Thrombosis Research Articles

Establishment of cutoff values for anti-β2 glycoprotein I antibodies in women of reproductive age in Southwest China

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by vascular thrombosis and obstetric morbidity, with accurate laboratory examination of antiphospholipid antibodies (aPLs) being crucial for diagnosis. This study focused on anti-β2 glycoprotein I (aβ2GPI) antibodies and aimed to establish the first population-based cutoff values for aβ2GPI IgA/IgM/IgG antibodies in non-pregnant women of reproductive age in Southwest China. The study cohort comprised 181 healthy women of reproductive age for study. Blood samples were collected on an early morning fast. Anti-β2GPI antibodies including IgA, IgM and IgG were measured in serum using the HOB® BioCLIA kit. According to the Clinical and Laboratory Standards Institute (CLSI) guidelines, the study used non-parametric percentile methods to calculate the 95th, 97.5th, and 99th percentiles cutoff values for aβ2GPI IgA/IgM/IgG antibodies, along with corresponding 90% confidence intervals (CI), while excluding outliers. A total of 168 independent samples were collected for verification, including 85 samples from healthy subjects and 83 samples from APS patients, in order to evaluate the analytical performance of the obtained cutoff values. The 99th percentile cutoff values were 3.36 RU/mL for aβ2GPI IgA, 27.54 RU/mL for aβ2GPI IgM and 1.81 RU/mL for aβ2GPI IgG, which indicated that the levels of aβ2GPI IgM antibodies were generally higher compared to those of IgA and IgG antibodies. Our established reference range was confirmed to be successful in validating the detected values of aβ2GPI antibodies in all healthy controls. With the 99th percentile cutoff value, the sensitivity was 14.46% for aβ2GPI IgA, 22.89% for aβ2GPI IgG, and 9.64% for aβ2GPI IgM in APS patients. This study established population-based cutoff values that are applicable to the local population for the accurate laboratory examination of aβ2GPI antibodies in non-pregnant women of reproductive age. The study also recommends paying more attention to IgM positivity in women of reproductive age.

THE effect of P2X7 receptor activation on functional responses of human left internal mammary artery.

The Purinoreceptor 7 (P2X7R) has become a promising drug target in many cardiovascular diseases, including coronary artery disease, since prolonged activation of P2X7R could promote vascular dysfunction, atherosclerosis, and thrombosis. Thus, we aimed to study the effects of P2X7R activation on vascular relaxation responses of the human left internal mammary artery (LIMA). Sections of redundant human LIMA were cut into 3-mm wide rings,, suspended in 20-mL organ baths containing physiologic salt solution, and attached to an isometric force transducer connected to a computer-based data acquisition system. Long-term (60min) incubation with specific P2X7R agonist Bz-ATP caused significant reductions in relaxation responses of LIMA to ATP and acetylcholine, which were reversed by selective P2X7R antagonists Brilliant Blue G or AZ11645373, whereas there were no changes in relaxation responses to endothelium-independent vasodilators isoprenaline, cAMP analog 8-Br-cAMP, and nitric oxide donor sodium nitroprusside. The impairment in relaxant responses of LIMA to endothelium-dependent vasodilators following activation of P2X7R for the long-term may contribute to postoperative LIMA vasospasm and hypertension. Modulation of P2X7R activity with selective agents may represent a new potential therapeutic approach in patients undergoing coronary artery bypass grafting surgery.

A Cross-Sectional Study of the A1 Phenotype in the Colombian Caribbean: A Shadow Behind Pulmonary Embolism.

Venous thromboembolic disease (VTE) is an episodic condition of multifactorial origin, commonly manifesting as deep vein thrombosis (DVT) and pulmonaryembolism (PE). VTE is a major cause of morbidity and mortality. As an acute condition, it has the potential for recurrence and is associated with major consequences; this disease poses significant challenges to the healthcare system. VTE is a widespread concern in developed and developing countries; therefore, it is not limited to specific regions or populations. To evaluate the risk factors associated with unprovoked PE in patients in a hospital center in Sincelejo, Colombia. This is an observational, analytical cross-sectional study utilizing retrospective data. From 2010 to 2023, we reviewed 126 medical records of patients who experienced their first unprovoked VTE events and met the inclusion criteria. We performed data analysis using R software version 3.5.1. Of the patients, 36.5% (n = 46) were women; 63.5% (n = 80) were men, with a mean age of 62.22 years (SD = 10.62). About 53% of women presented with PE, compared to 47% of men. The coagulation factor VIII acted as a PE risk factor (p = 0.098). The best model to predict PE development obtained an Akaikeinformationcriterion (AIC) of 176.67, indicating that the A1 positive phenotype is the risk factor with the highest prediction for PE occurrence. High levels of coagulation factor VIII and an A1-positive phenotype are risk factors that may increase PE development. These findings suggest the need for preventive strategies in this risk setting to reduce the incidence and recurrence of PE.

Thromboembolic Disease and COVID-19: Experience of a University and Emergency Hospital During the Pandemic.

COVID-19 leads to vasculopathy, which is linked to both a prothrombotic state and an impaired immune response. A notable increase in pulmonary embolism (PE) and deep venous thrombosis (DVT) has been documented. We conducted a retrospective analysis of all patients who were admitted with venous thromboembolic disease (VTD) in the largest university and emergency hospital in Romania, between May 1, 2020, and April 30, 2021. Patients were categorized into two groups based on the presence (Group 1) or absence (Group 2) of COVID-19 virus infection at the time of admission. The aim of this study was to assess the characteristics of VTD in COVID-19 patients and to compare the clinical and paraclinical parameters of the Group 1 and Group 2 patients admitted for VTD in an emergency hospital during the first two waves of the pandemic (12 months). We compared clinical, biological, and imaging parameters and applied binary logistic analysis for the predictive models. A total of 198 patients were diagnosed with VTD (at admission or during the hospitalization); out of 33,373 patients hospitalized, 43 (21.7%) were diagnosed with COVID-19 (12.2% with mild COVID-19, 61.0% moderate, and 26.8% severe). Group 1 showed higher heart rates and leukocytes, more severe pulmonary changes (p<0.05), higher N-terminal-pro-B-type natriuretic peptide (NTproBNP), and high sensitivity troponin I (hs-cTnI) (p>0.05). Not reaching statistical significance, the mortality tended to be higher in Group 1. These patients were admitted to the intensive care units for longer (3.5 vs. 1.5 days, p > 0.05). The minimum value of thrombocytes during hospitalization was inversely correlated with the risk of death. Interestingly, the Pulmonary Embolism Severity Index (PESI) score was not predictive for in-hospital death in Group 1, but only in Group 2 (area under the curve (AUC) = 0.821, CI 0.689-0.952). Individuals with severe manifestations of COVID-19 remain vulnerable to developing VTD and are prone to adverse outcomes. The efficacy of PESI as a predictive tool for in-hospital death is non-significant. Further refinement of specific predictive scores tailored to VTD associated with COVID-19 is needed.

Phenotypes in pulmonary hypertension.

The clinical classification of pulmonary hypertension (PH) has guided diagnosis and treatment of patients with PH for several decades. Discoveries relating to underlying mechanisms, pathobiology and responses to treatments for PH have informed the evolution in this clinical classification to describe the heterogeneity in PH phenotypes. In more recent years, advances in imaging, computational science and multi-omic approaches have yielded new insights into potential phenotypes and sub-phenotypes within the existing clinical classification. Identification of novel phenotypes in pulmonary arterial hypertension (PAH) with unique molecular profiles, for example, could lead to new precision therapies. Recent phenotyping studies have also identified groups of patients with PAH that more closely resemble patients with left heart disease (group 2 PH) and lung disease (group 3 PH), which has important prognostic and therapeutic implications. Within group 2 and group 3 PH, novel phenotypes have emerged that reflect a persistent and severe pulmonary vasculopathy that is associated with worse prognosis but still distinct from PAH. In group 4 PH (chronic thromboembolic pulmonary disease) and sarcoidosis (group 5 PH), the current approach to patient phenotyping integrates clinical, haemodynamic and imaging characteristics to guide treatment but applications of multi-omic approaches to sub-phenotyping in these areas are sparse. The next iterations of the PH clinical classification are likely to reflect several emerging PH phenotypes and improve the next generation of prognostication tools and clinical trial design, and improve treatment selection in clinical practice.

The utility of the normal thin section skin biopsy in the assessment of systemic/extracutaneous disease and small fiber neuropathy

Diseases reflective of multiorgan vascular injury of diverse etiology, peripheral nerve disease, dysautonomia syndromes, and intravascular lymphoma may exhibit abnormalities on a normal skin biopsy that may be instrumental in establishing a diagnosis. A retrospective review of our database was conducted to uncover cases where a normal skin biopsy was performed to rule in or out such systemic diseases as complement-driven thrombotic microvascular disease (including atypical hemolytic uremic syndrome, posttransplant thrombotic microangiopathy, and severe or critical COVID-19), systemic capillary leak syndrome, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) intravascular B cell lymphoma, small fiber neuropathy, dysautonomia syndromes, and mast cell activation syndrome. Among the special studies were immunohistochemical staining to detect C5b-9, CD56, and myxovirus resistance protein A, as well as mast cell, B and T cell markers. Characteristic patterns were critical in establishing diagnoses such as : increased C5b-9 microvascular deposition in the deltoid area (atypical hemolytic uremic syndrome, posttransplant thrombotic microangiopathy, catastrophic antiphospholipid antibody syndrome, and severe or critical COVID-19); enhanced type I interferon signaling (systemic capillary leak syndrome); ultrastructural arteriopathic changes (CADASIL); reduced cutaneous autonomic innervation in the lower extremities (small fiber neuropathy and postural orthostatic tachycardia syndrome); presence of intravascular lymphocytes on biopsy of abdominal, thigh, and buttock skin (intravascular B cell lymphoma); and a higher than normal density of mast cells in the absence of other inflammatory cell types (mast cell activation syndrome). The skin is clearly a critical window for understanding extracutaneous disease, a concept well exemplified by the myriad of diseases suggested by the microscopic and/or ultrastructural examination of clinically normal skin and therefore establishing the normal skin biopsy as an important tool for understanding certain extracutaneous reactive, neoplastic and paraneoplastic syndromes as well as small fiber neuropathy.

Anticoagulant therapy in venous thromboembolism and bleeding risk: focus on the use of predictive scores.

The standard treatment for venous thromboembolism (Vte) is anticoagulation. Drug selection and treatment duration will depend on the clinical presentation, the existence of provoking factors, bleeding risk, and the patient's preferences. Anticoagulation therapy is indicated for 3-6 months in all patients with acute Vte but may be extended, even indefinitely in some cases. The most severe side effect of anticoagulation is bleeding, with the highest risk occurring during the 1st months of therapy. Balancing the risk of bleeding and the risk of recurrence in patients with Vte remain a major issue. There are, currently, no simple and validated predictive scores to estimate the long-term bleeding risk in patients undergoing anticoagulant treatment and to safely select those patients with higher bleeding risk. In this review we will examine some of these scores, including the RIETE scores, the HAS-BLED SCORE, the VTE-BLEED score, the VTE- PREDICT and the ACCP guidelines and the timing for their application in the patient's population treated for Vte as well as the initial and long-term management and evaluation of thromboembolic disease.

MM-556 Risk Assessment of Thromboembolic Disease In Patients Treated For Multiple Myeloma

MM-556 Risk Assessment of Thromboembolic Disease In Patients Treated For Multiple Myeloma

Efficacy and safety of bemiparin as treatment of venous thromboembolic disease in the elderly.

As the elderly population continues to grow worldwide, it becomes crucial to explore safe and effective treatment options to manage venous thromboembolic disease in this vulnerable demographic group. We carried out a retrospective cohort study (January 2017-December2021) to analyse the efficacy and safety of bemiparin as a treatment for venous thromboembolic disease in 223 patients. We compared patients aged ≥65 years (elderly; n = 153) with patients aged less than 65 years (adults; n = 70) for a combined end point of death, recurrent thromboembolism, and major bleeding at 30 days. Elderly (mean age 79 ± 7.7 years) and adult patients (mean age 51.5 ± 11.6 years) received similar bemiparin doses 8470 ± 2362 International units (IU)/d versus 8754 ± 1593 IU/d, during a similar median [Interquartile range] period of 28 [9-118] versus 30 [10-90] days, respectively. At 30-day follow up a total of 24 elderly patients (15.7%), reached at least one of the end points, as compared with six adult patients (8.6%) (absolute difference 7.1%; 95% confidence interval [95%CI], -1.6 to 15.8). Recurrence of venous thromboembolic disease occurred in five elderly patients (3.3%) and in five adult patients (7.1%) (absolute difference -3.9%; 95%CI, -10.5 to 2.8).There were two episodes of major bleeding each in elderly (1.3%) and adult (2.9%) patients (absolute difference -1.6%; 95% CI, -5.8 to 2.7). Bemiparin showed a similar efficacy and safety profile in the treatment of venous thromboembolic disease in elderly and adult patients.

Obesity and cardiovascular disease: an ESC clinical consensus statement.

The global prevalence of obesity has more than doubled over the past four decades, currently affecting more than a billion individuals. Beyond its recognition as a high-risk condition that is causally linked to many chronic illnesses, obesity has been declared a disease per se that results in impaired quality of life and reduced life expectancy. Notably, two-thirds of obesity-related excess mortality is attributable to cardiovascular disease. Despite the increasingly appreciated link between obesity and a broad range of cardiovascular disease manifestations including atherosclerotic disease, heart failure, thromboembolic disease, arrhythmias, and sudden cardiac death, obesity has been underrecognized and sub-optimally addressed compared with other modifiable cardiovascular risk factors. In the view of major repercussions of the obesity epidemic on public health, attention has focused on population-based and personalized approaches to prevent excess weight gain and maintain a healthy body weight from early childhood and throughout adult life, as well as on comprehensive weight loss interventions for persons with established obesity. This clinical consensus statement by the European Society of Cardiology discusses current evidence on the epidemiology and aetiology of obesity; the interplay between obesity, cardiovascular risk factors and cardiac conditions; the clinical management of patients with cardiac disease and obesity; and weight loss strategies including lifestyle changes, interventional procedures, and anti-obesity medications with particular focus on their impact on cardiometabolic risk and cardiac outcomes. The document aims to raise awareness on obesity as a major risk factor and provide guidance for implementing evidence-based practices for its prevention and optimal management within the context of primary and secondary cardiovascular disease prevention.

Obesity and cardiovascular disease: an ESC clinical consensus statement.

The global prevalence of obesity has more than doubled over the past four decades, currently affecting more than a billion individuals. Beyond its recognition as a high-risk condition that is causally linked to many chronic illnesses, obesity has been declared a disease per se that results in impaired quality of life and reduced life expectancy. Notably, two-thirds of obesity-related excess mortality is attributable to cardiovascular disease. Despite the increasingly appreciated link between obesity and a broad range of cardiovascular disease manifestations including atherosclerotic disease, heart failure, thromboembolic disease, arrhythmias, and sudden cardiac death, obesity has been underrecognized and sub-optimally addressed compared with other modifiable cardiovascular risk factors. In the view of major repercussions of the obesity epidemic on public health, attention has focused on population-based and personalized approaches to prevent excess weight gain and maintain a healthy body weight from early childhood and throughout adult life, as well as on comprehensive weight loss interventions for persons with established obesity. This clinical consensus statement by the European Society of Cardiology discusses current evidence on the epidemiology and aetiology of obesity; the interplay between obesity, cardiovascular risk factors and cardiac conditions; the clinical management of patients with cardiac disease and obesity; and weight loss strategies including lifestyle changes, interventional procedures, and anti-obesity medications with particular focus on their impact on cardiometabolic risk and cardiac outcomes. The document aims to raise awareness on obesity as a major risk factor and provide guidance for implementing evidence-based practices for its prevention and optimal management within the context of primary and secondary cardiovascular disease prevention.

The Highs and Lows of ADAMTS13 Activity.

Severe deficiency of ADAMTS13 (<10 iu/dL) is diagnostic of thrombotic thrombocytopenic purpura (TTP) and leads to accumulation of ultra-large vWF multimers, platelet aggregation, and widespread microthrombi, which can be life-threatening. However, the clinical implications of a low ADAMTS13 activity level are not only important in an acute episode of TTP. In this article, we discuss the effects of low ADAMTS13 activity in congenital and immune-mediated TTP patients not only at presentation but once in a clinical remission. Evidence is emerging of the clinical effects of low ADAMTS13 activity in other disease areas outside of TTP, and here, we explore the wider impact of low ADAMTS13 activity on the vascular endothelium and the potential for recombinant ADAMTS13 therapy in other thrombotic disease states.

Chronic thromboembolic pulmonary disease.

Chronic thromboembolic pulmonary hypertension is a complication of pulmonary embolism and a treatable cause of pulmonary hypertension. The pathology is a unique combination of mechanical obstruction due to failure of clot resolution, and a variable degree of microvascular disease, that both contribute to pulmonary vascular resistance. Accordingly, multiple treatments have been developed to target the disease components. However, accurate diagnosis is often delayed. Evaluation includes high-quality imaging modalities, necessary for disease confirmation and for appropriate treatment planning. All patients with chronic thromboembolic pulmonary disease, and especially those with pulmonary hypertension, should be referred to expert centres for multidisciplinary team decision on treatment. The first decision remains assessment of operability, and the best improvement in symptoms and survival is achieved by the mechanical therapies, pulmonary endarterectomy and balloon pulmonary angioplasty. With the advances in multimodal therapies, excellent outcomes can be achieved with 3-year survival of >90%.

Pulmonary hypertension associated with left heart disease.

Left heart disease (LHD) is the most common cause of pulmonary hypertension (PH), which may be classified further as isolated post-capillary (ipcPH) or combined post- and pre-capillary PH (cpcPH). The 7th World Symposium on Pulmonary Hypertension PH-LHD task force reviewed newly reported randomised clinical trials and contemplated novel opportunities for improving outcome. Results from major randomised clinical trials reinforced prior recommendations against the use of pulmonary arterial hypertension therapy in PH-LHD outside of clinical trials, and suggested possible harm. Greater focus on phenotyping was viewed as one general strategy by which to ultimately improve clinical outcomes. This is potentially achievable by individualising ipcPH versus cpcPH diagnosis for patients with pulmonary arterial wedge pressure within a diagnostic grey zone (12-18 mmHg), and through a newly developed PH-LHD staging system. In this model, PH accompanies LHD across four stages (A=at risk, B=structural heart disease, C=symptomatic heart disease, D=advanced), with each stage characterised by progression in clinical characteristics, haemodynamics and potential therapeutic strategies. Along these lines, the task force proposed disaggregating PH-LHD to emphasise specific subtypes for which PH prevalence, pathophysiology and treatment are unique. This includes re-interpreting mitral and aortic valve stenosis through a contemporary lens, and focusing on PH within the hypertrophic cardiomyopathy and amyloid cardiomyopathy clinical spectra. Furthermore, appreciating LHD in the profile of PH patients with chronic lung disease and chronic thromboembolic pulmonary disease is essential. However, engaging LHD patients in clinical research more broadly is likely to require novel methodologies such as pragmatic trials and may benefit from next-generation analytics to interpret results.

Assessing the Effect of Magnetite Nanoflowers on Platelets in a Multiscale Approach in the Context of Thromboembolic Diseases

Assessing the Effect of Magnetite Nanoflowers on Platelets in a Multiscale Approach in the Context of Thromboembolic Diseases

Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios in bacterial infections: contributions to diagnostic strategies in a tertiary care hospital in Tunisia.

Bacterial infections continue to pose a global health challenge, driven by antibiotic resistance and septicemia. This study aimed to assess the diagnostic utility of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in bacterial infections versus non-infectious causes of inflammation. A prospective study included 164 adult patients who were divided into two groups: a group of patients with confirmed bacterial infections and a second group of patients with other diagnoses (inflammatory pathologies, neoplasms, venous thromboembolic diseases, etc.). NLR and PLR values were compared between the bacterial infection group and the non-infectious causes group and the diagnostic performances of NLR and PLR for detecting bacterial infections were evaluated in comparison with other infection markers. NLR and PLR were significantly higher in bacterial infections (p < 10 ^-6), and NLR was correlated positively with inflammation markers. NLR and PLR demonstrated significant potential in diagnosing bacterial infections, with an AUC of 0.72 and 0.60, respectively, using the following cutoff values: 4.3 for NLR and 183 for PLR. These findings underscore the importance of NLR and PLR as adjunctive tools for bacterial infection diagnosis.

Microsurgery in low- and middle-income countries: Results of 20 years of experience in Cambodia

BackgroundMicrosurgical free tissue transfer is the gold standard for reconstructing major bone or soft tissue defects but requires complex training, and specific resources. Therefore, some authors have stated that microsurgery is impossible in low- and middle-income countries. MethodsPatients from Khmer underwent free flap surgery at the Children’s Surgical Centre in Phnom Penh between 2004 and 2023. Two non-governmental organizations facilitated the program: Rose Charities Cambodia provided the facilities, patients and local staff, and Doctors of the World provided the surgeons, and anesthetists. At least one Khmer surgeon was trained during these operations. Digital data were collected retrospectively, and analyzed in June 2023. ResultsFifty-six free flaps in 54 patients have been performed since 2004. The most frequent sites requiring reconstruction were the head and neck (35.7%), lower limbs (30.4%), and upper limbs (21.4%). The most frequent free flaps were free fibula (44.6%), gracilis (19.6%), and anterolateral thigh (16.1%). Among the 56 flaps, 41 (= 73.2%) were viable long-term and 15 (26.7%) were microsurgical failures. Sixteen flaps underwent revision in the operating room. Twenty-three flap-related complications were reported in 21 patients with mostly vascular thrombosis (n = 12), hematoma (n = 3) and infections (3). However, 83.3% had improved or were cured of their initial pathology after final surgical management. ConclusionsFree flaps performed in our series as part of international surgical collaborations in a low-income country are feasible, but we experienced higher failure rates, and later revisions compared to the results in high-income countries. We identified several solutions to improve the microsurgery outcomes in low-income settings.

Differential effects of balloon pulmonary angioplasty on chronic thromboembolic pulmonary disease

BackgroundDecreased diffusing capacity of the lungs for carbon monoxide (DLco) is associated with microvascular damage in chronic thromboembolic pulmonary hypertension (CTEPH). Balloon pulmonary angioplasty (BPA) is an effective treatment for...

Risk Assessment of Thromboembolic Disease in Patients Treated for Multiple Myeloma

Risk Assessment of Thromboembolic Disease in Patients Treated for Multiple Myeloma

Research progress of pelvic acetabular fractures combined venous thromboembolic disease

Pelvic acetabular fractures(PAFs) are one of the most common types of pelvic fractures, mostly high-energy injuries, with complex pelvic acetabular structure and limited surgical methods. The trauma of the acetabular fracture itself and the need for long-term bed rest after surgery cause particularly complicated clinical complications. Venous thromboembolism (VTE) is one of its high incidence and serious complications. This review mainly focuses on VTE after PAFs, and describes the epidemiology, risk factors and prevention measures of VTE, aiming to help improve the prognosis and avoid the occurrence of serious complications.