The association between human blood clot analogue computed tomography imaging, composition, contraction, and mechanical characteristics.

BACKGROUND: Clot composition, contraction, and mechanical properties are likely determinants of endovascular thrombectomy success. A pre-interventional estimation of these properties is hypothesized to aid in selecting the most suitable treatment for different types of thrombi. Here we determined the association between the aforementioned properties and computed tomography (CT) characteristics using human blood clot analogues. METHODS: Clot analogues were prepared from the blood of 4 healthy human donors with 5 red blood cell (RBC) volume suspensions: 0%, 20%, 40%, 60% and 80% RBCs. Contraction was measured as the weight of the contracted clots as a percentage of the original suspension. The clots were imaged using CT with and without contrast to quantify clot density and density increase. Unconfined compression was performed to determine the high strain compressive stiffness. The RBC content was analysed using H&E staining. RESULTS: The 5 RBC suspensions formed only two groups of clots, fibrin-rich (0% RBCs) and RBC-rich (>90% RBCs), as determined by histology. The density of the fibrin-rich clots was significantly lower (31-38HU) compared to the RBC-rich clots (72-89HU), and the density increase of the fibrin-rich clots was significantly higher (82-127HU) compared to the RBC-rich clots (3-17HU). The compressive stiffness of the fibrin-rich clots was higher (178-1624 kPa) than the stiffness of the RBC-rich clots (6-526 kPa). Additionally, the degree of clot contraction was higher for the fibrin-rich clots (89-96%) compared to the RBC-rich clots (11-77%). CONCLUSIONS: CT imaging clearly reflects clot RBC content and seems to be related to the clot contraction and stiffness. CT imaging might be a useful tool in predicting the thrombus characteristics. However, future studies should confirm these findings by analysing clots with intermediate RBC and platelet content.

Incidence and outcomes of thromboembolic and bleeding events in patients with liver cirrhosis in the USA.

BACKGROUND & AIMS: Understanding the epidemiology of bleeding and thromboembolism (clotting) in liver cirrhosis provides important data for future studies and policymaking; however, head-to-head comparisons of bleeding and clotting remain limited. METHODS: This is a populational retrospective cohort study using the US National Readmission Database of 2018 to compare the incidence and outcomes of bleeding and clotting events in patients with liver cirrhosis. The primary outcomes were the 11-month incidence proportion of bleeding and clotting events. RESULTS: Of 1 304 815 participants, 26 569 had liver cirrhosis (45.0% women, mean age 57.2 [SD, 12.7] years). During the 11-month follow-up, in patients with cirrhosis, for bleeding and clotting events, the incidence proportions was 15.3% and 6.6%; the risk-standardized all-cause mortality rates were 2.4% and 1.0%; the rates of intensive care intervention were 4.1% and 1.9%; the rates of rehabilitation transfer were .2% and .2%; the cumulative length of stays were 45 100 and 23 566 days; total hospital costs were 147 and 84 million US dollars; total hospital charges were 620 and 365 million US dollars. Compared to non-cirrhosis, liver cirrhosis was associated with higher rates of bleeding (adjusted hazard ratio, 3.02 [95% CI, 2.85-3.20]) and portal vein thrombosis (PVT) (18.46 [14.86-22.92]), and slightly lower risks of other non-PVT venous thromboembolic events (.82 [.75-.89]). CONCLUSIONS: Bleeding is more common than thromboembolism in patients with liver cirrhosis, causes higher morbidity, mortality and resource utilization. Liver cirrhosis is an independent risk factor for bleeding and PVT, but not non-PVT thromboembolism including venous thromboembolism, acute myocardial infarction and ischemic stroke.

Citrullination in the pathology of inflammatory and autoimmune disorders: recent advances and future perspectives.

Numerous post-translational modifications (PTMs) govern the collective metabolism of a cell through altering the structure and functions of proteins. The action of the most prevalent PTMs, encompassing phosphorylation, methylation, acylations, ubiquitination and glycosylation is well documented. A less explored protein PTM, conversion of peptidylarginine to citrulline, is the subject of this review. The process of citrullination is catalysed by peptidylarginine deiminases (PADs), a family of conserved enzymes expressed in a variety of human tissues. Accumulating evidence suggest that citrullination plays a significant role in regulating cellular metabolism and gene expression by affecting a multitude of pathways and modulating the chromatin status. Here, we will discuss the biochemical nature of arginine citrullination, the enzymatic machinery behind it and also provide information on the pathological consequences of citrullination in the development of inflammatory diseases (rheumatoid arthritis, multiple sclerosis, psoriasis, systemic lupus erythematosus, periodontitis and COVID-19), cancer and thromboembolism. Finally, developments on inhibitors against protein citrullination and recent clinical trials providing a promising therapeutic approach to inflammatory disease by targeting citrullination are discussed.

Doble vena cava inferior y enfermedad tromboembólica / Double inferior vena cava and thromboembolic disease

La doble vena cava inferior (DVCI) es una anomalía congénita poco frecuente, pero con grandes implicaciones clínicas en la planificación quirúrgica y el intraoperatorio de cirugías en las que se aborda el retroperitoneo, así como en la enfermedad tromboembólica.En la siguiente revisión se presenta el caso de una paciente de noventa años con enfermedad tromboembólica y doble vena cava inferior.

Double inferior vena cava (DIVC) is a rare congenital anomaly, but with great clinical implications, both in the surgical and intraoperative planning of surgeries where the retroperitoneum is approached, as well as in thromboembolic disease.In the following report and review, a case of a 90-year-old patient with thromboembolic disease and DIVC is presented.

Endothelial dysfunction and thromboembolism in children, adolescents, and young adults with acute lymphoblastic leukemia.

Endothelial dysfunction has not previously been investigated as a thrombogenic risk factor among patients with acute lymphoblastic leukemia (ALL), known to be at high risk of thromboembolism. We retrospectively explored the association between three circulating biomarkers of endothelial dysfunction (thrombomodulin, syndecan-1, VEGFR-1) measured in prospectively collected blood samples and risk of thromboembolism in 55 cases and 165 time-matched controls, treated according to the NOPHO ALL2008 protocol. In age-, sex-, and risk group-adjusted analysis, increasing levels of thrombomodulin and VEGFR-1 were independently associated with increased odds of developing thromboembolism (OR 1.37 per 1 ng/mL [95% CI 1.20‒1.56, P < 0.0001] and OR 1.21 per 100 pg/mL [95% CI 1.02‒1.21, P = 0.005], respectively). These associations remained significant when including only samples drawn >30 days before thromboembolic diagnosis. Thrombomodulin levels were on average 3.2 ng/mL (95% CI 2.6-8.2 ng/mL) higher in samples with measurable asparaginase activity (P < 0.0001). Among single nucleotide variants located in or neighboring coding genes for the three biomarkers, none were significantly associated with odds of thromboembolism. If results are validated in another cohort, thrombomodulin and VEGFR-1 could serve as predictive biomarkers, identifying patients in need of preemptive antithrombotic prophylaxis.

Risk assessment and prognostic analysis of patients with splenic infarction in emergency department: a multicenter retrospective study.

Splenic infarction is a thromboembolic disease that is frequently missed in acute settings. Previous reviews were rarely presented from a clinical perspective. We aimed to evaluate the clinical characteristics, risk factors with diagnostic value, and prognostic factors using large cohort data and a matched case-control study method. A retrospective medical record review of six hospitals in Taiwan from January 1, 2005, to August 31, 2020, was conducted. All patients who underwent contrast CT with confirmed the diagnosis of splenic infarction were included. Their characteristics were presented and compared to a matched control group with similar presenting characteristics. Prognostic factors were also analyzed. A total of 130 cases were included, two-thirds of whom presented with abdominal pain. Atrial fibrillation was the most common associated predisposing condition, followed by hematologic disease. A higher proportion of tachycardia, positive qSOFA score, history of hypertension or atrial fibrillation, leukocytosis, and thrombocytopenia were found in splenic infarction patients compared to their counterparts. An underlying etiology of infective endocarditis was associated with a higher proportion of ICU admission. Splenic infarction patients often presented with left upper abdominal pain and tachycardia. A history of hypertension, atrial fibrillation, a laboratory result of leukocytosis or thrombocytopenia may provide a clue for clinicians to include splenic infarction in the differential list. Among the patients diagnosed with splenic infarction, those with an underlying etiology of infectious endocarditis may be prone to deterioration or ICU admission.

High Mobility Group Box 1 Protein in Cerebral Thromboemboli.

High-mobility group box 1 protein (HMGB1) is a damage-associated molecular pattern (DAMP) involved in neutrophil extracellular trap (NET) formation and thrombosis. NETs are regularly found in cerebral thromboemboli. We here analyzed associated HMGB1 expression in human thromboemboli retrieved via mechanical thrombectomy from 37 stroke patients with large vessel occlusion. HMGB1 was detected in all thromboemboli, accounting for 1.7% (IQR 0.6-6.2%) of the total thromboemboli area and was found to be colocalized with neutrophils and NETs and in spatial proximity to platelets. Correlation analysis revealed that the detection of HMGB1 was strongly related to the number of neutrophils (r = 0.58, p = 0.0002) and platelets (r = 0.51, p = 0.001). Our results demonstrate that HMGB1 is a substantial constituent of thromboemboli causing large vessel occlusion stroke.

Therapeutic efficacy of direct oral anticoagulants and vitamin K antagonists for left ventricular thrombus: Systematic review and meta-analysis.

BACKGROUND: Although several meta-analyses have compared efficacies of vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs) for treatment of left ventricular thrombus (LVT), those meta-analyses included no single-arm studies. METHODS AND RESULTS: PubMed, Scopus, and the Cochrane Library databases were searched for articles investigating thrombus resolution, stroke, any thromboembolism, major bleeding, any bleeding, or all-cause death in LVT treated with VKAs or DOACs, and single-class meta-analyses were also included (PROSPERO database, CRD42021230849). Event rates were pooled using a random effects model. Meta-regression analysis was performed to explore factors that may influence outcomes. 2,612 patients from 23 articles were included (VKAs: 2,004, DOACs: 608). There were no significant differences between VKAs and DOACs in the frequency of thrombus resolution (VKAs: 0.75 [95% confidence interval; 0.67 to 0.81], DOACs: 0.75 [0.67 to 0.82]), stroke (VKAs: 0.06 [0.04 to 0.10], DOACs: 0.02 [0.01 to 0.01]), any thromboembolism (VKAs: 0.08 [0.05 to 0.13], DOACs: 0.03 [0.01 to 0.10]), major bleeding (VKAs: 0.06 [0.04 to 0.09], DOACs: 0.03 [0.01 to 0.06]), any bleeding (VKAs: 0.08 [0.05 to 0.12], DOACs: 0.08 [0.06 to 0.10]), and all-cause death (VKAs: 0.07 [0.04 to 0.13], DOACs: 0.09 [0.05 to 0.16]). Meta-regression analysis revealed that increased duration of follow-up was associated with lower-rates of stroke (estimate: -0.040, p = 0.0495) with VKAs, but not with DOACs. There was significant publication bias for thrombus resolution, stroke, any thromboembolism, any bleeding, and all-cause death. CONCLUSIONS: Efficacy and adverse outcomes of therapy with DOACs and VKAs do not differ. Randomized controlled trials are needed to determine the optimal anticoagulant strategy.

Pseudoginsenoside-F11 ameliorates thromboembolic stroke injury in rats by reducing thromboinflammation.

Pseudoginsenoside-F11 (PF11), an ocotillol-type ginsenoside, has been reported to exert neuroprotective effects on ischemic stroke induced by permanent and transient middle cerebral artery occlusion in experimental animals. The aim of the present study was to investigate the effect of PF11 on thromboembolic stroke in rats and its possible mechanisms on thromboinflammation. PF11 (4, 12, 36 mg/kg) was injected intravenously (i.v.) once a day for 3 consecutive days to male Wistar rats followed by embolic middle cerebral artery occlusion (eMCAO). The results showed that PF11 significantly reduced the cerebral infarction volume, brain edema and neurological deficits induced by eMCAO. Meanwhile, the thromboinflammation in the ischemic hemisphere was observed at 24 h after eMCAO, as indicated by the increased number of microvascular thrombus and inflammatory response. Moreover, eMCAO resulted in the up-regulation of platelet glycoprotein Ibα (GPIbα) and VI (GPVI), as well as the activation of contact-kinin pathway. Notably, PF11 significantly reversed all these changes. Furthermore, PF11 prevented the eMCAO-induced loss of tight junction proteins and up-regulation of matrix metalloproteinase-9 (MMP-9), thus leading to the alleviation of blood-brain barrier (BBB) damage. In conclusion, the present study revealed that thromboinflammation was induced in the ischemic hemisphere of rats after eMCAO and PF11 exerted marked protective effects against thromboembolic stroke by attenuating thromboinflammation and preventing BBB damage. This research further identifies the potential therapeutic role of PF11 for ischemic stroke.

Viscoelastic testing reveals normalization of the coagulation profile 12 weeks after severe COVID-19.

COVID 19 is associated with a hypercoagulable state and frequent thromboembolic complications. For how long this acquired abnormality lasts potentially requiring preventive measures, such as anticoagulation remains to be delineated. We used viscoelastic rotational thrombelastometry (ROTEM) in a single center cohort of 13 critical ill patients and performed follow up examinations three months after discharge from ICU. We found clear signs of a hypercoagulable state due to severe hypofibrinolysis and a high rate of thromboembolic complications during the phase of acute illness. Three month follow up revealed normalization of the initial coagulation abnormality and no evidence of venous thrombosis in all thirteen patients. In our cohort the coagulation profile was completely normalized three months after COVID-19. Based on these findings, discontinuation of anticoagulation can be discussed in patients with complete venous reperfusion.

Cause of death based on systematic post-mortem studies in patients with positive SARS-CoV-2 tissue PCR during the COVID-19 pandemic.

IMPORTANCE: Assessment of the causative association between the COVID-19 and cause of death has been hampered by limited availability of systematically performed autopsies. We aimed to present autopsy-confirmed causes of death in patients who died with COVID-19 and to assess the association between thrombosis and diffuse alveolar damage consistent with COVID-19 (DAD). METHODS: Consecutive forensic (n = 60) and clinical (n = 42) autopsies with positive post-mortem SARS-CoV-2 PCR in lungs (age 73 ± 14 years, 50% men) were included. The cause of death analysis was based on a review of medical records and histological reports. Thrombotic phenomena in lungs were defined as pulmonary thromboembolism (PE), thrombosis in pulmonary artery branches or microangiopathy in capillary vessels. RESULTS: COVID-19 caused or contributed to death in 71% of clinical and 83% of forensic autopsies, in whom significant DAD was observed. Of the patients with COVID-19 as the primary cause of death, only 19% had no thrombotic phenomena in the lungs, as opposed to 38% amongst those with COVID-19 as a contributing cause of death and 54% amongst patients whose death was not related to COVID-19 (p = 0.002). PE was observed in 5 patients. Two patients fulfilled the criteria for lymphocyte myocarditis. CONCLUSIONS: Vast majority of all PCR-positive fatalities, including out-of-hospital deaths, during the SARS-CoV-2 pandemic were related to DAD caused by COVID-19. Pulmonary artery thrombosis and microangiopathy in pulmonary tissue were common and associated with the presence of DAD, whilst venous PE was rarely observed. Histology-confirmed lymphocyte myocarditis was a rare finding.

Aberrant cytokine expression in COVID-19 patients: Associations between cytokines and disease severity.

Cytokines play pleiotropic, antagonistic, and collaborative in viral disease. The high morbidity and mortality of coronavirus disease 2019 (COVID-19) make it a significant threat to global public health. Elucidating its pathogenesis is essential to finding effective therapy. A retrospective study was conducted on 71 patients hospitalized with COVID-19. Data on cytokines, T lymphocytes, and other clinical and laboratory characteristics were collected from patients with variable disease severity. The effects of cytokines on the overall survival (OS) and event-free survival (EFS) of patients were analyzed. The critically severe and severe patients had higher infection indexes and significant multiple organ function abnormalities than the mild patients (P < 0.05). IL-6 and IL-10 were significantly higher in the critically severe patients than in the severe and mild patients (P < 0.05). IL-6 and IL-10 were closely associated with white blood cells, neutrophils, T lymphocyte subsets, D-D dimer, blood urea nitrogen, complement C1q, procalcitonin C-reactive protein. Moreover, the IL-6 and IL-10 levels were closely correlated to dyspnea and dizziness (P < 0.05). The patients with higher IL-10 levels had shorter OS than the group with lower levels (P < 0.05). The older patients with higher levels of single IL-6 or IL-10 tended to have shorter EFS (P < 0.05), while the patients who had more elevated IL-6 and IL-10 had shorter OS (P < 0.05). The Cox proportional hazard model revealed that IL-6 was the independent factor affecting EFS. IL-6 and IL-10 play crucial roles in COVID-19 prognosis.

The Inflammatory Profile of CTEPH-Derived Endothelial Cells Is a Possible Driver of Disease Progression.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a form of pulmonary hypertension characterized by the presence of fibrotic intraluminal thrombi and causing obliteration of the pulmonary arteries. Although both endothelial cell (EC) dysfunction and inflammation are linked to CTEPH pathogenesis, regulation of the basal inflammatory response of ECs in CTEPH is not fully understood. Therefore, in the present study, we investigated the role of the nuclear factor (NF)-κB pro-inflammatory signaling pathway in ECs in CTEPH under basal conditions. Basal mRNA levels of interleukin (IL)-8, IL-1ß, monocyte chemoattractant protein-1 (MCP-1), C-C motif chemokine ligand 5 (CCL5), and vascular cell adhesion molecule-1 (VCAM-1) were upregulated in CTEPH-ECs compared to the control cells. To assess the involvement of NF-κB signaling in basal inflammatory activation, CTEPH-ECs were incubated with the NF-κB inhibitor Bay 11-7085. The increase in pro-inflammatory cytokines was abolished when cells were incubated with the NF-κB inhibitor. To determine if NF-κB was indeed activated, we stained pulmonary endarterectomy (PEA) specimens from CTEPH patients and ECs isolated from PEA specimens for phospho-NF-κB-P65 and found that especially the vessels within the thrombus and CTEPH-ECs are positive for phospho-NF-κB-P65. In summary, we show that CTEPH-ECs have a pro-inflammatory status under basal conditions, and blocking NF-κB signaling reduces the production of inflammatory factors in CTEPH-ECs. Therefore, our results show that the increased basal pro-inflammatory status of CTEPH-ECs is, at least partially, regulated through activation of NF-κB signaling and potentially contributes to the pathophysiology and progression of CTEPH.

Histopathologic Evaluation of COVID-19 Patients With Peripheral Arterial Thromboembolism: Does Clot Composition Make Any Sense?

BACKGROUND: Coronavirus disease 2019 (COVID-19) causes thromboembolic complications during or post-infection period despite a lack of conventional risk factors. The study aims to learn fundamental changes in COVID-19 patients who underwent embolectomy in terms of clinical characteristics and clot composition. METHODS: In a retrospective cohort study design, we evaluated 21 patients who underwent embolectomy in our clinic between March 12, 2020, and December 31, 2020. Demographics, characteristics, and laboratory values were abstracted and analyzed. Histopathological assessment was held in the pathology department. RESULTS: Of these 21 patients, 11 (52.3%) were SARS-CoV-2 positive and 10 (47.6%) were SARS-CoV-2 negative. There is no statistical difference in terms of anatomic distribution, diagnostic method, length of hospital stay, amputation or mortality levels. Thromboembolic material of COVID-19 patients include significantly less red blood cell (RBC) (21.2-32.6%; P= 0.01), more lymphocyte (14.1-2.6%; P< 0.001), and more leukocyte (27.1-22.1%; P= 0.05). There was no statistical difference between the fibrin ratio. CONCLUSIONS: Inflammatory cells are prominent in arterial thromboembolic material of COVID-19 patients. A combination of hyperinflammation and prothrombotic status may be responsible for this phenomenon.

Thromboembolic Adverse Drug Reactions in Janus Kinase (JAK) Inhibitors: Does the Inhibitor Specificity Play a Role?

Recent advances in immunology enabled the characterization of several signal transmitting pathways responsible for proper cytokine and chemokine signaling. Among them, Janus kinases (JAKs) are essential components of receptor activation systems. The discovery of JAK kinases enabled the synthesis of JAK kinase inhibitors (JAKi or Jakinibs), which have proven to be efficacious in the treatment of hematologic malignancies and several rheumatological disorders and continue to be investigated in many clinical indications. Blocking multiple cytokines belonging to several cytokine families with a single small molecule may, however, create a potential risk for the patients. Recently, a higher risk of thromboembolic complications, namely, deep vein thrombosis and pulmonary embolism, has been recognized as the main concern during treatment with Jakinibs. At present, it is not entirely clear whether this increased risk is related to direct cytokine blockade, the presence of concomitant diseases in treated patients or other unknown circumstances that work together to increase the risk of this side effect. In this review, we discuss data on the risk of thromboembolic side effects, with special emphasis on the mechanism that may be responsible for this increased risk. Many indirect data indicate that higher thromboembolic risk may be related to the specificity of JAK inhibitor action, such that preferentially blocking one signaling pathway upsets the balance between pro and anti-thrombotic activities.

Obesity in women: anaesthetic implications for peri-operative and peripartum management.

The prevalence, healthcare and socio-economic impact of obesity (defined as having a body mass index of ≥ 30 kg.m-2 ) are disproportionately higher in women than men. A combination of biological and social factors, including the adaptation of energy homeostasis to the increased demands of pregnancy and lactation and poor access to healthy foods or exercise facilities, contribute to the increasing prevalence of obesity in women. Obesity-related physiological changes stem from mass loading and increased metabolism of adipose tissue, as well as secretion of bioactive substances from adipocytes leading to chronic low-grade inflammation. As a result, obesity is associated with increased risks of: infertility; malignancy; sleep-disordered breathing; cardiovascular disease; diabetes; and thromboembolism. Hence, obese women are at markedly increased risk of peri-operative morbidity and mortality and require comprehensive evaluation and targeted comorbidity optimisation by a multidisciplinary team. In addition to routine obstetric challenges, pregnancy in women with obesity further exacerbates the above risks, making multidisciplinary management starting at pre-conception even more important. Weight loss, lifestyle management and optimisation of comorbidity are the cornerstone of reducing obesity-related risks. The anaesthetist plays a vital role within the multidisciplinary team by emphasising weight loss as part of pre-operative comorbidity optimisation, formulation of individualised peri-operative management plans, supervising postoperative care in the high dependency or intensive care settings and providing safe labour analgesia and careful peripartum management for obese parturients.

Protein network analyses of pulmonary endothelial cells in chronic thromboembolic pulmonary hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a vascular disease characterized by the presence of organized thromboembolic material in pulmonary arteries leading to increased vascular resistance, heart failure and death. Dysfunction of endothelial cells is involved in CTEPH. The present study describes for the first time the molecular processes underlying endothelial dysfunction in the development of the CTEPH. The advanced analytical approach and the protein network analyses of patient derived CTEPH endothelial cells allowed the quantitation of 3258 proteins. The 673 differentially regulated proteins were associated with functional and disease protein network modules. The protein network analyses resulted in the characterization of dysregulated pathways associated with endothelial dysfunction, such as mitochondrial dysfunction, oxidative phosphorylation, sirtuin signaling, inflammatory response, oxidative stress and fatty acid metabolism related pathways. In addition, the quantification of advanced oxidation protein products, total protein carbonyl content, and intracellular reactive oxygen species resulted increased attesting the dysregulation of oxidative stress response. In conclusion this is the first quantitative study to highlight the involvement of endothelial dysfunction in CTEPH using patient samples and by network medicine approach.

Thromboembolic involvement and its possible pathogenesis in COVID-19 mortality: lesson from post-mortem reports.

The emergence of Coronavirus Disease 19 (COVID-19) as a pandemic has claimed hundreds of thousands of lives worldwide since its initial breakout. With increasing reports from clinical observations and autopsy findings, it became clear that the disease causes acute respiratory distress syndrome (ARDS), as well as a broad spectrum of systemic and multiorgan pathologies, including angiopathy, endothelialitis, and thrombosis. Coagulopathy is associated with the activity of megakaryocytes, which play crucial roles in modulating the platelet homeostasis. Only a few autopsy reports include findings on thrombosis formation and the presence of megakaryocytes. Here we review and summarize the possible involvement and the pathophysiology of the thromboembolic events in COVID-19 patients based on post-mortem reports. We reviewed post-mortem reports from March 2020 to September 2020. Eleven autopsy reports that demonstrated thromboembolic involvement findings, either macroscopically or microscopically, were included in this review. All studies reported similar pulmonary gross findings. Not all studies described thrombi formation and megakaryocyte findings. Pulmonary embolism, coagulopathy, severe endothelial injury, and widespread thrombosis are frequent in COVID-19 patients, following many patients with high-level D-Dimer, increased fibrinogen, abnormal prothrombic coagulation, and thrombocytopenia. Reports showed that thrombus was also found in the lower extremities' deep veins and the prostatic venous plexus. In conclusion, a complex interaction of SARS-CoV-2 virus invasion with platelets, leukocytes, endothelial cells, inflammation, immune response, and the possible involvement of megakaryocytes may increase the cumulative risk of thrombosis by a yet unclear cellular and humoral interaction.

Risk of postpolypectomy bleeding in patients taking direct oral anticoagulants or clopidogrel.

The usage of direct oral anticoagulants (DOACs) to prevent and treat thromboembolic events is gradually increasing. We aimed to evaluate the outcomes of patients taking DOACs after polypectomy. We retrospectively reviewed 131 patients taking DOACs and 270 taking clopidogrel who underwent polypectomy between November 2010 and December 2017. The risk of delayed postpolypectomy bleeding (PPB) was evaluated and compared. A total of 989 polyps were removed (320 polyps in the DOAC and 669 polyps in the clopidogrel group). DOACs and clopidogrel were discontinued for 2.8 ± 1.7 days and 5.8 ± 2.5 days before polypectomy, respectively. DOACs and clopidogrel were restarted on 1.6 ± 2.9 days and 1.7 ± 1.1 days after polypectomy, respectively. According to per polyp analysis, delayed PPB rate was 1.6% in both groups (p = 0.924). Logistic regression analysis was performed after propensity score matching and revealed that DOACs did not increase the delayed PPB risk compared to clopidogrel (OR 0.929, 95% CI 0.436-1.975, p = 0.847). With the majority following the antithrombotic discontinuation guidelines, the incidence of delayed PPB was 3.1% in the patients taking DOACs. The delayed PPB risk was not greater in those taking DOACs than in those taking clopidogrel.

Acute and Life-threatening Complications in Cushing Syndrome: Prevalence, Predictors, and Mortality.

CONTEXT: Cushing syndrome (CS) results in significant morbidity and mortality. OBJECTIVE: To study acute and life-threatening complications in patients with active CS. METHODS: We performed a retrospective cohort study using inpatient and outpatient records of patients with CS in a tertiary center. A total of 242 patients with CS were included, including 213 with benign CS (pituitary n = 101, adrenal n = 99, ectopic n = 13), and 29 with malignant disease. We collected acute complications necessitating hospitalization, from appearance of first symptoms of hypercortisolism until 1 year after biochemical remission. Mortality data were obtained from the national registry. Baseline factors relating to and predicting acute complications were tested using uni- and multivariate analysis. RESULTS: The prevalence of acute complications was 62% in patients with benign pituitary CS, 40% in patients with benign adrenal CS, and 100% in patients with ectopic CS. Complications observed in patients with benign CS included infections (25%), thromboembolic events (17%), hypokalemia (13%), hypertensive crises (9%), cardiac arrhythmias (5%), and acute coronary events (3%). Among these patients, 23% had already been hospitalized for acute complications before CS was suspected, and half of complications occurred after the first surgery. Glycated hemoglobin (HbA1c) and 24-hour urinary free cortisol positively correlated with the number of acute complications per patient. Patients with malignant disease had significantly higher rates of acute complications. Mortality during the observation period was 2.8% and 59% in benign and malignant CS, respectively. CONCLUSIONS: This analysis highlights the whole spectrum of acute and life-threatening complications in CS, and their high prevalence even before disease diagnosis and after successful surgery.