The aim of the study was to investigate the effect of therapy by perindopril or telmisartan on endothelial/platelet function and on coagulation/fibrinolysis in 20 and 16 hypertensive patients, respectively. The measurements were carried out before and after 1 month of therapy. Both systolic blood pressure and diastolic blood pressure were reduced (P<0.001) or normalized due to each therapy. Plasma thrombomodulin (TM) and von Willebrand factor (vWF) as indicators of endothelial dysfunction, plasma beta-thromboglobulin (betaTG), platelet factor 4 (PF4), soluble P-selectin (sPsel) and soluble glycoprotein V (sGpV) as indicators of in vivo platelet activation, plasminogen activator inhibitor type 1 (PAI-1) antigen and tissue type plasminogen activator (tPA) antigen as markers of fibrinolytic activity, soluble endothelial protein C receptor (sEPCR) as a new marker of hypercoagulation and fibrinogen level as a known risk factor for vascular changes were investigated. A decrease of plasma vWF, sPsel, sGpV, PAI-1 and tPA antigen level (P<0.05, respectively) after 1 month of therapy by perindopril was observed. On the other hand, a decrease of plasma sEPCR and fibrinogen level (P<0.05, respectively) after 1 month of therapy by telmisartan was found. We failed to find changes of plasma TM, betaTG and PF4 due to any therapy investigated. The additional beneficial 'antithrombotic' effects of the renin-angiotensin system targeting agents (vasculoprotective, anti-platelet and profibrinolytic effects of perindopril and anticoagulant/rheological effects of telmisartan) may be important in terms of the favourable role of antihypertensive drugs in cardiovascular morbidity.

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The methods of computational chemistry have been used to elucidate the molecular properties of coumarinic anticoagulants (acenocoumarol, phenprocoumon, warfarin and tecarfarin) and direct thrombin inhibitors (melagatran, dabigatran and their prodrug forms).

Rheological, haemostatic, endothelial and platelet abnormalities appear to play a role in the thrombotic complications of hypertension. This prothrombotic/hypercoagulable state in hypertension may contribute to the increased risk and severity of target organ damage. It can be induced by the activated reninangiotensin system (RAS), with abnormalities in endothelial and platelet function, coagulation and fibrinolysis. Treatment of uncomplicated essential hypertension by RAS targeting antihypertensive therapy could result in a reversal of prothrombotic abnormalities, contributing to a reduction of thrombosis-related complications. Since angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) have two distinct mechanisms of RAS interruption, it is hypothesized that each therapy might have different impact on the prothrombotic state in hypertensive patients. Some studies demonstrate a beneficial effect of both ACE inhibitors and ARBs on prothrombotic state, in addition to their efficacy to normalize elevated blood pressure. The potentially antithrombotic effect of the RAS inhibiting agents may in turn support the preservation of cardiovascular function. Available data may offer an additional explanation for the efficacy of the RAS targeting agents in the prevention of cardiovascular events in patients with atherosclerotic vascular disease.

Theoretical chemistry methods have been used to study the molecular properties of antiplatelet agents (ticlopidine, clopidogrel, prasugrel, elinogrel, ticagrelor and cangrelor) and several thiol-containing active metabolites. The geometries and energies of most stable conformers of these drugs have been computed at the Becke3LYP/6-311++G(d,p) level of density functional theory. Computed dissociation constants show that the active metabolites of prodrugs (ticlopidine, clopidogrel and prasugrel) and drugs elinogrel and cangrelor are completely ionized at pH 7.4. Both ticagrelor and its active metabolite are present at pH = 7.4 in neutral undissociated form. The thienopyridine prodrugs ticlopidine, clopidogrel and prasugrel are lipophilic and insoluble in water. Their lipophilicity is very high (about 2.5-3.5 logP values). The polar surface area, with regard to the structurally-heterogeneous character of these antiplatelet drugs, is from very large interval of values of 3-255 Å 2 . Thienopyridine prodrugs, like ticlopidine, clopidogrel and prasugrel, with the lowest polar surface area (PSA) values, exhibit the largest absorption. A high value of polar surface area (PSA) of cangrelor (255 Å 2 ) results in substantial worsening of the absorption in comparison with thienopyridine drugs.

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Patients with severe pulmonary arterial hypertension suffer from life-threatening thrombotic and bleeding complications. The aim of this study was to compare selected platelet, endothelial, and coagulation parameters in healthy volunteers and patients with severe pulmonary arterial hypertension because of congenital heart defects. The study included healthy volunteers (n = 50) and patients with cyanotic congenital heart defects classified as Eisenmenger syndrome (n = 41). We investigated platelet count, mean platelet volume, and platelet aggregation - spontaneous and induced by various concentrations of five agonists. Von Willebrand factor (vWF), fibrinogen, factor VIII and XII, plasminogen activator inhibitor, antithrombin, D-dimer, and antiphospholipid antibodies were also investigated. We found a decreased platelet count [190 (147-225) vs. 248 (205-295) 10 l, P < 0.0001], higher mean platelet volume [10.9 (10.1-12.0) vs. 10.2 (9.4-10.4) fl, P < 0.0001], and significantly decreased platelet aggregation (induced by five agonists, in various concentrations) in patients with Eisenmenger syndrome compared with controls. These changes were accompanied by an increase of plasma vWF antigen [141.6 (108.9-179.1) vs. 117.4 (9.2-140.7) IU/dl, P = 0.022] and serum anti-β2-glycoprotein [2.07 (0.71-3.41) vs. 0.47 (0.18-0.99) U/ml, P < 0.0001]. Eisenmenger syndrome is accompanied by platelet abnormalities. Thrombocytopenia with increased platelet size is probably due to a higher platelet turnover associated with platelet activation. Impaired platelet aggregation can reflect specific platelet behaviour in patients with Eisenmenger syndrome. These changes can be related both to bleeding and to thrombotic events. A higher vWF antigen may be a consequence of endothelial damage in Eisenmenger syndrome, but the cause for an increase of anti-β2-glycoprotein is unknown.

The aim of the study was to investigate the effect of therapy by rilmenidine on endothelial and platelet function in 23 patients with the early stages of untreated essential hypertension. The measurements were carried out before therapy, after 1 week of placebo administration, after 1 week, after 1 month and after 3 months of therapy. After 1 week of therapy both systolic (SBP) and diastolic blood pressure (DBP) were reduced (P Ͻ 0.001) all over the study period. Plasma thrombomodulin (TM) and von Willebrand factor (vWF) as indicators of endothelial dysfunction, and plasma ␤-thromboglobulin (␤TG) as an indicator of in vivo platelet activation, were investigated. Fibrinogen as a risk factor for vascular changes was also assayed. Platelet aggregation without stimulation (spontaneous, SPA) and induced by adre-