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      Hypercoagulable state in patients with schizophrenia: different effects of acute and chronic antipsychotic medications

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          Abstract

          Background:

          Previous studies reported higher incidences of venous thromboembolism and cardiovascular disease in schizophrenia patients and higher indicators of thrombosis, thrombocyte activation, and platelet dysfunction.

          Objectives:

          To check if first-episode schizophrenia (FES) patients have a hypercoagulable state and determine whether acute and chronic antipsychotics have the same effect on blood coagulation or fibrinolysis-related biomarkers.

          Design:

          Case-control study.

          Methods:

          A total of 81 participants were grouped in FES, chronic schizophrenia (CS), and healthy controls (HCs). In addition to demographic data and clinical characteristics, immunological analyses were performed to measure plasma levels of D-dimer, plasminogen activator inhibitor-1 (PAI-1), soluble P selectin (sP-sel), tissue plasminogen activator (tPA), thrombotic precursor protein (TpP), and von Willebrand’s disease factor (vWF).

          Results:

          Compared to HC group, FES patients showed higher PAI-1 (28.61 ng/ml versus 15.69 ng/ml), sP-sel (2.78 ng/ml versus 1.18 ng/ml), and TpP (15.61 µg/ml versus 5.59 µg/ml) along with a higher PAI-1/tPA (3.12 versus 2.00). Acute antipsychotic medication reduced higher PAI-1 (28.61 → 21.99), sP-sel (2.78 → 1.87), tPA (9.59 → 5.83), TpP (15.61 → 10.54), and vWF (383.18 → 291.08) in FES patients. However, plasma sP-sel and vWF in CS patients returned to the pre-treatment levels in FES patients, and PAI-1/tPA significantly decreased compared to FES patients.

          Conclusion:

          These results suggest a hypercoagulable state in FES patients and demonstrate contrast effects of acute and chronic antipsychotics on coagulation or fibrinolysis in schizophrenia patients.

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          Most cited references46

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          Excess early mortality in schizophrenia.

          Schizophrenia is often referred to as one of the most severe mental disorders, primarily because of the very high mortality rates of those with the disorder. This article reviews the literature on excess early mortality in persons with schizophrenia and suggests reasons for the high mortality as well as possible ways to reduce it. Persons with schizophrenia have an exceptionally short life expectancy. High mortality is found in all age groups, resulting in a life expectancy of approximately 20 years below that of the general population. Evidence suggests that persons with schizophrenia may not have seen the same improvement in life expectancy as the general population during the past decades. Thus, the mortality gap not only persists but may actually have increased. The most urgent research agenda concerns primary candidates for modifiable risk factors contributing to this excess mortality, i.e., side effects of treatment and lifestyle factors, as well as sufficient prevention and treatment of physical comorbidity.
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            Biochemistry and genetics of von Willebrand factor.

            J Sadler (1998)
            Von Willebrand factor (VWF) is a blood glycoprotein that is required for normal hemostasis, and deficiency of VWF, or von Willebrand disease (VWD), is the most common inherited bleeding disorder. VWF mediates the adhesion of platelets to sites of vascular damage by binding to specific platelet membrane glycoproteins and to constituents of exposed connective tissue. These activities appear to be regulated by allosteric mechanisms and possibly by hydrodynamic shear forces. VWF also is a carrier protein for blood clotting factor VIII, and this interaction is required for normal factor VIII survival in the circulation. VWF is assembled from identical approximately 250 kDa subunits into disulfide-linked multimers that may be > 20,000 kDa. Mutations in VWD can disrupt this complex biosynthetic process at several steps to impair the assembly, intracellular targeting, or secretion of VWF multimers. Other VWD mutations impair the survival of VWF in plasma or the function of specific ligand binding sites. This growing body of information about VWF synthesis, structure, and function has allowed the reclassification of VWD based upon distinct pathophysiologic mechanisms that appear to correlate with clinical symptoms and the response to therapy.
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              Is Open Access

              Chronic Inflammation in Obesity and the Metabolic Syndrome

              The increasing incidence of obesity and the metabolic syndrome is disturbing. The activation of inflammatory pathways, used normally as host defence, reminds the seriousness of this condition. There is probably more than one cause for activation of inflammation. Apparently, metabolic overload evokes stress reactions, such as oxidative, inflammatory, organelle and cell hypertrophy, generating vicious cycles. Adipocyte hypertrophy, through physical reasons, facilitates cell rupture, what will evoke an inflammatory reaction. Inability of adipose tissue development to engulf incoming fat leads to deposition in other organs, mainly in the liver, with consequences on insulin resistance. The oxidative stress which accompanies feeding, particularly when there is excessive ingestion of fat and/or other macronutrients without concomitant ingestion of antioxidant-rich foods/beverages, may contribute to inflammation attributed to obesity. Moreover, data on the interaction of microbiota with food and obesity brought new hypothesis for the obesity/fat diet relationship with inflammation. Beyond these, other phenomena, for instance psychological and/or circadian rhythm disturbances, may likewise contribute to oxidative/inflammatory status. The difficulty in the management of obesity/metabolic syndrome is linked to their multifactorial nature where environmental, genetic and psychosocial factors interact through complex networks.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: MethodologyRole: Project administrationRole: Writing – original draft
                Role: InvestigationRole: Methodology
                Role: InvestigationRole: Project administration
                Role: ConceptualizationRole: Data curationRole: Project administrationRole: Supervision
                Role: ConceptualizationRole: SupervisionRole: ValidationRole: Writing – review & editing
                Journal
                Ther Adv Psychopharmacol
                Ther Adv Psychopharmacol
                TPP
                sptpp
                Therapeutic Advances in Psychopharmacology
                SAGE Publications (Sage UK: London, England )
                2045-1253
                2045-1261
                27 September 2023
                2023
                : 13
                : 20451253231200257
                Affiliations
                [1-20451253231200257]Mental Health Center of Shantou University, Shantou 515065, China
                [2-20451253231200257]Shantou University Medical College - Faculty of Medicine of University of Manitoba Joint Laboratory of Biological Psychiatry, Shantou 515065, China
                [3-20451253231200257]Shenzhen Mental Health Center/Shenzhen Kangning Hospital, Shenzhen 518020, China
                [4-20451253231200257]Mental Health Center, Shantou University Medical College, Shantou, 515065, China
                [5-20451253231200257]Shantou University Medical College - Faculty of Medicine of University of Manitoba Joint Laboratory of Biological Psychiatry, Shantou 515065, China
                [6-20451253231200257]Shenzhen Mental Health Center/Shenzhen Kangning Hospital, Shenzhen 518020, China
                [7-20451253231200257]Mental Health Center, Shantou University Medical College, Shantou, China
                [8-20451253231200257]Mental Health Center of Shantou University, Shantou 515065, China
                [9-20451253231200257]Shantou University Medical College - Faculty of Medicine of University of Manitoba Joint Laboratory of Biological Psychiatry, Shantou 515065, China
                [10-20451253231200257]School of Mental Health, Zhejiang Provincial Clinical Research Center for Mental Illness, Affiliated Kangning Hospital, Wenzhou Medical University, Wenzhou 325035, China
                Author notes
                Author information
                https://orcid.org/0000-0002-0752-6502
                Article
                10.1177_20451253231200257
                10.1177/20451253231200257
                10540600
                37781686
                74fa55bf-dba8-4e4c-8404-075ccdbee3d8
                © The Author(s), 2023

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 7 July 2023
                : 24 August 2023
                Funding
                Funded by: Science and Technology Department of Guangdong Province, ;
                Award ID: 200114175878159
                Categories
                Original Research
                Custom metadata
                January-December 2023
                ts1

                antipsychotics,coagulation,hypercoagulability,schizophrenia,venous thromboembolisms

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