. These data suggest that the DTIs, lepirudin and dabigatran, impair platelet activation measured during platelet aggregation induced by ristocetin/vWF or echicetin beads.

Topics: Animals; Antithrombins; Atrial Fibrillation; Blood Platelets; Cells, Cultured; Dabigatran; Female; Hirudins; Humans; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Platelet Aggregation; Platelet Glycoprotein GPIb-IX Complex; Protein Binding; Recombinant Proteins; Ristocetin; von Willebrand Factor

The aim of this study was to assess the plasma levels of von Willebrand factor antigen and ristocetin cofactor activity, which are well-known markers of endothelial function, in atrial fibrillation (AF) with or without mitral stenosis (MS). Forty-two patients (16 patients with MS and AF [MS(+)AF(+)], 13 patients with nonvalvular AF [MS(-)AF(+)], and 13 patients with MS and sinus rhythm [MS(+)AF(-)]) were included. Von Willebrand factor antigen levels and ristocetin cofactor activities in all participants were assessed. Overall, von Willebrand factor antigen levels and ristocetin cofactor activities in the AF(+) patients were higher than in the AF(-) patients (P = .003 and P = .002, respectively). Von Willebrand factor antigen levels and ristocetin cofactor activities in the 3 groups were found to be different (P = .012 and P = .01, respectively). Von Willebrand factor antigen levels were similar between the MS(+)AF(+) and MS(-)AF(+) groups and were higher than that of the MS(+)AF(-) group. Ristocetin cofactor activity in the MS(-)AF(+) group was significantly higher than in the other 2 groups. The ristocetin cofactor activity and von Willebrand factor antigen levels were significantly higher in diabetic or hypertensive patients than in nondiabetic or normotensive patients. According to the results of this study, circulating von Willebrand factor antigen levels and plasma ristocetin cofactor activities are affected by the presence of AF, MS, and associated comorbidities including type 2 diabetes mellitus and systemic hypertension. Further studies are needed to assess the role of von Willebrand factor antigen and ristocetin cofactor activity in predicting vascular thrombotic events in AF, MS, systemic hypertension, and diabetes mellitus.

Topics: Adult; Aged; Aged, 80 and over; Atrial Fibrillation; Comorbidity; Diabetic Angiopathies; Endothelium; Female; Humans; Hypertension; Male; Middle Aged; Mitral Valve Stenosis; Ristocetin; von Willebrand Factor