Arteriovenous Thrombosis Research Articles

A 72-year-old Woman with Dyspnea and Thrombocytosis

<p>原發性血小板增多症的臨床表徵並不典型且早期診斷不易，往往多數病人於診斷前已發生動靜脈血栓形成及出血併發症。本個案一位72歲女性，有高血壓及胃食道逆流病史並按時門診追蹤服藥，五天前注射新冠疫苗後，呼吸喘、乾咳併胸悶至診所就醫未改善，於急診初步診斷急性支氣管炎。入院後感心悸且胸悶，藉由病史詢問、檢驗及理學檢查，顯示心肌酵素正常但心電圖呈現陣發性心室上心搏過速，安排冠狀動脈血管攝影攝影後排除急性心肌梗塞，但呼吸急促未見好轉呈現低血氧，經胸腔電腦斷層為肺栓塞。疑似新冠疫苗後引起的免疫併發症，直到右手食指及中指末梢腫、痛且發紺症狀出現，筆者再次重新檢視病史資料，發現血小板異常，透過骨髓穿刺切片是發現巨核細胞（megakaryocyte）增生，病理報告判斷為骨髓增生性腫瘤，基因檢測結果為JAK2V617F 突變，最後確診是原發性血小板增多症併發肺栓塞，接受Hydroxyurea合併口服抗凝血劑治療，症狀改善且血小板數值趨於穩定。藉此案例分享提醒當發現病人有不明血栓產生時須考慮將相關血液疾病列入鑑別診斷，期能及早發現疾病，掌握治療時機。</p> <p> </p><p>The clinical symptoms of essential thrombocythemia are not typical and early diagnosis is difficult.Most patients have arteriovenous thrombosis and bleeding complications before diagnosis. In this case, a 72-year-old woman had a history of hypertension and gastroesophageal reflux and was taking medication regularly at the outpatient clinic. After being injected with the COVID-19 vaccine five days ago, her breathing, dry cough, and chest tightness did not improve when she went to the clinic. She was initially diagnosed with acute bronchitis in the emergency department. After being admitted to the hospital, she felt palpitations and chest tightness. The medical history, examination and physical examination showed that myocardial enzymes were normal, but the electrocardiogram showed Parox-ysmal supraventricular tachycardia. Coronary angiography was arranged to rule out acute myocardial infarction, but the shortness of breath persisted with hypoxemia, and the computed tomography of the chest showed pulmonary embolism. Immune complications caused by the COVID-19 vaccine were suspected, symptoms of swelling, pain and cyanosis appeared in the distal part of the right index fin-ger and middle finger appeared. The author re-examined the medical history data and found abnormal platelets. Through bone marrow aspiration and sectioning, megakaryocyte hyperplasia was found. Pa-thology report determined that the patient suffered from myeloproliferative neoplasm, and the genetic test result was the JAK2V617F mutation. The patient was finally diagnosed with essential thrombocythe-mia complicated by pulmonary embolism. She was treated with Hydroxyurea combined with oral an-ticoagulants. The symptoms improved and the platelet level stabilized. This case serves as a reminder that when a patient is found to have unknown thrombosis, related blood diseases must be considered in the differential diagnosis, so that the disease can be detected early and proper treatments can be pro-vided.</p> <p> </p>

Interaction of antiphospholipid antibodies with endothelial cells in antiphospholipid syndrome.

Antiphospholipid syndrome (APS) is an autoimmune disease with arteriovenous thrombosis and recurrent miscarriages as the main clinical manifestations. Due to the complexity of its mechanisms and the diversity of its manifestations, its diagnosis and treatment remain challenging issues. Antiphospholipid antibodies (aPL) not only serve as crucial "biomarkers" in diagnosing APS but also act as the "culprits" of the disease. Endothelial cells (ECs), as one of the core target cells of aPL, bridge the gap between the molecular level of these antibodies and the tissue and organ level of pathological changes. A more in-depth exploration of the relationship between ECs and the pathogenesis of APS holds the potential for significant advancements in the precise diagnosis, classification, and therapy of APS. Many researchers have highlighted the vital involvement of ECs in APS and the underlying mechanisms governing their functionality. Through extensive in vitro and in vivo experiments, they have identified multiple aPL receptors on the EC membrane and various intracellular pathways. This article furnishes a comprehensive overview and summary of these receptors and signaling pathways, offering prospective targets for APS therapy.

Surgical Intervention in Extensive Splanchnic Arteriovenous Thrombosis Associated with JAK-2 Mutation

Surgical Intervention in Extensive Splanchnic Arteriovenous Thrombosis Associated with JAK-2 Mutation

Investigating Thrombosis Risk Factors in Sickle Cell Disease Utilizing Archetypal Analysis

Background: Thrombosis in sickle cell disease (SCD) affects both the arterial and venous vasculature with devastating consequences. Individuals with SCD have an increased risk of venous thromboembolism (VTE). The risks are multifactorial with prior studies identifying both VTE-specific and SCD-specific risk factors. Machine learning (ML) offers the potential to detect non-linear relationships in complex multifactorial diseases and has successfully predicted outcomes in deeply phenotyped patients. We investigated whether archetypal analysis (AA), a method of ML would identify clinical and laboratory factors associated with arteriovenous thrombosis in patients with SCD. Methods: We retrospectively analyzed a prospective longitudinal cohort of patients with SCD (NCT00011648) studied between 2000-2017. A prior history of VTE and/or stroke at the time of study entry as captured by the electronic medical record was used to define index “cases”. SCD patients without a history of thrombosis were “controls”. The demographic and clinical characteristics of cases and controls were compared using Wilcoxon rank-sum test for continuous and Fisher's exact test for categorical variables. Unsupervised AA was used to identify patterns of clinical and laboratory test characteristics within the entire cohort of patients including cases and controls. AA identifies patterns are on the convex hull that encloses all patients in the cohort in the high-dimensional feature space. Once specific archetypes were identified, the frequency of each archetype was determined within cases and controls. In addition, we describe the age and laboratory characteristics of the archetypes that were significantly more prevalent in cases as compared to controls. Results: The cohort consisted of 633 out of 862 patients that had their whole exome sequenced. A combined total of 160 arterial and venous thrombosis events was detected in 148/633 patients (24%) with half (n=79) attributable to arterial stroke and half (n=81) attributable to VTE [Table 1]. A small proportion of patients had both arterial and venous thrombosis (n=12). The median age (31 years, p=0.94) and sex were similar between the cases (n=148) and controls (n=485). The distribution of genotypes was similar between the two groups (p=0.09). A significantly higher proportion of patient with thrombosis had a prior history of blood transfusion (p<0.0001) and history of insertion of a central venous access device (p=<0.0001) [Table 1]. History of medical management with hydroxyurea was similar among the cases and controls (p=0.70). Compared to controls, the cases had elevated laboratory parameters including AST levels (p=0.02), and serum ferritin (p<0.0001), while HbS percentages were significantly lower (p<0.0001). Based on the minimum error in matrix factorization, a total of 15 archetypes were identified in the cohort [Figure 1]. Each patient was decomposed as a weighted combination of the 15 archetypes. The contributing archetypes for each patient were those archetypes that have non-zero weights. Among those 15 archetypes, archetypes 9, 14 and 15 were significantly more enriched among the cases compared to controls (p<0.02) [Figure 1]. We observed elevated serum ferritin levels and low levels of HbS across the three archetypes, which are consistent with the previously identified risk factors [Figure 1]. Conclusions: Machine-identified archetypes are objective and reproducible feature representations. Archetype analysis-based machine learning appears to hold promise to identify both traditional VTE and SCD-specific risks for clinical thrombosis. Future studies will utilize archetypal analysis to investigate associations between clinical, laboratory and genetic markers for thrombosis and assess their reproducibility using validation cohorts.

Integrin β Expression as a New Diagnostic Marker for Arteriovenous Thrombosis: A Single-Center Prospective Study.

Integrin β plays an important role in the pathogenesis of thrombosis and inflammation, and it may be a shared pathogenic mechanism between arterial and venous thromboses. With the goal of identifying new treatment targets for thrombotic diseases and specific diagnostic markers for venous thromboembolism (VTE), this prospective clinical study was performed to clarify the relationship between integrin and thrombosis. The levels of integrin β1-3, interleukin-6 (IL-6), and C-reactive protein were significantly higher in patients with acute myocardial infarction (AMI; n = 44) and acute VTE (n = 43) compared to healthy controls (n = 33). The IL-6 and integrin β1-3 levels were also significantly higher in the AMI group compared to the VTE and control groups. Logistic regression analysis identified IL-6 and integrin β1-3 levels as independent risk factors for thrombotic disease. Based on the receiver-operating characteristic curve, Youden index, sensitivity, and specificity, the diagnostic accuracy value for VTE was greater than 0.8 when integrins β1, β2, and β3 were combined. Overall, these results suggest that integrin β levels can contribute to improving the diagnosis and treatment of arteriovenous thrombosis.

Thrombosis risk factors in ANCA-associated vasculitis

The article presents a review of current data on arteriovenous thrombosis risk factors in antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Thrombotic complications are among the most frequent prognostically unfavorable factors in AAV. In general, patients with AAV are at greater risk of mortality from cardiovascular events compared with the general population and patients with other forms of systemic vasculitis. Understanding the mechanisms of thrombosis, as well as pathogenic factors that cause an increased risk of arterial and venous thrombosis in AAV, can improve the quality of management of these patients. Therefore, the question of the need for primary and secondary prevention of thrombosis in AAV is of great practical importance. The presented data show the need to estimate the probability of thrombosis in patients with AAV, taking into account risk factors, as well as the influence of the disease itself and ongoing therapy. Assessment of the risk of thrombosis (both venous and arterial) is necessary for the timely administration of adequate preventive treatment of thrombotic complications in AAV.

Apoptosis is one cause of thrombocytopenia in patients with high-altitude polycythemia

High-altitude polycythemia (HAPC) can occur in individuals who are intolerant to high-altitude hypoxia. In patients with HAPC, erythrocytosis is often accompanied by a decrease in platelet count. Chronic hypoxia can increase the incidence of arteriovenous thrombosis and the risk of bleeding during antithrombotic treatment due to thrombocytopenia; therefore, understanding the cause of thrombocytopenia can reduce the risk of treatment-related bleeding. In this study, we examined platelet production and apoptosis to understand the cause of thrombocytopenia in patients with HAPC. The classification of myeloid-derived megakaryocytes (MKs) in HAPC patients was mainly granular MKs rather than mature MKs, suggesting impaired differentiation and maturation. However, the total number of MKs and newly generated reticulated platelets in the peripheral blood increased, indicating sufficient platelet generation in HAPC thrombocytopenia. Increased platelet apoptosis may be one of the causes of thrombocytopenia. Platelet activation and GP1bα pathway activation induced by thrombin and von Willebrand factor can lead to platelet apoptosis. Platelet production was not reduced in patients with HAPC, whereas platelet apoptosis was associated with thrombocytopenia. These findings provide a rationale for considering the bleeding risk in HAPC patient while treating thrombotic diseases.

In-hospital mortality of COVID-19 patients hospitalized with ST-segment elevation myocardial infarction: A meta-analysis.

Coronavirus Disease 2019 (COVID-19) has been associated with an increased risk of adverse cardiovascular events including arteriovenous thrombosis, myocarditis and acute myocardial injury.Relevant literature to date has reported widely varying estimates of mortality, ranging from approximately 2 to 11 times higher odds of mortality in COVID-19-positive STEMI (ST-segment elevation myocardial infarction) patients.Hence, we conducted this meta-analysis to resolve these inconsistencies and assess the impact of COVID-19 infection on mortality and other clinical outcomes in patients presenting with STEMI. This meta-analysis was registered in PROSPERO (CRD42021297458) and performed according to the Cochrane Handbook for Systematic Reviews of Interventions.PubMed and Embase were searched from inception to November 2021 (updated on April 2022) using a search strategy consisting of terms relating to COVID-19, STEMI, and mortality. We identified 435 studies through our initial search. After screening according to our eligibility criteria, a total of 11 studies were included.Compared with the non-COVID-19 STEMI patients, the in-hospital mortality rate was higher in COVID-19-positive STEMI patients.Similarly, the risk of cardiogenic shock was higher in the COVID-19-positive patients.Length of hospital staywas longer in STEMI patients with COVID-19. Our study highlights the necessity for early evaluation of COVID-19 status in all STEMI patients followed by risk stratification, prompt reperfusion and more aggressive management of COVID-19-positive patients.Further research is needed to elucidate the mechanisms behind poorer prognosis in such patients.

Comparison of color Doppler ultrasonography and computed tomography angiography (CTA) and computed tomography venography (CTV) in the diagnosis of arteriovenous thrombosis after simultaneous pancreas-kidney transplantation: a retrospective diagnostic accuracy study.

BackgroundSimultaneous pancreas-kidney transplantation is an important treatment approach for diabetic renal insufficiency, but pancreatic arteriovenous thrombosis is among the early serious surgical complications that can lead to graft loss and even be fatal. Ultrasound is considered to be a safe and non-invasive approach, but it is often affected by intestinal gas interference and operator proficiency, partial thromboses may be easily missed. Computed tomography angiography (CTA) and computed tomography venography (CTV) are highly accurate but radiative, requiring the use of contrast agents.MethodsA total of 194 patients with end-stage diabetic nephropathy who underwent simultaneous pancreas-kidney transplantation from September 2016 to May 2021 were selected, among which 32 patients with highly suspected arteriovenous thrombosis were enrolled as the research subjects. All patients were examined by color Doppler ultrasonography, CTA and CTV. CTA and CTV are the gold standard for diagnostic imaging. The diagnostic value of color Doppler ultrasound, CTA and CTV in the diagnosis of pancreatic arteriovenous thrombosis was compared. and Kappa coefficient was used for consistency test.ResultsAmong the 32 patients with high clinical suspicion of transplanted pancreatic arteriovenous thrombosis after simultaneous pancreas-kidney transplantation, 9 patients were diagnosed by CTA/CTV and 10 patients were diagnosed by color Doppler ultrasonography, of which 2 cases were false positive and 1 case false negative. After transplantation, the normal diameter of the donor splenic vein was 3.96±0.16 mm. The difference in the diameter of the donor splenic vein between those with and without donor splenic vein thrombosis was statistically significant (P<0.05). The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of color Doppler ultrasound in the diagnosis of arteriovenous thrombosis were 88.9%, 91.3%, 90.6%, 80%, and 95.5%, respectively. There was no significant difference between color Doppler ultrasound diagnosis of arteriovenous thrombosis and CTA and CTV results (McNemar test P=1). The diagnosis of arteriovenous thrombosis by color Doppler ultrasonography was consistent with that of CTA and CTV (Kappa coefficient =0.776).ConclusionsColor Doppler ultrasonography has the advantages of safety and radiation-free, and can be used as the first choice for diagnosis of pancreatic arteriovenous thrombosis after simultaneous pancreas-kidney transplantation.

The Impact of Seasonality on Prosthetic Arteriovenous Vascular Access Graft Thrombosis

Highlights Abstract Introduction: Arteriovenous prosthetic grafts are susceptible to recurrent thrombotic occlusions mainly due to venous outflow disease secondary to neointimal hyperplasia. Maintenance of vascular access for dialysis is a perpetual challenge for both patients and health care systems. In regions with hotter climates, there is a clinical impression that episodes of prosthetic arteriovenous vascular access graft thrombosis are more frequent during hot dry summers secondary to dehydration and increased blood viscosity. Seasonality of thrombotic events has been observed in multiple vascular beds. However, a seasonal pattern or any association of arteriovenous graft thrombosis with temperature and relative humidity levels has never been fully demonstrated. Methods: Data were collected prospectively from January 2014 until December 2020 but analyzed retrospectively. In this 7-year timeframe, 289 episodes of arteriovenous graft thrombosis were identified from 142 grafts fashioned. Results: No monthly variation (P = 0.35) or seasonal variation (P = 0.91) was identified. No statistically significant correlation between episodes of thrombosis and mean monthly temperature and mean relative humidity was noted. Conclusion: No evidence was identified to support this theory. However, multiple issues with assessments of events must be conceded. Graft thrombosis is multifactorial in nature, and venous outflow disease contributes toward a significant number of these events. Within our local cohort, a low primary patency rate was identified, which further contributes to graft interventions. Relatively small numbers were recruited, and therefore, potential correlations could have been missed.

Neurological Manifestations in Antiphospholipid Syndrome

Antiphospholipid syndrome (APS) is an autoimmune disease characterized by persistent presence of positive antiphospholipid antibodies (aPLs). Historically, aPLs first attracted attention at the beginning of the 1970s, as a risk factor for the development of myelitis via cross-reaction with cephalin and sphingomyelin as neuronal tissue-enriched phospholipids. Primary APS manifestations include arteriovenous thrombosis and pregnancy complications; however, in rare cases, aPL-related neurological disorders including cognitive dysfunction, chorea, and transverse myelitis are observed." The pathogenesis and therapeutic strategies for thrombosis, including cerebral infarction in APS, have been established from basic and clinical research to date. However, pathological insights and clinical perspectives have not yet been well-defined for aPL-related cognitive dysfunction, chorea, and myelitis. Based on past experiences and findings of small observational studies, some patients with aPL-related neurological disorders recover following antiplatelet and anticoagulation therapy, but in some cases, multidisciplinary treatments with glucocorticoids and/or immunosuppressive agents, including cyclophosphamide, azathioprine, mycophenolate and rituximab, plasmapheresis, and psychoeducational support are required. A detailed research on pathophysiology and nationwide or international multicenter clinical trials for therapeutic strategies are vital for establishing sufficient basic and clinical understanding of aPL-related neurological manifestations.

Endovascular treatment of arteriovenous graft dysfunction as a result of graft delamination and fracture

BackgroundGraft thrombosis due to fabric delamination is a rare cause of delayed failure of arteriovenous grafts. Graft delamination is primarily an imaging diagnosis and is confirmed with the help of ultrasound which shows the separation of graft fabric layers. Only two such cases have been described in the literature so far.Case presentationWe present a case of upper extremity arteriovenous graft thrombosis in a 79 year old COVID-19 positive patient with end-stage renal disease. The diagnosis was established on ultrasonography which revealed separation of the graft fabric layers with thrombosis within the “false” and “true” lumen of the graft. The patient was managed with angioplasty and embolectomy of the clot material followed by stent-graft placement across the delaminated portion of the graft. Post-procedural angiography confirmed brisk flow across the graft and patient could successfully have subsequent hemodialysis sessions.ConclusionsIdentification of graft delamination as a cause of graft failure is important as its management differs from other conventional causes since it requires stent-grafts to cover the area of delamination to re-establish flow and salvage the AV graft. The recognition of this phenomenon is essential to provide quality care and successful reuse of the AV graft.Level of evidenceLevel 4, Case Report.

Antiphospholipid syndrome: diagnosis and management

Antiphospholipid syndrome (APS) is an acquired thrombophilia associated with autoimmunity and is a syndrome that should always be considered when examining patients with thrombosis and pregnancy complications. As per the Sydney criteria, a diagnosis can be established with at least one clinical finding, such as arteriovenous thrombosis and the presence of at least one of the antiphospholipid antibodies (aPL), such as anticardiolipin antibodies (aCL). Moreover, phosphatidylserine-dependent anti-prothrombin antibody and anti-b2GPI-domain 1 antibody are correlated with APS manifestations and enable APS diagnosis. In addition to the inhibition of physiological coagulation inhibitors, such as protein C, the activation of vascular endothelial cells and complement activation by aPL is presumed to be the thrombus mechanism of APS. The mainstay of treatment is anticoagulant therapy with warfarin. For treating APS that has developed by arterial thrombosis, antiplatelet agent alone or in combination with warfarin is considered. In the triple positive aPL (aCL, anti-b2GPI antibodies, and lupus anticoagulant are detected at the same time) cases, sufficient anticoagulant therapy is required. Direct oral anticoagulants are not recommended in cases of triple positive aPL or arterial thrombosis. For patients with catastrophic APS, heparin therapy, plasmapheresis, and steroid pulse therapy are recommended.

Артерио-венозный тромбоз пуповины с позитивным исходом

The article presents a case of diagnostics of arteriovenous thrombosis of the umbilical cord. At the gestational age of 36+4, ovoid echogenic parietal inclusions in the umbilical vein lumen and fragmented increase in the venous wall echogenicity were detected. One day later, a healthy preterm male child was born through natural delivery with the Apgar score of 6-7 and weight of 2280g. Histological analysis of placenta identified arteriovenous thrombosis combined with cavernous haemangioma of the umbilical cord.

Clinical effect analysis of 146 cases of ipsilateral simultaneous pancreas and kidney transplantation

Objective: To investigate the clinical effect of ipsilateral simultaneous pancreas and kidney transplantation (SPK). Methods: A total of 146 cases of SPK surgeries completed in the Second Affiliated Hospital of Guangzhou Medical University from September 2016 to June 2020 were selected to summarize the outcome, curative effect and complications of the operation. Results: The patients were followed up for 1 to 45 months. Good clinical results were obtained in 146 patients. Renal function indicators suggest that on the 7th day after operation, the serum creatinine returned to normal level [142.4 (108.6, 213.4)μmol/L]. The index of pancreatic function decreased to the normal level as expected. The level of blood amylase was 160.5(109.3, 249.8) U/L within 7 days after operation, and then decreased. The trend of urinary amylase was similar to that of blood amylase, which was 240(121.0, 370.0) U/L 7 days after operation, and glycosylated hemoglobin decreased to the normal level (5.8%±1.4%) 1 month after operation. The main medical complications were infection including pulmonary infection (26.03%, 38/146), urinary tract infection (26.03%,38/146), and abdominal infection (4.79%,7/146), acute rejection including renal graft rejection (5.8%,8/146), pancreas/duodenum rejection (18.49%,27/146), and renal graft combined pancreatic graft rejeciton (6.85%,10/146), as well as gastrointestinal bleeding (30.82%,45/146), of which 5 cases were severe bleeding (3.42%, 5/146). The main surgical complications were poor incision healing (10.27%, 15/146), serious surgical complications including arteriovenous thrombosis of the transplanted pancreas (2.05%, 3/146) and intestinal leakage (0.68%,1/146). The 1-year and 3-year patient, renal and pancreatic survival rates were both 92.5%, 91.5% and 89.5%, respectively, and despite the death, the 1-year, 3-year transplanted kidney survival rate was both 99.3%, and 95% for the the 1-year, 3-year pancreas survival rate. Conclusion: Strict preoperative evaluation of the function of large organs, reasonable surgical methods, perioperative anticoagulation, and prompt diagnosis of complications can achieve good clinical results for patients with SPK.

Acute coronary syndrome with large thrombus successfully managed with no-stenting revascularization based on intravascular imaging in a patient with hyperhomocysteinemia: a case report

BackgroundHyperhomocysteinemia 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.Case presentationA 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.ConclusionsHyperhomocysteinemia 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.

Nanoparticle-Directed Targeting of Clustered PSGL-1 Mitigates Neutrophil-Derived Thrombosis in Antiphospholipid Antibody Syndrome

Multiorgan thromboses and subsequent organ failure are among the more devastating consequences of antiphospholipid antibody syndrome (APS). APS poses a relatively unique risk to patients by virtue of its propensity to cause thrombi of both the arterial and venous vascular systems. While recent studies have explored mechanisms of thrombosis in singular vascular beds, there remains a dearth of targetable effectors of arteriovenous thrombosis in APS. Here, we examine the potential of neutrophils as key players of both arterial and venous thrombosis in APS. From this and previous studies, we have also identified a critical transcriptional regulator in neutrophils whose loss mimics arterial and venous thrombosis susceptibility seen in APS. This factor, Krüppel-like factor 2 (KLF2), is down regulated in APS patients as well as in cells treated with antiphospholipid antibody (APLA) ex vivo. Loss of KLF2 in neutrophils contributes to classic neutrophil activation phenotypes including NETosis, increased tissue factor release, and heightened chemotaxis; remarkably, blocking each of these functions greatly abrogates the thrombotic phenotype. Utilizing the myeloid KLF2 knockout (K2KO) system as a model for aberrant neutrophil activation seen in APS, we have identified clustering of P-selectin glycoprotein ligand 1 (PSGL-1) secondary to actin rearrangement to be operative in neutrophil-mediated thrombosis in arterial and venous systems. While neutralizing antibodies against PSGL-1 have been explored as therapeutic options in APS, there remains a challenge in establishing local specificity to activated immune cells in order to increase efficacy. To circumvent this, we have designed a nanoparticle (NP) based approach that utilizes NPs decorated with anti-PSGL-1 immunoglobulins to better target clustered PSGL-1 on activated neutrophils. PSGL-1 NPs are more effective at inhibiting neutrophil rolling and adhesion in in vitro assays while, incubating activated neutrophils in PSGL-1 NPs prior to infusion attenuates their ability to contribute to both arterial and venous thrombosis. Further, injection of PSGL-1 NPs directly into K2KO mice reduces their extensive thrombotic phenotype. Importantly, this effect occurs at a substantially lower dose of PSGL-1 NPs than that which would be needed of PSGL-1 antibody alone. Finally, PSGL-1 NPs greatly reduce thrombotic burden in mice injected with APLA, diminishing clotting in both arteries and veins. Together, this work identifies key molecular and cellular players in APLA-induced arteriovenous thrombosis. Furthermore, it provides early pre-clinical evidence at specifically targeting clustered PSGL-1 on neutrophils as a viable option in combatting thrombosis in this particularly vulnerable patient population. Disclosures No relevant conflicts of interest to declare.

Entecavir as a P2X7R antagonist ameliorates platelet activation and thrombus formation

Platelet activation is the primary cause of thrombosis. The P2X7 receptor (P2X7R) is a therapeutic target of thrombosis. However, it is still unknown whether P2X7R activation affects platelet thrombus. Our molecular docking results showed that entecavir as a P2X7R antagonist interacted perfectly with the human P2X7R (hP2X7R) in silico simulation studies. Furthermore, our experimental data revealed that entecavir could act as a P2X7R antagonist to exert cytoprotective effects against platelet activation via protecting mitochondrial function, improving lipid peroxidation and increasing antioxidant activity. Correlated with this, entecavir inhibited platelet aggregation, dense-granule secretion, P-selectin expression, integrin activation and Ca2+ increase. In experimental mouse model, entecavir could significantly inhibit arteriovenous thrombosis and prolong the bleeding time. Furthermore, we found that entecavir had no significant effect on prothrombin time (PT), activated partial thrombin time (APTT), thrombin time (TT), fibrinogen (FIB), mean platelet volume (MPV) and platelet counts (PLT). This study demonstrates that entecavir markedly prevents platelet activation and thrombosis through inhibiting P2X7R without affecting coagulation system. Therefore, entecavir may be a potential candidate for treating thrombosis disease.

COVID-19 and hypertension-evidence and practical management: Guidance from the HOPE Asia Network.

There are several risk factors for worse outcomes in patients with coronavirus 2019 disease (COVID‐19). Patients with hypertension appear to have a poor prognosis, but there is no direct evidence that hypertension increases the risk of new infection or adverse outcomes independent of age and other risk factors. There is also concern about use of renin‐angiotensin system (RAS) inhibitors due to a key role of angiotensin‐converting enzyme 2 receptors in the entry of the SARS‐CoV‐2 virus into cells. However, there is little evidence that use of RAS inhibitors increases the risk of SARS‐CoV‐2 virus infection or worsens the course of COVID‐19. Therefore, antihypertensive therapy with these agents should be continued. In addition to acute respiratory distress syndrome, patients with severe COVID‐19 can develop myocardial injury and cytokine storm, resulting in heart failure, arteriovenous thrombosis, and kidney injury. Troponin, N‐terminal pro‐B‐type natriuretic peptide, D‐dimer, and serum creatinine are biomarkers for these complications and can be used to monitor patients with COVID‐19 and for risk stratification. Other factors that need to be incorporated into patient management strategies during the pandemic include regular exercise to maintain good health status and monitoring of psychological well‐being. For the ongoing management of patients with hypertension, telemedicine‐based home blood pressure monitoring strategies can facilitate maintenance of good blood pressure control while social distancing is maintained. Overall, multidisciplinary management of COVID‐19 based on a rapidly growing body of evidence will help ensure the best possible outcomes for patients, including those with risk factors such as hypertension.

FGA gene variation causing congenital dysfibrinogenemia with recurrent arteriovenous thrombosis

1例主诉为"间断腹痛、呕吐2个月余，加重3 d"的患儿就诊于北京儿童医院血液科，经过相关化验及基因测序检查，最终诊断为异常纤维蛋白原血症。以反复动、静脉血栓形成的异常纤维蛋白原血症临床罕见。.