BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) and venous thromboembolism (VTE) are thought to share many common risk factors. Our study aimed to determine the frequencies of 5 thrombosis-related gene single nucleotide polymorphisms (SNPs) associated with VTE in patients with CTEPH (n 129) compared with a control group of healthy individuals without a history of VTE (n 2637).
METHODS: The SNPs of the following genes were investigated: F5 (F V Leiden, rs6025), F2 prothrombin (rs1799963), fibrinogen gamma (FGG, rs2066865), F11 (rs2289252) and ABO (non-O, rs8176719) in both groups.
RESULTS: The study found that the rs1799963 variant was more common in patients with chronic thromboembolic pulmonary hypertension (CTEPH) compared to the control group (p < .0001). The GA heterozygous variant showed a significant increase with an odds ratio (OR) of 4.480 (95% CI: 2.344-8.562) or a finding by maximum likelihood analysis (MLA) with p < .0001. Additionally, there was a notable increase in the rs8176719 variant with p < .0001 in CTEPH patients. Both the homozygous G/G variant and the heterozygous -/G variant also showed an increase, with OR of 4.2317 (95% CI: 2.45571-7.2919) and 2.4324 (95% CI: 1.46435-4.0403) respectively, or MLA (p < .0001 and p .0006). The study also revealed a higher prevalence of the heterozygous C/T variant of rs2289252 in CTEPH patients, with an OR of 1.5543 (95% CI: 1.02503-2.3568) or MLA (p .0379).
CONCLUSIONS: The study suggests that the observed gene polymorphisms F2 (rs1799963), ABO (rs8176719), and F11 (rs2289252) may play a role as independent heritable risk factors in the development of CTEPH.

暂无摘要。

Background:  Embolization to multiple arterial beds associated with primary aortic mural thrombus (PAMT) could result in high morbidity and mortality. There are no recommendations to dictate the best management. This study aims to describe our experience in managing this rare disease. Methods:  A retrospective review of all patients affected by PAMT treated at our institution between January 2015 and December 2021 was performed. Recorded data included demographics, prothrombotic risk factors, imaging findings, clinical presentation, and treatment. Primary outcomes comprised thrombus recurrence, major amputation, and death. Results:  Thirteen patients with PAMT have been included. The median age was 52 years (36-68 years), and the male/female ratio was 1:1.6. The diagnosis of PAMT was made by computed tomography angiography (CTA) in all cases. Prothrombotic conditions were identified in 92% of cases, and most patients (92%) had thoracic PAMT. The most common presentation was acute limb ischemia after thrombus embolization (85%), requiring surgical revascularization. Anticoagulation was promptly started in all patients. Two patients developed heparin-induced thrombocytopenia. Recurrence of embolization/thrombosis was observed in 54% of patients; two underwent endovascular thrombus exclusion with a stent graft. We identified one PAMT-related death and one major amputation with a median follow-up time of 39 months (12-64 months). Conclusion:  Anticoagulation alone as initial therapy could completely resolve PAMT but is associated with high embolization recurrence. Thoracic endovascular aortic repair is feasible and could prevent additional embolization. However, the criteria for its use as a first-line therapy still need to be defined. Our study highlights the importance of closely monitoring these patients.

This case report details a 30-year-old pregnant woman with inherited protein C deficiency who developed severe preeclampsia (PE), intrauterine growth restriction, and pancytopenia. Despite treatment, including anticoagulants, her condition worsened, resulting in postpartum mortality. Protein C deficiency, integral to the coagulation cascade, can exacerbate pregnancy\'s hypercoagulable state, contributing to adverse outcomes like PE. Mutations in the protein C gene can cause type I or type II deficiency, affecting protein C antigen and activity levels. The patient\'s history of recurrent pregnancy losses and conception via in vitro fertilization despite advisories highlights the complexities of managing pregnancy complications with protein C deficiency. Although some studies do not establish a direct link between protein C levels and PE, further research should explore thrombophilia\'s role in PE development and recurrence. Prospective studies investigating antithrombotic strategies in thrombophilic pregnancies could offer insights into reducing PE recurrence risks. This case underscores the need for multidisciplinary management and ongoing research to enhance clinical strategies and outcomes in high-risk pregnancies involving protein C deficiency.

The etiology of childhood arterial ischemic stroke is complex, and identifying the underlying cause is crucial for optimizing treatment and preventing recurrence. Currently, the classification methods for childhood arterial ischemic stroke are largely based on data from international studies, but a unified consensus have not yet been reached. This paper reviews the existing classification methods and their subtype definitions, and points out some doubts and ambiguities. On this basisi, combined with the data collected by Beijing Children\'s Hospital on Chinese children with arterial ischemic stroke, a new classification method (COIST) was proposed according to the etiology and pathogenesis, namely: inflammation (I), abnormal vascular structure (S), thrombophilia (T), heart disease (C), other identifiable causes (O), and uncertain causes; and various subtypes are listed. It is hoped that this new classification method can attract the attention and discussion of domestic colleagues, with the aim of further refinement, in order to help clinicians better understand and quickly identify the etiologies of childhood ischemic stroke.
儿童动脉缺血性脑卒中的病因复杂，识别其病因是优化治疗和预防卒中复发的关键。关于儿童动脉缺血性脑卒中的分型方法，目前多参考国外研究数据，但尚未达成统一。本文梳理了现有的分型方法及其亚型定义，并指出了存在的一些疑问和歧义。在此基础上，结合北京儿童医院收集的中国儿童动脉缺血性卒中的数据，根据病因和发病机制，提出了新的分型方法（COIST分型方法），即：炎症性（I）、血管结构异常（S）、易栓症（T）、心脏疾病（C）、其他可确定病因（O）、原因不能确定；并列出了各亚型疾病。希望这一新的分型方法能引起国内同行的关注和讨论，以期进一步完善，从而方便临床医师更好地了解和快速识别儿童缺血性卒中的病因。.

BACKGROUND: Nephrotic syndrome (NS) is associated with a high risk of thrombotic complications. In this group of patients, routine local tests for assessing hemostasis do not accurately reflect hypercoagulable state. Global functional tests for assessing hemostasis, including thrombodynamics (TD), are considered promising for assessing disorders in the blood coagulation system of these patients.
OBJECTIVE: To compare the rate of hypercoagulability according to routine hemostatic tests and TD and to evaluate the factors associated with increased risk of thrombotic complications in patients with chronic glomerulonephritis (CGN).
METHODS: The study included 94 patients with active CGN who were not receiving anticoagulant therapy; 63 (80.3%) patients had NS, and 31 (19.7%) had active CGN without NS. Hemostasis parameters were assessed using local coagulation tests and TD test. Using logistic regression analysis, factors associated with the risk of thrombosis were assessed.
RESULTS: Of the 94 patients with active CGN in 63 without preventive anticoagulant therapy, hypercoagulability according to routine tests was detected in 6 (9.5%) patients with NS and in 3 (9.7%) patients without NS (p<0.05). Hypercoagulability according to the TD test was detected in 24 (53.9%) patients with NS and in 5 (32.2%) without NS (p<0.05). The formation of spontaneous clots was observed in 29 (30.9%) of patients with CGN, most of them 24 (83%) with NS. 10.6% of patients in our cohort experienced thromboembolic events. The risk of thromboembolic events according to the univariate regression analysis was associated with older age, higher lipid levels, use of glucocorticosteroids and detection of spontaneous clots by the TD test. No association of thromboembolic events with abnormalities in routine hemostasis tests was obtained.
CONCLUSIONS: In patients with CGN with nephrotic syndrome, hypercoagulability is detected in 9.5% of cases with routine coagulation tests and in 53.9% of cases with TD test. Detection of spontaneous clots by TD test is associated with a risk of thromboembolic events.
Обоснование. Нефротический синдром (НС) связан с высоким риском тромботических осложнений. У этой группы пациентов рутинные локальные тесты для оценки гемостаза не отражают точно состояние гиперкоагуляции. Перспективными для оценки нарушений в свертывающей системе крови этих больных считаются глобальные функциональные тесты оценки гемостаза, в том числе тромбодинамика (ТД). Цель. Сравнить частоту гиперкоагуляции по данным рутинных тестов оценки гемостаза и ТД и установить факторы риска тромботических осложнений у больных хроническим гломерулонефритом (ХГН). Материалы и методы. В исследование включены 94 больных активным ХГН, не получающих антикоагулянтную терапию. У 63 (80,3%) пациентов диагностирован НС, а у 31 (19,7%) – активный ХГН без НС. Параметры гемостаза оценивали с использованием локальных рутинных методов оценки и теста ТД. С помощью моно- и многофакторного логистического регрессионного анализа определены факторы, связанные с риском тромбообразования. Результаты. Из 94 больных ХГН у 63 без профилактической антикоагулянтной терапии гиперкоагуляция по рутинным тестам оценки гемостаза выявлена у 6 (9,5%) с НС и у 3 (9,7%) – без НС (p<0,05). Гиперкоагуляция по тесту ТД выявлена у 24 (53,9%) больных с НС и у 5 (32,2%) – без НС (p<0,05). Образование спонтанных сгустков отмечено у 29 (30,9)% больных ХГН, у большинства из них – 24 (83%) – c НС. У 10,6% больных в нашей когорте отмечались тромбоэмболические события. Риск развития тромбоэмболических событий по результатам монофакторного регрессионного анализа ассоциирован со старшим возрастом, более высоким уровнем липидов, приемом глюкокортикостероидов и выявлением спонтанных сгустков по тесту ТД. Достоверной связи тромбоэболических событий с отклонениями в рутинных тестах гемостаза не получено. Заключение. У больных ХГН с НС гиперкоагуляция выявляется в 9,5% случаев при выполнении рутинных тестов оценки гемостаза и в 53,9% случаев при выполнении теста ТД. Выявление спонтанных сгустков по тесту ТД сопряжено с риском тромбоэмболических событий.

BACKGROUND: Cholestatic liver diseases induce local and systemic hypercoagulation, with neutrophil extracellular traps (NETs) serving as major drivers. These NETs have been linked to decreased liver function in patients with obstructive jaundice. However, the impact of NETs on liver hypercoagulation in cholestatic liver disease remains unknown.
METHODS: We utilized bile duct ligation to create experimental mice and analyzed NETs formation in the liver. Fibrin deposition, tissue factor expression, and inflammation in the liver were visualized through western blot and immunohistochemical techniques. LSECs were incubated with isolated NETs, and we detected endothelial procoagulant activity using coagulation protein production assays and measuring endothelial permeability. In both in vivo and in vitro settings, DNase I was applied to clarify the effect of NETs on intrahepatic hypercoagulability, hepatotoxicity, LSEC, and macrophage activation or injury.
RESULTS: Bile duct ligation mice exhibited significantly increased levels of NETs in liver tissue, accompanied by neutrophil infiltration, tissue necrosis, fibrin deposition, and thrombophilia compared to sham mice. Notably, NETs resulted in phosphatidylserine and tissue factor exposure on LSEC, enhancing coagulation Factor Xa and thrombin production. The enhanced procoagulant activity could be reversed by degrading NETs with DNase I. Additionally, NETs-induced permeability changes in LSECs, characterized by increased VE-cadherin expression and F-actin retraction, which could be rescued by DNase I. Meanwhile, NET formation is associated with KC activation and the formation of inflammatory factors.
CONCLUSIONS: NETs promote intrahepatic activation of coagulation and inflammation, leading to liver tissue injury. Strategies targeting NET formation may offer a potential therapeutic approach for treating cholestatic liver disease.

OBJECTIVE: The prothrombin (PT) G20210A mutation is one of the most prevalent genetic variations associated with an increased susceptibility to the first episode of venous thromboembolism (VTE). However, it remains uncertain whether this inherited thrombophilic abnormality also poses a risk for recurrent VTE. This meta-analysis aimed to assess the relation of PT G20210A mutation to the risk of recurrent VTE.
METHODS: PubMed and Scopus were systematically searched for pertinent prospective studies. Relative risks (RR) and 95% confidence intervals (CI) were used to test the association. Sixteen studies, with 16,174 participants, were included.
RESULTS: Carriers of the G20210A mutation were at increased risk of recurrent VTE (RR=1.60, 95%CI=1.20-2.14), compared to noncarriers; the increased risk was observed in heterozygotes (GA vs. GG) (RR=1.79, 95%CI=1.24-2.57), but not in GA/AA mutation.
CONCLUSIONS: This association was found to be significant in the long term (≥5 years of follow-up), but not in the short-term (<5 years of follow-up).

Cancer-associated thrombosis (CAT) is a common complication and a major cause of morbidity and mortality in patients with active cancers. CAT is common in various malignancies, particularly pancreatic, ovarian, gastric, colorectal, and hematologic cancers. In fact, CAT is a complicated multifactorial complication that may be influenced by the type of cancer as well as by the genetic background and inheritance of thrombophilic variants and elevated concentrations of coagulation factors. Several studies have shown the prominent role of inherited thrombophilias, such as prothrombin 20210, factor V Leiden, factor XIII Val34Leu, MTHFR C677T, in the occurrence of CAT, while others have found no correlation between them and CAT. In the present review, we have attempted to investigate the possible role of inherited thrombophilia in the occurrence of CAT.

BACKGROUND: Inherited antithrombin, protein C, and protein S deficiency increase the risk of venous thromboembolism. The presence of defects can be identified by clinical laboratory assays. In most Chinese clinical laboratories, the screening tests for antithrombin, protein C, and protein S deficiency are their activity assays. Ensuring appropriate pre-analytical storage conditions for activity tests is essential. This study aimed to assess the effects of storage conditions on antithrombin, protein C, and protein S activity in frozen plasma.
METHODS: We collected the remaining plasma of 29 patients. The baseline of antithrombin, protein C, and protein S activity values were tested within 4 h. Then, each sample was sub-packaged into 4 EP tubes, and was stored at -20 °C for 3 days, -20 °C for 7 days, -80 °C for 3 days, and - 80 °C for 7 days, respectively. After thawing, samples were tested by two systems.
RESULTS: The percentage deviation of antithrombin and protein C activity assay was<10% compared with the initial values. Protein S activity showed a significant reduction in frozen plasma, with a deviation > 10%. Some samples, initially within the normal range, were classified as abnormal after freezing storage.
CONCLUSIONS: Our study indicated that antithrombin and protein C remain stable when stored at -20 °C or -80 °C in a week. We argued that Protein S activity is not stable in frozen plasma. The use of frozen-thawed plasma for PS activity assay may result in overdiagnosis of protein S deficiency.