In Search of the Perfect Thrombosis and Bleeding-Associated Cancer Scale.

Thrombosis and bleeding are commonly observed in cancer patients, and their management is crucial for positive patient outcomes. A comprehensive, prophylactic, and therapeutic management of venous thrombosis should focus on identifying the patients who would benefit most from treatment to reduce mortality and minimize the risk of thrombosis recurrence without significantly increasing the risk of bleeding. Existing cancer scales provide valuable information for assessing the overall burden of cancer and guiding treatment decisions, but their ability to predict thrombotic and bleeding events remains limited. With increasing knowledge of the pathophysiology of cancer and the availability of advanced anticancer therapies, new risk factors for cancer-associated thrombosis and bleeding are being identified. In this report, we analyze the current literature and identify new risk factors for venous thrombosis and bleeding which are not included in routinely used risk scores. While some existing cancer scales partially capture the risk of thrombosis and bleeding, there is a need for more specific and accurate scales tailored to these complications. The development of such scales could improve risk stratification, aid in treatment selection, and enhance patient care. Therefore, further research and development of novel cancer scales focused on thrombosis and bleeding are warranted to optimize patient management and outcomes.

Inflammation and vascular diseases.

Chronic venous disease and cardiovascular atherothrombotic diseases have a high prevalence worldwide. The aetiopathogenesis of both these vascular conditions may share certain aetiopathogenetic moments. Abnormal blood flow, altered intravascular tension, and subsequent endothelial dysfunction may all play an important role. Another plausible alternative is the correlation of some risk factors of both diseases, in particular obesity and metabolic syndrome with all its components and an impact on atherogenesis as well as chronic venous disease. The relationship may even be causal, that is a chronic vessel wall inflammation which is present in advanced venous insufficiency might accelerate atherogenesis. On the other hand, altered haemodynamics in right ventricular dysfunction with a subsequent elevation in venous pressure can worsen or induce venous insufficiency, and/or undoubtedly cause symptoms and signs typical of chronic venous disease. As suggested by the findings published recently in the Gutenberg Health Study, particularly its subanalysis regarding the relationship of venous disease and cardiovascular diseases, the venous and arterial beds can be affected by common aetiopathogenetic factors or both the systems can interfere with each other.

Diosmin/hesperidin: a cooperating tandem, or is diosmin crucial and hesperidin an inactive ingredient only?

With the advent of novel monocomponent venoactive drugs containing the flavonoid diosmin, the need has arisen to answer the question of therapeutic equivalence of the widely used micronized purified flavonoid fraction (MPFF) contained in Detralex and of the currently introduced monocomponent venoactive drugs. Experimental work provides evidence that each of the two dominant components, i.e. diosmin and hesperidin, has its specific and distinctive pharmacodynamic effect. There is also evidence of a mutual synergistic effect, e.g. in antiexudative action. Clinical studies have been carried out with MPFF for the most part, and effect has clearly been established in this particular form. Conversely, the results of studies documenting the effect of diosmin alone have been conflicting. Mutual comparisons failed to confirm equivalence of MPFF and monocomponent diosmin in any of the studies. This fact is clearly reflected in the relevant guidelines where the use of MPFF in chronic venous disease is recommended unequivocally (level of evidence 1 and strength of evidence B) while, in the case of monocomponent diosmin, it is stated that treatment can be considered (2C). It can be concluded that both experimental and clinical studies document that only a complex of biologically active flavonoids - a micronized purified flavonoid fraction - has evidence of effect and is recommended by relevant guidelines.

Guidance for the Management of Patients with Vascular Disease or Cardiovascular Risk Factors and COVID-19: Position Paper from VAS-European Independent Foundation in Angiology/Vascular Medicine.

COVID-19 is also manifested with hypercoagulability, pulmonary intravascular coagulation, microangiopathy, and venous thromboembolism (VTE) or arterial thrombosis. Predisposing risk factors to severe COVID-19 are male sex, underlying cardiovascular disease, or cardiovascular risk factors including noncontrolled diabetes mellitus or arterial hypertension, obesity, and advanced age. The VAS-European Independent Foundation in Angiology/Vascular Medicine draws attention to patients with vascular disease (VD) and presents an integral strategy for the management of patients with VD or cardiovascular risk factors (VD-CVR) and COVID-19. VAS recommends (1) a COVID-19-oriented primary health care network for patients with VD-CVR for identification of patients with VD-CVR in the community and patients' education for disease symptoms, use of eHealth technology, adherence to the antithrombotic and vascular regulating treatments, and (2) close medical follow-up for efficacious control of VD progression and prompt application of physical and social distancing measures in case of new epidemic waves. For patients with VD-CVR who receive home treatment for COVID-19, VAS recommends assessment for (1) disease worsening risk and prioritized hospitalization of those at high risk and (2) VTE risk assessment and thromboprophylaxis with rivaroxaban, betrixaban, or low-molecular-weight heparin (LMWH) for those at high risk. For hospitalized patients with VD-CVR and COVID-19, VAS recommends (1) routine thromboprophylaxis with weight-adjusted intermediate doses of LMWH (unless contraindication); (2) LMWH as the drug of choice over unfractionated heparin or direct oral anticoagulants for the treatment of VTE or hypercoagulability; (3) careful evaluation of the risk for disease worsening and prompt application of targeted antiviral or convalescence treatments; (4) monitoring of D-dimer for optimization of the antithrombotic treatment; and (5) evaluation of the risk of VTE before hospital discharge using the IMPROVE-D-dimer score and prolonged post-discharge thromboprophylaxis with rivaroxaban, betrixaban, or LMWH.

Anticoagulant therapy in the elderly.

Elderly and fragile patients have a higher risk of atrial fibrillation, a higher risk of systemic embolism. They are therefore often candidates for long-term anticoagulation medication. At the same time, they have an increased risk of bleeding due to age and co-morbidities, which anticoagulation therapy necessarily potentiates. New Oral Direct Anticoagulants (NOAC) registered in the Czech Republic - dabigatran, rivaroxaban, apixaban or edoxaban - are a good alternative to the currently dominant warfarin in many of these indications. Their great advantage is that they do not need to be regularly monitored on a laboratory basis and are considered to be safer, especially to significant reduction of the risk of intracranial haemorrhage. Each drug in the group of direct oral anticoagulants has some specificity resulting from pharmacological properties or the results of registration studies, so it is possible to individually determine an optimal anticoagulation strategy. Older, respectively fragile patients are characterized by reduced body weight, limited renal function, and multiple comorbidities (associated with many co-medications). For a number of seniors, it is advantageous to use a reduced dose of these drugs. Consideration of benefit and risk is often complicated in elderly patients, but this should be repeatedly done during the therapy. Key words: anticoagulation therapy - apixaban - dabigatran - edoxaban - fragile patient - geriatrics - rivaroxaban.

Erectile Dysfunction in Young Myocardial Infarction Survivors: Evaluation, Follow Up.

Erectile dysfunction significantly affects quality of life in young men. Authors have evaluated erectile function in men with coronary artery disease (CAD) and the relationship between the degree of erectile dysfunction (ED) and the age of their first acute myocardial infarction (AMI). The incidence of erectile dysfunction in three groups of patients of AMI survivors was investigated: AMI survivors younger than 45 years, AMI survivors older than 65 years, and normal male population aged between 30 and 60 years. Erectile function was assessed by the International Index of Erectile Function (IIEF-5) questionnaire. In post-AMI male patients younger than 45 years ( n = 76), mild ED occurred in 26% and severe in 7%. In the older AMI group, mild ED occurred in 52% and severe in 38%. In the control group age matched to younger survivors, 96% denied ED and only one control patient had a score of 20 on the IIEF-5. A paradoxical result was observed in patients using beta blockers (BB), who had better scores than the group without BB. Statin treatment had a positive influence on the score in questionnaires. Those on statins had an average score of 21.0 ± 4.9 vs. without statin 17.7 ± 5.7, p = .03. The current findings identified that the prevalence of ED is relatively high in young patients with CAD and is related to treatment of the CAD. The overall increase in ED presence suggests that the background of their coronary event is not due to destabilization of single focused atheroma but may reflect a generalized atherosclerotic process.

Multiple thrombophilia mutations as a possible cause of premature myocardial infarction.

The incidence of acute myocardial infarction (AMI) increases with clustering of predisposing risk factors. In younger subjects with a positive family history of AMI occurring in relatives under the age of 60 years without obvious risk factors for atherosclerosis, there is a potential for strong inherited traits contributing to the risk of coronary disease. Among them there is increasing evidence that hereditary thrombophilia may play a major role. We present a unique case of a patient developing AMI at the age of 48 years. In this patient, without traditional risk factors for atherosclerosis, eight mutations and polymorphisms in six different genes were identified: polymorphism of factor V Leiden (1691 GA), factor II prothrombin (20210 GA), methylenetetrahydrofolate reductase (MTHFR, 677 CT and 1298 AC), plasminogen activator inhibitor 1 (PAI-1) polymorphism 4G/5G and glycoprotein VI (GP6, 13254 TC, Ser219Pro). All could be involved in the pathogenesis of the arterial thrombosis. Although such associations are extremely rare, it underlines the importance of thrombophilia assessment in cases with otherwise unexpected coronary disease occurring at young age. According to our experience, in the case of documented hereditary thrombophilia lineal relatives should be examined and/or followed up.

A congenital diverticulum of the left ventricular apex manifested by stroke and recurrent ventricular tachycardia.

Ventricular outpouchings include acquired abnormalities (aneurysms and pseudoaneurysms) and congenital ventricular diverticula (CVD). CVD represent rare cardiac pathologies. Although CVD is often associated with other cardiac and extracardiac congenital anomalies, it can also be incidentally observed in otherwise healthy subjects. CVD may lead to significant morbidity and even have lethal consequences. We describe a case of arrhythmogenic left ventricle (LV) apical CVD revealed by cardiac magnetic resonance imaging (CMRI) after being initially overlooked by echocardiography. The paper includes the review of the literature also. This clinical case highlights the possible association of this pathology with recurrent ventricular tachycardia and stroke, and illustrates the importance of multimodal imaging approach in differential diagnosis.

Clinical efficacy and safety of a new 1000-mg suspension versus twice-daily 500-mg tablets of MPFF in patients with symptomatic chronic venous disorders: a randomized controlled trial.

BACKGROUND: Chronic venous disorders (CVD) is estimated to affect 30% to 50% of women and 10% to 30% of men. The most widely prescribed treatment for CVD worldwide is micronized purified flavonoid fraction 500 mg (MPFF). The aim of this clinical trial was to develop a new once daily 1000-mg oral suspension of MPFF. METHODS: In an international, randomized, double-blind, parallel-group study, symptomatic individuals classified CEAP C0s to C4s were randomized in either treatment arm and treated for 8 weeks. Lower limb symptoms (discomfort, pain and heaviness) were assessed using Visual Analog Scales (VAS), and quality of life (QoL) was measured with the CIVIQ-20 Questionnaire. RESULTS: A total of 1139 patients were included in the study. Both MPFF treatment regimens were well tolerated and associated with a significant reduction in lower limb symptoms. A non-inferiority of MPFF 1000-mg oral suspension once daily compared to MPFF 500-mg tablet twice daily (P<0.0001) was found for lower limb discomfort (-3.33 cm for MPFF 1000 mg and -3.37 cm for MPFF 500 mg), leg pain (-3.27 cm for MPFF 1000 mg and -3.31 cm for MPFF 500 mg) and leg heaviness (-3.41 cm for MPFF 1000 mg and -3.46 cm for MPFF 500 mg). The patients' QoL was improved by about 20 points on the CIVIQ scale in both groups (19.33 points for MPFF 1000 mg and 20.28 points for MPFF 500 mg). CONCLUSIONS: MPFF 1000-mg oral suspension and MPFF 500-mg tablets treatments were associated with similar reductions in lower limb symptoms and QoL improvement. The new once daily MPFF1000-mg oral suspension has a similar safety profile to two tablets of MPFF 500 mg, with the advantage of one daily intake, potentially associated with improved patient adherence and easier CVD management.

[Angiology is moving forward]. / Angiologie krácí vpred.

Vascular medicine treats many diseases - ischemic syndromes of different arterial bed (with the specifics of their territorial function), venous and lymphatic diseases. A number of states in angiology are urgent, potentially life-threating. Examples include aneurysm rupture, acute limb ischemia, or deep vein thrombosis and pulmonary embolism.On the other hand, chronic vascular disease (eg., peripheral arterial disease or chronic disease of superficial veins) require a differentiated approach according to the manifestation and the emphasis is given on prevention and treatment of disposing conditions.The optimal care for patients bring the specialist in vascular medicine who is able to build a diagnostic and treatment work-up quickly. He works closely with vascular surgeons and interventional radiologists.The article gives an overview of the major innovations in the field of angiology.

[A rare case of mobile atherosclerotic plaque with a high embolic potential in the femoral artery]. / Vzácný prípad mobilního aterosklerotického plátu ve femorální tepne s vysokým embolizacním potenciálem.

Atherosclerosis is a diffuse disease which may lead to the development of unstable atherosclerotic plaque. Its rupture can result in acute ischemic event. The atherosclerotic plaques with a mobile component are typical presentations of such instability and patients with these plaques are at high risk of acute ischemic events. In the current literature, substantial data regarding the mobile atherosclerotic plaques in carotid arteries and thoracic aorta is published. However there are almost no data concerning the mobile plaques in the peripheral arteries of the lower limbs. We present a rare case of a patient with generalized atherosclerosis, in whom an asymptomatic mobile atherosclerotic plaque in the common femoral artery with a high embolic potential was diagnosed. This plaque was successfully removed by femoral endarterectomy. On the basis of this case, we review the possibilities and limitations of the current imaging methods in detection of mobile plaques in the peripheral arteries. Moreover optimal therapeutic approaches in such patients are discussed.

[Extended options of anticoagulant treatment in thromboembolism]. / Rozsirující se moznosti antikoagulacní lécby tromboembolické nemoci.

Thromboembolic disease (TD) is a relatively common disease with acute risk of death and potential long-term consequences in term of postthrombotic syndrome or chronic pulmonary hypertension. Anticoagulant therapy is the basic therapeutic procedure; thrombolytic therapy and the introduction cava filter are appropriately indicated for individual cases. In past few years, new direct oral anticoagulant drugs (NOAC) have occurred - Xa factor or thrombin inhibitors which have demonstrated the same efficacy and even higher safety in comparison to conventional treatment. In mid 2014, 3 drugs of this group are registered in Czech Republic - rivaroxaban (Xarelto®), dabigatran (Pradaxa®) and apixaban (Eliquis®). These drugs have comparable efficacy and safety but they differ in schedule of dose administration. Rivaroxaban and apixaban can be administered immediately after diagnosis of venous thrombosis or hemodynamically stable pulmonary embolism. LMWH application has to precede few days the administration of dabigatran. Limitation of new drugs is their price. Unavailability of antidotes is temporary because current researches continue to find one for dabigatran and another for both of xabans. Duration of anticoagulant treatment after acute phase depends on the presence of thrombosis risk factors and the individual bleeding risk. Minimal duration of anticoagulant therapy is 3 months, commonly 6-12 months and in high risk patients it is "long term" treatment. Good results of new anticoagulant drugs in trials in term of thromboembolism recurrence prevention may change established habits in TD patients with long term treatment.

The Czech ABI Project - prevalence of peripheral arterial disease in patients at risk using the ankle-brachial index in general practice (a cross-sectional study).

OBJECTIVES: It has been demonstrated that the deleterious effect of smoking on the cardiovascular system is mediated through a decrease in protective HDL cholesterol. In addition, women are more sensitive to the negative effects of smoking, although the exact mechanism underlying this phenomenon is currently unknown. In this study, we evaluated whether smoking habits could modify the association of HDL cholesterol and apolipoprotein A1 (ApoA1) with reverse cholesterol transport (RCT), as measured by cholesterol efflux (CHE), in middle-aged women. DESIGN: The study group consisted of 39 healthy middle-aged women, 21 non-smokers (age 51.8±2.5 years, BMI 25.1±2.8 kg/m2) and 18 smokers (age 50.5±3.2 years, BMI 24.8±3.5 kg/m2). In addition to all traditional cardiovascular risk factors, CHE from macrophages, labelled during a 48-hour incubation in a medium containing [14C] cholesterol, to plasma acceptors in study subjects was established as a marker of reverse cholesterol transport. RESULTS: CHE was significantly higher in non-smokers than in smokers (14.22±1.75% vs. 13.17±1.33%; p<0.05). Smoking habit had no effect on the association of HDL with ApoA1 or HDL with CHE. However, in contrast to the strong association of ApoA1 with CHE in non-smokers (r=0.62; p<0.01), no such strong association was found in smokers (r=0.38; n.s.). MAIN FINDINGS AND CONCLUSION: Based on our results, smoking can alter ApoA1-mediated reverse cholesterol transport in women.

[Deep calf vein thrombosis]. / Flebotrombóza lýtkových zil.

Isolated calf vein thrombosis in the population of patients with deep vein thrombosis is found approximately in 10 to 25 % of cases. We present 3 cases of calf vein thrombosis which occurred due to unusual causes. Specific characteristics of this form of thromboembolic disease are discussed and compared to proximal deep vein thrombosis with emphasis to symptoms, risk of complications, prognosis and therapeutic approach.

Carotid intima-media thickness in young survivors of acute myocardial infarction.

BACKGROUND: Carotid intima-media thickness (CIMT) is considered to be a useful surrogate marker of coronary atherosclerosis. However, it is unclear whether this applies to young patients with acute myocardial infarction (AMI), in whom most cases are attributable to the destabilization of focal atheroma. OBJECTIVE: To assess CIMT in patients experiencing AMI at a young age. METHODS: CIMT was investigated in young survivors of AMI (78 male and 20 female) occurring before 45 years of age in men and before 50 years of age in women. CIMT values were compared with those of a sex-, age- and smoking status-matched sample selected from participants of a large epidemiological survey (115 men and 144 women). CIMT was measured on the anterior and posterior walls of the distal common carotid artery. RESULTS: In post-AMI male patients, the mean average CIMT, comprised of measurements of both the near and far walls on both sides, was significantly increased compared with controls (0.67±0.10 mm versus 0.60±0.09 mm; P<0.001), while it did not differ in post-AMI female patients (0.60±0.07 mm versus 0.60±0.10 mm). Mean maximum CIMT was greater in both male and female post-AMI patients (0.94±0.15 mm versus 0.81±0.13 mm; P<0.001 in men and 0.89±0.14 mm versus 0.80±0.11 mm; P=0.001 in women). CONCLUSIONS: In young AMI survivors, CIMT appeared to be significantly increased to a greater extent in men than in women. Although most patients had single- or double-vessel coronary disease, the overall increase in CIMT suggests that their coronary events were not due to destabilization of a single focal atheroma but may have reflected a generalized atherosclerotic process.

[Carotid plaque exulcerated]. / Exulcerovaný karotický plát.

The authors report a case of a 77 years old male patient with mild stenosis of the carotid artery caused by an exulcerated plaque in the carotid bifurcation. The patient presented with recurrent ipsilateral strokes which were treated with intravenous thrombolysis. A brief review of the literature related to the management of unstable exulcerated carotid plaque is presented in this article with emphasis on current treatment options. Carotid endarterectomy if often performed in such cases. However, the outcome of the procedure remains still very controversial. In the described case, conservative approach using optimal medical treatment with lipid lowering agents, antiplatelet and antihypertensive therapy was chosen mainly because of patient preference and resulted in favourable outcome.

Association between cardiac energy metabolism and gain of left ventricular mass in Fabry disease.

Left ventricular (LV) hypertrophy is the hallmark of cardiac involvement in Fabry disease (FD). However, its pathogenesis is not clearly understood as pathologic substrate accumulation represents only 1-2% of the total cardiac mass. Abnormal myocardial energy metabolism has been previously demonstrated in different forms of cardiomyopathies. We hypothesized that myocardial energy status at the time of diagnosis could have a relationship to gain of LV mass in FD. In the group of 16 affected subjects, the indicators of energetic state of cardiac muscle determined by magnetic resonance spectroscopy showed significant negative correlation with annual increase in LV mass, evaluated during long-term follow-up (8 ± 3 years). Myocardial energy metabolism may therefore represent one of the mechanisms contributing to development of FD-related cardiomyopathy.

Right ventricular involvement in Fabry disease.

The aim of the study was to describe right ventricular (RV) structural and functional changes in Fabry disease (FD). A detailed echocardiographic examination was performed in 58 patients with proven FD (mean age 40 +/- 16 years, 24 men). RV hypertrophy (RVH) was present in 40% of affected subjects with similar prevalence in both genders. Approximately two thirds of patients with left ventricular hypertrophy (LVH) also exhibited RVH. RV dilatation was not present in any subject. RV systolic dysfunction was noted in only 1 female subject. RV diastolic dysfunction was present in 47% of 45 subjects in whom RV filling was assessed. RV diastolic dysfunction was associated with the presence of RVH. A significant correlation between RV wall thickness and age (r = 0.52, P < .001) and left ventricular mass index (r = 0.70, P < .001) was noted. RVH with normal chamber size and preserved systolic but impaired diastolic function represents a typical RV structural change in FD. Its prevalence and degree are related to the prevalence and degree of LVH and the age of the patient.