• CSTB2022BSXM-JCX0075 Chongqing Postdoctoral Science Foundation
• cstc2020jyj-msxmX0985 Natural Science Foundation of Chongqing Municipality

• case report
• intraventricular hemorrhage (IVH)
• near-term
• necrotizing enterocolitis (NEC)
• thrombophilia

• dvt
• fatigue
• macrocytosis
• pernicious anemia
• vitamin b12

• cerebral venous thrombosis
• drug
• homocysteine
• nitrous oxide
• vitamin B12

• Humans
• Anesthetics, Inhalation/adverse effects
• Anticoagulants/therapeutic use
• Intracranial Thrombosis/chemically induced
• Nitrous Oxide/poisoning
• Nitrous Oxide/adverse effects
• Substance-Related Disorders/complications
• Venous Thrombosis/chemically induced

• Humans
• Bibliometrics
• Periodicals as Topic
• Journal Impact Factor
• Vascular Diseases/epidemiology
• Vascular Diseases/therapy
• Vascular Diseases/diagnosis
• COVID-19/epidemiology
• Retrospective Studies
• Vascular Surgical Procedures
• Veins

• COVID-19
• D-dimer
• Homocysteine
• Intensive care unit (ICU)
• Platelet count

• Humans
• COVID-19/blood
• COVID-19/complications
• COVID-19/diagnosis
• COVID-19/mortality
• Homocysteine/blood
• Fibrin Fibrinogen Degradation Products/analysis
• Fibrin Fibrinogen Degradation Products/metabolism
• Platelet Count
• Male
• Female
• Thrombosis/blood
• Thrombosis/etiology
• Middle Aged
• Case-Control Studies
• Biomarkers/blood
• Adult
• SARS-CoV-2/isolation & purification
• Aged
• Risk Factors

• adenosine
• arginine methylation
• methionine cycle
• peripheral artery disease
• vascular calcification

• Adenosine/metabolism
• Humans
• Vascular Calcification/metabolism
• Vascular Calcification/pathology
• Signal Transduction
• Animals
• Methionine/metabolism
• Atherosclerosis/metabolism
• Atherosclerosis/pathology

• K22 HL117917 NHLBI NIH HHS
• R01 HL142932 NHLBI NIH HHS
• K22HL117917 HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI)
• 24POST1186619 American Heart Association (AHA)

• Humans
• Thrombophilia/complications
• Thrombophilia/genetics
• Thrombophilia/blood
• Neoplasms/complications
• Neoplasms/genetics
• Neoplasms/blood
• Thrombosis/etiology
• Factor V/genetics
• Methylenetetrahydrofolate Reductase (NADPH2)/genetics

• Ageing
• Cognition
• Homocysteine
• Hyperhomocysteinemia
• Neuroimaging
• Risk factor

• Humans
• Hyperhomocysteinemia
• Female
• Male
• Middle Aged
• Aged
• Aging/physiology
• Homocysteine/blood
• Cognition/physiology
• Magnetic Resonance Imaging
• Language
• Longitudinal Studies
• Neuropsychological Tests
• White Matter/diagnostic imaging
• Brain/diagnostic imaging
• Brain/metabolism

• B12 DEFICIENCY
• CLINICAL NEUROLOGY
• SINUS THROMBOSIS

• Barts and The London School of Medicine and Dentistry
• Tower Hamlets Council

• cardiovascular diseases
• cardiovascular prevention
• conventional risk factors
• emerging risk factors

• folic acid
• hyperhomocysteinemia
• nitrous oxide
• thrombosis
• vitamin B12

Background and Objectives: The diagnostic value of thrombophilia remains unknown in young patients with patent foramen ovale (PFO) and stroke. In this study we hypothesized that inherited thrombophilias that lead to venous thrombosis are more prevalent in patients with PFO. Materials and Methods: The study included patients of the tertiary center Vilnius University Hospital Santaros Klinikos who had a cryptogenic ischemic stroke between the ages of 18 and 50 between the years 2008 and 2021. Transient ischemic attacks were excluded. Contrast-enhanced transcranial Doppler ultrasound and extensive laboratory testing were performed. Results: The study included 161 cryptogenic stroke patients (mean age 39.2 ± 7.6 years; 54% female), and a right-to-left shunt was found in 112 (69.6%). The mean time between stroke and thrombophilia testing was 210 days (median 98 days). In total, 61 (39.8%) patients were diagnosed with thrombophilia. The most common finding was hyperhomocysteinemia (26.7%), 14.3% of which were genetically confirmed. Two patients (1.2%) were diagnosed with factor V Leiden mutation, three patients (1.9%) with prothrombin G20210A mutation, one patient (0.6%) had a protein C mutation and one patient (0.6%) had a protein S mutation. No antithrombin mutations were diagnosed in our study population. A total of 45.5% of patients with inherited thrombophilia had a right-to-left shunt, while 54.5% did not, p = 0.092. Personal thrombosis anamnesis was positive significantly more often in patients with antiphospholipid syndrome. Conclusions: The hypothesis of the study was rejected since inherited venous thrombophilia was not significantly more common in patients with PFO. Due to the rarity of thrombophilias in general, more research with a larger sample size is required to further verify our findings.

• Autoimmunity
• coagulation
• inflammation
• platelets

• Cerebral venous thrombosis
• Hyperhomocysteinemia
• Nitrous oxide recreational abuse

• Cytokinesis-blocked micronucleus assay
• Genotoxic stress
• Homocysteine metabolism
• Micronuclei
• Mouse bone marrow micronucleus test

Retinal vein occlusion (RVO) is a heterogenous disorder in which the formation of a thrombus results in the retinal venous system narrowing and obstructing venous return from the retinal circulation. The pathogenesis of RVO remains uncertain, but it is believed to be multifactorial and to depend on both local and systemic factors, which can be divided into vascular, platelet, and hypercoagulable factors. The vascular factors include dyslipidaemia, high blood pressure, and diabetes mellitus. Regarding the platelet factors, platelet function, mean platelet volume (MPV), platelet distribution width (PDW), and platelet large cell ratio (PLCR) play key roles in the diagnosis of retinal vein occlusion and should be monitored. Nevertheless, the role of a hypercoagulable state in retinal vein occlusion remains unclear and requires further studies. Therefore, the following article will present the risk factors of RVO associated with coagulation disorders, as well as the acquired and genetic risk factors of thrombophilia. According to Virchow’s triad, all factors mentioned above lead to thrombus formation, which causes pathophysiological changes inside venous vessels in the fundus of the eye, which in turn results in the vessel occlusion. Therefore, a diagnosis of retinal vein occlusion should be based on both eye examination and general examination, including laboratory tests.

• RVO
• haemostasis
• platelets
• retinal vein occlusion
• thrombophilia
• thrombosis

• anticoagulant
• femoral head
• hereditary thrombophilia
• hypofibrinolysis
• osteonecrosis

• Animals
• Biomarkers
• Blood Coagulation Disorders, Inherited/blood
• Blood Coagulation Disorders, Inherited/complications
• Blood Coagulation Disorders, Inherited/etiology
• Combined Modality Therapy
• Disease Management
• Disease Susceptibility
• Femur Head Necrosis/etiology
• Femur Head Necrosis/therapy
• Genetic Predisposition to Disease
• Humans
• Thrombophilia/blood
• Thrombophilia/complications
• Thrombophilia/etiology
• Treatment Outcome

• biomarker
• homocysteine
• plasma
• pulmonary embolism
• venous thromboembolism

• Aging
• Astronaut
• Commercial spaceflight
• Exploration mission
• Human spaceflight
• International Space Station
• Mars
• Microgravity
• Moon
• Thrombotic risk
• Touristic spaceflight
• Weightlessness

Homocysteine (Hct) is a substance produced in the metabolism of methionine. It is an essential type of amino acid gained from the daily diet. Methylenetetrahydrofolate reductase (MTHFR) gene mutation is related to elevated total homocysteine (tHct) expressions, in particular, among women with low folate intake. Hyperhomocysteinemia (HHct) is caused by numerous factors, such as genetic defects, lack of folic acid, vitamin B₆ and B₁₂ deficiency, hypothyroidism, drugs, aging, and renal dysfunction. Increased Hct in peripheral blood may lead to vascular illnesses, coronary artery dysfunction, atherosclerotic changes, and embolic diseases. Compared to nonpregnant women, the Hct level is lower in normal pregnancies. Recent studies have reported that HHct was associated with numerous pregnancy complications, including recurrent pregnancy loss (RPL), preeclampsia (PE), preterm delivery, placental abruption, fetal growth restriction (FGR), and gestational diabetes mellitus (GDM). Besides, it was discovered that neonatal birth weight and maternal Hct levels were negatively correlated. However, a number of these findings lack consistency. In this review, we summarized the metabolic process of Hct in the human body, the levels of Hct in different stages of normal pregnancy reported in previous studies, and the relationship between Hct and pregnancy complications. The work done is helpful for obstetricians to improve the likelihood of a positive outcome during pregnancy complications. Reducing the Hct level with a high dosage of folic acid supplements during the next pregnancy could be helpful for females who have suffered pregnancy complications due to HHct.

• NK cell cytotoxicity
• homocysteine
• methylenetetrahydrofolate reductase
• recurrent pregnancy losses
• vitamin D

• Genetic thrombophilia
• Thrombophilia screening
• Venous thromboembolism

• anticoagulants
• pulmonary embolism
• thrombophilia
• venous thromboembolism

• Anticoagulants
• Female
• Humans
• Pregnancy
• Pregnancy Complications, Cardiovascular/diagnosis
• Risk Factors
• Thrombosis
• Venous Thromboembolism

• MTHFR
• Occurrence
• Pulmonary embolism
• Rare variants
• Recurrence

• anti-β2 glycoprotein I antibody
• anticardiolipin antibody
• homocysteine
• liver cirrhosis
• portal vein
• thrombosis

• Adult
• Aged
• Aged, 80 and over
• Antibodies, Anticardiolipin/metabolism
• Homocysteine/metabolism
• Humans
• Liver Cirrhosis/blood
• Middle Aged
• Venous Thrombosis/blood
• Young Adult
• beta 2-Glycoprotein I/metabolism

• Science and Technology Plan Project of Liaoning Province

• Chronic kidney disease-5
• FVG1691A Leiden
• MTHFR C677T
• PTG20210A
• Thrombophilic mutations

• Adult
• Aged
• Factor V/genetics
• Female
• Follow-Up Studies
• Heterozygote
• Humans
• Kaplan-Meier Estimate
• Male
• Methylenetetrahydrofolate Reductase (NADPH2)/genetics
• Middle Aged
• Polymorphism, Single Nucleotide
• Renal Dialysis
• Renal Insufficiency, Chronic/etiology
• Renal Insufficiency, Chronic/mortality
• Renal Insufficiency, Chronic/therapy
• Risk Factors
• Thrombophilia/pathology

Hyperhomocysteinemia is caused by genetic and environmental factors, which can result in systemic arteriosclerosis and arteriovenous thrombosis including acute coronary syndrome. Thrombus burden in patients with acute coronary syndrome and hyperhomocysteinemia might involve the culprit lesion as compared with those without any coagulopathy. The primary percutaneous coronary intervention with stent implantation had been established as the treatment strategy for patients with acute coronary syndrome. However, in patients with acute coronary syndrome with high thrombus burden or uncontrolled coagulopathy, stent implantation might lead to slow-flow phenomenon or stent thrombosis. Therefore, the treatment strategy in these patients was not established.

A 49-year-old Japanese man with history of splenic infarction of unknown cause had continued anticoagulant therapy since its diagnosis, but stopped taking the medication several months ago. He presented with sudden-onset chest dorsalgia. Contrast computed tomography showed a small pulmonary embolism and his troponin I level was elevated on initial laboratory test. Coronary angiography revealed a contrast defect caused by a large thrombus from the proximal to mid portion of the left anterior descending artery. Near-infrared spectroscopy–intravascular ultrasonography showed a large amount of thrombus without lipid plaque. Therefore, revascularization was performed using a thrombus-aspiration catheter and intracoronary thrombolysis. In addition, , hyperhomocysteinemia and a deep vein thrombosis occurred. He was diagnosed with acute coronary syndrome complicated with pulmonary embolism and deep vein thrombosis simultaneously induced by hyperhomocysteinemia. After 1 week of antithrombotic therapy, near-infrared spectroscopy–intravascular ultrasonography and optical coherence tomography revealed a decreased thrombus and no significant residual organic stenosis in the left anterior descending artery. He continued conservative therapy with antithrombotic medications including aspirin and warfarin and had no cardiovascular events after discharge. Follow-up coronary angiography and optical coherence tomography at 9 months revealed complete disappearance of the thrombus and no severe stenosis.

Hyperhomocysteinemia should be considered as a cause of arterial vein thrombosis of unknown cause. The antithrombotic therapy and percutaneous revascularization without stenting based on intravascular imaging might be a safe and effective treatment option in patients with acute coronary syndrome complicated with hyperhomocysteinemia.

• acute coronary syndrome
• hyperhomocysteinemia
• non-stenting revascularization

• deep vein thrombosis
• prevalence
• ultrasound
• uterine venous plexus thrombosis
• venous thromboembolism

• Cross-Sectional Studies
• Female
• Humans
• Odds Ratio
• Prevalence
• Risk Factors
• Veins
• Venous Thrombosis/diagnostic imaging
• Venous Thrombosis/epidemiology

• Enzyme-linked immunosorbent assay
• Lagos
• hyperhomocysteinemia
• low-birth weight
• preterm birth
• preterm birth Mots-clés: Enzyme-linked immunosorbent assay

• Acute Porphyrias
• Ala-Synthase1
• Homocysteine
• Hyperhomocysteinemia
• Vitamin B6

• Cystathionine beta-Synthase
• Homocysteine
• Humans
• Hyperhomocysteinemia/epidemiology
• Porphyria, Acute Intermittent/complications
• Porphyria, Acute Intermittent/epidemiology
• Vitamin B 12

• MTHFR
• central retinal vein occlusion
• hypercoagulability
• protein S
• thrombosis

• Blood Coagulation
• Cholesterol, LDL/blood
• Female
• Humans
• Ischemia/genetics
• Ischemia/pathology
• Methylenetetrahydrofolate Reductase (NADPH2)/genetics
• Middle Aged
• Mutation, Missense
• Protein S/metabolism
• Retinal Vein Occlusion/genetics
• Retinal Vein Occlusion/pathology
• Vitamin D/blood

• R24 EY027285 NEI NIH HHS
• R01 EY018213 NEI NIH HHS
• U54 OD020351 NIH HHS
• R01 EY024698 NEI NIH HHS
• P30 EY019007 NEI NIH HHS
• P30 CA013696 NCI NIH HHS
• U01 EY030580 NEI NIH HHS
• R21 AG050437 NIA NIH HHS
• R01 EY026682 NEI NIH HHS
• Foundation Fighting Blindness
• Research to Prevent Blindness
• National Institutes of Health
• National Cancer Institute

• Bariatric surgery
• Folate
• Gastric bypass
• Homocysteine
• Obesity
• Vitamin B12

The aim is to study risk factors for retinal vein occlusion (RVO), such as thrombophilic and cardiovascular risk factors (CRF). A retrospective consecutive case series of 60 patients with RVO was made, tested for CRF, hyperhomocysteinemia, lupic anticoagulant, antiphospholipid antibody and 5 gene variants: factor V (FV) Leiden (G1691A), factor II (PT G20210A), 5,1-methylenetetra-hydrofolate reductase (MTHFR; 677 C > T and 1298 A > C), plasminogen activator inhibitor 1 (PAI-1; 4 G/5 G). More than 1 CRF were present in 36 patients (60%), which had a significantly higher mean age at diagnosis (66.7 ± 12.9 versus 59.5 ± 13.7 with ≤1 CRF, [t(57) = −2.05, p = 0.045, d = 0.54). Patients with thermolabile MTHFR forms with decreased enzyme activity (T677T or C677T/A1298C) had a significant lower mean age [57.6 ± 15.1; t (58) = 3.32; p = 0.002; d = 0.846] than patients with normal MTHFR enzyme activity (68.5 ± 10.2). Regarding CRF and thermolabile forms of MTHFR, the mean age at diagnosis could be significantly predicted [F(2,56) = 7.18; p = 0.002] by the equation: 64.8 − 10.3 × (thermolabile MTHFR) − 5.31 × ( ≤ 1CRF). Screening of MTHFR polymorphisms may be useful in younger RVO patients, particularly when multiple CRF are absent.

Nitrous oxide (N₂O) has gained increasing popularity as a recreational drug, causing hallucinations, excitation, and psychological dependence. However, side effects have been reported in recent years. Our case report proposes a correlation among N₂O, pulmonary embolism (PE), and deep vein thrombosis (DVT) and emphasizes the role of homocysteine (Hcy) in thrombotic events.

A 29-year-old man with long-term N₂O abuse sought evaluation after acute chest pain. A diagnostic workup revealed PE, DVT, and hyperhomocysteinemia. The patient was successfully treated with thrombolytic and anticoagulant therapy. Moreover, his Hcy level decreased and returned to normal after Hcy-lowering therapy.

Chronic N₂O abuse might increase the risk of PE and DVT, although there have been few studies previously.

• Nitrous oxide
• Pulmonary embolism
• Deep vein thrombosis
• Homocysteine
• Case report

• Atherosclerosis
• Hepatic venous doppler waveform
• Portal hypertension
• Sickle cell disease
• Sickle hepatopathy

• Doppler ultrasonography
• bowel ischemia
• mesenteric arteries
• sickle cell disease

• Adolescent
• Adult
• Anemia, Sickle Cell/diagnosis
• Anemia, Sickle Cell/physiopathology
• Blood Flow Velocity/physiology
• Celiac Artery/diagnostic imaging
• Celiac Artery/physiopathology
• Female
• Humans
• Male
• Mesenteric Arteries/diagnostic imaging
• Mesenteric Arteries/physiopathology
• Ultrasonography, Doppler, Duplex/methods
• Young Adult

• Anemia
• Elderly patients
• Vitamin B12

The risk of adverse effects of nitrous oxide (N₂O) exposure is insufficiently recognized despite its widespread use. These effects are mainly reported through case reports. We conducted an individual patient data meta-analysis to assess the prevalence of clinical, laboratory, and magnetic resonance findings in association with N₂O exposure in medical and recreational settings. We calculated the pooled estimates for the studied outcomes and assessed the potential bias related to population stratification using principal component analysis. Eighty-five publications met the inclusion criteria and reported on 100 patients with a median age of 27 years and 57% of recreational users. The most frequent outcomes were subacute combined degeneration (28%), myelopathy (26%), and generalized demyelinating polyneuropathy (23%). A T2 signal hyperintensity in the spinal cord was reported in 68% (57.2–78.8%) of patients. The most frequent clinical manifestations included paresthesia (80%; 72.0–88.0%), unsteady gait (58%; 48.2–67.8%), and weakness (43%; 33.1–52.9%). At least one hematological abnormality was retrieved in 71.7% (59.9–83.4%) of patients. Most patients had vitamin B12 deficiency: vitamin B12 <150 pmol/L (70.7%; 60.7–80.8%), homocysteine >15 µmol/L (90.3%; 79.3–100%), and methylmalonic acid >0.4 µmol/L (93.8%; 80.4–100%). Consistently, 85% of patients exhibited a possibly or probably deficient vitamin B12 status according to the cB12 scoring system. N₂O can produce severe outcomes, with neurological or hematological disorders in almost all published cases. More than half of them are reported in the setting of recreational use. The N₂O-related burden is dominated by vitamin B12 deficiency. This highlights the need to evaluate whether correcting B12 deficiency would prevent N₂O-related toxicity, particularly in countries with a high prevalence of B12 deficiency.

• global burden related to nitrous oxide exposure
• global health
• homocysteine
• individual patient data meta-analysis
• medical and recreational settings
• methylmalonic acid
• nitrous oxide-related toxicity
• one-carbon metabolism
• vitamin B12 deficiency

• Antiphospholipid syndrome
• Antithrombin deficiency
• Thrombophilia
• Thrombophilia screening
• Venous thromboembolism

Deep venous thrombosis (DVT), even though resolved, may damage the valves and may lead to chronic venous insufficiency (CVI). We designed the present study to examine the thrombotic markers or other ultrasound features in the absence of active thrombosis in patients presenting with features suggestive of CVI.

It was a cross-sectional study of 50 DVT patients. We collected a detailed history of presenting symptoms (onset, progression, and duration) and associated history of aggravating factors. After classifying the patients, color Doppler investigation for DVT and venous incompetence and blood investigations such as Factor V, D-Dimer, total cholesterol, total triglycerides, homocysteine, high-density lipoproteins, low-density lipoproteins (LDL), and very LDL were done.

We found a raised Factor V significantly more in patients classified as severe under clinical classification compared with nonsevere (19% and 0%; P = 0.05) and in patients with a high Venous Severity Clinical Score (VSCS) compared to those with a low VSCS score (17% and 0%; P = 0.03). We also found that perforators were significantly more in patients with a high VSCS score (88% and 58%; P = 0.02), in patients with a primary venous etiology compared with those without any venous etiology (97% and 1%; P < 0.0001), in patients with obstruction/reflux compared to those without any pathology (95% and 0%; P < 0.0001), and in patients with severe clinical classification compared with nonsevere patient (95% and 55%; P = 0.002).

Clinical or subclinical DVT, an important cause of CVI, may not always be seen on ultrasound, especially after resolution. However, they may have the presence of blood parameters (Factor V and hyperhomocysteinemia) suggestive of DVT; these can be used as proxy markers for the current or previous DVT.

• Chronic venous insufficiency
• deep venous thrombosis
• serology
• ultrasonography

• Factor V Leiden heterozygosity
• hypofibrinolysis
• lipoprotein (a)
• lupus anticoagulant
• testosterone
• thrombophilia
• thrombosis
• venous thromboembolism (VTE)

• arterial thrombosis
• hypercoagulable states
• thrombophilia
• venous thromboembolism (VTE)

• Adult
• Anemia, Sickle Cell/complications
• Anemia, Sickle Cell/pathology
• Biomarkers/analysis
• Body Mass Index
• Carotid Intima-Media Thickness
• Case-Control Studies
• Cross-Sectional Studies
• Female
• Femoral Artery/diagnostic imaging
• Humans
• Leg Ulcer/diagnosis
• Leg Ulcer/etiology
• Logistic Models
• Male
• Odds Ratio
• Risk Factors
• Young Adult