Thrombus Formation
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2021 ◽  
Vol 6 (4) ◽  
pp. 243-249
Tara Roshni Paul ◽  
Sobiya Mahnaz Ayesha ◽  
Shantveer G Uppin ◽  
Megha S Uppin

Non-granulomatous necrotizing lymphadenopathy (NGNL) is not a specific entity. It is seen in various conditions like Kikuchi-Fujimoto disease (KFD), Systemic Lupus Erythematosus (SLE), tuberculosis, lymphoma/metastasis and lymph node infarction. These conditions mimic each other histologically but it is necessary to identify the correct pathology as the treatment differs significantly. To highlight the subtle morphological features which lead to the etiological diagnosis in NGNL. The lymphnode biopsies (N=198), reported in our institute as NGNL, over 4½ year study period, were retrieved. Of these, the benign cases were 64 in total, with 40 cases of KFD and 8 cases of SLE. H&E, special stains and immunohistochemistry slides were reviewed by two pathologists. Histomorphological features like amount of necrosis, apoptotic debris, vasculitis, presence of neutrophils, eosinophils, histiocytes, plasma cells, hematoxylin bodies, Azzopardi phenomenon and thrombus formation were studied. Logistic regression analysis was performed to identify the most significant histopathological parameter with each disease. Kendall’s Tau matrix plot analysis was used to measure the correlation between the disease and the histopathologic variables. Features like vasculitis, hematoxylin bodies and Azzopardi phenomenon showed strong correlation with SLE and inverse correlation with KFD. Apoptotic debris, paucity of neutrophils and eosinophils had a strong positive association with KFD. The histological features help in differentiating the various entities associated with NGNL. It is necessary to correlate with clinical details and various laboratory parameters to reach a conclusive diagnosis because these conditions have varied treatment modalities.

Hoda Hatoum ◽  
Shelly Singh-Gryzbon ◽  
Fateme Esmailie ◽  
Philipp Ruile ◽  
Franz-Josef Neumann ◽  

2021 ◽  
Ylva Hedberg-Alm ◽  
Eva Tydén ◽  
Lena-Mari Tamminen ◽  
Lisa Lindström ◽  
Karin Anlén ◽  

Abstract Background: Peritonitis in horses secondary to non-strangulating infarction (NSII) has a grave prognosis, even after intestinal resection. In contrast, horses with idiopathic peritonitis respond well to medical treatment. Affected horses in both cases often show signs of both colic and systemic inflammation, but early diagnosis is crucial for optimal treatment and an accurate prognosis. One cause of NSII is thrombus formation secondary to Strongylus vulgaris larval migration. There has been a documented increase in S. vulgaris prevalence in Sweden since the implementation of selective anthelmintic treatment in 2007, which subsequently could result in a rise in NSII cases. In a retrospective clinical study, medical records from cases diagnosed with NSII or idiopathic peritonitis from three equine referral hospitals in Sweden during 2017-2020 were reviewed. Information including demographic data, relevant medical history, and clinical- and laboratory parameters were obtained from patient records. To facilitate the differentiation between cases of idiopathic peritonitis and cases with confirmed NSII, the aim of the study was to compare clinical and laboratory parameters, clinical progression and initial response to antimicrobial treatment as well as survival-rates.Results: Horses with NSII (n = 20) were significantly more likely to present during the winter months with a poorer response to medical treatment within 48 hours. Cases of idiopathic peritonitis (n = 115) had a 99.1 % survival rate with medical treatment. In comparison, all confirmed NSII cases were non-responsive to antimicrobial treatment and had a low survival rate (25%) with surgical treatment. Specific rectal findings and peripheral blood neutropenia were strongly associated with NSII. Conclusions: In Sweden, idiopathic peritonitis cases still predominate over S. vulgaris associated NSII cases and have an excellent survival rate with antimicrobial treatment. However, horses presenting with septic peritonitis during the winter months with a palpable rectal mass and continuing fever and colic signs beyond 48 hours of medical treatment are likely to suffer from NSII and should be considered for abdominal surgery.

2021 ◽  
Markus Brandhofer ◽  
Adrian Hoffmann ◽  
Xavier Blanchet ◽  
Elena Siminkovitch ◽  
Anne-Katrin Rohlfing ◽  

To fulfil their orchestrating function in immune cell trafficking in homeostasis and disease, a network of 49 chemokines and 23 receptors capitalizes on features of specificity, redundancy, and functional selectivity such as biased agonism. The discovery of the chemokine interactome, i.e. heteromeric chemokine-chemokine interactions, even across CC- and CXC-class borders, has further expanded the complexity within the network. Moreover, some inflammatory mediators, which are not structurally linked to classical CC-, CXC-, CX3C-, or C-chemokines, can bind to chemokine receptors and behave as atypical chemokines (ACKs). We identified the cytokine macrophage migration inhibitory factor (MIF) as an ACK that binds to the chemokine receptors CXCR2 and CXCR4 to promote atherogenic leukocyte recruitment. Here, we hypothesized that chemokine-chemokine interactions extend to ACKs and that MIF may form heterocomplexes with classical chemokines. We tested this hypothesis, applying an unbiased chemokine protein binding array. The platelet chemokine CXCL4L1, but not its variant CXCL4 or the CXCR2/CXCR4 ligands CXCL8 or CXCL12, was identified as a candidate interactor. MIF/CXCL4L1 complexation was verified by co-immunoprecipitation, surface plasmon-resonance analysis, and microscale thermophoresis, which also established high-affinity binding (KD=100-150 nM). The binding interface was predicted by peptide array-based mapping and molecular docking. We next determined whether heterocomplex formation modulates inflammatory and atherogenic activities of MIF. MIF-elicited T-cell chemotaxis as assessed in a 3D-matrix-based live cell-imaging set-up was abrogated, when cells were co-incubated with MIF and CXCL4L1. Heterocomplexation also blocked MIF-triggered migration of Egfp+ microglia in cortical cultures in situ. Of note, CXCL4L1 blocked the binding of Alexa-MIF to a soluble ectodomain mimic of CXCR4 and co-incubation with CXCL4L1 attenuated MIF-triggered dynamic mass redistribution in HEK293-CXCR4 transfectants, indicating that complex formation interferes with MIF/CXCR4 pathways. As MIF and CXCL4L1 are abundant platelet products, we finally tested their role in platelet activation. Multi-photon microscopy, FLIM-FRET, and proximity ligation assay visualized heterocomplexes in platelet aggregates and clinical human thrombus sections. Moreover, heterocomplex formation inhibited MIF-stimulated thrombus formation under flow and skewed the morphology of adhering platelets from a large to a small lamellipodia phenotype. Together, our study establishes a novel molecular interaction, adding to the complexity of the chemokine interactome and chemokine/receptor network. MIF/CXCL4L1, or more generally, ACK/CXC-motif chemokine heterocomplexes may be promising target structures to modulate inflammation and thrombosis.

2021 ◽  
Vol 8 (12) ◽  
pp. 161
Yukiharu Sugimura ◽  
Sebastian Bauer ◽  
Moritz Benjamin Immohr ◽  
Derik Franz Hermsen ◽  
Ralf Westenfeld ◽  

Despite the critical feature of heparin-induced thrombocytopenia (HIT) for patients on mechanical circulatory support, reports on its incidence and outcome are still scarce. Thus, we report on clinical features of HIT in patients under Impella 5.0 or 5.5 (Abiomed Inc., Danvers, MA, USA) (Impella 5+) support for acute cardiogenic shock (CS) by focusing on observed thrombotic events. Between November 2018 and December 2020, a total of 56 consecutive patients were enrolled in a single-center retrospective study. A total of 21 patients (37.5%) were tested for HIT, and 6 (10.7%) proved positive for HIT at 10.5 ± 2.89 days after the first heparin administration during current admission. Interestingly, thrombocyte counts dropped under Impella support in all groups (all cases, no HIT test, and HIT negative group: p < 0.001, HIT-positive group: p = 0.001). All HIT-positive patients were switched from heparin to argatroban. HIT-associated thrombotic events were observed in two cases resulting in Impella dysfunction due to pump thrombosis (n = 1) and left ventricular (LV) thrombus formation (n = 1). Under large Impella support, the prevalence of HIT was relatively high. Further, thrombocytopenia does not deliver a high specificity in the setting of Impella 5+ support. Considering HIT manifestation, a routine HIT test may be considered to avoid critical thrombotic adverse events.

2021 ◽  
Vol 11 (1) ◽  
Vanessa Göb ◽  
Maximilian G. Voll ◽  
Lena Zimmermann ◽  
Katherina Hemmen ◽  
Guido Stoll ◽  

AbstractIschemic stroke is among the leading causes of disability and death worldwide. In acute ischemic stroke, successful recanalization of occluded vessels is the primary therapeutic aim, but even if it is achieved, not all patients benefit. Although blockade of platelet aggregation did not prevent infarct progression, cerebral thrombosis as cause of secondary infarct growth has remained a matter of debate. As cerebral thrombi are frequently observed after experimental stroke, a thrombus-induced impairment of the brain microcirculation is considered to contribute to tissue damage. Here, we combine the model of transient middle cerebral artery occlusion (tMCAO) with light sheet fluorescence microscopy and immunohistochemistry of brain slices to investigate the kinetics of thrombus formation and infarct progression. Our data reveal that tissue damage already peaks after 8 h of reperfusion following 60 min MCAO, while cerebral thrombi are only observed at later time points. Thus, cerebral thrombosis is not causative for secondary infarct growth during ischemic stroke.

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Osayi Lawani ◽  
Edward Baptista

As an independent risk factor for stroke, atrial fibrillation has been shown to be associated with a fivefold increase in the cause of embolic stroke in comparison to healthy individuals without atrial fibrillation. This risk may be compounded by other factors; however, the main probable cause of stroke leading from atrial fibrillation is thrombus formation in the left atrial appendage. In patients for whom anticoagulation is contraindicated, left atrial appendage occlusion has become a leading alternative option for therapeutic prevention of thromboembolism and stroke in patients with this condition. Unfortunately, these devices (particularly the WATCHMAN) have been associated with a 3-6% incidence of intracardiac thrombus development postimplantation. Some risk factors for the development of device-related thrombus are high platelet count, permanent atrial fibrillation, resistance to clopidogrel, and prior transient ischemic attack or stroke. Despite following an anticoagulant regimen, thrombus formation was reported in 5.6% of participants of a randomized clinical trial, and further analysis showed that some of these patients continued to develop either ischemic stroke or thromboembolism five years later as compared to patients without initial thrombus development. We present a case of an elderly male with prior history of stroke and transient ischemic attack who developed a large device-related thrombus five months following WATCHMAN FLX™ implantation. Currently, there are no specific recommendations on the management of this rare complication; however, we discuss possible consideration of initially prolonging anticoagulation therapy following implantation for high-risk individuals, as there is an increased possibility for thrombus formation in this population. Management options should continue to be studied for therapeutic benefit in streamlining postprocedural therapy and improve future outcomes in the use of left atrial appendage occlusion devices, as well as continual thrombus prevention.

TH Open ◽  
2021 ◽  
Diana Adrienne Gorog ◽  
J. Yamamoto

Herein, we set out a rebuttal to the publication by Claveria and co-workers published in TH Open this month entitled “Global Thrombosis Test: Occlusion by Coagulation or SIPA?” We strongly believe that the conclusions of their paper, suggesting that occlusion (OT) in the Global Thrombosis Test (GTT) is due to coagulation, rather than shear-induced platelet thrombus formation, is incorrect and the evidence and arguments they present are fundamentally flawed, with major errors both in the experimental approach and in the interpretations of the results. The evidence which they demonstrate, shows that occlusion in the GTT is, in fact, caused by high shear induced platelet thrombus formations. We set out herein the evidence for that, based on histology of the thrombus from the GTT in earlier work using electron microscopy showing large platelet aggregates, the very brief timescale of OT in the GTT compared to coagulation time and the sensitivity of the OT in the GTT to the effects of heparin, t-PA and P2Y12 inhibitors. In addition, we revisit the known pathomechanism of high shear-mediated platelet aggregation to underpin our rationale and show that the modifications to the instrument proposed by Claveria and co-authors would render the technique unphysiological. We highlight several methodological concerns and apparent misinterpreted of the data obtained. We present evidence predominantly from the authors’ own data, together with our earlier published data and evidence from the literature, showing that occlusion in the GTT occurs do to shear-induced platelet aggregation.

2021 ◽  
Vol 11 (1) ◽  
Agata Rolnik ◽  
Bartosz Skalski ◽  
Anna Stochmal ◽  
Beata Olas

AbstractIncreased blood platelet activation plays an important role in cardiovascular diseases (CVDs). Recent experiments indicate that certain fruits and vegetables, including onion, garlic, and beetroot, have anti-platelet potential and therefore may reduce the likelihood of CVDs. While vegetables from the Cucuritaceae family are known to exerting beneficial antioxidant and anti-inflammatory effects, their effects on blood platelet activation are poorly understood. Therefore, the aim of the present study was to determine the effect on platelet adhesion of preparations from selected cucurbits: pumpkin (Cucurbita pepo; fruit without seeds), zucchini (Cucurbita pepo convar. giromontina; fruit with seeds), cucumber (Cucumis sativus; fruit with seeds), white pattypan squash (Cucurbita pepo var. patisoniana; fruit without seeds) and yellow pattypan squash (Cucurbita pepo var. patisoniana, fruit without seeds). It also evaluates the activity of these preparations on enzymatic lipid peroxidation in thrombin-activated washed blood platelets by TBARS assay. The study also determines the anti-platelet properties of these five cucurbit preparations in whole blood by flow cytometry and with the total thrombus-formation analysis system (T-TAS) and evaluates the cytotoxicity of the tested preparations against platelets based on LDH activity. The results indicate that the yellow Cucurbita pepo var. patisoniana preparation demonstrated stronger anti-platelet properties than the other tested preparations, reducing the adhesion of thrombin-activated platelets to collagen/fibrinogen, and inhibiting arachidonic acid metabolism and GPIIb/IIIa expression on 10 µM ADP-activated platelets. None of the preparations was found to cause platelet lysis. Our findings provide new information on the anti-platelet activity of the tested cucurbit preparations and their potential for treating CVDs associated with platelet hyperactivity.

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