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Inflammation
Published in George Feuer, Felix A. de la Iglesia, Molecular Biochemistry of Human Disease, 2020
George Feuer, Felix A. de la Iglesia
Fibrin in the blood clot is comparatively stable; under certain circumstances, however, it is lysed rapidly. The rapid lysis is not associated with increased proteolytic activity of the tissues or leukocytes, but it is the result of the activation of a proenzyme, the plasminogen activator in the blood itself. Plasminogen is converted to a proteolytic enzyme called plasmin or fibrinolysin. Plasminogen is present in the blood, in lymph, in some other body fluids and tissues, and in exudates in certain conditions. Plasminogen is a protein constituted as a single polypeptide chain with a molecular weight of 81,000 to 92,000 Da. Plasmin contains two chains connected by a disulfide bond, with a molecular weight of about 73,000 to 84,000. The conversion of plasminogen to plasmin due to the cleavage of a single bond resulting in the active molecule and the release of a peptide from the NH2-terminus of the molecule, weighing 8000 Da.379,382
Hyperfibrinolysis in Liver Cirrhosis
Published in Pia Glas-Greenwalt, Fibrinolysis in Disease Molecular and Hemovascular Aspects of Fibrinolysis, 2019
It can be concluded that several changes in fibrinolysis variables occur in liver cirrhosis. The historical studies already suggested an increase in plasminogen activator activity and a decreased inhibition of fibrinolysis in patients with liver disease. Recent studies have clearly identified the exact changes that occur in these patients: increase of t-PA and u-PA antigen, an increase of the concentration of PAI-1, and decreased levels of the main inhibitor of plasmin, α2-antiplasmin. In some patients the increase of plasminogen activators is not appropriately counterbalanced by an increase of plasminogen activator inhibitors. This might result in an increased overall fibrinolytic activity in some patients with liver cirrhosis, which makes them prone to bleeding complications.
Hereditary and Acquired Causes of a Hypercoagulable State
Published in Harold R. Schumacher, William A. Rock, Sanford A. Stass, Handbook of Hematologic Pathology, 2019
Commercially available assays for plasminogen are available, and plasminogen deficiency has been reported to be a cause of inherited thrombophilia. We rarely perform plasminogen testing, except in compelling cases of thrombophilia in which other more common defects are not identified.
The potential association between metabolic syndrome and risk of post-surgical adhesion
Published in Archives of Physiology and Biochemistry, 2023
Gordon A Ferns, Milad Shahini Shams Abadi, Mohammad-Hassan Arjmand
Adhesion formation is a part of the wound healing process in tissues after trauma and surgeries. Both inflammation and fibrin clot deposition are the main mechanisms during the early phase of the normal or pathological healing process. Briefly, a rapid immune response begins with local and circulating immune cells, secretion of pro-inflammatory cytokines, and the formation of a fibrin matrix are an important mechanism in normal healing (diZerega & Campeau 2001). The balance between fibrin matrix deposition and degradation, or fibrinolytic activity, is important. The coagulation cascade is activated in response to injury to blood vessels and inflammation in the traumatised area with increases the permeability of vessels to increase exudate fluid and flow more inflammatory cells to the site. Fibrin matrix gel is lysed within a few days by the fibrinolytic system (Buckman et al. 1976). Plasmin is responsible for a physiological fibrinolytic sequence that result from plasminogen activation by tissue plasminogen activator (tPA) (Holmdahl et al. 1996). After surgery, a decrease of tPA activity is associated with an increased susceptibility to adhesions (Sulaiman et al. 2002).
Tranexamic acid for the prevention and the treatment of primary postpartum haemorrhage: a systematic review
Published in Journal of Obstetrics and Gynaecology, 2022
Filippo Alberto Ferrari, Simone Garzon, Ricciarda Raffaelli, Antonella Cromi, Jvan Casarin, Fabio Ghezzi, Stefano Uccella, Massimo Franchi
TA has been extensively investigated for the treatment and prevention of bleeding during surgery and after traumatic events. The antifibrinolytic effect mediated by the inhibition of plasminogen activation in plasmin has been reported effective and safe in these two contexts (Ker et al. 2012; Roberts et al. 2013). Consistently, TA was declared effective in managing PPH after vaginal delivery and caesarean section, as demonstrated by the secondary outcomes of the WOMAN trial (Shakur et al. 2017). Mainly based on these trial results, the WHO updated the guidelines for the PPH management, adding the use of TA. In women with a clinical diagnosis of PPH, both after vaginal delivery and caesarean section (≥500 mL and ≥1,000 mL, respectively), the WHO recommends intravenously administer 1 g of TA in addition to the standard obstetric care, regardless of the cause of bleeding. If the bleeding persists after 30 minutes or restarts within 24 hours, the second dose of 1 g can be administered (Vogel et al. 2019). The WHO strongly suggests administering TA as soon as possible within the first three hours. Indeed, efficacy appears to decrease by 10% for every 15 min of delay, and with no reported benefit after three hours from delivery (Vogel et al. 2018). Conversely, although the adoption of TA for the management of PPH has been introduced in different guidelines (PBN 2017; PMPH 2017), the generalisability of the WOMAN trial and the degree of effect was considered uncertain by other guidelines and the use of TA is suggested when first-line medical treatment fails (PBN 2017; PMPH 2017).
Factors affecting the dynamics and heterogeneity of the EPR effect: pathophysiological and pathoanatomic features, drug formulations and physicochemical factors
Published in Expert Opinion on Drug Delivery, 2022
Rayhanul Islam, Hiroshi Maeda, Jun Fang
Plasminogen activators secreted by tumor cells are important in cancer metastasis, but they can serve as EPR effect enhancers, a strategy that Zhang et al. [61] reported. Plasminogen is responsible in fibrinolysis to break down fibrin gel or fibrin clots after activation to plasmin in tumor blood vessels, or in the vicinity of tumor or stromal tissues, thereby restoring and improving tumor blood flow and opening endothelial gaps. Thus, barriers are removed and drug penetration and accumulation in tumors are facilitated. Mei et al. [62] also developed a novel approach with plasminogen activator incorporated into a redox-responsive nanoparticle; they found marked drug accumulation in tumors by virtue of the EPR effect and at the same time observed tumor suppression via reactive oxygen species and cytokine modulation.