Daytime plasma cortisol and cortisol response to dexamethasone suppression are associated with a prothrombotic state in hypertension.

Background and aims: A prothrombotic state was demonstrated in patients with Cushing's syndrome and is involved in the development and progression of cardiovascular and renal damage in hypertensive patients. This study was designed to examine the relationships between cortisol secretion and the hemostatic and fibrinolytic systems in hypertension. Methods: In 149 middle-aged, nondiabetic, essential hypertensive patients free of cardiovascular and renal complications, we measured hemostatic markers that express the spontaneous activation of the coagulation and fibrinolytic systems and assessed daily cortisol levels (8 AM, 3 PM, 12 AM; area under the curve, AUC-cortisol) together with the cortisol response to dexamethasone overnight suppression (DST-cortisol). Results: Plasma levels of D-dimer (D-dim), prothrombin fragment 1 + 2 (F1 + 2), and von Willebrand factor (vWF) were progressively and significantly higher across tertiles of AUC-cortisol and DST-cortisol, whereas no differences were observed in fibrinogen, tissue plasminogen activator, plasminogen activator inhibitor-1, antithrombin III, protein C, and protein S. D-dim, F1 + 2, and vWF were significantly and directly correlated with age and both AUC-cortisol and DST-cortisol. Multivariate regression analysis showed that both AUC-cortisol and DST-cortisol were related to plasma D-dim, F1 + 2, and vWF independently of age, body mass index, blood pressure, and renal function. Conclusion: Greater daily cortisol profile and cortisol response to overnight suppression are independently associated with a prothrombotic state in hypertensive patients and might contribute to the development of organ damage and higher risk of cardiovascular complications.

The incidence of thrombosis with co-occurring thrombocytopenia prior to the SARS-CoV2 pandemic: A population-based study.

BACKGROUND: Thrombosis with thrombocytopenia syndrome (TTS) is a very rare prothrombotic disorder that is a safety concern for some COVID-19 vaccines. We aimed to devise a case definition to estimate the incidence of thrombosis with thrombocytopenia as a proxy for TTS in a national insurance claims database. METHODS: We conducted a retrospective observational study using the National Health Insurance Research Database (NHIRD) in Taiwan over the three-year period prior to the SARS-COV-2 pandemic (2017-2019). Our case definition was all patients with newly diagnosed thrombosis co-occurring with a diagnosis of thrombocytopenia within seven days before or after the thrombosis diagnosis. Cases were identified using International Classification of Disease-10 codes. FINDINGS: We identified 2010 patients with newly diagnosed thrombosis co-occurring with thrombocytopenia during the study period. The mean age was 64.71 years; female:male ratio 1:1.45. The most frequent thrombotic events were coronary artery disease (18.81%), cerebral infarction (16.87%), and disseminated intravascular coagulation (13.13%). Cerebral venous sinus thrombosis was rare (<0.1%). The average annual incidence rate of co-occurring new diagnoses of thrombosis and thrombocytopenia was 2.84 per 100 000 population. Incidence rates were higher in men than women, except in 20-39 year-olds (higher in females). 20.6% of patients died within the first month after diagnosis. INTERPRETATION: We observed that the demographic and clinical characteristics of thrombosis with co-occurring thrombocytopenia using our case definition is different from that of TTS. Further research is needed to refine the case definition of TTS in the post-COVID-19 vaccination period.

Effect of veno-arterial extracorporeal membrane oxygenation lower-extremity cannulation on intra-arterial flow characteristics, oxygen content, and thrombosis risk.

PURPOSE: This study aimed to investigate the effects of lower-extremity cannulation on the intra-arterial hemodynamic environment, oxygen content, blood damage, and thrombosis risk under different levels of veno-arterial (V-A) ECMO support. METHODS: Computational fluid dynamics methods were used to investigate the effects of different levels of ECMO support (ECMO flow ratios supplying oxygen-rich blood 100-40 %). Flow rates and oxygen content in each arterial branch were used to determine organ perfusion. A new thrombosis model considering platelet activation and deposition was proposed to determine the platelet activation and thrombosis risk at different levels of ECMO support. A red blood cell damage model was used to explore the risk of hemolysis. RESULTS: Our study found that partial recovery of cardiac function improved the intra-arterial hemodynamic environment, with reduced impingement of the intra-arterial flow field by high-velocity blood flow from the cannula, a flow rate per unit time into each arterial branch closer to physiological levels, and improved perfusion in the lower extremities. Partial recovery of cardiac function helps reduce intra-arterial high shear stress and residence time, thereby reducing blood damage. The overall level of hemolysis and platelet activation in the aorta decreased with the gradual recovery of cardiac contraction function. The areas at high risk of thrombosis under V-A ECMO femoral cannulation support were the aortic root and the area distal to the cannula, which moved to the descending aorta when cardiac function recovered to 40-60 %. However, with the recovery of cardiac contraction function, hypoxic blood pumped by the heart is insufficient in supplying oxygen to the front of the aortic arch, which may result in upper extremity hypoxia. CONCLUSION: We developed a thrombosis risk prediction model applicable to ECMO cannulation and validated the model accuracy using clinical data. Partial recovery of cardiac function contributed to an improvement in the aortic hemodynamic environment and a reduction in the risk of blood damage; however, there is a potential risk of insufficient perfusion of oxygen-rich blood to organs.

Recurrent intra-cardiac thrombosis: A rare manifestation of Behçet's disease.

Behçet's disease is a systemic vasculitis characterized by recurrent bipolar aphtosis and ophthalmic disorders. Cardiac involvement is rarely reported and could be associated to poor prognosis. Intracardiac thrombosis is exceptional and represents a therapeutic issue. We report the case of a young man admitted in internal medicine department for management of prolonged fever and recurrent mouth ulcers.

Evaluation of the position of the central venous catheter tip of implantable venous access devices in the occurrence of postoperative thrombotic and non-thrombotic complications.

BACKGROUND: The position of the catheter tip of totally implantable venous access devices (TIVAD) is a risk factor for postoperative complications. The study aim was to assess the early and late complications (EC and LC) associated with the position of the catheter tip in cancer patients. METHODS: We reviewed cancer patients who had a TIVAD placed in 2020. EC (≤ 90 days), LC (> 90 days) and risk factors for TIVAD-associated complications were assessed. The vertical mismatch of the catheter tip was compared to an "ideal position" (> 10 mm below the carina and ≥ 20 mm below the right main bronchus (RMB)) using chest x-ray, post-implantation. RESULTS: 301 patients were included. Median follow-up after TIVAD implantation was 9.4 months. All TIVAD catheters were inserted via the internal jugular vein (IJV). The mean distance between the catheter tip and the carina and the RMB was 21.3 mm and 6.63 mm respectively. In total, 11.3% patients developed EC and 5.6% had LC. An association was found between the position of the catheter tip from the carina (≤ 10 mm vs. > 10 mm) and the occurrence of EC (18.3% vs. 8.6%, p = 0.01) and for the catheter insertion side (left IJV vs. right IJV) (19.1% vs. 9.0% p = 0.02). Multivariate analysis showed that left IJV catheter insertion (OR 2.76), and a catheter tip located ≤ 10 mm below the carina (OR 2.71) are significant independent risk factors of EC. CONCLUSIONS: TIVAD catheter tip located at ≤ 10 mm below the carina, and a left-side inserted catheter, are higher risk of EC.

Comparison of apixaban versus aspirin for the prevention of latent bioprosthetic aortic valve thrombosis: study protocol for a prospective randomized trial.

BACKGROUND: The optimal antithrombotic strategy early after aortic valve replacement surgery with a biological valve remains controversial due to lack of high-quality evidence. Either oral anticoagulants or acetylsalicylic acid should be considered for the first 3 months. Hypo-attenuated leaflet thickening on cardiac computed tomography has been associated with latent bioprosthetic valve thrombosis and may be prevented with anticoagulation. We hypothesize that anticoagulation with apixaban is superior to single antiplatelet therapy with acetylsalicylic acid in reducing hypo-attenuated leaflet thickening of bioprosthetic aortic valve prostheses. METHODS: In this prospective, open-label, randomized trial, patients undergoing isolated aortic valve replacement surgery with rapid deployment bioprosthetic valves will be randomized. The treatment group will receive 5 mg of apixaban twice a day for the first 3 months and 100 mg of acetylsalicylic acid thereafter. The control group will be administered 100 mg of acetylsalicylic acid once a day, indefinitely. After the 3-month treatment period, a contrast-enhanced electrocardiogram-gated cardiac computed tomography will be performed to identify hypo-attenuated leaflet thickening of the bioprosthetic valve. The primary objective of the study is to assess the impact of apixaban on the prevention of hypo-attenuated leaflet thickening at 3 months. The secondary and exploratory endpoints will be clinical outcomes and safety profiles of the two strategies. DISCUSSION: Antithrombotic therapy after aortic valve replacement is used to prevent valve thrombosis and systemic thromboembolism. Latent bioprosthetic valve thrombosis is a precursor of clinically significant prosthetic valve dysfunction or thromboembolic events. The hallmark feature of latent bioprosthetic valve thrombosis is hypo-attenuated leaflet thickening on cardiac computed tomography. Subclinical leaflet thrombosis occurs frequently in bioprosthetic aortic valves, more commonly in transcatheter than in surgical valves. There is no evidence on the effect of direct oral anticoagulants on the incidence of hypo-attenuated leaflet thickening after surgical aortic valve replacement with rapid deployment bioprostheses. TRIAL REGISTRATION: ClinicalTrials.gov NCT06184113. Registered on December 28, 2023.

The Etiology of the Thrombotic Phenomena Involved in the Process of Coronary Artery Disease-What Is the Role of Thrombophilic Genes in the Development of This Pathology?

Cardiovascular diseases, among which includes coronary artery disease, represent one of the most important causes of mortality and morbidity worldwide. Research aimed at determining the risk factors involved recognizes a group of "traditional" risk factors, but also more recent studies identified over 100 "novel" ones which may have a role in the disease. Among the latter is the thrombophilia profile of a patient, a pathology well-established for its involvement in venous thromboembolism, but with less studied implications in arterial thrombosis. This paper reviews the literature, explaining the pathophysiology of the thrombophilia causes associated most with coronary thrombosis events. Results of several studies on the subject, including a meta-analysis with over 60,000 subjects, determined the significant involvement of factor V Leiden, prothrombin G20210A mutation, plasminogen activator inhibitor-1 and antiphospholipid syndrome in the development of coronary artery disease. The mechanisms involved are currently at different stages of research, with some already established and used as therapeutic targets.

Application value of real-time 3D speckle tracking imaging in left atrial function evaluation of patients with paroxysmal atrial fibrillation.

OBJECTIVE: To evaluate left atrial volume and function in patients with paroxysmal atrial fibrillation (AF) combined with left atrial appendage thrombosis and patients with paroxysmal AF without left atrial appendage thrombosis by 3-dimensional speckle tracking imaging (3D-STI), and to explore the application value of this set of parameters in the evaluation of left atrial function in patients with paroxysmal AF. MATERIALS AND METHODS: A total of 40 patients with paroxysmal AF admitted from December 2018 to December 2020 were selected as the observation group. All patients with paroxysmal AF in the observation group underwent transesophageal echocardiography. According to the presence of left atrial appendage thrombosis, the patients were divided into the AF without thrombosis group (24 cases) and the AF with thrombosis group (16 cases). Thirty normal people were selected as control group who were chosen as having no heart-related disease. The left atrial volume parameters (Left atrial maximum volume LAVmax, Left atrial minimum volume LAVmin, Left atrial volume before atrial contraction LAVpre-A, Left atrial stroke volume LAEV), left atrial ejection fraction (LAEF) and left atrial strain parameters (Left atrial reservoir longitudinal strain LASr, Left atrial conduit longitudinal strain LAScd, Left atrial contraction longitudinal strain LASct, Left atrial reservoir circumferential strain LASr-c, Left atrial conduit circumferential strain LAScd-c, Left atrial contraction circumferential strain LASct-c) of the 3 groups were measured by 3D-STI. RESULTS: With the progression of paroxysmal AF, the left atrial volume increased, and the reservoir, conduit and contractile function were damaged. The left atrial volume continued to increase, and the reservoir, conduit and contractile function further decreased significantly in patients with AF combined with left atrial appendage thrombosis. LAEF was positively correlated with LASr and LASr_c. CONCLUSION: Real-time 3-dimensional spot tracking imaging (3D-STI) can evaluate the changes in left atrial volume and function in patients with paroxysmal AF, and has a certain reference value for clinical judgment of disease progression and prognosis.

Myocardial ischemia-reperfusion injury released cellular fibronectin containing domain A (CFN-EDA): A destructive positive loop amplifying arterial thrombosis formation and exacerbating myocardial reperfusion injury.

Previous research has identified intravascular platelet thrombi in regions affected by myocardial ischemia-reperfusion (MI/R) injury and neighbouring areas. However, the occurrence of arterial thrombosis in the context of MI/R injury remains unexplored. This study utilizes intravital microscopy to investigate carotid artery thrombosis during MI/R injury in rats, establishing a connection with the presence of prothrombotic cellular fibronectin containing extra domain A (CFN-EDA) protein. Additionally, the study examines samples from patients with coronary artery disease (CAD) both before and after coronary artery bypass grafting (CABG). Levels of CFN-EDA significantly increase following MI with further elevation observed following reperfusion of the ischemic myocardium. Thrombotic events, such as thrombus formation and growth, show a significant increase, while the time to complete cessation of blood flow in the carotid artery significantly decreases following MI/R injury induced by ferric chloride. The acute infusion of purified CFN-EDA protein accelerates in-vivo thrombotic events in healthy rats and significantly enhances in-vitro adenosine diphosphate and collagen-induced platelet aggregation. Treatment with anti-CFN-EDA antibodies protected the rat against MI/R injury and significantly improved cardiac function as evidenced by increased end-systolic pressure-volume relationship slope and preload recruitable stroke work compared to control. Similarly, in a human study, plasma CFN-EDA levels were notably elevated in CAD patients undergoing CABG. Post-surgery, these levels continued to rise over time, alongside cardiac injury biomarkers such as cardiac troponin and B-type natriuretic peptide. The study highlights that increased CFN-EDA due to CAD or MI initiates a destructive positive feedback loop by amplifying arterial thrombus formation, potentially exacerbating MI/R injury.

A retrospective review of antiphospholipid syndrome: a single tertiary centre experience.

INTRODUCTION: Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterised by thrombosis and pregnancy morbidity in the presence of antiphospholipid antibodies (aPL). Our study aims to study the clinical and laboratory characteristics, treatment strategies and outcomes of APS patients retrospectively. MATERIALS AND METHODS: A retrospective review of all APS patients treated in Rheumatology Unit, Hospital Pulau Pinang between October 2021 and October 2022 was conducted. RESULTS: A total of 53 APS patients (age 42.4±13.9 years) including 22 (41.5%) primary and 31 (58.5%) secondary APS patients were identified. Thrombosis was the most common clinical manifestation (51/53; 96.2%) followed by pregnancy morbidity (15/45; 33.3%). For other clinical manifestations, aPL-associated thrombocytopenia was the most frequently observed manifestation (26.4%) followed by autoimmune haemolytic anaemia (18.9%). Lupus anticoagulant (LA) (88.7%) was the most commonly found aPL followed by anticardiolipin antibody (aCL) (50.9%) and anti-beta 2 glycoprotein 1 antibody (B2GP1) (30.2%). 10 (18.9%) patients tested positive for all three aPL. The majority of our patients (86.8%) receive warfarin as anticoagulation therapy while the remaining receive aspirin or direct oral anticoagulants. CONCLUSION: Our population cohort demonstrated a high incidence of pregnancy morbidities and a similar incidence of thrombotic events compared to other population cohorts in both Asian and the European countries.

Repeated acute coronary syndrome caused by a mind-bending mural thrombus in ascending aorta: a case report and review of the literature.

BACKGROUND: Acute coronary syndrome due to coronary artery embolism in the setting of ascending aortic thrombus is an uncommon condition, even rarer when there is no aortic pathology such as aneurysm, severe atherosclerosis, aortic dissection, or thrombophilia (whether inherited or acquired). CASE PRESENTATION: We report a case of a 58-year-old male presented with acute chest pain, electrocardiogram showing non-ST-elevation acute coronary syndrome. The computed tomography angiography of coronary artery revealed a mural thrombus in the proximal part of ascending aorta, located above the left coronary artery ostium, without any aortic pathologies. With the exception of hypertension and cigarette smoking, no other risk factors were identified in this patient that may increase the risk of thrombosis. Given the life-threatening risk of interventional therapy and surgery, the patient determinedly opted for anticoagulant and dual antiplatelet therapy. Then he experienced the reoccurrence of chest pain after 6-day treatment, progressed to anterior and inferior ST-segment elevation myocardial infarction. Coronary artery embolism originating from the ascending aortic thrombus was suspected. Considering the hemodynamic instability of the patient, the medical treatment was continued and bridged to warfarin and aspirin after discharge. Follow-up computed tomography angiography at 6 months showed no obstruction in coronary artery and complete resolution of the thrombus. No thromboembolic events occurred henceforward. CONCLUSIONS: Acute coronary syndrome could be a manifestation of secondary coronary embolism due to ascending aortic thrombus. Currently, there is no standardized guideline for the treatment of aortic mural thrombus, individualized treatment is recommended. When surgical therapy is not applicable for the patient, anticoagulation and dual antiplatelet treatment are alternative treatments that may successfully lead to the resolution of the aortic thrombus.

Factors predicting resolution of left ventricular thrombus in different time windows after myocardial infarction.

BACKGROUND: Left ventricular thrombus (LVT) is a serious complication after myocardial infarction. However, due to its asymptomatic nature, early detection is challenging. We aimed to explore the differences in clinical correlates of LVT found in acute to subacute and chronic phases of myocardial infarction. METHODS: We collected data from 153 patients who were diagnosed with LVT after myocardial infarction at the Affiliated Hospital of Qingdao University from January 2013 to December 2022. Baseline information, inflammatory markers, transthoracic echocardiograph (TTE) data and other clinical correlates were collected. Patients were categorized into acute to subacute phase group (< 30 days) and chronic phase group (30 days and after) according to the time at which echocardiograph was performed. The resolution of thrombus within 90 days is regarded as the primary endpoint event. We fitted logistic regression models to relating clinical correlates with phase-specific thrombus resolution. RESULTS: For acute to subacute phase thrombus patients: C-reactive protein levels (OR: 0.95, 95% CI: 0.918-0.983, p = 0.003) were significantly associated with thrombus resolution. For chronic phase thrombus patients: anticoagulant treatment was associated with 5.717-fold odds of thrombus resolution (OR: 5.717, 95% CI: 1.543-21.18, p = 0.009). CONCLUSIONS: Higher levels of CRP were associated with lower likelihood of LVT resolution in acute phase myocardial infarction; Anticoagulant therapy is still needed for thrombus in the chronic stage of myocardial infarction.

Delayed Diagnosis of Pulmonary Artery Thrombosis in a Patient Undergoing Mitral Valve Replacement.

ABSTRACT: The occurrence of pulmonary artery thrombus in association with rheumatic mitral stenosis is a rare complication. Pulmonary artery thrombus formation may worsen pulmonary artery pressures, and this may precipitate acute right heart failure. The possible mechanisms behind pulmonary artery thrombus formation during mitral valve replacement surgery could be acute coagulopathy following surgery, the presence of chronic pulmonary thromboembolism, or chronic atrial fibrillation. We report an unusual case of pulmonary artery thrombus in a patient with rheumatic MS which was diagnosed with transoesophageal echocardiography after MVR.

How We Interpret Thrombosis with Thrombocytopenia Syndrome?

Platelets play an important role in hemostasis, and a low platelet count usually increases the risk of bleeding. Conditions in which thrombosis occurs despite low platelet counts are referred to as thrombosis with thrombocytopenia syndrome, including heparin-induced thrombocytopenia, vaccine-induced immune thrombotic thrombocytopenia, paroxysmal nocturnal hemoglobinuria, antiphospholipid syndrome, thrombotic microangiopathy (TMA), and disseminated intravascular coagulation. TMA includes thrombotic thrombocytopenic purpura, Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome (HUS), and atypical HUS. Patients with these pathologies present with thrombosis and consumptive thrombocytopenia associated with the activation of platelets and the coagulation system. Treatment varies from disease to disease, and many diseases have direct impacts on mortality and organ prognosis if therapeutic interventions are not promptly implemented. Underlying diseases and the results of physical examinations and general laboratory tests as part of a thorough workup for patients should promptly lead to therapeutic intervention before definitive diagnosis. For some diseases, the diagnosis and initial treatment must proceed in parallel. Utilization of not only laboratory tests but also various scoring systems is important for validating therapeutic interventions based on clinical information.

Acute-on-Chronic Axillary Artery Thrombus After Reverse Total Shoulder Arthroplasty for Failed Proximal Humerus Open Reduction and Internal Fixation: A Case Report.

CASE: A 71-year-old woman presented with post-traumatic arthritis 11 months after open reduction and internal fixation for a left proximal humerus fracture (PHF) dislocation. After revision to reverse total shoulder arthroplasty (rTSA), the patient's left upper extremity was found to be avascular. An emergent thrombectomy was performed with restoration of arterial flow after removal of an acute-on-chronic axillary artery thrombus. CONCLUSION: Although rare, as rTSA becomes more common for management of PHF, incidence of associated vascular injuries is likely to rise. Screening methods and clinical vigilance in diagnosis are advised for patients with anterior PHF dislocations and arterial injury risk factors.