An international survey of venous thromboembolic events and current practices of peri-operative VTE prophylaxis after living donor hepatectomy.

BACKGROUND: Venous thromboembolic complications are an uncommon but significant cause of morbidity & mortality after live donor hepatectomy . The precise incidence of these events and the current practices of centers performing living donor liver transplantation worldwide are unknown. METHODS: An online survey was shared amongst living donor liver transplantation centers containing questions regarding center activity, center protocols for donor screening, peri-operative thromboembolic prophylaxis and an audit of -perioperative venous thromboembolic events after live donor hepatectomy in the previous five years (2016-2020). RESULTS: Fifty-one centers from twenty countries completed the survey. These centers had cumulatively performed 11500 living donor liver transplants between 2016-2020. All centers included pre-operative l assessment for thromboembolic risk amongst potential liver donors in their protocols. Testing for inherited prothrombotic conditions was performed by 58% of centers. Dual-mode prophylaxis was the most common practice (65%), while eight and four centers used single mode or no routine prophylaxis respectively. Twenty (39%) and 15 (29%) centers reported atleast one perioperative deep venous thrmobosis or pulmonary embolism event respectively. There was one donor mortality directly related to post-operative pulmonary embolism. Overall incidence of deep venous thrombosis and pulmonary embolism events was 3.65 and 1.74 per 1000 live donor hepatectomies respectively. Significant variations in center practices and incidence of thromboembolic events was identified in the survey primarily divided along world regions. 75% of participating centers agreed on the need for clear international guidelines. CONCLUSION: Venous thromboembolic events after live donor hepatectomy are an uncommon but important cause of donor morbidity. There is significant variation in practice among centers. Evidence-based guidelines regarding risk assessment, and peri-operative prophylaxis are needed.

Comprehensive evaluation of genetic and acquired thrombophilia markers for an individualized prediction of clinical thrombosis in patients with lymphoma and multiple myeloma.

Patients diagnosed with lymphoma or multiple myeloma are at elevated risk of venous thromboembolism (VTE). Optimum risk stratification and effective thromboprophylaxis can only be achieved through the development of a multiple-specific risk score that successfully captures all aspects of the heterogeneous prothrombotic environment existing in these patients. Our aim was to identify risk factors for thrombosis and suggest an improved tool combining clinical data, thrombo-inflammatory biomarkers and genetic (Thrombo inCode® test) variables for predicting thrombotic risk in patients with lymphoma and multiple myeloma. A prospective longitudinal study was conducted on newly-diagnosed lymphoma and multiple myeloma patients who presented at our institution between February 2020 and January 2021. The study included 47 patients with lymphoma and 16 patients with multiple myeloma. We performed a follow-up of 1 year or until September 2021. The incidence of venous thrombosis and associated risk factors were analysed, including the genetic Thrombo inCode® test. Khorana and ThroLy scores for lymphoma patients and IMPEDE VTE score for myeloma patients were calculated. At a median follow-up of 9.1 months, VTE incidence was 9.5% (6/63), with 4 and 2 patients with lymphoma and myeloma who developed the events, respectively. Univariate analysis showed that the incidence of thrombosis was significantly higher in patients with ECOG ≥ 2 and prior immobility. Median factor VIII levels were significantly higher in patients with thrombosis (with increased values in all of them). Moreover, there was a trend in genetic variant rs5985 (factor XIII) as a protective factor, and a trend to higher thrombotic risk in patients with factor V Leiden, rs2232698 variant (serpinA10), low total protein S activity, elevated D-dimer, aggressive lymphoma and treatment with dexamethasone. The results of our study demonstrate promise for the potential use of widely accessible markers to increase precision in risk prediction for VTE in patients with lymphoma and multiple myeloma, particularly ECOG ≥ 2, immobility and higher factor VIII levels, as well as lymphoma aggressiveness, treatment with dexamethasone and the haemostatic biomarkers D-dimer and total protein S activity. Additionally, genetic variants factor V Leiden, serpinA10 rs2232698 and factor XIII-A Val34Leu warrant further investigation for use in the research setting.

Inflammatory and Prothrombotic Biomarkers Contribute to the Persistence of Sequelae in Recovered COVID-19 Patients.

The presence of long COVID (LC) following SARS-CoV-2 infection is a common condition that affects the quality of life of patients and represents a diagnostic challenge due to the diversity of symptoms that may coexist. We still do not have accurate information regarding the pathophysiological pathways that generate the presence of LC, and so it is important to know the inflammatory and immunothrombotic biomarker profiles and their implications in order to characterize risk subgroups and establish early therapeutic strategies. We performed the determination of inflammatory and immunothrombotic biomarkers in volunteers with previous diagnoses of SARS-CoV-2. The inflammatory biomarkers were analyzed in plasma by flow cytometry, and we analyzed the von Willebrand factor (vWF) in the plasma samples using ELISA. The clinical variables and the presence or absence of long COVID symptoms were then analyzed. IL-6, sCD40L, p-Selectin, PSGL-1, PAI-1, tPA, D-Dimer, TF, and Factor IX levels were elevated in the groups with LC, especially in the subgroup of patients with metabolic syndrome (MetS). VWF levels were found to be increased in patients with sequelae and MetS. Our results confirmed the persistence of an active immunothrombotic state, and so it is important to identify the population at risk in order to provide adequate clinical follow-up.

Beyond the Acute Phase: Long-Term Impact of COVID-19 on Functional Capacity and Prothrombotic Risk-A Pilot Study.

Background and Objectives: Assessment of the prothrombotic, proinflammatory, and functional status of a cohort of COVID-19 patients at least two years after the acute infection to identify parameters with potential therapeutic and prognostic value. Materials and Methods: We conducted a retrospective, descriptive study that included 117 consecutive patients admitted to Iasi Pulmonary Rehabilitation Clinic for reassessment and a rehabilitation program at least two years after a COVID-19 infection. The cohort was divided into two groups based on the presence (n = 49) or absence (n = 68) of pulmonary fibrosis, documented through high-resolution computer tomography. Results: The cohort comprises 117 patients, 69.23% females, with a mean age of 65.74 ± 10.19 years and abnormal body mass index (31.42 ± 5.71 kg/m2). Patients with pulmonary fibrosis have significantly higher levels of C-reactive protein (CRP) (p < 0.05), WBC (7.45 ± 7.86/mm3 vs. 9.18 ± 17.24/mm3, p = 0.053), neutrophils (4.68 ± 7.88/mm3 vs. 9.07 ± 17.44/mm3, p < 0.05), mean platelet volume (MPV) (7.22 ± 0.93 vs. 10.25 ± 0.86 fL, p < 0.05), lactate dehydrogenase (p < 0.05), and D-dimers (p < 0.05), but not ferritin (p = 0.470), reflecting the chronic proinflammatory and prothrombotic status. Additionally, patients with associated pulmonary fibrosis had a higher mean heart rate (p < 0.05) and corrected QT interval (p < 0.05). D-dimers were strongly and negatively correlated with diffusion capacity corrected for hemoglobin (DLCO corr), and ROC analysis showed that the persistence of high D-dimers values is a predictor for low DLCO values (ROC analysis: area under the curve of 0.772, p < 0.001). The results of pulmonary function tests (spirometry, body plethysmography) and the 6-minute walk test demonstrated no significant difference between groups, without notable impairment within either group. Conclusions: Patients with COVID-19-related pulmonary fibrosis have a persistent long-term proinflammatory, prothrombotic status, despite the functional recovery. The persistence of elevated D-dimer levels could emerge as a predictive factor associated with impaired DLCO.

Relationships between indicators of prothrombotic activity and coronary microvascular dysfunction in patients with myocardial infarction with obstructive and non-obstructive coronary artery disease.

The relationship between prothrombotic activity and coronary microvascular dysfunction (MVD) is limited. This study aimed to perform a comparative analysis of the relationship between prothrombotic activity and MVD in patients with myocardial infarction without obstructive coronary artery disease (MINOCA) and myocardial infarction with obstructive coronary artery disease (MI-CAD). MATERIAL AND METHODS: A total of 37 patients were enrolled in the study; the main group included 16 MINOCA patients, and 21 MI-CAD patients were included in the control group. Blood samples for protein C, antithrombin, WF, plasminogen, and homocysteine were performed on the 4th ± 1 day of admission. CZT-SPECT data were used to determine the standard indices of myocardial perfusion dis-orders (SSS, SRS, and SDS), as well as stress and rest myocardial blood flow (MBF), myocardial flow reserve (MFR), and difference flows (DF). MVD was defined as MFR (≤ 1.91 ml/min); coronary slow flow (CSF) was defined as corrected TIMI frame count (21 ± 3). RESULTS: We performed a step-by-step analysis of prothrombotic activity of the hemostasis system in binary logistic regression for MINOCA patients to identify factors associated with MVD (MFR ≤ 1.91 ml/min). A predictive model was developed to estimate the probability of reduced MFR. A low MFR is related to only plasminogen in MINOCA patients, whereas only wall motion score index (WMSI) in MI-CAD group was associated with a low MFR. CONCLUSION: This small-scale study revealed the relationship between indicators of prothrombotic activity and MVD. The key factors that affect MVD in MINOCA patients was plasminogen, whereas, in patients with MI-CAD, WMSI was the key factor. Measurements of MVD may enhance the risk stratification and facilitate future targeting of adjunctive antithrombotic therapies in MINOCA and MI-CAD patients.

Prothrombotic state and calcium deficiency in early pregnancy are risk factors for gestational diabetes mellitus: a retrospective cohort study.

OBJECTIVES: To investigate whether the prothrombotic state (PTS), calcium deficiency and iron deficiency anemia (IDA) in early pregnancy is associated with the risk of gestational diabetes mellitus (GDM). METHODS: We conducted a retrospective cohort study, including consecutive pregnant women tested for PTS, calcium deficiency and IDA before 20 weeks' gestation between September 1, 2017 and March 21, 2021. For routine prenatal care, pregnant women underwent a 75-g oral glucose tolerance test (OGTT) to make a GDM diagnosis during 24-28 weeks of gestation. Testing data and relevant clinical information were obtained from Shenzhen Baoan Women's and Children's Hospital. To estimate GDM risk of exposures (PTS, calcium deficiency and IDA) in early pregnancy, we used logistic regression to obtain odds ratio (OR) adjusted for maternal age, parity, family history of diabetes and pre-pregnancy body mass index. RESULTS: The cohort included 8396 pregnant women with complete data of exposures and GDM outcomes. Baseline characteristics were not comparable between exposure and control groups. PTS (adjusted OR 2.38, 95% CI 1.61-3.52) or calcium deficiency (adjusted OR 1.23, 95% CI 1.02-1.49) in early pregnancy was independently associated with increased GDM risk after adjusting covariates. There was no significant association between IDA status and GDM risk (adjusted OR 0.86, 95% CI 0.63-1.18). CONCLUSIONS: PTS and calcium deficiency in early pregnancy may be independent risk factors of GDM. These findings need further validation in well-designed prospective cohorts.

Inflammatory and Prothrombotic Biomarkers, DNA Polymorphisms, MicroRNAs and Personalized Medicine for Patients with Peripheral Arterial Disease.

Classical risk factors play a major role in the initiation and development of atherosclerosis. However, the estimation of risk for cardiovascular events based only on risk factors is often insufficient. Efforts have been made to identify biomarkers that indicate ongoing atherosclerosis. Among important circulating biomarkers associated with peripheral arterial disease (PAD) are inflammatory markers which are determined by the expression of different genes and epigenetic processes. Among these proinflammatory molecules, interleukin-6, C-reactive protein, several adhesion molecules, CD40 ligand, osteoprotegerin and others are associated with the presence and progression of PAD. Additionally, several circulating prothrombotic markers have a predictive value in PAD. Genetic polymorphisms significantly, albeit moderately, affect risk factors for PAD via altered lipoprotein metabolism, diabetes, arterial hypertension, smoking, inflammation and thrombosis. However, most of the risk variants for PAD are located in noncoding regions of the genome and their influence on gene expression remains to be explored. MicroRNAs (miRNAs) are single-stranded, noncoding RNAs that modulate gene expression at the post-transcriptional level. Patterns of miRNA expression, to some extent, vary in different atherosclerotic cardiovascular diseases. miRNAs appear to be useful in the detection of PAD and the prediction of progression and revascularization outcomes. In conclusion, taking into account one's predisposition to PAD, i.e., DNA polymorphisms and miRNAs, together with circulating inflammatory and coagulation markers, holds promise for more accurate prediction models and personalized therapeutic options.

Exosome Proteomics Reveals the Deregulation of Coagulation, Complement and Lipid Metabolism Proteins in Gestational Diabetes Mellitus.

Exosomes are small extracellular vesicles with a variable protein cargo in consonance with cell origin and pathophysiological conditions. Gestational diabetes mellitus (GDM) is characterized by different levels of chronic low-grade inflammation and vascular dysfunction; however, there are few data characterizing the serum exosomal protein cargo of GDM patients and associated signaling pathways. Eighteen pregnant women were enrolled in the study: 8 controls (CG) and 10 patients with GDM. Blood samples were collected from patients, for exosomes' concentration. Protein abundance alterations were demonstrated by relative mass spectrometric analysis and their association with clinical parameters in GDM patients was performed using Pearson's correlation analysis. The proteomics analysis revealed 78 significantly altered proteins when comparing GDM to CG, related to complement and coagulation cascades, platelet activation, prothrombotic factors and cholesterol metabolism. Down-regulation of Complement C3 (C3), Complement C5 (C5), C4-B (C4B), C4b-binding protein beta chain (C4BPB) and C4b-binding protein alpha chain (C4BPA), and up-regulation of C7, C9 and F12 were found in GDM. Our data indicated significant correlations between factors involved in the pathogenesis of GDM and clinical parameters that may improve the understanding of GDM pathophysiology. Data are available via ProteomeXchange with identifier PXD035673.

Hyper-reactive platelets and type 2 diabetes. / 高敏性血小板与2åž‹ç³–å°¿ç— .

Type 2 diabetes mellitus is a progressive process. With the course of the disease progress, microvascular and macrovascular complications always happen. Thrombotic events caused by macrovascular complications, including coronary heart diseases and cerebrovascular diseases, are the main fatal factor for the patients with type 2 diabetes. Endothelial dysfunction, coagulative activation, impaired fibrinolysis, together with hyper-reactive platelets contribute to the diabetic prothrombotic state, which is strongly related to the macrovascular complications. In particular, the hyper-reactive platelets play a fundamental role among them. Type 2 diabetes is characterized by several metabolic dysfunctions such as hyperglycemia, insulin resistance and shortage, oxidative stress, systemic inflammation, obesity, and dyslipidemia. These metabolic dysfunctions work together to promote the formation of hyper-reactive platelets, which are distinctive in type 2 diabetes. The regular antiplatelet drugs, like aspirin, show limited inhibitory effect on them. Hence, studying the mechanism behind the hyper-reactive platelets could provide a brand-new view on the prevention of macrovascular complications and cardiovascular events in type 2 diabetes.

Spectrum of Vascular Thrombosis in Critically Ill COVID-19 Patients: From Bench to the Bedside.

Proinflammatory cytokines and procoagulant factors released by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lead to thrombosis and ischemia. Pathogenesis and clinical significance of hypercoagulability and an ensuing gamut of vascular complications are explained here. How to cite this article: Vadi S, Pednekar A, Raut A. Spectrum of Vascular Thrombosis in Critically Ill COVID-19 Patients: From Bench to the Bedside. Indian J Crit Care Med 2022;26(12):1237-1243.

Case of Suspected SARS-CoV-2 Vaccine-induced Immune Thrombotic Thrombocytopenia: Dilemma for Organ Donation.

Several vaccines were developed and rolled out at an unprecedented rate in response to the coronavirus disease-2019 (COVID-19) pandemic. Most vaccines approved globally by WHO for emergency use to combat the pandemic were deemed remarkably effective and safe. Despite the safety, rare incidences of vaccine-induced thrombosis and thrombocytopenia (VITT), sometimes known as vaccine-induced prothrombotic thrombocytopenia (VIPIT), have been reported. We report a case of young female with prothrombotic conditions and suspected VITT who developed catastrophic cerebral venous sinus thrombosis (CVST) and progressed to brain death. We highlight hurdles of organ retrieval from a brain-dead patient with suspected SARS-CoV-2 vaccine-induced immune thrombotic thrombocytopenia. There is limited data and lack of substantial evidence regarding transplantation of organs from brain-dead patients with suspected VITT. How to cite this article: Tiwari AM, Zirpe KG, Gurav SK, Bhirud LB, Suryawanshi RS, Kulkarni SS. Case of Suspected SARS-CoV-2 Vaccine-induced Immune Thrombotic Thrombocytopenia: Dilemma for Organ Donation. Indian J Crit Care Med 2022;26(4):514-517.

Inflammatory cytokines enhance procoagulant activity of platelets and endothelial cells through phosphatidylserine exposure in patients with essential hypertension.

The exact mechanism of the prothrombotic state of essential hypertension (EH) patients remains elusive. Our objective was to assess whether phosphatidylserine (PS) exposure on endothelial cells (ECs), platelets, and microparticles (MPs) can account for the hypercoagulability in EH patients. PS exposure on cells and MPs, mainly from platelets and ECs was analyzed with flow cytometry. Procoagulant activity (PCA) was evaluated by purified coagulation complex assays, clotting time, and fibrin turbidity. We found that EH patients exhibited elevated levels of PS+ platelets, serum-cultured ECs, MPs, endothelial-derived MPs and platelet-derived MPs compared to the controls (all P < 0.05). Moreover, platelets and MPs from the patients and their sera-cultured ECs showed markedly enhanced intrinsic/extrinsic FXa, thrombin, and fibrin generation, and greatly shortened coagulation time. This PCA could be blocked approximately 80%, by the addition of lactadherin. Furthermore, we detected elevated levels of IL-8, IL-6, and TNF-α in EH patients could activate platelets/ECs and induce elevated PS exposure on their membranes. Our results suggest that inflammatory cytokines could enhance procoagulant activity of platelets and endothelial cells via their PS exposure in EH patients. As such, a PS blockade may be a viable therapeutic strategy for treating such patients.

Incidence of Antithrombin Deficiency and Anti-Cardiolipin Antibodies After Severe Traumatic Brain Injury: A Prospective Cohort Study.

BACKGROUND: Animal studies suggested that cerebral mitochondrial cardiolipin phospholipids were released after severe traumatic brain injury (TBI), contributing to the pathogenesis of thromboembolism. OBJECTIVES: To determine the incidence of anti-cardiolipin antibodies after severe TBI and whether this was related to the severity of TBI and development of venous thromboembolism. METHODS: Serial anti-cardiolipin antibodies, antithrombin levels, viscoelastic testing, and coagulation parameters were measured on admission, day-1, and between day-5 and day-7 in patients with severe TBI requiring intracranial pressure monitoring. RESULTS: Of the 40 patients included (85% male and median age 42 years), 7 (18%) had a raised Ig-G or Ig-M anti-cardiolipin antibody titer after TBI. Antithrombin levels were below the normal level-especially on day-0 and day-1-in 15 patients (38%), and 14 patients (38%) developed an increase in maximum clot firmness on the viscoelastic test in conjunction with elevations in fibrinogen concentration and platelet count. Four patients (10%) developed deep vein thrombosis, and 10 patients (25%) died, both of which were not significantly related to the presence of anti-cardiolipin antibodies (P = 0.619 and P = 0.638, respectively). CONCLUSIONS: A reduction in antithrombin level and development of anti-cardiolipin antibodies were not rare immediately after severe TBI; these abnormalities were followed by an increase in in vitro clot strength due to elevations in fibrinogen concentration and platelet count. The quantitative relationships between the development of anti-cardiolipin antibodies and severity of TBI or clinical thromboembolic events deserve further investigation.

Large Cerebellar Stroke in a Young COVID-19-Positive Patient: Case Report.

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), most frequently presents with respiratory symptoms, such as fever, dyspnea, shortness of breath, cough, or myalgias. There is now a growing body of evidence that demonstrates that severe SARS-CoV-2 infections can develop clinically significant coagulopathy, inflammation, and cardiomyopathy, which have been implicated in COVID-19-associated cerebrovascular accidents (CVAs). CASE REPORT: We report an uncommon presentation of a 32-year-old man who sustained a large vessel cerebellar stroke associated with a severe COVID-19 infection. He presented with a headache, worse than his usual migraine, dizziness, rotary nystagmus, and dysmetria on examination, but had no respiratory symptoms initially. He was not a candidate for thrombolytic therapy or endovascular therapy and was managed with clopidogrel, aspirin, and atorvastatin. During hospital admission he developed COVID-19-related hypoxia and pneumonia, but ultimately he was discharged to home rehabilitation. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: We present this case to increase awareness among emergency physicians of the growing number of reports of neurologic and vascular complications, such as ischemic CVAs, in otherwise healthy individuals who are diagnosed with SARS-CoV-2 infection. A brief review of the current literature will help elucidate possible mechanisms, risk factors, and current treatments for CVA associated with SARS-CoV-2.

Thromboembolic Adverse Drug Reactions in Janus Kinase (JAK) Inhibitors: Does the Inhibitor Specificity Play a Role?

Recent advances in immunology enabled the characterization of several signal transmitting pathways responsible for proper cytokine and chemokine signaling. Among them, Janus kinases (JAKs) are essential components of receptor activation systems. The discovery of JAK kinases enabled the synthesis of JAK kinase inhibitors (JAKi or Jakinibs), which have proven to be efficacious in the treatment of hematologic malignancies and several rheumatological disorders and continue to be investigated in many clinical indications. Blocking multiple cytokines belonging to several cytokine families with a single small molecule may, however, create a potential risk for the patients. Recently, a higher risk of thromboembolic complications, namely, deep vein thrombosis and pulmonary embolism, has been recognized as the main concern during treatment with Jakinibs. At present, it is not entirely clear whether this increased risk is related to direct cytokine blockade, the presence of concomitant diseases in treated patients or other unknown circumstances that work together to increase the risk of this side effect. In this review, we discuss data on the risk of thromboembolic side effects, with special emphasis on the mechanism that may be responsible for this increased risk. Many indirect data indicate that higher thromboembolic risk may be related to the specificity of JAK inhibitor action, such that preferentially blocking one signaling pathway upsets the balance between pro and anti-thrombotic activities.

Addressing Vaccine-Induced Immune Thrombotic Thrombocytopenia (VITT) Following COVID-19 Vaccination: A Mini-Review of Practical Strategies.

In response to the COVID-19 pandemic, several vaccines were developed and rolled out at unprecedented speed, and notwithstanding this rapid pace of development, the results from initial clinical trials involving tens of thousands of adult subjects generally indicated that most vaccines were remarkably effective and safe, with no major safety warnings noted. However, with more than 2 billion vaccination doses administered to date, reports of rare adverse events following immunization (AEFI) are beginning to emerge. In late February 2021, atypical thrombotic events following immunization with the adenoviral vector-based ChAdOx1 nCov-19 vaccine were first reported, and similar events have also been observed in recipients of the adenoviral vector-based Ad26.COV2.S vaccine and the mRNA-based BNT162b2 and mRNA-1273 vaccines. These manifestations of atypical thrombosis and thrombocytopenia following COVID-19 vaccine immunization are now collectively referred to as vaccine-induced immune thrombotic thrombocytopenia (VITT). Although the reported incidence remains very low and does not affect the overall benefit of immunization, it is also true that if left untreated, VITT can be debilitating or even fatal. Therefore, this review seeks to provide a comprehensive overview regarding the incidence, pathogenesis, presentation, diagnosis, and treatment of VITT, as well as considerations for special populations, based on the currently available evidence in the literature. It is hoped that this will enhance awareness of this vaccine side effect, so that cases of VITT may be identified and treated in a timely and appropriate manner.

High prevalence of pro-thrombotic conditions in adult patients with moyamoya disease and moyamoya syndrome: a single center study.

BACKGROUND: Moyamoya Disease (MMD) and moyamoya Syndrome (MMS) have been reported to be associated with pro-thrombotic states in some patients. To date, however, such reports have been limited to case reports or small case series. We sought to determine the prevalence of pro-thrombotic states among a large cohort of both MMD and MMS patients. METHODS: We retrospectively reviewed the medical records of all adult patients who were diagnosed with MMD or MMS from our institution. In addition to basic demographic and clinical data, the presence of certain pro-thrombotic conditions was noted. The presence of such conditions was determined based on review of clinical diagnoses and laboratory reports. The length of follow-up and the presence of interval ischemic events were obtained. RESULTS: Out of a total of 180 patients diagnosed with MMD or MMS, 33 were found to have a concomitant pro-thrombotic condition (18.3%). Of 147 patients with MMD, 23 were found to have a pro-thrombotic condition (15.6%). There were 10 out of 33 total patients (30.3%) in the MMS cohort that had a concomitant pro-thrombotic condition. There were no differences in specific pro-thrombotic conditions between MMD and MMS cohorts. There were no differences in future ischemic events between moyamoya patients with pro-thrombotic tendencies compared to those without (13.3% versus 23.7%, respectively, P = 0.32), and this was also true for patients who underwent revascularization procedures (22.6% versus 29.4%, P = 0.76). There was also no difference in prevalence of revascularization graft occlusion between moyamoya patients with pro-thrombotic tendencies and those without at follow-up (1.2% versus 5.9%, P = 0.31). CONCLUSIONS: It is likely that both MMD and MMS are associated with or predispose to pro-thrombotic conditions in adult patients, although the clinical and surgical significance is uncertain. Further study is needed in order to further elucidate and characterize this potential association.

Pulmonary Artery Thrombosis: A Diagnosis That Strives for Its Independence.

According to a widespread theory, thrombotic masses are not formed in the pulmonary artery (PA) but result from migration of blood clots from the venous system. This concept has prevailed in clinical practice for more than a century. However, a new technologic era has brought forth more diagnostic possibilities, and it has been shown that thrombotic masses in the PA could, in many cases, be found without any obvious source of emboli. Chronic obstructive pulmonary disease, asthma, sickle cell anemia, emergency and elective surgery, viral pneumonia, and other conditions could be complicated by PA thrombosis development without concomitant deep vein thrombosis (DVT). Different pathologies have different causes for local PA thrombotic process. As evidenced by experimental results and clinical observations, endothelial and platelet activation are the crucial mechanisms of this process. Endothelial dysfunction can impair antithrombotic function of the arterial wall through downregulation of endothelial nitric oxide synthase (eNOS) or via stimulation of adhesion receptor expression. Hypoxia, proinflammatory cytokines, or genetic mutations may underlie the procoagulant phenotype of the PA endothelium. Both endotheliocytes and platelets could be activated by protease mediated receptor (PAR)- and receptors for advanced glycation end (RAGE)-dependent mechanisms. Hypoxia, in particular induced by high altitudes, could play a role in thrombotic complications as a trigger of platelet activity. In this review, we discuss potential mechanisms of PA thrombosis in situ.

Acute exposure to nocturnal train noise induces endothelial dysfunction and pro-thromboinflammatory changes of the plasma proteome in healthy subjects.

Nocturnal train noise exposure has been associated with hypertension and myocardial infarction. It remains unclear whether acute nighttime train exposure may induce subclinical atherosclerosis, such as endothelial dysfunction and other functional and/or biochemical changes. Thus, we aimed to expose healthy subjects to nocturnal train noise and to assess endothelial function, changes in plasma protein levels and clinical parameters. In a randomized crossover study, we exposed 70 healthy volunteers to either background or two different simulated train noise scenarios in their homes during three nights. After each night, participants visited the study center for measurement of vascular function and assessment of other biomedical and biochemical parameters. The three nighttime noise scenarios were exposure to either background noise (control), 30 or 60 train noise events (Noise30 or Noise60), with average sound pressure levels of 33, 52 and 54 dB(A), respectively. Flow-mediated dilation (FMD) of the brachial artery was 11.23 ± 4.68% for control, compared to 8.71 ± 3.83% for Noise30 and 8.47 ± 3.73% for Noise60 (p < 0.001 vs. control). Sleep quality was impaired after both Noise30 and Noise60 nights (p < 0.001 vs. control). Targeted proteomic analysis showed substantial changes of plasma proteins after the Noise60 night, mainly centered on redox, pro-thrombotic and proinflammatory pathways. Exposure to simulated nocturnal train noise impaired endothelial function. The proteomic changes point toward a proinflammatory and pro-thrombotic phenotype in response to nocturnal train noise and provide a molecular basis to explain the increased cardiovascular risk observed in epidemiological noise studies.

Acute portal vein thrombosis in noncirrhotic patients - different prognoses based on presence of inflammatory markers: a long-term multicenter retrospective analysis.

Background: Portal vein thrombosis (PVT) is a partial or complete thrombotic occlusion of the portal vein and is rare in noncirrhotic patients.Patients and methods: 78 adult patients with noncirrhotic acute PVT without known malignity were evaluated. Patients with initial CRP level 61-149 mg/l were excluded.Results: Patients were divided into two groups - the first one (33 patients) was characterized with signs of inflammation and CRP over 149 mg/l. The second group (45 patients) was without signs of inflammation and CRP level less than 61 mg/l. The frequency of prothrombotic hematologic factors was statistically significantly different in levels of factor VIII and MTHFR 677 C mutation. All patients from both groups underwent the same oncologic and hemato-oncologic screening which was positive in 23 patients (51.1%) in the group without signs of inflammation. In the group of patients with clinical and laboratory signs of inflammation oncologic and hemato-oncologic screening was positive only in 1 patient (3.0%). Complete portal vein recanalization was achieved in 19.2%, partial recanalization in 26.9%.Conclusions: Patients with clinical signs of inflammation and acute PVT have a low risk of malignancy in contrast to patients without signs of inflammation and acute PVT, which have a high risk of oncologic or hemato-oncologic disease. Patients with negative hemato-oncologic screening should be carefully observed over time because we expect they are at higher risk for the development of hemato-oncologic disease, independent from the presence and number of procoagulation risk factors.