Local Thrombosis Research Articles

From rare to aware: confronting Lemierre syndrome.

Lemierre syndrome is a life-threatening condition characterized by an acute head/neck bacterial infection due to anaerobes (namely Fusobacterium necrophorum), local septic vein thrombosis and distance septic embolism...

Evaluation of Novel Biomarker of Early Atherosclerosis in Patients With Chronic Kidney Disease in Wasit Governorate

The aim of the study was to evaluate some Biomarkers in patients with athreoscelerosis in Wasit Province. Atherosclerosis is a chronic arterial disease and a major cause of vascular death. Fatty streaks in arterial walls gradually develop into atheroma and characteristic plaques. The acute rupture of these atheromatous plaques causes local thrombosis, leading to partial or total occlusion of the affected artery. The clinical consequences of these plaques depend on their site and the degree and speed of vessel occlusion . Its major clinical manifestations include ischemic heart disease (IHD), ischemic stroke, and peripheral arterial disease. The study took place in the a hemodialysis unit Al-Zahraa Teaching Hospital in Wasit Governorate during the period from November 2023 to April 2024. This study aimed to examine risk factors (age, gender, high blood pressure, smoking, left ventricular hypertrophy, diabetes mellitus, dyslipidemia, physical inactivity) for atherosclerosis in the general population and patients with chronic kidney disease. Also studying the effect of some novel biomarkers (Homocysteine, Fibrinogen, myeloperoxidase, lipoprotein-associated phospholipase A2, pentraxin 3). The study include (90) samples: (60) patients suffering from early atherosclerosis and chronic kidney disease (dialysis stage) and 30 samples of healthy people (control group), their ages ranged from (40 to 70 years). The samples were divided into two age groups, where the first group had an average age of 40-55 years and the second group was 56-70 years old , the categories were divided equally into males and females Samples were collected based on the incidence of kidney disease first, and then the main risk factors of early atherosclerosis were relied upon, which are (smoking, age, sex, dyslipidemia, hypertension, diabetes, left ventricle valve, physical inactivity). The results of our study regarding diagnostic markers of atherosclerosis showed a significant increase in biomarkers (MPO, PTX3, HCy, FG and LpPLA2)of infected people at p ≥ 0.5. In patients with atherosclerosis the level of new biomarkers showed a significant increase in serum of infected people compared to healthy people at p<0.5. This is an important indication of the importance of these biomarkers in detecting the disease.

New Insights into the Pathophysiology of Coronary Artery Aneurysms.

Coronary aneurysms are typically defined as sections of a coronary artery where the diameter is more than 1.5 times that of an adjacent normal segment. In rare circumstances, these aneurysms can become exceedingly large, leading to the classification of giant coronary artery aneurysms. Despite their occurrence, there is no clear consensus on the precise definition of giant coronary artery aneurysms, and their etiology remains somewhat ambiguous. Numerous potential causes have been suggested, with atherosclerosis being the most prevalent in adults, accounting for up to 50% of cases. In pediatric populations, Kawasaki disease and Takayasu arteritis are the primary causes. Although often discovered incidentally, coronary artery aneurysms can lead to severe complications. These complications include local thrombosis, distal embolization, rupture, and vasospasm, which can result in ischemia, heart failure, and arrhythmias. The optimal approach to medical, interventional, or surgical management of these aneurysms is still under debate and requires further clarification. This literature review aims to consolidate current knowledge regarding coronary artery aneurysms' pathophysiology, emphasizing their definition, causes, complications, and treatment strategies. Recent research has begun to explore the molecular mechanisms involved in the formation and progression of coronary artery aneurysms. Various molecules, such as matrix metalloproteinases (MMPs), inflammatory cytokines, and growth factors, play crucial roles in the degradation of the extracellular matrix and the remodeling of vascular walls. Elevated levels of MMPs, particularly MMP-9, have been associated with the weakening of the arterial wall, contributing to aneurysm development. Inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukins (IL-1β and IL-6) have been implicated in promoting inflammatory responses that further degrade vascular integrity. Additionally, growth factors such as vascular endothelial growth factor (VEGF) may influence angiogenesis and vascular remodeling processes. Understanding these molecular pathways is essential for developing targeted therapies aimed at preventing the progression of coronary artery aneurysms and improving patient outcomes.

Coronary Artery Aneurysm or Ectasia as a Form of Coronary Artery Remodeling: Etiology, Pathogenesis, Diagnostics, Complications, and Treatment.

Coronary artery aneurysm or ectasia (CAAE) is a term that includes both coronary artery ectasia (CAE) and coronary artery aneurysm (CAA), despite distinct phenotypes and definitions. This anomaly can be found in 0.15-5.3% of coronary angiography. CAE is a diffuse dilatation of the coronary artery at least 1.5 times wider than the diameter of the normal coronary artery in a patient with a length of over 20 mm or greater than one-third of the vessel. CAE can be further subdivided into diffuse and focal dilations by the number and the length of the dilated vessels. Histologically, it presents with extensive destruction of musculoelastic elements, marked degradation of collagen and elastic fibers, and disruption of the elastic lamina. Conversely, CAA is a focal lesion manifesting as focal dilatation, which can be fusiform (if the longitudinal diameter is greater than the transverse) or saccular (if the longitudinal diameter is smaller than the transverse). Giant CAA is defined as a 4-fold enlargement of the vessel diameter and is observed in only 0.02% of patients after coronary. An aneurysmal lesion can be either single or multiple. It can be either a congenital or acquired phenomenon. The pathophysiological mechanisms responsible for the formation of CAAE are not well understood. Atherosclerosis is the most common etiology of CAAE in adults, while Kawasaki disease is the most common in children. Other etiological factors include systemic connective tissue diseases, infectious diseases, vasculitis, congenital anomalies, genetic factors, and idiopathic CAA. Invasive assessment of CAAE is based on coronary angiography. Coronary computed tomography (CT) is a noninvasive method that enables accurate evaluation of aneurysm size and location. The most common complications are coronary spasm, local thrombosis, distal embolization, coronary artery rupture, and compression of adjacent structures by giant coronary aneurysms. The approach to each patient with CAAE should depend on the severity of symptoms, anatomical structure, size, and location of the aneurysm. Treatment methods should be carefully considered to avoid possible complications of CAAE. Simultaneously, we should not unnecessarily expose the patient to the risk of intervention or surgical treatment. Patients can be offered conservative or invasive treatment. However, there are still numerous controversies and ambiguities regarding the etiology, prognosis, and treatment of patients with coronary artery aneurysms. This study summarizes the current knowledge about this disease's etiology, pathogenesis, and management.

Hemodynamic Stroke: Emerging Concepts, Risk Estimation, and Treatment.

Ischemic stroke can arise from the sudden occlusion of a brain-feeding artery by a clot (embolic), or local thrombosis. Hemodynamic stroke occurs when blood flow does not sufficiently meet the metabolic demand of a brain region at a certain time. This discrepancy between demand and supply can occur with cerebropetal arterial occlusion or high-grade stenosis but also arises with systemic conditions reducing blood pressure. Treatment of hemodynamic stroke is targeted toward increasing blood flow to the affected area by either systemically or locally enhancing perfusion. Thus, blood pressure is often maintained above normal values, and extra-intracranial flow augmentation bypass surgery is increasingly considered. Still, current evidence supporting the superiority of pressure or flow increase over conservative measures is limited. However, methods assessing hemodynamic impairment and identifying patients at risk of hemodynamic stroke are rapidly evolving. Sophisticated models incorporating clinical and imaging factors have been suggested to aid patient selection. In this narrative review, we provide current state-of-the-art knowledge about hemodynamic stroke, tools for assessment, and treatment options.

Real-time identification of life-threatening necrotizing soft-tissue infections using indocyanine green fluorescence imaging.

Necrotizing soft-tissue infections (NSTIs) are life-threatening infections with a cumulative case fatality rate of 21%. The initial presentation of an NSTI is non-specific, frequently leading to misdiagnosis and delays in care. No current strategies yield an accurate, real-time diagnosis of an NSTI. A first-in-kind, observational, clinical pilot study tested the hypothesis that measurable fluorescence signal voids occur in NSTI-affected tissues following intravenous administration and imaging of perfusion-based indocyanine green (ICG) fluorescence. This hypothesis is based on the established knowledge that NSTI is associated with local microvascular thrombosis. Adult patients presenting to the Emergency Department of a tertiary care medical center at high risk for NSTI were prospectively enrolled and imaged with a commercial fluorescence imager. Single-frame fluorescence snapshot and first-pass perfusion kinetic parameters-ingress slope (IS), time-to-peak (TTP) intensity, and maximum fluorescence intensity (IMAX)-were quantified using a dynamic contrast-enhanced fluorescence imaging technique. Clinical variables (comorbidities, blood laboratory values), fluorescence parameters, and fluorescence signal-to-background ratios (SBRs) were compared to final infection diagnosis. Fourteen patients were enrolled and imaged (six NSTI, six cellulitis, one diabetes mellitus-associated gangrene, and one osteomyelitis). Clinical variables demonstrated no statistically significant differences between NSTI and non-NSTI patient groups (). All NSTI cases exhibited prominent fluorescence signal voids in affected tissues, including tissue features not visible to the naked eye. All cellulitis cases exhibited a hyperemic response with increased fluorescence and no distinct signal voids. Median lesion-to-background tissue SBRs based on snapshot, IS, TTP, and IMAX parameter maps ranged from 3.2 to 9.1, 2.2 to 33.8, 1.0 to 7.5, and 1.5 to 12.7, respectively, for the NSTI patient group. All fluorescence parameters except TTP demonstrated statistically significant differences between NSTI and cellulitis patient groups (). Real-time, accurate discrimination of NSTIs compared with non-necrotizing infections may be possible with perfusion-based ICG fluorescence imaging.

Anti-fouling coating with ROS-Triggered On-Demand regulation of inflammation to favor tissue healing on vascular devices

Unhealthy vascular tissue healing after stenting is primarily triggered by endothelial dysfunction and excessive smooth muscle cell proliferation, which is induced and aggravated by local thrombosis and excessive inflammation. Excessive inflammatory response is closely related to elevated concentrations of reactive oxygen species (ROS). Here, an environment-friendly coating strategy termed “Anti-fouling plus” with inflammatory self-regulation ability was proposed. Upon this, membrane-mimicking copolymer MA(PCLA) served as the antifouling coating, effectively inhibiting coagulation and inflammation during the early stage of implantation. Furthermore, a ROS-responsive prodrug was drawn into the coating to promote tissue healing. A molecular prodrug of thioketal-bearing dexamethasone was engineered to be released in a controlled and responsive manner in response to externally high levels of ROS. The released dexamethasone exhibited highly effective anti-inflammation properties after implantation. The combination of ROS-responsive prodrug and membrane-mimicking antifouling interface strategy intelligently integrated inflammation responsiveness and regulation, which could mediate a gentle vascular microenvironment and thus promote vascular remodeling. In vivo stent implantation studies demonstrated that the proposed “Anti-fouling plus” coating effectively inhibited neointima hyperplasia, modulated the inflammatory response and promoted endothelialization, offering promising surface modification approaches for vascular stents.

Pulmonary thrombosis associated with COVID-19 pneumonia: Beyond classical pulmonary thromboembolism.

Classical pulmonary thromboembolism (TE) and local pulmonary thrombosis (PT) have been suggested as mechanisms of thrombosis in COVID-19. However, robust evidence is still lacking because this was mainly based on retrospective studies, in which patients were included when TE was suspected. All patients with COVID-19 pneumonia underwent computed tomography and pulmonary angiography in a prospective study. The main objective was to determine the number and percentage of thrombi surrounded by lung opacification (TSO) in each patient, as well as their relationship with percentage of lung involvement (TLI), to distinguish classical TE (with a random location of thrombi that should correspond to a percentage of TSO equivalent to the TLI) from PT. We determined TLI by artificial intelligence. Analyses at patient level (TLI and percentage of TSO) and at thrombi level (TLI and TSO) were performed. We diagnosed TE in 70 out of 184 patients. Three (2-8) thrombi/patient were detected. The percentage of TSO was 100% (75-100) per patient, and TLI was 19.9% (4.6-35.2). Sixty-five patients (92.9%) were above the random scenario with higher percentage of TSO than TLI. Most thrombi were TSO (n = 299, 75.1%). When evaluating by TLI (<10%, 10%-20%, 20%-30% and >30%), percentage of TSO was higher in most groups. Thrombi were mainly in subsegmental/segmental arteries, and percentage of TSO was higher in all locations. Thrombi in COVID-19 were found within lung opacities in a higher percentage than lung involvement, regardless of TLI and clot location, supporting the hypothesis of local PT rather than "classic TE".

The efficacy and safety of vincristine, irinotecan and anlotinib in Epithelioid Sarcoma

BackgroundEpithelioid sarcoma is a rare soft tissue sarcoma characterized by SMARCB1/INI1 deficiency. Much attention has been paid to the selective EZH2 inhibitor tazemetostat, where other systemic treatments are generally ignored. To explore alternative treatment options, we studied the effects of irinotecan-based chemotherapy in a series of epithelioid sarcoma patients.MethodsWe retrospectively reviewed data from patients with metastatic or unresectable epithelioid sarcoma at the Peking University People’s Hospital treated with irinotecan (50 mg/m2/d d1-5 Q3W) in combination with Anlotinib (12 mg Qd, 2 weeks on and 1 week off) from July 2015 to November 2021.ResultsA total of 54 courses were administered. With a median follow up of 21.2 months (95% CI, 12.2, 68.1), the 5-year overall survival rate was 83.3%. Five of eight (62.5%) patients presented with unresectable localized lesions, including local tumor thrombosis and lymphatic metastasis. The other patients had unresectable pulmonary metastases. Six of eight (75%) patients had progressed following two lines of systemic therapy. The objective response rate reached 37.5% (three of eight patients) while stabilized disease was observed in 62.5% (five of eight) of patients. No patient had progressed at initial evaluation. At the last follow up, two patients were still using the combination and three patients had ceased the therapy due to toxicities such as diarrhea, nausea, and emesis. One patient changed to tazemetostat for maintenance and one patient stopped treatment due to coronavirus disease 2019 (COVID-19). Another patient stopped therapy as residual lesions had been radiated.ConclusionsThe combination of irinotecan and Anlotinib as a salvage regimen may be considered another effective treatment option for refractory epithelioid sarcoma.Trial registrationThis study was approved in the Medical Ethics Committee of Peking University People’s Hospital on October 28, 2022 (No.: 2022PHD015-002). The study was registered in Clinicaltrials.gov with identifier no. NCT05656222.

Necrotizing Raynaud's phenomenon after recurrent COVID-19 infection

Raynaud's phenomenon (RP), which can be primary or secondary, is a common vascular clinical syndrome due to abnormal arteriolar vasospasm. Its treatment is most often conservative depending on the etiology. In recent years, there have been reports of RP as a syndrome after a previous SARS-CoV-2 infection, in patients of different genders and ages. As an etiological factor for the development of vascular pathology in these cases, two main mechanisms are assumed: an autoimmune process or the thrombosis of arterial vessels, leading to tissue ischemia, and the so-called necrotizing Raynaud's phenomenon. In the pathogenesis of Raynaud's phenomenon, the influence of local, neuronal and hormonal mediators is emphasized. Some studies prove the role of estrogens, which explains the higher incidence of RP among women. At present, there is no convincing evidence for "candidate genes" to be associated with Raynaud's phenomenon, despite studies by some authors (Susol et al., 2000; Pistorius et al., 2006). Vasospasm in digital ischemia may be further complicated by COVID-19 infection. Another potential component is hypercoagulation (further complicated by the presence of antiphospholipid antibodies in certain patients) and elevated levels of D-dimer. A state of hypercoagulation is caused by the so-called cytokine storm. This inflammatory state, as a result of endovascular damage, increased platelet activity and coagulation cascade, causes the so-called phenomenon of immunothrombosis. Overactivation of the coagulation pathway during cytokine storm results from increased activity of thrombin, which has an additional role in the inflammatory process through proteinase-activated receptors (PARs). Acrocyanosis due to excessive coagulation status has been described in critically ill patients with COVID-19. In these patients, gangrene may arise from impaired blood flow and insufficient healing of digital wounds, which is associated with elevated levels of C-reactive protein (CRP). Ischemic limb lesions, usually seen in older patients with severe clinical course of the disease, represent a dangerous, although rare, complication associated with COVID-19 and are due to arterial occlusions. They are extremely difficult to treat and often lead to amputations. In patients with antiphospholipid syndrome, arterial and venous thrombi are primarily caused by the formation of neutrophil extracellular traps (NET), which in turn activate platelets, and their excessive formation can lead to local thrombosis. In addition to platelet activation, neutrophils release tissue factor, which initiates the coagulation cascade. NETs bind coagulation factor XII and activate it, and also induce an inflammatory reaction in the vessel wall. According to the available knowledge to date, the hypothesis that digital necrosis in patients with COVID-19 is primarily related to the formation of NETs has been developed.&#x0D; Necrotizing Raynaud's phenomenon (NRP) is a vascular clinical syndrome characterized by vasoconstriction of distal resistance vessels following low temperatures or states of anxiety and stress. The first symptom is pain, due to lack of oxygen, which leads to tissue ischemia. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause endotheliopathy with microvascular and macrovascular thrombotic events. COVID-19 induces hypercoagulation, thrombosis, endothelial damage, and inflammation leading to vasculitis. The coagulopathy, inflammation, and thrombosis seen in COVID-19 are potentiated by increased activity of clotting factors, loss of protective glycocalyx function, and decreased nitric oxide levels. The effects of COVID-19 in patients with RP are still being elucidated.&#x0D; This review presents a series of selected clinical cases associated with Raynaud's phenomenon (necrotic, new-onset, exacerbated, or as part of another systemic connective tissue disease) secondary to past COVID-19 infection or vaccination.&#x0D;

Case Report: Abdominal variant of Lemierre’s syndrome

Lemierre's syndrome is a rare condition characterized by Fusobacterium bacteremia from an oropharyngeal source with septic emboli causing internal jugular vein (IVJ) thrombophlebitis in an otherwise young and healthy host. Rare variants of this rare disease have been described impacting the gastrointestinal, pulmonary, neurologic, musculoskeletal, soft tissue, and genitourinary systems. We discuss a case of an abdominal variant of Lemierre's syndrome. An otherwise young and healthy male presented with two pyogenic hepatic abscesses, Fusobacterium necrophorum bacteremia, and local hepatic venous thrombosis. The hepatic abscesses were percutaneously drained, he received broad-spectrum antibiotics and therapeutic-level anticoagulation, and he showed marked clinical improvement over a six-day hospital course. He was discharged with four weeks of daily oral and intravenous (IV) antibiotics, six months of direct oral anticoagulation, and close follow up. Clinicians should consider thrombophlebitis in more anatomical locations than the IVJ which is found classically in Lemierre’s syndrome in the setting of Fusobacterium bacteremia.

Intravital imaging of three different microvascular beds in SARS-CoV-2–infected mice

AbstractSevere acute respiratory syndrome coronavirus–2 (SARS-CoV-2) enters the respiratory tract, where it infects the alveoli epithelial lining. However, patients have sequelae that extend well beyond the alveoli into the pulmonary vasculature and, perhaps, beyond to the brain and other organs. Because of the dynamic events within blood vessels, histology does not report platelet and neutrophil behavior. Because of the rapid nontranscriptional response of these cells, neither single-cell RNA sequencing nor proteomics report robustly on their critical behaviors. We used intravital microscopy in level-3 containment to examine the pathogenesis of SARS-CoV-2 within 3 organs in mice expressing human angiotensin converting enzyme 2 (ACE-2) ubiquitously (CAG-AC-70) or on epithelium (K18-promoter). Using a neon-green SARS-CoV-2, we observed both the epithelium and endothelium infected in AC70 mice but only the epithelium in K18 mice. There were increased neutrophils in the microcirculation but not in the alveoli of the lungs of AC70 mice. Platelets formed large aggregates in the pulmonary capillaries. Despite only neurons being infected within the brain, profound neutrophil adhesion forming the nidus of large platelet aggregates were observed in the cerebral microcirculation, with many nonperfused microvessels. Neutrophils breached the brain endothelial layer associated with a significant disruption of the blood-brain-barrier. Despite ubiquitous ACE-2 expression, CAG-AC-70 mice had very small increases in blood cytokine, no increase in thrombin, no infected circulating cells, and no liver involvement suggesting limited systemic effects. In summary, our imaging of SARS-CoV-2–infected mice gave direct evidence that there is a significant perturbation locally in the lung and brain microcirculation induced by local viral infection leading to increased local inflammation and thrombosis in these organs.

Accuracy of efficient data methods to determine the incidence of hospital-acquired thrombosis and major bleeding in medical and surgical inpatients: a multicentre observational cohort study in four UK hospitals

ObjectivesWe evaluated the accuracy of using routine health service data to identify hospital-acquired thrombosis (HAT) and major bleeding events (MBE) compared with a reference standard of case note review.DesignA multicentre...

A case of early pulmonary embolism following blunt trauma to chest and a long bone fracture: a case report

BackgroundAfter substantial trauma, pulmonary embolism (PE) carries a high risk of morbidity and mortality. Early post-traumatic PE in the absence of deep vein thrombosis (DVT) is a distinct entity that might be connected to rare mechanisms or unidentified biochemical processes.Case presentationA driver of a car was presented with worsening chest pain and shortness of breath (SOB) following a road traffic accident in which he suffered an impact on the chest against the steering wheel and a closed fracture of the right femur. Radiological investigations revealed a pulmonary embolism in the left posterior segment pulmonary artery, without evidence of internal chest injuries or DVT within 12 h from the incident. D-dimer, troponin I, and creatinine kinase were elevated without evidence of myocardial infarction or myocardial injury. Other parameters were within the normal range.ConclusionsPossibilities of early PE in the absence of detectable DVT could be due to hyper-coagulability states, clots from the lower extremity completely getting detached and embolizing to the pulmonary circulation, screening errors, and “de novo” thrombi in the pulmonary circulation. Chest trauma is an identified risk factor for early or late pulmonary embolism. Action of the post-traumatic adrenergic response causing vascular endothelial inflammation and the synthesis of circulating adhesion molecules leading to localized thrombosis have also been suggested as causes for this phenomenon. A greater understanding of rare risk factors for early PE and the possibility of rare complications of chest trauma is useful in detecting and treating them in time, reducing morbidity and mortality.

Comparing Complication Rates of Midline Catheter vs Peripherally Inserted Central Catheter. A Systematic Review and Meta-analysis.

Peripherally inserted central catheters (PICCs) and midlines are commonly used devices for reliable vascular access. Infection and thrombosis are the main adverse effects of these catheters. We aimed to evaluate the relative risk of complications from midlines and PICCs. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies. The primary outcomes were catheter-related bloodstream infection (CRBSI) and thrombosis. Secondary outcomes evaluated included mortality, failure to complete therapy, catheter occlusion, phlebitis, and catheter fracture. The certainty of evidence was assessed using the GRADE approach. Of 8368 citations identified, 20 studies met the eligibility criteria, including 1 RCT and 19 observational studies. Midline use was associated with fewer patients with CRBSI compared with PICCs (odds ratio [OR], 0.24; 95% CI, 0.15-0.38). This association was not observed when we evaluated risk per catheter. No significant association was found between catheters when evaluating risk of localized thrombosis and pulmonary embolism. A subgroup analysis based on location of thrombosis showed higher rates of superficial venous thrombosis in patients using midlines (OR, 2.30; 95% CI, 1.48-3.57). We did not identify any significant difference between midlines and PICCs for the secondary outcomes. Our findings suggest that patients who use midlines might experience fewer CRBSIs than those who use PICCs. However, the use of midline catheters was associated with greater risk of superficial vein thrombosis. These findings can help guide future cost-benefit analyses and direct comparative RCTs to further characterize the efficacy and risks of PICCs vs midline catheters.

Emerging Biomarkers for Predicting Clinical Outcomes in Patients with Heart Disease.

Cardiovascular disease is most frequently caused by the development and progression of atherosclerosis. When coronary arteries are afflicted, and the stenoses caused by atherosclerotic plaques are severe enough, the metabolic supply-and-offer balance is disturbed, leading to myocardial ischemia. If atherosclerotic plaques become unstable and local thrombosis develops, a myocardial infarction occurs. Sometimes, myocardial ischemia and infarction may result in significant and irreversible heart failure. To prevent severe complications, such as acute coronary syndromes and ischemia-related heart failure, extensive efforts have been made for developing biomarkers that would help identify patients at increased risk for cardiovascular events. In this two-part study, we attempted to provide a review of existing knowledge of blood biomarkers that may be used in this setting. The first part of this work was dedicated to conventional biomarkers, which are already used in clinical practice. In the second part, here presented, we discuss emerging biomarkers which have not yet become mainstream.

Incidence and factors predictive of recurrent thrombosis in people with non-cirrhotic portal vein thrombosis

Clinical guidelines do not recommend long-term anticoagulation in non-cirrhotic splanchnic vein thrombosis (NC-SVT) without underlying thrombophilia because it is assumed that there is a very low risk of recurrent thrombosis (RT). Our first aim was to describe the incidence of RT in people with NC-SVT without an indication for long-term anticoagulation. The second aim was to identify RT risk factors and afterwards verify them in a validation cohort. This is a multicentre, retrospective observational study evaluating risk factors for RT in 64 people with NC-SVT of idiopathic/local factor aetiology. In a subgroup of 48 individuals, the potential value of additional thrombophilic parameters to predict RT was analysed. Findings were validated in 70 individuals with idiopathic/local factor NC-SVT. Of the 64 participants in the training cohort, 17 (26%) presented splanchnic and/or extrasplanchnic RT (overall-RT) during follow-up (cumulative incidence: 2, 10, 19, and 34% at 1, 2, 5, and 10 years, respectively). In addition, 53% of people with splanchnic RT were asymptomatic. No clinical or biochemical parameters predicted overall-RT. However, in the 48 people with an additional comprehensive thrombophilic study, factor VIII ≥150% was the only independent factor predicting overall-RT (hazard ratio 7.10, 95% CI 2.17-23.17, p <0.01). In the validation cohort, 19 individuals (27%) presented overall-RT, and it was also independently predicted by factor VIII >150% (hazard ratio 3.71, 95% CI 1.31-10.5, p <0.01). The predictive value of factor VIII was confirmed in both people with idiopathic/local factor aetiology associated NC-SVT. People with idiopathic/local factor NC-SVT are at risk of overall-RT. Splanchnic RT can be asymptomatic and requires screening for its detection. Values of factor VIII ≥150% may help identify individuals at high risk of overall-RT who could benefit from long-term anticoagulation. People with idiopathic/isolated local factor non-cirrhotic portal vein thrombosis were previously thought to be at minimal risk of re-thrombosis and therefore did not receive scheduled follow-up. The results of this study are of special interest for hepatologists treating people with non-cirrhotic splanchnic thrombosis, as they show a 25% incidence of re-thrombosis and support the close follow-up of people with factor VIII >150% to ensure the early identification of new thrombotic events.

Recent Advances in Antithrombin Therapy for Acute Coronary Syndromes

Unstable angina and acute myocardial infarction are leading causes of hospital admissions worldwide. Following the initiating event of atherosclerotic plaque rupture, activation of the coagulation cascade plays an important role in mediating local thrombosis. Novel antithrombotic agents have recently been developed and applied in clinical practice.

Atherothrombosis‐on‐Chip: A Site‐Specific Microfluidic Model for Thrombus Formation and Drug Discovery (Adv. Biology 7/2022)

Atherothrombosis-on-Chip In article 2101316, Ta and co-workers conducted a study to mimic the site-specific atherothrombosis formation on the chip and design a unique microfluidic device with two interconnected microchannels. The device allows the site-specific introduction of plaque components to develop localized thrombosis and provides a universal platform for studying the crosstalk between blood cells and plaque components. The device is expected to benefit drug testing and carrier designing.

Possible association between adenomyosis and disseminated intravascular coagulation and thromboembolism: A systematic review

Adenomyosis is an estrogen‑dependent gynecologic disease characterized by the presence of endometrial tissue within the myometrium. Adenomyosis presents with abnormal uterine bleeding, pelvic pain and infertility. Recently, patients with adenomyosis with life‑threatening disseminated intravascular coagulation (DIC) or thromboembolic events have been reported. The purpose of the present systematic review was to examine the possible associations between adenomyosis and severe complications, and to investigate the clinical characteristics, risk factors and potential mechanisms. A literature search was performed for case reports, reviews of the literature, and preclinical and clinical studies published between January, 2000 and November, 2021 in the PubMed and Google Scholar databases using a combination of specific terms. A total of 20 articles reported these complications. Adenomyosis is characterized by morphologically and functionally abnormal blood vessels, with increased intramural pressure, increased expression of pro‑angiogenic markers, excessive angiogenesis and increased microvascular density. Changes in blood coagulation‑fibrinolysis markers are encountered even in asymptomatic women during menstruation. Repeated bleeding in larger lesions causes coagulopathy that may result in localized thrombosis or DIC. In addition, elevated levels of mucinous tumor markers, CA125 and CA19‑9, induce blood hyperviscosity and hypercoagulability that predispose patients to thromboembolism. On the whole, as demonstrated herein, adenomyosis may cause a wide range of symptoms from asymptomatic to life‑threatening DIC and/or thromboembolism.