Thrombotic Mechanisms Research Articles

Neurovascular complications of antiphospholipid syndrome: a narrative review.

Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by thrombosis, pregnancy complications, and other nonthrombotic manifestations in the presence of antiphospholipid antibodies. Neurovascular complications, including ischemic stroke, cerebral venous thrombosis and cognitive impairment, pose significant challenges in management. To comprehensively review relevant and updated clinical aspects of neurovascular manifestations of APS. We conducted a narrative review using the PubMed, EMBASE, and Cochrane Library databases with medical terms related to APS and its neurovascular manifestations. English-language studies, published between January 1, 2015, and March 2024, were included. Key publications outside this timeframe were also considered. Studies with higher levels of evidence, such as randomized controlled trials and meta-analyses, were prioritized for inclusion. Stroke is a prevalent complication in APS, with arterial thrombosis being a predominant mechanism. Despite recent trials, direct oral anticoagulants (DOACs) have not shown superiority over vitamin K antagonists (VKAs) for secondary prevention in this population. Cerebral venous thrombosis (CVT), although rare, can also occur in APS, and while DOACs have shown promise as a treatment in a general population, caution is warranted due to potential harm. Cognitive impairment affects a considerable proportion of APS patients, with thrombotic and nonthrombotic mechanisms contributing to its pathophysiology. Future research should focus on optimal management strategies for cognitive impairment and the efficacy of anticoagulation and immunosuppression. Understanding the complex interplay of neurovascular manifestations in APS is essential for guiding clinical decisions and improving patient outcomes. Despite advancements, some challenges remain in establishing effective preventive and treatment measures, highlighting the need for further research in this field.

Hemostasis disorders, thrombosis and thrombocytopenia in patients with covid-19 and pneumonia with complicated acute renal injury

«Hemostasis disorders, thrombosis and thrombocytopenia in patients with covid-19 and pneumonia with complicated acute renal injury» Relevance. Thrombosis is one of the most dangerous complications of COVID-19 not only at the peak of the disease, but also in the long term. During the pandemic, the issues of medical prevention of thrombotic complications have been repeatedly reviewed, clarified and supplemented, but the only correct tactics for their prevention and treatment do not yet exist.The purpose of the study. To determine the frequency and nature of the development of venous and arterial thrombosis and thrombocytopenia in severe patients with COVID-19 and pneumonia, complicated by acute renal damage, the course of the disease, including fatal ones.Material and methods. Data on inpatient treatment and diagnosis of 216 COVID-19 patients with viral pneumonia and signs of acute renal injury (AKI) according to KDIGO 2012 criteria. Group 1. Deceased patients with severe COVID-19 and pneumonia, with unreliable signs of AKI, 75 (men 19, women 56), ratio 1:2.9. Age from 29 to 87 years. Ventilation in 56 (74.7 %) Group 2. Deceased patients with COVID-19 and pneumonia with significant signs of AKI, 77 (men 34, women 43), ratio 1:1.3. Age from 41 to 88 years. Ventilation in 53 (70.7 %) Group 3. Recovered patients with AKI or CKD, 64 (men 41, women 23, ratio 1:0.56, age from 43 to 89 years). Ventilation in 1 (1.6 %). The study of hemostasis. Activated partial thromboplastin time according to the modified method of plasma recalcification reaction according to Baluda V. P. et al. (1980). The level of fibrinogen in blood plasma by the ethanol method according to Breen F., Tullis J. (1982). The concentration of D-dimer in the blood by microlatex agglutination with photometric registration of the reaction (immunoturbidimetry).Results. In deceased inpatient patients with Covid-19 and pneumonia, a high incidence of arterial and venous thrombosis of various localization was detected, up to 46–56 %. The thrombotic danger was largely associated with an increased level of D-dimer and the duration of its increase in the blood of patients. Thrombocytopenia was diagnosed in 47–58 % of patients and was a significant risk factor for the development of fatal outcomes. In cases of detection of thrombocytopenia in patients below 20 thousand cells in microl., its character was assessed on a 4Ts scale to identify the syndrome of heparin-associated thrombocytopenia. 92–97 % of patients were prescribed heparins, including such fractionated (low molecular weight) ones as enoxaparin, nadroparin, dalteparin and fundaparinux. Only a small proportion of cases of combination of thrombosis and thrombocytopenia (about 2.3 %) were due to the nature of drug therapy and the development of heparin-associated thrombocytopenia syndrome.Conclusion. The data obtained indicate the high importance of thrombotic mechanisms involving D-dimer in the pathogenesis and outcomes of the disease in groups of deceased patients with covid-19, pneumonia and AKI and the predominant importance of vascular damage in the activation of the thrombotic cascade in them.

Heterozygous Prothrombin Mutation-Associated Thrombophilia.

Venous thromboembolism (VTE) is predisposed by thrombotic mutations in patients with hereditary thrombophilia. Although prothrombin deficiencies caused by homozygous or compound heterozygous mutations are associated with bleeding diathesis, rare cases have shown a correlation between heterozygous prothrombin mutations and thrombosis. We surveyed genetic variants involved in thrombosis and hemostasis in 347 patients with unprovoked VTE or having a positive family history of thrombosis. For patients identified with heterozygous prothrombin mutations, we conducted family investigations and performed a thrombin generation test (TGT) to elucidate the thrombotic risk. Novel mutants were expressed and subjected to functional assays to clarify the underlying thrombotic mechanisms. Heterozygous prothrombin mutations were identified in 3.5% of patients (12/347), including three novel mutations Phe382Ser, Phe382Leu, and Asp597Tyr found in one patient each, as well as previously reported Arg541Trp mutation in four patients and Arg596Gln mutation in five patients. A total of 42 mutation carriers were identified within the 12 pedigrees, among whom 64.3% (27/42) had experienced thrombotic events. TGT results demonstrated hypercoagulability for carriers of the five mutations, with Arg596Gln showing the highest thrombin generation potential followed by Arg541Trp. The Phe382-associated mutations severely impaired thrombomodulin-binding ability of thrombin, resulting in obviously reduced protein C (PC) activation. The Asp597Tyr mutation exhibited a mild reduction in both inactivation by antithrombin and PC activation reactions. The presence of heterozygous prothrombin mutations represents a potential genetic predisposition for VTE. All thrombosis-associated mutations potentiate coagulation activity by either conferring antithrombin resistance and/or impairing PC pathway activity.

A novel factor V compound heterozygous mutation associated with thrombosis (Y1961C; FV-Kanazawa, together with 1982_1983del)

BackgroundFactor (F)V is pivotal in both procoagulant and anticoagulant mechanisms. The present report describes a novel F5 mutation in a FV-deficient patient (FV activity, 6 IU/dL; FV antigen, 32 IU/dL) complicated by recurrent deep vein thrombosis. The patient demonstrated activated protein C resistance (APCR) with compound heterozygous mutations consisting of FV-Y1961C (FVKanazawa) and FV-1982_1983del. ObjectivesTo clarify thrombotic mechanisms associated with this FV abnormality. Methods and ResultsLevels of FV-1982_1983del were below the detection sensitivity in our expression experiments using human embryonic kidney 293T cells, and analyses were targeted, therefore, on the FV-Y1961C mutation. Activated partial thromboplastin time–based clotting assays demonstrated that FV-Y1961C exhibited APCR and that the reduced activated protein C (APC) susceptibility in FVa-Y1961C resulted in a marked depression of APC-catalyzed inactivation with delayed cleavage at Arg506 and little cleavage at Arg306 with or without protein S. The APC cofactor activity of FV-Y1961C in APC-catalyzed FVIIIa inactivation promoted by Arg336 cleavage in FVIII was impaired. The binding affinity of FVa-Y1961C to phospholipid membranes was reduced in reactions involving APC/protein S–catalyzed inactivation and in prothrombinase activity. Furthermore, the addition of FVa-Y1961C to plasma failed to inhibit tissue factor–induced procoagulant function. These characteristics were similar to those of FV-W1920R (FVNara) and FV-A2086D (FVBesançon). ConclusionWe identified a compound heterozygous FV-Y1961C mutation in the C1 domain representing a novel FV mutation (FVKanazawa) resulting in not only APCR due to impaired FVa susceptibility and FV cofactor activity for APC function but also impaired inhibition of tissue factor–induced procoagulant function. These defects in anticoagulant function associated with FV in FV-Y1961C contributed to a prothrombotic state.

A CLINICAL CASE OF CRITICAL ISCHEMIA OF THE LOWER LIMB DUE TO ANTIPHOSPHOLIPID SYNDROME IN A PATIENT WITH NEWLY DIAGNOSED SYSTEMIC LUPUS ERYTHEMATOSUS

Background. Antiphospholipid syndrome (APS) is a systemic autoimmune disease with a wide range of vascular and obstetric manifestations associated with thrombotic and inflammatory mechanisms initiated by antiphospholipid antibodies.
 Aims: to demonstrate an early onset of secondary APS in the newly diagnosed systemic lupus erythematosus, data literature analysis.
 Materials and methods. We analyzed the clinical case of the patient, similar clinical cases that were published, and the latest diagnostic criteria, and recommendations for the diagnosis, treatment, and prevention of APS.
 Description of the clinical case. The patient, 27 years old, was admitted to the Rheumatology department at Communal non-commercial institution "Olexandrivska Clinical Hospital" in April 2023 with complaints of phantom pain of the amputated toes of the right foot, chilliness of the hands and feet, and joint pain. 
 She has been ill since January 2021, and since then, she has had joint pain and discoloration of the skin of her fingers and feet in the cold. Significant worsening started in January 2022. The patient was hospitalized at the National Scientific Center of Surgery and Transplantology named after O.O. Shalimov, and the distal phalanges of the 1-3 toes of the right foot were amputated. As far as the patient previously had COVID-19, and took a combined oral contraceptive comprehensive differential diagnosis was carried out. The examination in the Rheumatology department revealed systemic lupus erythematosus according to diagnostic criteria ACR/EULAR 2019 and secondary antiphospholipid syndrome based on ACR/EULAR criteria 2023. The patient was prescribed hydroxychloroquine, methylprednisolone, nifedipine, iloprost, and warfarin. The patient was discharged in good condition and continues treatment ambulatory under rheumatologist control.
 Conclusion. This clinical case demonstrates the importance of a multidisciplinary approach in patients with APS. Patients with venous or arterial thrombotic events, especially young adults without risk factors, should be screened for antiphospholipid antibodies.

Plausible Mechanisms of Causation of Immediate Stroke by Cervical Spine Manipulation: A Narrative Review.

It has been proposed that cervical spine manipulation (CSM) can cause dissection in healthy cervical arteries, with resultant immediate stroke. However, research does not support a causal association between CSM and cervical artery dissection (CAD) in healthy cervical arteries. The objective of this study was to review the literature to identify plausible mechanisms of causation of immediate stroke by CSM. Immediate stroke is defined as a stroke occurring within seconds or minutes of CSM. Our review found plausible thromboembolic and thrombotic mechanisms of causation of immediate stroke by CSM in the literature. The common premise of these mechanisms is CAD being present before CSM, not occurring as a result of CSM. These mechanisms of causation have clinical and medicolegal implications for physicians performing CSM.

Thrombin Generation Assay in Antiphospholipid Antibodies Positive Subjects as a Personalized Thrombotic Risk Assessment: State of the Art and Perspectives.

Thrombotic risk assessment in antiphospholipid positive (aPL +) subjects is a major challenge, and the study of in vitro thrombin generation (thrombin generation assays (TGA)) could provide useful information. Activated protein C (APC) sensitivity is involved in thrombotic events in antiphospholipid syndrome patients. We summarized methods used to assess APC sensitivity with TGA and evaluated the prognostic role of APC resistance through literature search. APC resistance induced by aPL is a complex pathway. Several cross-sectional studies assessed APC sensitivity to understand thrombotic event mechanisms in aPL + subjects. Only one prospective cohort had investigated the prognostic impact of APC resistance in aPL + subjects, with a positive and significant correlation between APC sensitivity and the risk of thrombosis during the follow up (hazard ratio, 6.07 [95% CI, 1.69-21.87]). APC resistance assessed with TGA could be associated with thrombotic events in aPL + subjects.

Alleviation of endothelial dysfunction of Pheretima guillemi (Michaelsen)-derived protein DPf3 in ponatinib-induced thrombotic zebrafish and mechanisms explored through ox-LDL-induced HUVECs and TMT-based proteomics

Ethnopharmacological relevanceThrombus generation is one of the leading causes of death in human, and vascular endothelial dysfunction is a major contributor to thrombosis. Pheretima guillemi (Michaelsen), a traditional medicinal animal known as “Dilong”, has been utilized to cure thrombotic disorders for many years. DPf3, a group of functional proteins extracted from P. guillemi, has been characterized and identified to possess antithrombotic bioactivity via in vitro and ex vivo experiments. Aim of the studyThis study is aimed to investigate the vascular-protection activity and related mechanism of antithrombotic protein DPf3 purified from Pheretima guillelmi systematically. Materials and methodsThe antithrombotic activity and vascular endothelium protection effect of DPf3 was explored in vivo using ponatinib-induced vascular endothelial injury zebrafish thrombus model. Then, (hi) ox-LDL-induced HUVECs was applied to investigate the protection mechanism of DPf3 against the injury of vascular endothelium. In addition, TMT-based proteomics analysis was used to study the biomarkers, biological processes and signal pathways involved in the antithrombotic and vascular protective effects of DPf3 holistically. ResultsDPf3 exerted robust in vivo antithrombosis and vascular endothelial protection ability. DPf3 was identified to prevent HUVECs from damage by reducing ROS production, and to reduce monocyte adhesion by decreasing the protein content of adhesion factor VCAM 1. DPf3 was also observed to weaken the migration ability of injured cells and inhibit abnormal angiogenesis. The mechanism of DPf3's antithrombotic and vascular protective activity was mainly related to the regulation of lipid metabolism, energy metabolism, complement and coagulation system, ECM receptor interaction, MAPK signal pathway, etc. ConclusionsThis study demonstrates that DPf3 has strong antithrombotic and endothelial protective effects. The endothelial protective ability and related mechanisms of DPf3 provide a scientific reference for the traditional use of earthworms in the treatment of thrombosis.

Increased Risk of Thrombosis in Patients with Polycystic Ovarian Syndrome

Polycystic Ovarian Syndrome (PCOS) is the most common endocrine-metabolic disorder in reproductive age women, with an estimated prevalence of 6-12% of assigned female at birth women in the US. We identified a pattern in our coagulation diagnostic management team, wherein women with PCOS had increased rates of and repeated histories of thrombotic events, such as strokes, heart attacks, pulmonary embolisms, and deep vein thromboses. However, clinical coagulation assays on these PCOS patients with repeated thrombotic events were all within the normal reference range. Our goal was to investigate the validity of this pattern and its occurrence in both local and national populations. This was accomplished by 1) Determining the incidence rate of thrombosis in PCOS and 2) Analyzing clinical presentations of thrombosis in PCOS. Methods/Study populations : Analyses on the rate of thrombotic events in PCOS patients locally at UTMB and in the US were performed on the TriNetX health research network. Using the incidence and prevalence and compared outcomes analytic functions on TriNetX, we determined the rate of thrombosis from 2013-2018 and explored patient characteristics. We further analyzed thrombosis in PCOS with the Symptom-Disease Pair Analysis of Diagnostic Error (SPADE) method. Through the compare outcomes analysis on the TriNetX platform, we looked at PCOS and control patients who experienced thrombotic events between 2013-2018 and analyzed clinical presentations that occurred in the 90 days prior to the index event. Patient queries included the diagnostic code for PCOS, ICD10 E28.2, women age 15-75, who had a clinical encounter since 2013. Exclusion criteria included inherited thrombotic disorders, smoking history, and human immunodeficiency virus. Events of interest included myocardial infarctions, cerebral infarctions, pulmonary embolisms, arterial embolisms and thrombosis, and portal vein thromboses. Statistical analysis: For evaluating statistical significance of the rate of thrombosis, we performed a compare outcome analysis on the UTMB network, with propensity score matching for current age. A Kaplan-Meier Analysis and a student's t-test were performed on the number of instances/events, and statistical significance was defined as a p-value <0.0001. Results:Between 2013-2018, the incidence rate of thrombosis in PCOS patients was 4.35% with 5.36% prevalence, this was statistically significantly higher than the control cohort at 2.66% incidence and 3.5% prevalence. The incidence rate of thrombosis in PCOS increased dramatically in post-menopausal women. Of the 60 outcomes investigated, 24 were determined to be statistically significant between control and PCOS, 22 symptoms and 2 procedures. Discussion: This is the first study to analyze the rate of thrombotic events in PCOS. We identified significant presentations and gaps that could assist in the early detection of thrombotic events in PCOS. However, the mechanisms of thrombosis in PCOS are unknown and are poorly detected with current clinical assays. Future studies will examine clinical assays in the detection of thrombosis in PCOS and investigate thrombotic mechanisms in PCOS.

Myocarditis and COVID-19 related issues.

The recent COVID-19 (Coronavirus Disease 2019) pandemic by SARS-CoV2 infection has caused millions of deaths and hospitalizations across the globe. In the early pandemic phases, the infection had been initially considered a primary pulmonary disease. However, increasing evidence has demonstrated a wide range of possible cardiac involvement. Most of systemic and cardiac damage is likely sustained by a complex interplay between inflammatory, immune-related and thrombotic mechanisms. Biventricular failure and myocardial damage with elevation of cardiac biomarkers have been reported in COVID-19 patients, although histological demonstration of acute myocarditis has been rarely documented. Indeed while cardiac magnetic resonance findings include different patterns of myocardial involvement in terms of late gadolinium enhancement, histological data from necropsy and endomyocardial biopsy showed peculiar inflammatory patterns, mostly composed by macrophages. On the other hand COVID-19 vaccines based on mRN technology have been also associated with increased risk of myocarditis. COVID-19 and mRNA vaccine-related myocarditis present different clinical and imaging presentations and recent data suggest the presence of distinctive immunological mechanisms involved.

Assessing disease activity and damage in antiphospholipid syndrome

Antiphospholipid syndrome (APS) has been characterized by a variety of vascular and pregnancy manifestations related to an interplay between thrombotic and inflammatory mechanisms, a progressive accrual of irreversible organ damage and increased morbidity and mortality rates, supporting a high need of optimal treatment approach. The lack of standardized outcome measures is a significant barrier in the design of clinical studies in APS. Disease activity (in principle reversible) and its distinction from disease damage (in principle irreversible) needs to be evaluated by validated scores for use in clinical trials but also in daily clinical practice in APS. A disease damage score in APS, the DIAPS score, has been developed and validated in external cohorts. The development of a disease activity score that will provide an accurate and reproducible rating of each disease domain, can help clinicians and researchers to comprehensively assess the activity of disease and the response to treatment, in an attempt to prevent future damage.

Impaired factor V-related anticoagulant mechanisms and deep vein thrombosis associated with A2086D and W1920R mutations.

Factor V (FV) plays pivotal roles in both procoagulant and anticoagulant mechanisms. Genetic mutations, FV-W1920R (FVNara) and FV-A2086D (FVBesançon), in the C1 and C2 domains of FV light chain, respectively, seem to be associated with deep vein thrombosis. However, the detailed mechanism(s) through which these mutations are linked to thrombophilia remains to be fully explored. The aim of this study was to clarify thrombotic mechanism(s) in the presence of these FV abnormalities. Full-length wild-type (WT) and mutated FV were prepared using stable, human cell lines (HEK293T) and the piggyBac transposon system. Susceptibility of FVa-A2086D to activated protein C (APC) was reduced, resulting in significant inhibition of APC-catalyzed inactivation with limited cleavage at Arg306 and delayed cleavage at Arg506. Furthermore, APC cofactor activity of FV-A2086D in APC-catalyzed inactivation of FVIIIa through cleavage at Arg336 was impaired. Surface plasmon resonance-based assays demonstrated that FV-A2086D bound to Glu-Gly-Arg-chloromethylketone active site-blocked APC and protein S (P) with similar affinities to that of FV-WT. However, weakened interaction between FVa-A2086D and phospholipid membranes was evident through the prothrombinase assay. Moreover, addition of FVa-A2086D to plasma failed to inhibit tissue factor (TF)-induced thrombin generation and reduce prothrombin times. This inhibitory effect was independent of PC, PS, and antithrombin. The coagulant and anticoagulant characteristics of FV(a)-W1920R were similar to those of FV(a)-A2086D. FV-A2086D presented defects in the APC mechanisms associated with FVa inactivation and FV cofactor activity, similar to FV-W1920R. Moreover, both FV proteins that were mutated in the light chain impaired inhibition of TF-induced coagulation reactions. These defects were consistent with congenital thrombophilia.

Otogenic Cerebral Sinus Thrombosis in Children: A Narrative Review.

Cerebral venous thrombosis (CVT) is a rare entity that remains a diagnostic challenge due to various clinical manifestations and a wide variety of causative agents. Local infections, such as acute (AOM) or chronic otitis media, can play a role in the pathogenesis of CVT. The proximity of the tympanic cavity and temporal bone air cells to the dural venous sinuses predisposes them to secondary thrombosis. The release of inflammatory cytokines and activation of the coagulation pathway in the middle ear space in response to infection may trigger the thrombotic mechanism in venous sinuses of the central nervous system. There is no consensus in the literature concerning the treatment of otogenic cerebral venous sinus thrombosis (CVST). Both the extent of the surgery and the use of anticoagulants are disputable. The aim of the study was to provide a thorough analysis of the literature concerning CVST in patients with AOM and acute mastoiditis (AM). The current surgical and conventional treatment strategies are presented. Special attention has been attached to the predisposing factors, the extent of the surgery, and the role of anticoagulants in the treatment of septic otogenic CVST.

Focus on the Prevention of Acute Limb Ischemia: Centrality of the General Practitioner from the Point of View of the Internist.

The thrombotic mechanism, being common to peripheral arterial disease (PAD), acute myocardial infarction (AMI), and stroke, is responsible for the highest number of deaths in the western world. However, while much has been done for the prevention, early diagnosis, therapy of AMI and stroke, the same cannot be said for PAD, which is a negative prognostic indicator for cardiovascular death. Acute limb ischemia (ALI) and chronic limb ischemia (CLI) are the most severe manifestations of PAD. They both are defined by the presence of PAD, rest pain, gangrene, or ulceration and we consider ALI if symptoms last less than 2 weeks and CLI if they last more than 2 weeks. The most frequent causes are certainly atherosclerotic and embolic mechanisms and, to a lesser extent, traumatic or surgical mechanisms. From a pathophysiological point of view, atherosclerotic, thromboembolic, inflammatory mechanisms are implicated. ALI is a medical emergency that puts both limb and the patient's life at risk. In patients over age 80 undergoing surgery, mortality remains high reaching approximately 40% as well as amputation approximately 11%. The purpose of this paper is to summarize the scientific evidence on the possibilities of primary and secondary prevention of ALI and to raise awareness among doctors involved in the management of ALI, in particular by describing the central role of the general practitioner.

Thrombotic Mechanism Involving Platelet Activation, Hypercoagulability and Hypofibrinolysis in Coronavirus Disease 2019.

Coronavirus disease 2019 (COVID-19) has spread, with thrombotic complications being increasingly frequently reported. Although thrombosis is frequently complicated in septic patients, there are some differences in the thrombosis noted with COVID-19 and that noted with bacterial infections. The incidence (6-26%) of thrombosis varied among reports in patients with COVID-19; the incidences of venous thromboembolism and acute arterial thrombosis were 4.8-21.0% and 0.7-3.7%, respectively. Although disseminated intravascular coagulation (DIC) is frequently associated with bacterial infections, a few cases of DIC have been reported in association with COVID-19. Fibrin-related markers, such as D-dimer levels, are extremely high in bacterial infections, whereas soluble C-type lectin-like receptor 2 (sCLEC-2) levels are high in COVID-19, suggesting that hypercoagulable and hyperfibrinolytic states are predominant in bacterial infections, whereas hypercoagulable and hypofibrinolytic states with platelet activation are predominant in COVID-19. Marked platelet activation, hypercoagulability and hypofibrinolytic states may cause thrombosis in patients with COVID-19.

Improved Oral Health Status Is Associated with a Lower Risk of Venous Thromboembolism: A Nationwide Cohort Study.

Oral health is reportedly associated with several systemic diseases, particularly cardiovascular diseases, through systemic inflammatory and thrombotic mechanisms. This study aimed to investigate the association between oral health status, oral hygiene behavior, and venous thromboembolism (VTE) in a nationwide, population-based cohort database in a longitudinal setting. Data of participants who underwent oral health screening by dentists between January and December 2003 (n = 2,415,963) were retrieved from the National Health Insurance Database of the Korean National Health Insurance Service. Periodontitis was identified using claims or oral health screening data. Periodontal pockets and the number of missing teeth were examined by dentists during oral health screenings. Data on oral hygiene behaviors (tooth brushing, dental visits, and dental scaling) were collected. VTE was defined as two or more claims of one of the following ICD-10 codes: deep (I80.2-80.3), pulmonary (I26, I26.0, I26.9), intra-abdominal (I81, I82, I82.2, I82.3), and other (I82.8, I82.9) VTE and concurrent medication (anticoagulants and antiplatelets). VTE was analyzed using the Cox proportional hazard model according to periodontitis, number of missing teeth, tooth brushing frequency, dental visits, and dental scaling. VTE occurred in 39,851 (1.8%) participants within a median of 17.0 (interquartile range 16.3-17.7) years. Periodontitis was associated with VTE (adjusted hazard ratio (HR), 1.2; 95% confidence interval (CI), 1.15-1.28; p < 0.001). An increased number of missing teeth was associated with an increased risk of VTE; the adjusted HR (versus participants without missing teeth) was 1.58 (95% CI, 1.46-1.71; p < 0.001, p for trend < 0.001) for participants with ≥15 missing teeth. Furthermore, tooth brushing ≥3 times a day was negatively correlated with VTE (adjusted HR, 0.67; 95% CI, 0.65-0.69; p < 0.001, p for trend < 0.001). Dental scaling within one year was associated with a significantly lower risk of VTE (adjusted HR, 0.95; 95% CI, 0.93-0.98; p < 0.001). Improved oral hygiene, including tooth brushing and dental scaling, may be associated with a decreased risk of VTE. Periodontitis and an increased number of missing teeth may increase the risk of VTE.

Neuropsychiatric disorders in patients with heart failure: not to be ignored.

Among various neuropsychiatric disorders, depression and anxiety are commonly encountered in patients with heart failure (HF), reported in ≥ 50% of patients attending a HF clinic, but may frequently elude clinician's attention. Both disorders are associated with the development and progression of HF, incurring higher rates of morbidity/mortality, probably via physiologic and behavioral mechanisms. Patients with devices and/or advanced HF are more severely affected, especially early following device receipt. In addition, various other neuropsychiatric and neuropsychological disorders and symptoms of these and other disorders occur in and impact HF patients, including sleep disorders and cognitive impairment, which further interact with and amplify depression and anxiety. Mechanisms involved in the link between neuropsychiatric/neuropsychological disorders and HF may relate to pathophysiological processes, lifestyle factors, and behavioral patterns. Among the pathophysiological factors, inflammation, autonomic dysfunction, endothelial dysfunction, thrombotic mechanisms, and dysregulation of the hypothalamic-pituitary-adrenal axis may play a significant role as they are implicated in the pathogenesis, progression, and prognosis of HF. Multimodal psychiatric management strategies with flexible approaches, using antidepressants/anxiolytics/atypical antipsychotics and various psychotherapies such as cognitive behavioral therapy combined with exercise adjusted to patients' care and needs, appear promising in this patient group. Choosing agents with a higher efficacy/safety profile is a prudent strategy. Although depression and anxiety are risk factors for mortality in HF patients, indiscriminate use of psychiatric medications may not improve or even worsen survival when one neglects to closely monitor for potential proarrhythmic and other side effects. Newer meta-analytic data in HF patients indicate no increase in mortality for newer antidepressants, while secondary analyses show improved survival in patients who achieved remission of depressive symptoms.

101 LIPOPROTEIN ASSOCIATED PHOSPHOLIPASE A2 IN STEMI VS NSTE-ACS PATIENTS: A MARKER OF CARDIOVASCULAR ATHEROSCLEROTIC RISK RATHER THAN THROMBOSIS

Abstract Background The precise role of Lipoprotein associated phospholipase A2 (Lp-PlA2) in the pathogenesis of acute coronary syndromes (ACS) and in the prediction of future cardiovascular events is still debated. So far, few data exist on the variations of Lp-PlA2 activity in ACS and especially in NSTE-ACS vs STEMI patients, where thrombotic and atherosclerotic mechanisms could play a differential role. The aim of the present study was, then, to compare Lp-PlA2 activity according to the type of ACS presentation. Methods A consecutive cohort of patients undergoing coronary angiography for acute coronary syndrome (ACS) were included and divided according to presentation for non ST-segment elevation-ACS or ST-segment elevation Myocardial Infarction (STEMI). Lp-PLA2 activity was assessed on blood samples drawn at admission using the Diazyme Lp-PlA2 Activity Assay. Results We included in our study 117 patients, of whom 31 (26.5%) presented with STEMI. STEMI patients were significantly younger (p=0.05), displayed a lower rate of hypertension (p=0.002), previous MI (p=0.001) and PCI (p=0.01) and used less frequently statins (p=0.01) and clopidogrel (p=0.02). White blood cells and admission glycemia were increased in STEMI (p=0.001, respectively). The prevalence and severity of CAD was not different according to ACS types, but for a higher prevalence of thrombus (p<0.001) and lower TIMI flow (p=0.002) in STEMI. The levels of Lp-PlA2 were significantly lower in STEMI as compared to NSTE-ACS patients, (132±41.1 vs 154.6 ±40.9 nmol/min/mL, p=0.01). In fact, the rate of patients with Lp-PlA2 above the median (148 nmol/min/mL) was significantly lower in STEMI patients as compared to NSTE-ACS (32.3% vs 57%, p=0.02, adjusted OR[95% CI]=0.20[0.06-0.68], p=0.010). Moreover, a direct linear relationship was observed between Lp-PlA2 and LDL-C (r=0.47, p<0.001), but not with inflammatory biomarkers. Conclusion The present study shows that among ACS patients, the levels of Lp-PlA2 are inversely associated with STEMI presentation and thrombotic coronary occlusion, being instead increased in NSTE-ACS patients, and with recurrent cardiovascular events, therefore potentially representing a marker of a more aggressive atherosclerotic disease and higher cardiovascular burden and risk.

Thrombotic mechanisms in low-thrombogenicity mechanical mitral valve prostheses.

Thrombotic mechanisms in low-thrombogenicity mechanical mitral valve prostheses.

Incidence and predictors of radial artery occlusion following transradial coronary angiography: the proRadial trial

ObjectivesThis study investigated the contemporary incidence and predictors of radial artery occlusion as well as the effectiveness of antithrombotic treatment for radial artery occlusion following transradial coronary angiography.BackgroundThe radial artery is the standard access for coronary angiography and even complex interventions. Postprocedural radial artery occlusion is still a common and significant complication.MethodsThis prospective study enrolled 2004 patients following transradial coronary angiography. After sheath removal, hemostasis was obtained in a standardized fashion. Radial artery patency was evaluated by duplex ultrasonography in all patients. In case of occlusion, oral anticoagulation was recommended and patients were scheduled for a 30-day follow-up including Doppler ultrasonography.ResultsA new-diagnosed radial occlusion was found in 4.6% of patients. The strongest independent predictors of radial occlusion were female sex and active smoking status. In the subgroup of patients with percutaneous coronary interventions, female sex followed by sheath size > 6 French were the strongest predictors of radial occlusion. 76 of 93 patients with radial occlusion received an oral anticoagulation for 30 days. However, reperfusion at 30 days was found in 32% of patients on oral anticoagulation.ConclusionThe incidence of radial artery occlusion following coronary angiography in contemporary practice appears with 4.6% to be lower as compared to previous cohorts. Female sex and smoking status are the strongest independent predictors of radial occlusion followed by procedural variables. The limited effectiveness of oral anticoagulation for treatment of radial artery occlusion suggests a primarily traumatic than thrombotic mechanism of this complication.Graphical abstract