Cause Of Thrombosis Research Articles

Three-dimensional extent of flow stagnation in transcatheter heart valves.

The recent unexpected discovery of thrombosis in transcatheter heart valves (THVs) has led to increased concerns of long-term valve durability. Based on the clinical evidence combined with Virchow's triad, the primary hypothesis is that low-velocity blood flow around the valve could be a primary cause for thrombosis. However, due to limited optical access in such unsteady three-dimensional biomedical flows, measurements are challenging. In this study, for the first time, we employ a novel single camera volumetric velocimetry technique to investigate unsteady three-dimensional cardiovascular flows. Validation of the novel volumetric velocimetry technique with standard planar particle image velocimetry (PIV) technique demonstrated the feasibility of adopting this new technique to investigate biomedical flows. This technique was used to quantify the three-dimensional velocity field in the vicinity of a validated, custom developed, transparent THV in a bench-top pulsatile flow loop. Large volumetric regions of flow stagnation were observed in the neo-sinus throughout the cardiac cycle, with stagnation defined as a velocity magnitude lower than 0.05 m s-1. The volumetric scalar viscous shear stress quantified via the three-dimensional shear stress tensor was within the range of low shear-inducing thrombosis observed in the literature. Such high-fidelity volumetric quantitative data and novel imaging techniques used to obtain it will enable fundamental investigation of heart valve thrombosis in addition to providing a reliable and robust database for validation of computational tools.

Results of coronary angiography in patients with recurrent angina pectoris in long-term period after coronary artery bypass grafting

There were 78 patients (75 (96.2%) men and 3 (3.8%) women) with recurrent angina pectoris after CABG. Postoperative follow-up period ranged from 1 month to 8 years. There were 104 and 39 local stenoses and occlusions de novo, respectively. New local stenoses appeared in 31 arteries with patent bypass grafts and in 18 arteries with closed graft. There were 143 (60.3%) patent and 94 (39.7%) occluded grafts. All grafts (n=4, 100%) were patent after bypass grafting of one coronary artery, 3 (13.7%) grafts were occluded after bypass grafting of 2 coronary arteries. Occlusion of 57 (45.2%) out of 126 grafts was noted after bypass grafting of 3 coronary arteries, in case of grafting of 4coronary arteries - 34 (40%) out of 85 grafts. Thus, the main causes of thrombosis of the grafts were poor distal vessels, technical errors in harvesting and implantation of the grafts, mediastinitis, overestimated indications for surgery (coronary stenoses <50%), progression of atherosclerotic process, usage of venous grafts. Also, there is a direct relationship between transplant thrombosis and the number of bypassed coronary arteries.

Pediatric Thrombotic Events: Incidence, Clinical Risk Factors and Outcome.

To study the incidence, clinical risk factors and outcome of thrombotic events in pediatric age group of 1 mo-12 y. This prospective observational study was conducted in a tertiary care institute from September 2015 through October 2017. Forty nine children with thrombosis from 1 mo-12 y were enrolled. Out of 49 cases, 30 (61.2%) were due to venous thromboembolism (VTE) and 19 (38.8%) were of arterial thromboembolism (ATE). The cumulative average annual incidence for VTEs was found to be 38.2 (n = 30) and for ATEs it was found to be 24.2 (n = 19) per 10,000 hospital admissions over 2 y of study period. With total of 19 (38.7%), catheters were the leading cause of thrombosis followed by infection numbering to 10 cases (20.4%). Total 42.8% cases (n = 21) achieved complete resolution. Partial resolution was noted in 53.2% of cases (n = 26) and no resolution in 4% cases (n = 2). Total seven (14.3%) deaths were recorded during the study period. The present study showed that thrombosis is an emerging problem in tertiary care setting adding to both mortality and morbidity in children. Central venous catheters followed by infection were the leading cause of thrombosis in this study.

An atypical case of pulmonary embolism from a jugular vein

SummaryNeck venous malformations and their potentially life-threatening complications are rarely reported in the available literature. Cases of aneurysmal or hypo-plastic jugular vein thrombosis associated with systemic embolization have not been frequently reported. We present the case of a 60-year-old male, without any known risk factors for thromboembolic disease, admitted for sudden onset dyspnea. The physical examination was remarkable for a right lateral cervical mass, expanding with Valsalva maneuver. Thoracic CT with contrast established the diagnosis of bilateral pulmonary embolism and raised the suspicion of superior vena cava and right atrial thrombosis. Bedside transthoracic echocardiography confirmed the presence of a large right atrial thrombus, with intermittent protrusion through the tricuspid valve. Systemic thrombolysis with Alteplase was initiated shortly after diagnosis, in parallel with unfractionated heparin, with complete resolution of the intracavitary thrombus documented by echocardiography. The patient showed significant improvement in symptoms and was later started on oral anticoagulation. Computed vascular tomography of the neck was performed before discharge, showing hypoplasia of the left internal jugular vein and aneurismal dilation of the contralateral internal jugular vein, without thrombosis. There were no identifiable systemic causes for thrombosis. Surgical resection of the aneurismal jugular vein was excluded, because of its potential to cause intracranial hypertension. The preferred therapeutic option in this case was long-term oral anticoagulation.

To Test or Not to Test? Quantifying and Reducing Inappropriate Hypercoagulable Workups in the Inpatient Setting

Background: Since the proposal of Virchow's Triad in 1856, the concept of hypercoagulability has been useful in analyzing causes of thromboembolic events. In the inpatient setting, evaluation of underlying causes of thrombosis is often complicated by unclear indications for testing, unreliability of individual assays, and confounding factors such as thrombosis itself and use of anticoagulant medications. We endeavored to quantify the occurrence of inappropriate hypercoagulable work-ups (HCW) in the inpatient setting in our institution, and then to implement a resident-focused educational intervention with the goal of limiting this unnecessary and potentially harmful use of resources.Methods: We retrospectively reviewed all patient charts containing an order for Factor V Leiden assay in 2017, 61 in total. If sufficient data were available, Hematology had not been consulted, and family history was not positive for thromboembolic events, orders were classified as inappropriate based on the recommendations of Pruthi1: temporary risk factors, active anticoagulation therapy, arterial thrombosis, or indefinite anticoagulation already indicated. We calculated the percentage of total charts with inappropriate orders. For our quality improvement intervention, we used a pre- and post-test design to assess knowledge before and after an educational presentation on HCW given to internal medicine and neurology residents. The pre- and post-tests were identical and consisted of 12 questions. SPSS statistical software was used to compare results using Chi-Square analysis. A p value <0.05 was considered significant.Results: A total of 37 charts were evaluated after exclusions, and 29 (78.4%) contained inappropriate orders for HCW. Of these, 16 (55.2%) were ordered as work-up of arterial thrombosis in patients with CVA or TIA but no cardiac shunt. 4 (13.8%) of the inappropriate orders followed provoked events. Apart from Factor V Leiden, additional assays were ordered with the following frequencies: Prothrombin gene mutation 92%, Anti-cardiolipin antibodies 78%, Homocysteine 43%, Antithrombin 42%, Protein C 42%, Protein S 42%, Anti-B-2-glycoprotein antibodies 25% and Dilute Russell's Viper Venom Test 22%. For our intervention, 85 resident tests were analyzed. An increase in correct responses occurred with statistical significance for questions regarding workup of CVA, as well as acute and chronic venous thrombosis. After the intervention, fewer residents stated that HCW would change their management of patients following a thromboembolic event (p<0.05). Residents correctly identified on pre-tests that anticoagulation would skew results of HCW. However, statistically significant improvement did occur in identifying appropriate timing of HCW between the pre- and post- test results (p<0.001).Conclusion: Thromboembolic events are commonly encountered in the inpatient setting, and often lead to inappropriate HCW, particularly in the setting of CVA and TIA without an intracardiac shunt. The set of assays ordered may also demonstrate high variability, which suggests uncertainty about which tests are most appropriate. HCW education in our resident population resulted in a statistically significant increase in correct responses to hypothetical clinical scenarios. This may predict decreased rates of inappropriate HCW, but further study with this endpoint would be beneficial. In addition, further interventions should be investigated, including hard stops and order sets in electronic health records. Through studies of this nature, which our data suggest are needed, unnecessary and potentially harmful use of resources could be reduced.1 Pruthi RK. Optimal utilization of thrombophilia testing. Int J Lab Hem. 2017;39(Suppl. 1):104-110. https://doi.org/10.1111/ijlh.12672 DisclosuresNo relevant conflicts of interest to declare.

Венозний тромбоемболізм у травмованих із тяжкою поєднаною травмою живота

Introduction. According to the modern data, in the structure of peacetime injuries, the part of severe combined abdominal trauma (SCAT) occupies 5-20%, leading to disability in 25.2% of cases. Venous thromboembolism is a frequent complication of SCAT. Despite of progress in diagnostics, treatment and prevention, number of randomized multicenter studies on venous thromboembolism in the injured is insufficient, world standards and prevention recommendations remain sometimes controversial.The aim of the study. To improve the outcomes of the treatment of patients with SCAT by differentiated prophylaxis of venous thromboembolism.Materials and methods. One hundred and five patients with SCAT (ISS score result 16-35 (18.4±7.4) points), who underwent inpatient treatment at the Lviv city emergency clinical hospital, were comprehensively examined. Twenty-seven (25.7%) had deep vein thrombosis, which were operated for SCAT in 2012-2016.Results and discussion. Twenty-seven (25.7%) cases of thrombosis were verified in the basin of the lower vena cava, 10 (37.0%) of which were manifested clinically, namely by limb edema, pastosity and pain. The remaining (17-63%) cases were asymptomatic and were verified by ultrasonic compression angioscanning of the veins of the lower extremities. Thrombosis of tibial veins and the sural sinuses was asymptomatic and was verified in 7 (25.9%) cases, thrombosis of the popliteal vein was seen in 4 (14.8%), of superficial femoral vein in 5 (18.5%) and the common femoral vein was diagnosed in 8 (29.6%) patients. The cause of thrombosis of deep veins in the injured with SCAT is a combination of factors in preoperative (age over 50, time from injury to hospitalization for more than 6 hours, body mass index over 28, history of venous thrombosis and embolism) and postoperative (duration of operation over 160 minutes, ISS score result over 21 points, postoperative immobilization over 48 hours) periods, vascular damage, massive blood loss, use of hemostatic drugs, traumatic shock.Conclusions. In the absence of prevention, the incidence of deep vein thrombosis in patients with SCAT reaches 25.7%. The method of ultrasonic compression angioscanning of the veins of the lower extremities had revealed a predominance of the proximal nature of thrombosis; risk of fragmentation and potential thromboembolism of the pulmonary artery were detected in 13.7% of the injured. There are 18 significant (p&lt;0,05) parameters associated with the development of postoperative venous thrombosis and embolism in patients with SCAT, of which 4 are independent risk factors of deep vein thrombosis in the preoperative period (age over 50, time from injury to hospitalization over 6 hours, body mass index over 28, history of venous thrombosis and embolism) and 3 in the postoperative period (duration of operation over 160 minutes, ISS score result over 21 points, postoperative immobilization over 48 hours).

Аspects of the methodology of laboratory studies of hemostasis in pediatric hematology-oncology and general approaches in the pathology of hemostasis in leukemia

Children with acute leukemia are faced with high risks of thrombotic and hemorrhagic complications. The pathogenesis of haemostasis disorders in hemoblastoses is complex because, in addition to the disease itself, the aggressiveness of the therapy and the need for numerous invasive manipulations also make a significant contribution. Patients with hemoblastoses are equally susceptible to thrombosis and hemorrhage, which makes it possible to speak of multidirectional shifts in the balance of the hemostatic system in each individual patient. Standard laboratory hemostasis tests (clotting times, marker tests) are designed to assess the concentrations of individual proteins and the functioning of individual components of the hemostasis, and in do not assess the balance between its procoagulant and anticoagulant components. Global hemostatic tests designed to assess the coagulation balance, such as thromboelastography, thrombin generation test, and thrombodynamics, can be the alternative for the standard coagulation assays. The review focuses on the mechanisms of various laboratory hemostasis tests, as well as an assessment of their informative value in frequent complications of the underlying disease (sepsis leading to the development of disseminated intravascular coagulation (DIC) syndrome, thrombocytopenia) and catheterization, which is present in the majority of patients with hemoblastosis. General screening tests of the blood coagulation system have little diagnostic value in the DIC syndrome in patients with acute leukemia, mainly due to their insensitivity to hypercoagulability. Standard markers (for example, D-dimers) are non-specific and only confirm the clinical manifestations of clotting disorder in sepsis and septic shock, but are unable to predict the dynamics of this process at earlier stages of the inflammatory response. In this case, the thrombin generation test and thrombodynamics make it possible to reveal the hypercoagulable phase of the DIC syndrome. Thrombocytopenia accompanies almost all protocols of chemotherapy. In this case, the degree of bleeding does not always depend only on the concentration of platelets, since chemotherapeutic drugs can affect not only the quantity, but also the functional characteristics of platelets, which are not determined by standard examination of patients. The catheterization that accompanies the treatment of hemoblastoses is the leading cause of thrombosis in children with acute leukemia. Thromboembolism of the pulmonary artery due to thrombosis in the central vein system occurs in 8–15 % of patients. The prediction of catheter-associated thromboses using standard laboratory methods for assessing the state of the hemostasis is not possible. Absence of sensitive tests in modern diagnostic schemes leads to the fact that the attending physician is forced to focus exclusively on the clinical picture of thrombosis or bleeding. The development of new functional methods of hemostasis allows one to think that today the existing standard panel of coagulation tests can be expanded and made much more informative in terms of the prediction of thrombohemorrhagic complications in pediatric hematology-oncology.

Hypereosinophilic Cardiac Involvement Presenting With Left Ventricular Massive Thrombus and Cardioembolic Stroke: A Case Report

Introduction: It is well known that the tendency toward thrombosis is increased in cancer patients. The increase in cancer procoagulant and tissue factor levels, endothelial damage, and stasis due to compression are among the most accused causes of thrombosis in cancer patients. Hypereosinophilia is a rare condition that causes endothelial damage leading to thrombosis. Case Presentation: We present a 64-year-old male patient with cardiac involvement of hypereosinophilia which developed in the T-cell lymphoma ground resulting in a fatal cardioembolic stroke. Despite normal left ventricular (LV) contractions, almost half of the ventricular volume was full of thrombus in this case. Conclusion: Hypereosinophilia is a rare cause of thrombus formation in the left ventricle in patients with preserved ejection fraction. However, hypereosinophilic cardiac involvement can lead to rapid, progressive, life-threatening complications.

тромбозы при болезни Бехчета: от патогенеза к лечению

Введение. Болезнь Бехчета (ББ) – системный васкулит неизвестной этиологии, характеризующийся рецидивами язвенного процесса в ротовой полости и на гениталиях, частым поражением глаз и рядом проявлений, включающих патологию суставов, желудочно-кишечного тракта, нервной системы и сосудов. Цель исследования: определить частоту и локализацию сосудистых проявлений у больных с ББ, уточнить связь последних с полом, возрастом и другой клинической симптоматикой ББ. Материалы и методы. Обследовано 250 больных ББ, сосудистая патология выявлена у 63 (25,2%) пациентов. Возраст больных с сосудистыми проявлениями составил 34,8 ± 10,4 лет, соотношение мужчины:женщины – 3,5:1. Сосуды вовлекались в процесс чаще в течение первых трех лет болезни. Поражалось в основном венозное русло, доля больных с артериальной патологией составила 9,5%. Результаты. У пациентов с сосудистой патологией по сравнению с больными без тромбозов достоверно чаще выявлялись узловатая эритема (71% против 44%; р = 0,002) и эпидидимит (22,4 % против 10,9%; р = 0,04), а генерализованный увеит (17,4% против 32%; р = 0,002) и ангиит сетчатки (22% против 40,6%; р = 0,008) встречались достоверно реже. В системе коагуляции у больных ББ с и без сосудистой патологии достоверных различий не выявлено. Заключение. Сосудистые нарушения выявлены у ¼ больных (преимущественно мужчин молодого возраста), развивались чаще в первые три года болезни и ассоциировались с узловатой эритемой, эпидидимитом и положительным тестом патергии. Introduction. Behcet's disease (BB) is a systemic vasculitis of unknown etiology; it is characterized by recurrent aphthous stomatitis, genital ulcers, uveitis and other manifestations including arthritis, pathology of gastrointestinal tract, nervous system and blood vessels. The aim of study: to determine frequency and localization of vascular manifestations in patients with BB, to clarify the relationship of manifestations with sex, age and other clinical symptoms of BB. Materials and methods. We examined 250 patients with BB, vascular pathology was revealed in 63 (25,2%) patients. The age of patients with vascular manifestations was 34,8 ± 10,4 years, the ratio of men:women was 3,5:1. Vessels were involved in the process more often during the first three years of the disease. Mainly veins were affected, arterial pathology had 9,5% of patients. Results. In patients with vascular pathology erythema nodosum (71% vs. 44%, p = 0,002) and epididymitis (22,4% vs. 10.9%; p = 0,04) were significantly more frequent than in patients without thromboses, and panuveitis (17,4% vs. 32%; p = 0,002) and retinal vasculitis (22% vs. 40,6%; p = 0,008) were found significantly more rarely. There were no significant differences in coagulation system between patients with and without vascular pathology. Conclusion. Vascular disorders were detected in ¼ of patients (predominantly in men of young age), developed more often in the first three years of the disease and associated with erythema nodosum, epididymitis and a positive pathergy test.

Paroxysmal nocturnal hemoglobinuria and thrombosis in the era of eculizumab

Paroxysmal nocturnal hemoglobinuria (PNH) arises as a consequence of clonal expansion of hematopoietic stem cells that have acquired a somatic mutation in the PIGA gene. The resulting hematopoietic cells have deficiencies in the GPI-anchored complement regulatory proteins CD55 and CD59, which account for the intravascular hemolysis that is the primary clinical manifestation of PNH. Thromboembolism is a major cause of morbidity and mortality in PNH, particularly in Caucasian patients. In a previous report on the clinical course of PNH patients in the United States and Japan, we showed that thrombosis was significantly more prevalent in white PNH patients than in Asian PNH patients. The pathophysiological mechanisms underlying thrombosis in PNH have not been fully clarified, and multiple factors are likely to be involved. Eculizumab, a humanized monoclonal antibody, targets the terminal complement protein C5 and inhibits terminal complement-mediated hemolysis associated with PNH. Brodsky et al. reported that eculizumab treatment reduces the risk of clinical thromboembolism in patients with PNH. These facts strongly suggest that the main cause of thrombosis in PNH is complement activation and/or hemolysis. In this review, the pathophysiology of thrombosis in PNH is discussed in the context of observations in PNH patients treated with eculizumab.

Clinical analysis of lower limb thrombosis caused by paraquat poisoning

Objective: To investigate the causes of peripheral vascular thrombosis in patients with paraquat poisoning. Methods: The patients with paraquat poisoning who were admitted to our department in recent two years were observed to screen out the patients with large vessel thrombosis. The data on toxic exposure history, clinical features, and treatment were collected to analyze the causes of thrombosis in the patients with paraquat poisoning. Results: Three patients had typical lower limb thrombosis. There was one case of right common femoral vein thrombosis, one case of bilateral calf muscle vein thrombosis, and one case of right calf superficial vein thrombosis and right calf muscle vein thrombosis. Conclusions: After paraquat poisoning, the blood is in a hypercoagulable state and prolonged bed rest may increase the risk of thrombosis.

Prospective rAndomized, single-blind, mulTicenter study of sirolimus-eluting coRonary stent “Calypso” vs everolimus-eluting cOronary stenT “XiencePrime”: results of the PATRIOT trial

Aim. This trial was aimed at comparing the efficacy and safety of sirolimus-eluting coronary stent “Calypso” (Angioline) and everolimus-eluting coronary stent “XiencePrime” (Abbott Vascular) when used for treatment of ischemic heart disease patients.Methods. The trial included patients suitable for coronary revascularization with coronary stenting. They underwent a standard revascularization procedure and were randomized in 2:1 ratio to receive “Calypso” coronary stent (Angioline) (n = 407) or “XiencePrime” coronary stent (AbbottVascular) (n = 203). The follow-up period was 12 months. In order to detect restenosis (secondary endpoint), angiographic follow-up was performed in 20% of cases at 12 months. The trial protocol had no limitations regarding the length of lesions, number of target lesions and number of implanted stents. The main exclusion criterion was STEMI. The composite primary endpoint included one-year target lesion-related complications determined as cardiogenic death, target vessel myocardial infarction, clinically indicated target lesion revascularization. The primary endpoint data were evaluated by an independent committee.Results. In the trial, 55% of patients had acute coronary syndrome with ST elevation and type C lesions were detected in 46% of cases. In “Calypso” and “XiencePrime” groups, TLF occurred in 5.4% and 6.4% respectively (absolute risk difference in TLF accounted for 1%, 95% CI [---;2.1%]; p non-inferiority = 0.017). Thus, the hypothesis of non-inferiority of “Calypso” as compared to “XiencePrime” was confirmed. The incidence of stent thrombosis (definite and probable) was relatively low and had no significant differences between “Calypso” and “XiencePrime” groups (0.73% and 0%; p&gt;0.05). Definite stent thrombosis was noted in two cases in the “Calypso” group (0.49%), in one case the cause of thrombosis turned out to be incomplete stent expansion after implantation.Conclusion. “Calypso” sirolimus eluting stent was not inferior to “XiencePrime” everolimus-eluting stent in treating patients with coronary heart disease.Received 7 November 2017. Revised 13 November 2017. Accepted 20 November 2017.Funding: The study was funded by “Angioline Interventional Devices” (Novosibirsk, Russian Federation). The supporting source had no involvement in study design; collection, analysis and interpretation of data; writing of the report; and in the decision to submit the article for publication.Conflict of interest: The authors declare no conflict of interest.

Antiphospholipid syndrome: an update for clinicians and scientists.

Antiphospholipid syndrome (APS) is a leading acquired cause of thrombosis and pregnancy loss. Upon diagnosis (which is unlikely to be made until at least one morbid event has occurred), anticoagulant medications are typically prescribed in an attempt to prevent future events. This approach is not uniformly effective and does not prevent associated autoimmune and inflammatory complications. The goal of this review is to update clinicians and scientists on mechanistic and clinically relevant studies from the past 18 months, which have especially focused on inflammatory aspects of APS pathophysiology. How antiphospholipid antibodies leverage receptors and signaling pathways to activate cells is being increasingly defined. Although established mediators of disease pathogenesis (like endothelial cells and the complement system) continue to receive intensive study, emerging concepts (such as the role of neutrophils) are also receiving increasing attention. In-vivo animal studies and small clinical trials are demonstrating how repurposed medications (hydroxychloroquine, statins, and rivaroxaban) may have clinical benefit in APS, with these concepts importantly supported by mechanistic data. As anticoagulant medications are not uniformly effective and do not comprehensively target the underlying pathophysiology of APS, there is a continued need to reveal the inflammatory aspects of APS, which may be modulated by novel and repurposed therapies.

Dysfunctional fibrinolysis and cerebral venous thrombosis

Cerebral venous thrombosis (CVT) is an uncommon neurological disease with high morbidity and mortality. Even after extensive thrombophilia screening, majority of the thrombosis cases remain with unknown etiology. Hypofibrinolysis due to acquired or congenital deficiencies or abnormalities in factors in the fibrinolytic cascade is a known cause of thrombosis at any site. In the present study 104 cases of radiologically confirmed CVT cases were investigated for the conventional thrombophilia along with factors in the fibrinolytic cascade to find a possible etiology for the clinical manifestation. Conventional thrombophilia markers which included PC, PS, AT and FVL mutation were detected in 16.3% of the patients. Approximately 19% cases had grossly elevated plasma PAI-1 levels. PAI-1 4G/4G genotype was found to be strongly associated with high PAI-1 levels. 2.9% cases had reduced tPA levels, 1.9% had plasminogen deficiency and 1.9% cases had increased alpha-2-antiplasmin levels. Along with conventional thrombophilia, dysfunctional fibrinolysis is found to be strongly associated with CVT. Understanding the role of risk factors is important for appropriate treatment of this serious disorder.

IMPACT OF HEREDITARY CAUSES OF THROMBOSIS ON ISCHEMIC STROKE BETWEEN THE YEARS 2008 THROUGH 2012: NATIONWIDE INPATIENT SAMPLE DATA ANALYSIS

Background: Ischemic Stroke (IS) is associated with traditional risk factors of diabetes, hypertension, hyperlipidemia and smoking. However, impact of hereditary causes of thrombosis (HT) on IS is largely unknown. HT includes primary hypercoagulable state, activated protein C resistance,

A study on demographic and clinical profile of children with extra hepatic portal venous obstruction and with special reference to thrombophilic factors

Background: Extra-hepatic portal vein obstruction (EHPVO) due to portal vein thrombosis is an important cause of portal hypertension in several region including India. The cause of thrombosis in these patients remains unclear. Objective of the study was to study the demographic features, etiology, clinical, laboratory findings with special reference to thrombophilic factors like protein C, protein S and antithrombin III deficiency in children with EHPVO.Methods: The prospective analysis of 62 patients of EHPVO (&lt;14 years of age) was done in the Department of Hepatology, SCB medical College, Cuttack. After detailed history, clinical examination, Ultrasound abdomen /color Doppler and Upper GI endoscopy, the subjects were analyzed for any deficiency of thrombophilic factors like protein C, protein S and antithrombin III.Results: A total of 62 patients (37 Male, 25 Female) with mean age of 8.3+3.1 years were studied. Growth retardation was present in the form of wasting (alone) 20.9%, stunting (alone) 25.8% and both wasting and stunting was found in 9.8% cases. History of neonatal, umbilical sepsis and umbilical vein catheterization was found in 15.9% and 10.2% of cases respectively. Haemorrhage from oesophageal varices was prevalent symptoms in 85.9% patients. Splenomegaly was found in 91.9% patients and ascites in 9.4% patients. 47 patients studied for protein C, S and antithromibin III. 14 patients were found to have thrombophilia: protein C deficiency in 9, protein S deficiency in 8, Antithrombin III deficiency in 6.Conclusions: The etiology of EHPVO in the majority of patients remain still unclear. It is commonly associated impaired somatic growth. The risk of EHPVO increases in the presence of thrombophilia, resulting from deficiency of naturally occurring anticoagulant proteins like Protein C, Protein S and Antithrombin III.

結合型エストロゲン製剤（プレマリン&lt;sup&gt;&amp;reg;&lt;/sup&gt;）を内服中の脳梗塞を発症した成人もやもや病患者の1例

We report a case of cerebral infarction associated with adult moyamoya disease in a patient using oral conjugated estrogen (Premarin®). A 44-year-old woman with adult moyamoya disease presented with a right-sided cerebral infarction. She had been administered oral conjugated estrogen for ovarian insufficiency. Direct revascularization could not be achieved owing to thrombosis of anastomosis sites. After surgery, we examined the cause of thrombosis of the anastomosis sites and discontinued use of oral conjugated estrogen, which was substituted with Kampo medicine (Chinese herbal medicine) for ovarian insufficiency. An anastomosis site was recanalized 3 months after surgery. We conclude that use of conjugated estrogens increases the risk of stroke and propose that oral conjugated estrogens should be used with caution in the perioperative period, especially in stroke patients.

Humanized Von Willebrand Factor-Glycoprotein Ibα Interaction in Mouse Models of Hemostasis and Thrombosis

Introduction: The interaction between von Willebrand Factor (VWF) and platelet glycoprotein (GP) Ibα is key for initiating the response to vascular injury that leads to hemostasis or, in pathological conditions, may be a cause of thrombosis. VWF binding to GPIbα occurs through the A1 domain (VWFA1) and its role in platelet adhesion and aggregation becomes progressively more important with increasing shear rates, i.e., in arterioles or pathologically stenosed arteries. Owing to the key role in platelet adhesion/aggregation under arterial flow conditions, VWFA1 has been considered an obvious target for antithrombotic intervention. However, efforts to develop this concept have been complicated by the lack of suitable animal models due to species-specificity in VWFA1-GPIb binding. To obviate the problem, we have generated new mouse strains with humanized VWF-GPIb interaction and characterized the resulting phenotypes in experimental ex vivo and in vivo models of hemostasis and thrombosis.Methods: In the human VWF gene, and in the mouse Vwf ortholog, exon 28 encodes domains A1 and A2, including the VWFA1 GPIb-binding site. We generated a knock-in mouse by targeted insertion of human VWF exon 28 (VWFh28) into the mouse Vwf exon28 locus such that mouse platelet GPIbα (M1) interacted with mouse VWF containing human A1 domain (HA); the strain was designated M1HA (Table). These mice were cross-bred with the previously described transgenic strain (mGPIbαnull;hIbαTg) in which human GPIbα is expressed on the platelet surface in the context of the mouse GPIb-IX-V complex (strain designation: H1MA). The resulting strain was thus designated H1HA, with humanized GPIb-VWF interaction. The unmodified wild type mouse strain used for reference was designated M1MA (Table). All mouse strains were in C57BL/6 genetic background. VWF plasma concentration was measured by ELISA and function ex vivo was evaluated by ristocetin-induced platelet aggregation. In vivo, we measured the tail bleeding time to gauge hemostatic efficiency as well as the propensity to support pathological thrombosis in the carotid artery injured by exposure to ferric chloride.Results: Plasma of VWFh28 mice expressing mouse or human platelet GPIbα had VWF levels (M1HA: 876.4 ± 209.5 mU/ml, n = 16; H1HA: 848.9 ± 121.0 mU/ml, n = 15) not significantly different from wild type mice (M1MA: 1022 ± 267.4 mU/ml, n = 23). Addition of 1.5 mg/ml ristocetin into platelet-rich plasma (PRP) from M1MA, M1HA and H1MA mice elicited no response; only in PRP of H1HA mice did ristocetin cause platelet aggregation that, as in human PRP, was inhibited by the anti-human VWFA1 monoclonal antibody, NMC-4. The tail bleeding time was abnormally prolonged in the M1HA strain expressing human VWFA1/mouse GPIbα, but normal in the H1HA strain expressing human VWFA1/human GPIbα (6.0 ± 3.8 min vs. 1.5 ± 0.9 min; n = 12); the latter was similar to the bleeding time in the M1MA strain (1.0 ± 0.1 min, n = 10). Thrombus formation (time to occlusion) following a carotid artery injury with 9% FeCl3·6H2O was greatly delayed in the M1HA strain (1760.0 ± 538.5 s, n = 6) but similar to WT M1MA in the H1HA strain (485.2 ± 63.7 s vs. 598.3 ± 84.0 s, n = 6, respectively).Conclusions: Knock-in of human VWF exon 28 into the mouse Vwf locus led to successful biosynthesis of chimeric mouse-human VWF protein in vivo under endogenous promoter control, maintaining normal physiologic expression in endothelial cells and megakaryocytes/platelets. Tail bleeding time and in vivo thrombosis assays confirmed the normal functional interaction of mouse VWF containing human A1 domain with hGPIbα. Moreover, the normal response to ristocetin with platelet aggregation, and inhibition of the latter by the specific NMC4 antibody, indicates that the "humanized" H1HA mouse strain could be a powerful tool to select and develop new interventions for the diagnosis and treatment of hemostatic and thrombotic disorders. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Cardiovascular disease in inflammatory rheumatic diseases.

Chronic inflammatory rheumatic diseases (IRD), including rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis, are prevalent conditions worldwide, with a considerable burden on healthcare systems. They are associated with increased cardiovascular (CV) morbidity and mortality. In this review, we focused on the epidemiology, traditional CV risk factors, genetics, and the link between chronic inflammation, atherosclerosis, and CV disease. Remarkably, patients with IRD have higher vulnerability to atheromatous plaques. The risk of unstable plaques is higher in patients with rheumatoid arthritis than in controls. Active disease is a characteristic ascribed to vulnerability and rupture of plaques and a cause of thrombosis in IRD. Management of CV risk in patients with IRD includes optimal control of disease activity. CV risk stratification by applying risk charts is also essential. Imaging techniques might be useful to determine the actual CV risk of patients with IRD who are included in the category of intermediate or moderate CV risk.

Aspirin plus tirofiban inhibit the thrombosis induced by Russell's viper venom.

BackgroundThrombosis and coagulopathy are the commonest hematological manifestations of envenomation of Russell’s viper venom (RVV). Factor X is activated by a factor X-activating enzyme from Russell’s viper venom (RVV-X) to start the coagulation cascade. We established an animal model with local ischemic effects induced by RVV. We tried to treat RVV envenomation with antiplatelets and anticoagulants without recourse to antivenom.MethodsRVV was injected into the foot pad of mice. We observed the effects at different intervals and compared local changes in ischemia with drug treatment after 30 min.ResultsA combination of aspirin plus tirofiban could prevent the ischemic change induced by RVV. The antithrombotic effects of single-use of aspirin or tirofiban were better than single-use of heparin or clopidogrel.ConclusionThe aspirin + tirofiban group had a better outcome with respect to prevention of tissue ischemia and gangrene. This indicates that the activation and aggregation of platelets is the major cause of thrombosis induced by RVV.