The inflammatory response is a well-established part of, and a prerequisite for, venous thrombosis. To better understand the pathophysiology of venous thrombosis and to identify improved diagnostic biomarkers, further studies of the relationship between inflammation and coagulation are needed. We review previous studies concerning inflammatory biomarkers in venous thromboembolism, in particular cytokines, soluble adhesion molecules and matrix metalloproteases as predisposing, diagnostic and prognostic factors in venous thrombosis. Elevated cytokines and genetic alterations coding for cytokines are found in several patient cohorts which indicate that cytokines are involved as predisposing factors in venous thrombosis development. Increased levels of pro-inflammatory cytokines are detected both in animal models and in patients with acute venous thrombosis and clinical trials, although currently without evident diagnostic value. Adhesion molecules are crucial in the development of venous thrombosis, especially P-selectin seems important in initiating leukocyte accumulation and adhesion to endothelium for subsequent platelet accumulation. Several studies have demonstrated increased soluble P-selectin levels in patients with venous thrombosis, emphasizing its potential role as diagnostic marker and also as a therapeutic target. Matrix metalloproteases are essential effectors during venous thrombosis resolution and may impact vessel wall fibrosis, and together with their natural occurring inhibitors are crucial in acute and chronic thrombosis pathophysiology. Furthermore, studies in animal models of venous thrombosis have demonstrated anti-inflammatory treatment to be effective in terms of thrombus resolution and reduction of vessel wall damage, without increase in bleeding risk during the course of treatment. Thus, soluble mediators should be further investigated both as possible biomarkers and therapeutic targets in venous thromboembolic disease.
Acute myeloid leukemia (AML) is an aggressive bone marrow malignancy where the immature leukemia cells communicate with neighboring cells through constitutive cytokine release and through their cell surface adhesion molecules. The primary AML cells express various integrins. These heterodimeric molecules containing an α and a β chain are cell surface molecules that bind extracellular matrix molecules, cell surface molecules and soluble mediators. The β3 integrin (ITGB3) chain can form heterodimers only with the two α chains αIIb and αV. These integrins are among the most promiscuous and bind to a large number of ligands, including extracellular matrix molecules, cell surface molecules and soluble mediators. Recent studies suggest that the two β3 integrins are important for leukemogenesis and chemosensitivity in human AML. Firstly, αIIb and β3 are both important for adhesion of AML cells to vitronectin and fibronectin. Secondly, β3 is important for the development of murine AML and also for the homing and maintenance of the proliferation for xenografted primary human AML cells, and for maintaining a stem cell transcriptional program. These last effects seem to be mediated through Syk kinase. The β3 expression seems to be regulated by HomeboxA9 (HoxA9) and HoxA10, and the increased β3 expression then activates spleen tyrosine kinase (Syk) and thereby contributes to cytokine hypersensitivity and activation of β2 integrins. Finally, high integrin αV/β3 expression is associated with an adverse prognosis in AML and decreased sensitivity to the kinase inhibitor sorafenib; this integrin can also be essential for osteopontin-induced sorafenib resistance in AML. In the present article, we review the experimental and clinical evidence for a role of β3 integrins for leukemogenesis and chemosensitivity in AML.
Human papillomavirus (HPV) is associated with cervical intraepithelial neoplasia and cervical cancer. Vaccination against major oncogenic types of HPV has proven benefit in preventing these conditions. 1 HPV vaccines have been used for more than a decade, and their use is increasing worldwide. 2 Recently, a syndrome of thrombosis and thrombocytopenia occurring 5-24 days after vaccination with ChAdOx1 nCoV-19 (AstraZeneca) and Ad26.COV2.S (Johnson & Johnson), both recombinant adenoviral vector vaccines encoding the spike protein antigen of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was described. [3][4][5][6] This syndrome has been named vaccine-induced immune thrombotic thrombocytopenia (VITT) or
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