Plasma fibrin clot properties as determinants of bleeding time in human subjects : association with histidine-rich glycoprotein

Aims. Fibrin formation and histidine-rich glycoprotein (HRG) are involved in primary hemostasis and wound healing. Little is known regarding the relationship of clot characteristics, bleeding time, and wound healing. Methods and Results. We studied 154 patients with coronary artery disease (CAD) and 154 subjects free of CAD matched for age, obesity, and current smoking. We evaluated bleeding time (BT) using standardized skin incisions on a forearm, along with plasma clot permeability (s), clot lysis time (CLT), and histidine-rich glycoprotein (HRG). Compared with controls, BT was 45% shorter in CAD cases. CAD patients had 32% lower s and 17% longer CLT as well as 50% lower HRG compared with controls (all ). After adjusting for potential confounders, s and HRG levels were independent predictors of prolonged BT in CAD patients (OR 23.70, 95% CI 4.65-120.8 and OR 10.27, 95% CI 2.05-51.31, respectively) and controls (OR 10.89, 95% CI 2.31-51.11 and OR 4.54, 95% CI 1.07-19.27, respectively). Scar formation (, 25.6%) was independently predicted by both short and prolonged BT in CAD cases (OR 21.87, 95% CI 7.41-64.55 and OR 10.17, 95% CI 2.88-35.97) and controls (OR 5.94, 95% CI 2.29-15.41 and OR 14.76, 95% CI 4.29-50.77, respectively). Conclusions. The study shows that plasma fibrin clot density and HRG may influence BT and that appropriate skin wound healing is associated with medium BT. Translational Perspective. Elucidation of the complex relationships between plasma fibrin clot phenotype and wound healing might have important practical implications

Inhibition of thrombin generation by simvastatin and lack of additive effects of aspirin in patients with marked hypercholesterolemia

AbstractOBJECTIVESTo assess the effects of aspirin compared with simvastatin on thrombin generation in hypercholesterolemic men, and to establish whether the reduction of elevated blood cholesterol by simvastatin would affect the action of aspirin on thrombin formation.BACKGROUNDAspirin inhibits thrombin formation, but its performance is blunted in hypercholesterolemia. By virtue of altering lipid profile, statins could be expected to influence thrombin generation.METHODSThirty-three men, aged 34 to 61 years, with minimal or no clinical symptoms, serum total cholesterol >6.5 mmol/liter and serum triglycerides <4.6 mmol/liter, completed the study consisting of three treatment phases. First, they received 300 mg of aspirin daily for two weeks (phase I), which was then replaced by simvastatin at the average dose of 24 mg/d for three months (phase II). In phase III, aspirin, 300 mg/day, was added for two weeks to simvastatin, the dose of which remained unchanged. Thrombin generation was assessed: 1) in vivo, by measuring levels of fibrinopeptide A (FPA) and prothrombin fragment 1+2 (F1+2) in venous blood; and 2) ex vivo, by monitoring the rates of increase of FPA and F1+2 in blood emerging from standardized skin incisions of a forearm. A mathematical model was used to describe the kinetics of thrombin formation at the site of microvascular injury.RESULTSTwo-week treatment with aspirin had no effect on thrombin markers in vivo, while ex vivo it depressed the total amount of thrombin formed, though not the reaction rate. After simvastatin treatment, serum cholesterol decreased by 31% and LDL cholesterol by 42%, while thrombin generation became markedly depressed. In venous blood, FPA was significantly reduced. Concomitantly, the initial thrombin concentration and total amount of thrombin generated decreased significantly. Addition of aspirin to simvastatin (phase III) had no further effect on any of these parameters.CONCLUSIONSIn men with hypercholesterolemia, lowering serum cholesterol level by a three-month simvastatin treatment is accompanied by a marked reduction of thrombin generation both at basal conditions in venous blood and after activation of hemostasis by microvascular injury. Once blood cholesterol became reduced, adding aspirin to simvastatin did not enhance dampening of thrombin formation

Adherence to treatment – a pivotal issue in long-term treatment of patients with cardiovascular diseases. An expert stand-point

The adherence to treatment is defined as the extent to which a person’s behaviour, including taking medication, following a diet, and/or executing lifestyle changes, corresponds with agreed recommendations from a health-care provider. Non-adherence to medication may lead to increased morbidity, mortality, and costs to the healthcare system. Therefore, it is pivotal to know the patient’s true adherence to medication, understand the causes of low adherence, and take actions to improve adherence. The authors assumed that individual, complex health education started during hospitalisation and continued after discharge, explaining the pathophysiology and symptoms of the disease, elucidating goals and potential benefits of treatment, and highlighting the risk of premature termination of therapy, with use of additional methods helping patients to remember treatment schedule will enhance adherence to treatment. There is an urgent need to develop and test a dedicated procedure covering all these activities. Introduction. A substantial proportion of patients with cardiovascular diseases do not respond to the treatment sufficiently [1–3]. Several factors of poor response to medication should be taken into ac-count, including inadequate drug intake [4–6]. To systematise the phenomenon of following medical recommendations, the term “adherence” was proposed. The World Health Organisation (WHO) defines “adherence” as “the extent to which a person’s behaviour, including taking medication, following a diet, and/or executing lifestyle changes, corresponds with agreed recommendations from a healthcare pro-vider” [7]. Adherence has been also defined as the “active, voluntary, and collaborative involvement of the patient in a mutually acceptable course of behaviour to produce a therapeutic result” [8]. Previously the term ‘compliance’ was widely used, particularly in negative concord as ‘non-compliance’. Nowadays ‘compliance’ is associated with a more pejorative connotation than ‘adherence’ because ‘non-compliance issues’ are mostly patient-oriented without a deeper view into the different set of factors, e.g. obstacles identified in the healthcare system. Thus, currently in scientific deliberations we usually prefer usage of the term ‘adherence’ [9].The adherence to treatment is defined as the extent to which a person’s behavior including taking medication, following a diet, and/or executing lifestyle changes, corresponds with agreed recommendations from a health care provider. Non-adherence to medication may lead to increased morbidity, mortality, and costs to the healthcare system. Therefore it is pivotal to know the true patient's adherence to medication, understand the causes of low adherence and take actions to improve adherence. The authors assumed that the individual, complex health education started during hospitalization and continued after discharge, explaining the pathophysiology and symptoms of the disease, elucidating goals and potential benefits of treatment, highlighting the risk of premature termination of therapy, with use of additional methods helping patients to remember treatment schedule will enhance adherence to treatment. There is an urgent need to develop and test a dedicated procedure covering all of these activities

Cardiovascular risk management in type 2 diabetes of more than 10-year duration: Results of Polish ARETAEUS2-Grupa Study

Background: ARETAEUS 1 study showed that a great majority of patients with type 2 dia­betes mellitus (T2DM) of short duration did not meet all of the treatment goals. Since then the treatment goals in T2DM have been changed. The aim of the ARETAEUS 2-Grupa Study was to assess cardiovascular (CV) risk management and meeting treatment goals in the population of T2DM of more than 10-year duration. Methods: ARETAEUS2-Grupa was a cross-sectional questionnaire-based study conducted in Poland in 2012. Randomly selected physicians recruited 1,740 patients with T2DM diag­nosed more than 10 years before the study. Results: Lipid treatment goals were met respectively: for total cholesterol in 34.5% of all patients, triglycerides in 53.8%, low density lipoprotein cholesterol (LDL-C) in 26.5% and high density lipoprotein cholesterol (HDL-C) in 38.2%. Most of patients with and without coronary artery disease were receiving aspirin (90.3% and 60%, respectively) and statins (84.4% and 67.7%, respectively). The current blood pressure (BP) goal (140/90 mm Hg) was met in 43.5% of pa­tients and the previous goal (&lt; 130/80 mm Hg) in 12.4%. The patients were mainly treated with ≥ 3 antihypertensive drugs. All treatment goals (for HbA1c, BP and LDL-C) were reached only by 8.2% of patients, any two goals by 26.3% of patients, one goal by 39.8% of patients, none by 25.6% of patients. Conclusions: The new less restrictive treatment goals are reached more frequently but still much is to be done in the field of clinical practice guidelines implementation and CV prevention in T2DM population

Management and treatment goals in Polish patients with type 2 diabetes of more than ten years’ duration — results of ARETAEUS2-Grupa Study

Wstęp: W poprzednich badaniach wykazano niewystarczającą kontrolę choroby u chorych na cukrzycę. Polskie Towarzystwo Diabetologiczne zmieniło wartości docelowe HbA1c i ciśnienia tętniczego u chorych na cukrzycę w wytycznych z 2011 roku, które zostały utrzymane w kolejnych edycjach wytycznych. Badanie przeprowadzono w celu oceny leczenia cukrzycy i wyboru metod leczenia u chorych na cukrzycę typu 2 o czasie trwania &gt; 10 lat oraz określenia stopnia spełniania kryteriów kontroli cukrzycy zalecanych w wytycznych Polskiego Towarzystwa Diabetologicznego z 2012 roku.Materiał i metody: Badanie ARETAEUS2-Grupa było przekrojowym badaniem kwestionariuszowym przeprowadzonym w Polsce w 2012 roku (kwiecień–czerwiec). Badaniem objęto 1740 chorych na cukrzycę typu 2 w każdym wieku i obu płci rozpoznaną ponad 10 lat przed rozpoczęciem badania, włączonych do badania przez losowo wybranych lekarzy.Wyniki: Wszyscy chorzy otrzymywali leczenie farmakologiczne, większość — leczenie skojarzone lub insulinę w monoterapii. 40% chorych spełniło kryterium kontroli HbA1c (≤ 7%), a mediana odsetka HbA1c była powyżej zalecanej wartości (7,2%). W całej populacji jedynie 8% chorych spełniło wszystkie kryteria kontroli choroby (HbA1c, ciśnienie tętnicze i profil lipidowy), 26% — dwa z tych kryteriów, 40%— jedno z tych kryteriów. Ponad 25% chorych nie spełniło żadnego z tych kryteriów.Wnioski: Zaobserwowano duże odstępstwa od celów leczenia zalecanych w aktualnych wytycznych postępowania u chorych na cukrzycę typu 2 o czasie trwania &gt; 10 lat. Częstość występowania sercowo-naczyniowych czynników ryzyka i późnych powikłań cukrzycy była duża, a stosunkowo duży odsetek chorych nie był badany w kierunku późnych powikłań cukrzycy.Introduction: Previous studies have shown insufficient diabetes control in patients with type 2 diabetes (T2DM). Diabetes Poland changed the target HbA1c and blood pressure (BP) values in diabetic patients in their practice guidelines in 2011, that were further sustained. To assess the management and treatment choices in T2DM of more than ten years’ duration and the degree to which diabetic control criteria recommended by the Diabetes Poland clinical practice guidelines 2012 are being met.Material and methods: ARETAEUS2-Grupa was a cross-sectional questionnaire-based study conducted in Poland in 2012 (April–June). It involved 1,740 patients of any age and both genders, with T2DM diagnosed more than ten years before the study, and recruited by randomly selected physicians.Results: All patients received pharmacological treatment, most of them combination therapy or insulin in monotherapy. 40% of patients met the goal for HbA1c control (≤ 7%) and the median value of HbA1c was above the recommended threshold (7.2%). Only 8% of thetotal population met all three goals (HbA1c, BP and lipid levels), 26% — two goals, and 40% — only one goal. Over 25% of patients did not meet any of the treatment goals.Conclusions: We observed considerable deviations from treatment targets recommended by current clinical practice guidelines for patients with T2DM of more than ten years’ duration. The frequency of cardiovascular risk factors and late diabetes complications was high, while a relatively high percentage of patients was not examined for late diabetes complications