No abstract

Thrombin generation was investigated in platelet-rich plasma (PRP) from 11 healthy controls, 17 patients with severe haemophilia A and 7 patients with severe haemophilia B. Mean endogenous thrombin potential (ETP) in arbitrary fluorescence units (FU) was 226.9 +/- 44.6, 186.4 +/- 22.5, 154.2 +/- 41.3 in controls, haemophilia A and B, respectively, all at a platelet count of 200 x 10(9)/l (p = 0.004 for controls vs. haemophilia A, p = 0.003 for controls vs. haemophilia B, no significant difference between haemophilia A and B). The contribution of FVIII to thrombin generation in haemophilia A was 1.31 +/- 0.16 FU/% of FVIII:C activity, while for FIX in haemophilia B this was 0.80 +/- 0.21 FU/% of FIX activity. There was an almost linear relationship between increasing platelet count and thrombin generation up to a mean platelet count of 100 x 10(9)/l. Further increase in platelet count has only a marginal influence on thrombin generation. Platelets increase ETP in haemophilia A by 0.184 +/- 0.022 FU/10(9) platelets/l and in haemophilia B by 0.319 +/- 0.085 FU/10(9) platelets/l, and this was significantly different between the two groups (p = 0.0002). This influence of plate-lets diminishes with increasing concentration of either FVIII or FIX. In conclusion, there is a difference in thrombin generation between haemophilia A and B, and this may be attributed to the role of platelets in the assembly of the tenase complex on their surface.

Aspirin resistance in stroke patients is not uncommon. The clinical usefulness of routine platelet function tests needs to be proved by further trials.

Background Monitoring of anticoagulant activity of direct oral anticoagulants (DOACs) can be necessary in special situations. DOAC plasma levels have a high inter‐ and intraindividual variation and do not necessarily reflect the coagulation status of the patient. Thrombin generation (TG) is a global hemostatic assay with the capacity to overcome this limitation. The aim of this study was to show correlations between DOAC plasma levels and TG parameters using the fully automated ST Genesia system. Methods A total of 380 blood samples (120 with apixaban, 79 with dabigatran, 79 with edoxaban, and 102 with rivaroxaban) from patients at different time points after DOAC intake were included in the analysis. DOAC plasma levels were analyzed using calibrated anti‐Xa or anti‐IIa tests. Thrombin generation was measured using the ST Genesia system and STG‐DrugScreen reagent. Results There was a significant correlation between the drug levels of all DOACs and the TG parameters’ lag time and time to peak. Peak thrombin and velocity index show a negative correlation following an exponential regression curve with all anti‐Xa DOACs but not with dabigatran. Apart from a weak correlation with rivaroxaban, there was no correlation between drug levels of all other DOACs and endogenous thrombin potential. Conclusion TG parameters measured with ST Genesia correlate with the drug levels of anti‐Xa DOACs. Peak thrombin and velocity index are of special interest for the determination of residual anticoagulant effect at low drug levels. For dabigatran‐treated patients, only lag time shows a correlation with the dabigatran plasma levels.

For the delivery of drugs into the brain, the use of nanoparticles as carriers has been described as a promising approach. Here, we prepared nanoparticles as carriers for the model drugs thioflavin T and thioflavin S that bind fibrillar amyloid beta peptides (Abeta). These polymer colloids are composed of a polystyrene core and a degradable PBCA [poly(butyl-2-cyanoacrylate)] shell with a diameter of 90-100nm as shown by dynamic light scattering. Fluorescence spectrophotometric analysis revealed that encapsulated thioflavin T exhibited significantly stronger fluorescence than the free fluorophore. The enzymatic degradation of core-shell nanoparticles, as required in vivo, was shown after their treatment with porcine liver esterase, a non-specific esterase, in vitro. Shells of nanoparticles were dose-dependently degraded while their polystyrene cores remained intact. In the cortices of 7-14 months old APP/PS1 mice with age-dependent beta-amyloidosis, thioflavins selectively targeted fibrillar Abeta after biodegradation-induced release from their nanoparticulate carriers upon intracerebral injection. Collectively, our data suggest that core-shell nanoparticles with controlled degradation in vivo can become versatile tools to trace and clear Abeta in the brain.