Ex vivo Vitamin D supplementation improves viscoelastic profiles in prostate cancer patients.

BACKGROUND: Increased risk of thromboembolic events is associated with prostate cancer, specifically linked to activation of tissue factor. Vitamin D has potential anticoagulant effects by the downregulation of tissue factor expression. OBJECTIVES: To evaluate the effects on clot formation, the morphological and viscoelastic profiles of prostate cancer patients, before and after ex vivo supplementation of Vitamin D was studied. METHODS: Participants were recruited into a metastatic, non-metastatic and reference group. Whole blood samples were treated ex vivo with a dose of 0.5µg/kg Calcitriol. Clot kinetics were assessed using Thromboelastography®. Morphology of the blood components were studied using scanning electron microscopy (SEM). RESULTS: Results from the Thromboelastography® and SEM indicated no major differences between the non-metastatic group before and after treatment compared to the reference group. The Thromboelastography® showed that the metastatic group had an increased viscoelastic profile relating to a hypercoagulable state. Visible changes with regards to platelet activation and fibrin morphology were demonstrated with SEM analysis of the metastatic group. The viscoelastic and morphological properties for the non-metastatic group after treatment improved to be comparable to the reference group. CONCLUSION: Vitamin D supplementation may lead to a more favorable viscoelastic profile, with less dangerous clots forming.

Poorly controlled type 2 diabetes is accompanied by significant morphological and ultrastructural changes in both erythrocytes and in thrombin-generated fibrin: implications for diagnostics.

We have noted in previous work, in a variety of inflammatory diseases, where iron dysregulation occurs, a strong tendency for erythrocytes to lose their normal discoid shape and to adopt a skewed morphology (as judged by their axial ratios in the light microscope and by their ultrastructure in the SEM). Similarly, the polymerization of fibrinogen, as induced in vitro by added thrombin, leads not to the common 'spaghetti-like' structures but to dense matted deposits. Type 2 diabetes is a known inflammatory disease. In the present work, we found that the axial ratio of the erythrocytes of poorly controlled (as suggested by increased HbA1c levels) type 2 diabetics was significantly increased, and that their fibrin morphologies were again highly aberrant. As judged by scanning electron microscopy and in the atomic force microscope, these could be reversed, to some degree, by the addition of the iron chelators deferoxamine (DFO) or deferasirox (DFX). As well as their demonstrated diagnostic significance, these morphological indicators may have prognostic value.