Systemic Thrombosis Research Articles

Central retinal artery and Common Carotid artery occlusions following COVID-19 infection: A case report.

To report a case of central retinal artery and common carotid artery occlusions following COVID-19 infection in a young female with no other risk factors. Retrospective analysis of the medical notes of a patient hospitalized with COVID 19 infection at University Hospital Southampton. The patient was found to have dural venous sinus thrombosis and an acute infarct within the right parietal lobe. There was an occlusive thrombus within the right common carotid artery. Subsequently she was found to have a right central artery occlusion secondary to the right common carotid artery occlusion. COVID-19 infection can cause retinal artery occlusion via systemic thrombosis in previously healthy patients.

Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in retinal artery occlusion: a meta-analysis.

The goal of this meta-analysis is to examine the association between Neutrophil-to-Lymphocyte Ratio (NLR) and Platelet-to-Lymphocyte Ratio (PLR) in patients with Retinal Artery Occlusion (RAO). The analysis aims to provide insight into the potential of NLR and PLR as inflammatory biomarkers for RAO. Following PRISMA guidelines, a systematic search in PubMed, Embase, and Scopus identified eight eligible studies. The analysis assessed serum NLR and PLR levels in RAO and non-RAO groups by employing standardized mean differences (SMDs). Sensitivity analyses and publication bias were examined. The diagnostic performance of these markers was evaluated with a quantitative synthesis. The meta-analysis, involving 1,444 participants, demonstrated significantly elevated NLR (SMD = 0.88, 95% CI: 0.49-1.28, P < 0.001) and PLR (SMD = 0.45, 95% CI: 0.16-0.73, P < 0.001) levels in individuals with RAO. Significant heterogeneity was noted. Sensitivity analysis showed robustness and no significant publication bias was found. Summary results of diagnostic performance revealed promising discriminatory power for NLR and PLR. The results support a possible connection between systemic inflammation, as indicated by NLR and PLR, and the occurrence of RAO. Although there was heterogeneity, sensitivity analyses showed the findings to be robust. While immediate diagnostic applications are limited, understanding the role of NLR and PLR in the pathological process of RAO provides valuable insights for developing future predictive models, risk management approaches, and treatment strategies. Further research exploring mechanistic insights and conducting prospective studies is warranted to validate their clinical utility. What is known Retinal artery occlusion (RAO) is a serious condition with potential links to systemic inflammation and thrombosis. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are emerging inflammatory markers. What is new This is the first meta-analysis examining the association between NLR, PLR and RAO. Elevated NLR and PLR levels were observed in patients with RAO compared to controls. NLR and PLR show potential as indicators of systemic inflammation in RAO pathogenesis.

A rare occurence of systemic venous thrombosis as a late complication of splenic artery embolisation

A rare occurence of systemic venous thrombosis as a late complication of splenic artery embolisation

Chronic systemic thrombosis of unknown etiology with concurrent essential thrombocythemia and recurrent stroke: A case report

Here, we report a male patient under hypercoagulable state of unproven etiology, who used to present with recurrent thrombotic episodes since young age after he stopped taking anticoagulant. At the age of 73, he was detected to have essential thrombocythemia while grappling with recurrent strokes. On both occasions, he presented with a basilar thrombus. His National Institutes of Health Stroke Scale (NIHSS) score improved from 18 to 2 on the first occasion and from 17 to 2 sixteen days later on the second occasion. Thrombolysis was done on both occasions, but endovascular therapy was not done on either occasion due to chronicity of the thrombus and remarkably improved NIHSS post-thrombolysis. For patients with recurrent thrombotic events of undetermined etiology, an anticoagulant should be indicated. Repeat thrombolysis can be performed without endovascular therapy within a brief gap of 16 days, even in stroke patients with moderate to high NIHSS.

Real-World Electronic Medical Records Data Identify Risk Factors for Myelofibrosis and Can Be Used to Validate Established Prognostic Scores.

Myelofibrosis (MF) is a myeloproliferative neoplasia arising de novo as primary myelofibrosis (PMF) or secondary to polycythemia vera or essential thrombocythemia. Patients experience a high symptom burden and a marked reduction in life expectancy. Despite progress in molecular understanding and treatment, the clinical and prognostic heterogeneity of MF complicates treatment decisions. The International Prognostic Scoring System (IPSS) integrates clinical factors for risk stratification in MF. This study leverages the TriNetX database with more than 64,000 MF patients to assess the impact of accessible parameters on survival and complicating events, including AML transformation, cachexia, increased systemic inflammation, thrombosis and hemorrhage. Age over 65 years correlated with increased risks of death, AML transformation, thrombosis and hemorrhage. Anemia (Hb < 10 g/dL), leukocytosis (>25 × 103/µL) and thrombocytopenia (<150 × 103/µL) reduced survival and increased risks across all assessed events. Monocytosis is associated with decreased survival, whereas eosinophilia and basophilia were linked to improved survival. Further, as proof of concept for the applicability of TriNetX for clinical scores, we devised a simplified IPSS, and confirmed its value in predicting outcomes. This comprehensive study underscores the importance of age, anemia, leukocytosis and thrombocytopenia in predicting disease trajectory and contributes to refining prognostic models, addressing the challenges posed by the disease's heterogeneity.

Safety of the injectable expanding biopolymer foam for non-compressible truncal bleeding in swine

BackgroundA novel hydrophobically modified chitosan (hm-chitosan) polymer has been previously shown to improve survival in a non-compressible intra-abdominal bleeding model in swine. We performed a 28-day survival study to evaluate the safety of the hm-chitosan polymer in swine. MethodsFemale Yorkshire swine (40–50 kg) were used. A mild, non-compressible, closed-cavity bleeding model was created with splenic transection. The hm-chitosan polymer was applied intra-abdominally through an umbilical nozzle in the same composition and dose previously shown to improve survival. Animals were monitored intraoperatively and followed 28 days postoperatively for survival, signs of pain, and end-organ function. Gross pathological and microscopic evaluations were performed at the conclusion of the experiment. ResultsA total of 10 animals were included (hm-chitosan = 8; control = 2). The 2 control animals survived through 28 days, and 7 of the 8 animals from the hm-chitosan group survived without any adverse events. One animal from the hm-chitosan group required early termination of the study for signs of pain, and superficial colonic ulcers were found on autopsy. Laboratory tests showed no signs of end-organ dysfunction after exposure to hm-chitosan after 28 days. On gross pathological examination, small (<0.5 cm) peritoneal nodules were noticed in the hm-chitosan group, which were consistent with giant-cell foreign body reaction in microscopy, presumably related to polymer remnants. Microscopically, no signs of systemic polymer embolization or thrombosis were noticed. ConclusionProlonged intraperitoneal exposure to the hm-chitosan polymer was tolerated without any adverse event in the majority of animals. In the single animal that required early termination, the material did not appear to be associated with end-organ dysfunction in swine. Superficial colonic ulcers that would require surgical repair were identified in 1 out of 8 animals exposed to hm-chitosan.

Outcomes of thrombotic thrombocytopenic purpura patients submitted to therapeutic plasma exchange in a single center in Brazil

IntroductionImmune thrombotic thrombocytopenic purpura (iTTP) is characterized by acute systemic microvascular thrombosis and is associated with a high morbidity and mortality, especially in delayed diagnosis (later than 6–7 days from symptoms). iTTP data in Brazil is scarce, so we aimed to characterize the clinical presentation and identify predictors of death risk in patients with this disease in Brazil. MethodsIn this single-center retrospective study the patients who underwent therapeutic plasma exchange (TPE) for presumptive or confirmed iTTP were evaluated regarding the epidemiological, clinical, laboratorial characteristics and management. ResultsA total of 50 patients (90 % female), with median age (IQR) of 34.1 (27–47) years, were enrolled, of which 12 (24 %) died. The most frequent symptoms were neurological (96 %), bleeding (76 %), gastrointestinal (52 %), fever (38 %), and cardiovascular (22 %). Neurological focal deficit and cardiovascular symptoms were more frequently observed in the non-survivor group (P = 0.0019 and P = 0.007, respectively). The mean ± SD number of days from beginning of symptoms to first TPE was 12.22 ± 7.91. We identified an association regarding mortality rate with a score MITS ≥ 2 points (P = 0.04), a higher indirect bilirubin (P = 0.0006), a higher number of transfused red blood cell units (P = 0.025), and platelet transfusion (P = 0.027). ConclusionDelayed diagnosis appears to be associated with a higher frequency of neurological symptoms and mortality. Intensity of hemolysis and signs of organ ischemia, such as cardiovascular symptoms and focal neurological deficit, are indicators of death risk.

Clinical outcomes in patients receiving oral anticoagulation stratified by the presence of dose reduction criteria and older age: a subanalysis of ENVISAGE-TAVI AF

Abstract Background/Introduction In the ENVISAGE-TAVI AF (Edoxaban vs Standard of Care and Their Effects on Clinical Outcomes in Patients Having Undergone Transcatheter Aortic Valve Implantation–Atrial Fibrillation) trial, edoxaban (EDX) was noninferior to vitamin K antagonists (VKAs) for preventing most adverse clinical events but was associated with increased major bleeding (MB). Presence of EDX dose reduction criteria applied in the trial (DRC; body weight ≤60 kg, CrCL 15–50 mL/min, concomitant use of selected P-glycoprotein-inhibitors) indicates a more vulnerable patient phenotype. Purpose Compare clinical outcomes after TAVI for AF patients with and without DRC stratified by anticoagulation strategy and age. Methods ENVISAGE-TAVI AF (NCT02943785) was a multicentre, open-label, randomised, controlled trial comparing EDX vs VKA in patients with AF as the indication for oral anticoagulation (OAC) after successful TAVI. In this analysis, outcomes—which included net adverse clinical events (NACE; composite all-cause death, myocardial infarction, ischaemic stroke, systemic thromboembolic event, valve thrombosis, or MB), intracranial haemorrhage, ischaemic stroke, all-cause death, cardiovascular (CV) death, non-CV death, MB bleeding, fatal MB bleeding, and major gastrointestinal bleeding (MGIB) —were compared in patients with vs without DRC, further stratified by OAC use, and age (&amp;lt; or ≥80 years [y]). Results Patients meeting DRC (n=637) were older, more often female, and had lower baseline CrCL than those without (n=740). In addition, these patients had significantly higher rates of NACE (P=0.0375) and all-cause death (P=0.0136). There were no differences in MB or MGIB rates between patients with vs without DRC. EDX resulted in more MB (hazard ratio [95% CI], 1.6 [1.1–2.5] and MGIB (2.6 [1.2–5.8]) than VKA only in patients without DRC. In patients aged &amp;lt;80 y meeting DRC, rates of all-cause death (P=0.0366) and CV death (P=0.0042) were significantly higher than those without DRC. Among patients aged &amp;lt;80 y, there were no differences in rates of clinical outcomes between EDX and VKA regardless of the presence or absence of DRC; Figure 1). In patients aged ≥80 y, there were no differences in rates of all-cause death, MB, or MGIB in those with or without DRC; Figure 2). Additionally in this age group, there was no difference in MB between patients on EDX and VKA both with and without DRC. However, there was more MGIB with EDX when there were no DRC. In patients aged ≥80 y with DRC, all-cause death was lower with EDX. Conclusions In this subanalysis of ENVISAGE-TAVI AF, the presence of DRC indicates a more vulnerable patient phenotype at higher risk for all-cause death after TAVI and in whom a lower EDX dose may have substantial benefits in terms of outcomes, including bleeding events, particularly in patients ≥80 y.Figure 1Figure 2

The Role of Coagulation Gene Polymorphisms in Sars-CoV2 Infection in the Bergamo Area

Introduction: Given the great variability of the individual response to SARS-CoV2 infection, it is important to understand whether and how biological and genetic factors might predispose to the infection and to the degree of severity, including the development of systemic coagulopathy and thrombosis. In this study, we evaluated the frequency of prothrombotic allelic variants (AVs) in coagulation genes in a population of COVID-19 patients, to verify whether these polymorphisms, alone or in combination, are associated to an increased susceptibility to develop COVID-19 and/or a greater severity. Methods: A cohort of 358 patients (257M/101F; median age: 55 years) from the Bergamo area with two different degrees of COVID-19 severity, i.e., severe disease (hospitalized, n=212) or mild disease (non-hospitalized, n=146), was enrolled from April 2020 to June 2021 and followed-up for disease outcome and thrombosis. A cohort of 377 healthy subjects (177M/200F; median age: 49 years) from the same area without COVID-19 acted as a control group. DNA was analyzed for a panel of prothrombotic/inflammatory single nucleotide polymorphisms (SNPs) including FII rs1799963, FV rs6025, FV rs118203907, FXIIIA1 rs5985, FGB rs1800790, MTHFR rs1801131 and MTHFR rs1801133 as well as two SNPs located in the coding region of angiotensin-converting enzyme (ACE2) gene, namely ACE2 rs140312271 and ACE2 rs41303171. Statistical analysis was performed using SPSS statistical software. Results: Among the AVs analyzed, the rs6025 polymorphism of FV gene (FV Leiden) was more frequent in COVID-19 patients than in the control group. By a logistic regression corrected for age and gender, FV Leiden was associated with a 3-fold risk of developing COVID-19 (OR: 3.2 [95% CI 1.02-10]). In contrast, the rs41303171 polymorphism of the ACE2 gene was more frequent in the control group and was a protective factor for COVID-19 (OR: 0.12 [95% CI 0.02-0.99]) even after correction for age and gender. No significant differences appeared in the frequency of the other SNPs alone or in combination. Within the COVID-19 patient cohort, the rs1801131 SNP of MTHFR gene was associated with less severe COVID-19 disease. In the hospitalized severe cohort, 17 (8%) patients developed an overt venous thromboembolic event, and 7 COVID-19-related deaths (4%) were recorded. No significant associations were found between any of the AVs analyzed and the outcomes of thrombosis and death. However, the analyses of circulating biomarkers of clotting (i.e. D-dimer, FVIII, fibrinogen, prothrombin fragment 1+2 [F1+2], and FXIII), fibrinolysis (i.e. tissue plasminogen activator [tPA], and plasminogen activator inhibitor-1 [PAI-1]) and endothelial cell activation (i.e. thrombomodulin [TM], and von Willebrand Factor [vWF]), and the neutrophil-to-lymphocyte ratio (NLR) as an inflammatory biomarker revealed thathaving fibrinogen (OR: 4.9 [95% CI 1.04-23.1]), vWF:Ag (OR: 11.8 [95% CI 2.1-66.9]) and NLR (OR: 26.1 [95% CI 2.9-237] levels above the 75th percentile was significantly associated with death. Of interest, in the same hospitalized patient group, but not in the control group, the presence of FXIII SNPs was significantly associated with high levels of F1+2. Conclusions: Our study shows that the FV Leiden polymorphism predisposes to COVID-19 infection, while the rs41303171 ACE2 polymorphism has a protective role. In addition, the rs1801131 SNP of gene MTHFR correlates with a milder COVID-19 disease. In patients with severe COVID-19, the inflammatory marker NLR, and the circulating hemostatic proteins vWF and fibrinogen are associated with mortality.

Abstract 117: Digitally Subtracted Angiogram &amp; Biopsy Negative Recurrent Spontaneous Bilateral Anterior Cerebral Artery Territory Intracranial Hemorrhage

Introduction Up to 18% of spontaneous intracerebral hemorrhages are cryptogenic despite a thorough workup, usually noted in a lobar location. Although undetected on DSA, a significant proportion of these represent ruptured micro‐AVM/AVF or cavernous malformations that ultimately are amenable to surgical resection if detected on biopsy. However, occult cerebral amyloid angiopathy can also present similarly, and their management is markedly different. Methods We present a case of recurrent bilateral medial frontal hemorrhage in a patient without known cerebrovascular disease that evaded diagnosis despite hematologic evaluation, MRI, CTA, two DSAs, three clot evacuations with pathology, and brain biopsy. Results The patient is a 60‐year‐old previously healthy woman who presented with sudden onset right hemiparesis and speech arrest. CT revealed a left parasagittal hemorrhage. She was brought to the OR for clot evacuation. Pathology from the clot revealed blood vessels of multiple sizes consistent with meningeal vessels or underlying AVM/AVF. A 6‐vessel cerebral angiogram as unremarkable. The patient’s inpatient course was complicated by new onset Afib with RVR and asymptomatic DVT with PE, however no etiology of coagulopathy was detected. MRI brain showed no evidence of cerebral microbleed or other underlying pathology, noting only DWI + FLAIR hyperintensity in the left ACA territory. The patient was diagnosed with ACA territory stroke complicated by PH2‐type hemorrhagic conversion. She was initially placed on IV Heparin, before transition to apixaban uneventfully. She continued to recover in the hospital and was eventually discharged to rehab. She re‐presented 1 month later with worsening behavioral arrest and right hemiparesis. CT head revealed recurrence of left parasagittal ICH. She underwent clot evacuation in the OR again and repeat pathology was unrevealing. A repeat MRI showed only the evident bleed and a subtle hyperintensity in the right occipital cortex suspicious for an interval subacute occipital lobe stroke with laminar necrosis, ostensibly from Afib. She improved clinically and was discharged to rehab with a diagnosis of recurrent hemorrhage attributed to anticoagulant use and recent stroke. She was discharged this time on no anticoagulant or antiplatelets. She re‐presented 1 month later with sudden onset speech arrest, but now with left hemiparesis. CT revealed a right parasagittal hemorrhage. She was brought to the OR for emergent clot evacuation and parenchymal biopsy – which was initially normal. A repeat 6‐vessel DSA was again unremarkable as was repeat brain MRI. The patient’s parenchymal biopsy was sent for specific congo‐red and immunohistochemistry for beta‐amyloid. IHC revealed beta‐amyloid plaques in the parenchyma and vessel walls, confirming a diagnosis of CAA. Conclusion Apparently cryptogenic lobar hemorrhage may be caused by both occult micro‐AVM/fistula and CAA. As in this case, when a patient experiences recurrent DSA negative lobar hemorrhages, biopsy should be pursued. This case was particularly challenging given the anatomical plausibility of parasagittal AVM/fistula given its midline location and venous drainage, considering the patient’s evident predisposition to systemic venous thrombosis hemorrhagic venous infarction mimicking lobar ICH is also possible. We present this case to raise awareness of the potential need for early biopsy, especially in patients who may also require anticoagulation or antiplatelet medications.

A case of a systemic cancer-associated thrombosis successfully treated with multi-disciplinary treatment including anticoagulation therapy and anticancer drug therapy

Abstract Background Cancer-associated thrombosis (CAT) is one of the major complications during the treatment course of cancer, which often challenges clinicians in daily clinical practice despite anticoagulation therapy. Case summary A 57-year-old man with a history of a liver transplantation was diagnosed with post-transplant lymphoproliferative disorders. He developed severe systemic thromboses including a massive pulmonary embolism and was treated with anticoagulation therapy including a factor Xa inhibitor. However, the systemic thromboses worsened despite the anticoagulation therapy. During the acute treatment course of the thromboses, we administered anticancer drug therapy in hopes of an improvement in the activity of the cancer status leading to a favourable effect on the thrombosis status. Multi-disciplinary treatment including anticoagulation therapy and anticancer drug therapy successfully improved the systemic thrombosis. Discussion Anticoagulation therapy is a standard treatment for CAT; however, some cases of CAT do not successfully improve despite anticoagulation therapy, partly due to a highly active cancer status. Anticancer drug therapy might increase the risk of a thrombosis, whereas it could improve the activity of the cancer status leading to a decreased risk of a thrombosis. A multi-disciplinary therapy might be a reasonable option especially for CAT with a highly active cancer status.

Bothrops atrox and Bothrops lanceolatus Venoms In Vitro Investigation: Composition, Procoagulant Effects, Co-Factor Dependency, and Correction Using Antivenoms.

Bothrops venoms are rich in enzymes acting on platelets and coagulation. This action is dependent on two major co-factors, i.e., calcium and phospholipids, while antivenoms variably neutralize venom-related coagulopathy effects. Our aims were (i) to describe the composition of B. atrox and B. lanceolatus venoms; (ii) to study their activity on the whole blood using rotational thromboelastometry (ROTEM); (iii) to evaluate the contribution of calcium and phospholipids in their activity; and (iv) to compare the effectiveness of four antivenoms (Bothrofav™, Inoserp™ South America, Antivipmyn™ TRI, and PoliVal-ICP™) on the procoagulant activity of these two venoms. Venom composition was comparable. Both venoms exhibited hypercoagulant effects. B. lanceolatus venom was completely dependent on calcium but less dependent on phospholipids than B. atrox venom to induce in vitro coagulation. The four antivenoms neutralized the procoagulant activity of the two venoms; however, with quantitative differences. Bothrofav™ was more effective against both venoms than the three other antivenoms. The relatively similar venom-induced effects in vitro were unexpected considering the opposite clinical manifestations resulting from envenomation (i.e., systemic bleeding with B. atrox and thrombosis with B. lanceolatus). In vivo studies are warranted to better understand the pathophysiology of systemic bleeding and thrombosis associated with Bothrops bites.

Long-term prognostic significance of history of cancer and atrial fibrillation in coronary artery disease

BackgroundLimited data exist on the prognostic significance of a history of cancer and atrial fibrillation (AF) in patients with coronary artery disease (CAD). This study aimed to evaluate the associations among a history of cancer, AF, and long-term prognosis in patients with CAD. MethodsWe studied 3,233 patients with CAD (69 ± 11 years; women, 23%) in a multicenter hospital-based cohort study, the CHART-2 and related a history of cancer and AF to cardiovascular outcomes with a median follow-up of 10.8 years. ResultsOf the 3,233 patients enrolled, 10.7% and 11.2% had a history of cancer and AF, respectively, while 2.8% had both. Patients with AF and a history of cancer were characterized by older age, male sex, and higher BNP levels. Anticoagulant use with warfarin or direct oral anticoagulants increased from 43% at baseline to 56% at 10 years in patients with CAD with AF and no history of cancer and increased from 49% to 83% in those with both. Patients with CAD with both comorbidities had a higher risk of a composite outcome including stroke, thrombosis, and major bleeding (Hazard Ratio [HRadjusted], 2.26; 1.50–3.40, P < 0.001). Furthermore, patients with both comorbidities had a higher risk of all-cause death (1.55; 95% confidence interval [CI] 1.12–2.12, P = 0.007) including cancer death (2.62; 1.51–4.54, P = 0.001), and new-onset heart failure (HF) requiring hospitalization (2.47; 1.54–3.96, P < 0.001). ConclusionsThese results demonstrate that CAD patients with a history of cancer and AF have an increased risk of composite outcomes, including stroke, systemic thrombosis, major bleeding, all-cause death, cancer-related death, and new-onset HF.

Krebs von den Lungen-6 (KL-6) Levels in Post-COVID Follow-Up: Differences According to the Severity of COVID-19.

To evaluate KL-6 levels in medium-term post-COVID and to compare them in three groups categorised by the severity of COVID-19, we conducted a real-world, retrospective, cohort study. Data from the COVID-19 episode and follow-up during the post-COVID phase were extracted from the COVID@HULP and POSTCOVID@HULP databases, respectively. For the post-COVID period we included demographics, medical history, symptoms, quality of life, physical activity, anxiety and depression status and laboratory results. Patients were categorised into three groups based on the severity of COVID-19: Group 1 (inpatient critical), Group 2 (inpatient non-critical) and Group 3 (hospitalised at home). KL-6 was measured during the follow-up of the three groups. In all, 802 patients were included (Group 1 = 59; Group 2 = 296; Group 3 = 447 patients). The median age was 59 years (48-70), and 362 (45.2%) were males. At admission, fibrinogen and ferritin levels were lower in Group 3 than in the other groups (p < 0.001). Follow-up data were obtained 124 days (97-149) after the diagnosis of COVID-19. The median levels of fibrinogen, ferritin and KL-6 at follow-up were 336 mg/dL (276-413), 80.5 ng/mL (36-174.3) and 326 U/mL (240.3-440.3), respectively. KL-6 levels were lower in Group 3 than in the other groups (298 U/mL (231.5-398) vs. 381.5 U/mL (304-511.8) (Group 1) and 372 U/mL (249-483) (Group 2) (p < 0.001)). KL-6 was associated with ferritin (p < 0.001), fibrinogen (p < 0.001), D-dimer (p < 0.001) and gamma-glutamyl transferase (p < 0.001). KL-6 levels are less elevated at medium-term post-COVID follow-up in patients with mild COVID-19 than in those with moderate or severe disease. KL-6 is associated with systemic inflammatory, hepatic enzyme and thrombosis biomarkers.

Intratumoral thrombosis as a histological biomarker for predicting epidermal growth factor receptor alteration and poor prognosis in patients with glioblastomas.

Intratumoral thrombosis is a specific finding in glioblastomas and considered the origin of palisading necrosis. Its distribution and contribution to the glioblastoma pathophysiology and systemic thrombosis are obscure, although deep vein thrombosis is a common complication in glioblastoma cases. Clinicopathological and genetic analyses were performed on 97 glioblastoma tissue specimens to elucidate the role of thrombotic events and associated molecular abnormalities. Morphologically, intratumoral thrombosis was observed more frequently in vessels composed of single-layered CD34-positive endothelium and/or αSMA-positive pericytes in the tumor periphery, compared to microvascular proliferation with multi-channeled and pericyte-proliferating vessels in the tumor center. Intratumoral thrombosis was significantly correlated with the female sex, high preoperative D-dimer levels, and epidermal growth factor receptor (EGFR) amplification. The presence of one or more thrombi in 20 high-power fields was a predictive marker of EGFR amplification, with a sensitivity of 81.5% and specificity of 52.6%. RNA sequencing demonstrated that the group with many thrombi had higher EGFR gene expression levels than the group with few thrombi. The tumor cells invading along the vessels in the tumor periphery were positive for wild-type EGFR but negative for EGFRvIII, whereas the cells around the microvascular proliferation (MVP) in the tumor center were positive for both wild-type EGFR and EGFRvIII. Intratumoral thrombosis is an independent poor prognostic factor. Aberrant but exquisitely regulated EGFR can induce thrombosis in non-MVP vessels in the tumor invasion area and then promote palisading necrosis, followed by hypoxia, abnormal angiogenesis, and further tumor cell invasion.

Clinical significance of antinuclear antibodies in primary immune thrombocytopenia.

There are discrepancies across guidelines about whether the dosage of antinuclear antibodies (ANAs) is of use at the diagnosis of primary immune thrombocytopenia (ITP). This review describes the current knowledge about ANA prevalence in patients with primary ITP, and their potential usefulness as biomarkers for ITP evolution, response to treatments and increased risk of subsequent development of systemic lupus and thrombosis.

The Management of COVID-19-Related Coagulopathy: A Focus on the Challenges of Metabolic and Vascular Diseases.

The course of COVID-19 is highly dependent on the associated cardiometabolic comorbidities of the patient, which worsen the prognosis of coronavirus infection, mainly due to systemic inflammation, endothelium dysfunction, and thrombosis. A search on the recent medical literature was performed in five languages, using the PubMed, Embase, Cochrane, and Google Scholar databases, for the review of data regarding the management of patients with a high risk for severe COVID-19, focusing on the associated coagulopathy. Special features of COVID-19 management are presented, based on the underlying conditions (obesity, diabetes mellitus, and cardiovascular diseases), emphasizing the necessity of a modern, holistic approach to thromboembolic states. The latest findings regarding the most efficient therapeutic approaches are included in the article, offering guidance for medical professionals in severe, complicated cases of SARS-CoV-2 infection. We can conclude that severe COVID-19 is closely related to vascular inflammation and intense cytokine release leading to hemostasis disorders. Overweight, hyperglycemia, cardiovascular diseases, and old age are important risk factors for severe outcomes of coronavirus infection, involving a hypercoagulable state. Early diagnosis and proper therapy in complicated SARS-CoV-2-infected cases could reduce mortality and the need for intensive care during hospitalization in patients with cardiometabolic comorbidities.

Sepsis - it is all about the platelets.

Sepsis is accompanied by thrombocytopenia and the severity of the thrombocytopenia is associated with mortality. This thrombocytopenia is characteristic of disseminated intravascular coagulation (DIC), the sepsis-associated coagulopathy. Many of the pathogens, both bacterial and viral, that cause sepsis also directly activate platelets, which suggests that pathogen-induced platelet activation leads to systemic thrombosis and drives the multi-organ failure of DIC. In this paper we review the mechanisms of platelet activation by pathogens and the evidence for a role for anti-platelet agents in the management of sepsis.

Vagus nerve stimulation primes platelets and reduces bleeding in hemophilia A male mice

Deficiency of coagulation factor VIII in hemophilia A disrupts clotting and prolongs bleeding. While the current mainstay of therapy is infusion of factor VIII concentrates, inhibitor antibodies often render these ineffective. Because preclinical evidence shows electrical vagus nerve stimulation accelerates clotting to reduce hemorrhage without precipitating systemic thrombosis, we reasoned it might reduce bleeding in hemophilia A. Using two different male murine hemorrhage and thrombosis models, we show vagus nerve stimulation bypasses the factor VIII deficiency of hemophilia A to decrease bleeding and accelerate clotting. Vagus nerve stimulation targets acetylcholine-producing T lymphocytes in spleen and α7 nicotinic acetylcholine receptors (α7nAChR) on platelets to increase calcium uptake and enhance alpha granule release. Splenectomy or genetic deletion of T cells or α7nAChR abolishes vagal control of platelet activation, thrombus formation, and bleeding in male mice. Vagus nerve stimulation warrants clinical study as a therapy for coagulation disorders and surgical or traumatic bleeding.

Cell membrane derived liposomes loaded with DNase I target neutrophil extracellular traps which inhibits colorectal cancer liver metastases

Neutrophil extracellular traps (NETs) are web-like chromatin structures that are coated with granule proteins and trap microorganisms. However, NETs can damage the host tissue, contribute to the development of autoimmunity and lead to other dysfunctional outcomes in noninfectious diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), diabetes, atherosclerosis, vasculitis, thrombosis, and cancer. As a potential therapeutic approach, targeted ablation of neutrophil extracellular traps is of utmost importance for the treatment of NET-associated diseases. Here, the specific interaction between CCDC25 and NETs was exploited to produce biomimetic CCDC25-overexpressing cell membrane hybrid liposomes capable of targeting NETs in NET-associated diseases. The hybrid liposomes were constructed by fusing cell membrane nanovesicles derived from genetically engineered cells, which stably express CCDC25, and the resulting cell membrane hybrid liposomes exhibited enhanced affinity for NETs in two different NET-associated disease models. Furthermore, after encapsulation of DNase I in the liposomes, the nanoformulation efficiently eliminated NETs and significantly suppressed the recruitment of neutrophils. Overall, we present a bionic nanocarrier that specifically targets NETs in vivo and successfully inhibits colorectal cancer liver metastases; importantly, this could be a promising therapeutic approach for the treatment of NET-associated diseases.