Bariatric surgery in morbidly obese individuals affects plasma levels of protein C and thrombomodulin

Rega‐Kaun, Gersina; Kaun, Christoph; Ebenbauer, B.; Jaegersberger, G.; Prager, Manfred; Wojta, Johann; Hohensinner, Philipp J.

doi:10.1007/s11239-018-1744-9

Cited by 18 publications

(13 citation statements)

References 33 publications

(33 reference statements)

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“…This surgical intervention results in massive weight loss within the first year after surgery [14]. The weight loss is associated with dramatic changes such as a reduced inflammatory state and reduced hepatic stress [15,16,17].…”

Section: Introductionmentioning

confidence: 99%

Changes of Circulating Extracellular Vesicles from the Liver after Roux-en-Y Bariatric Surgery

Rega‐Kaun

Ritzel

Kaun

et al. 2019

IJMS

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Circulating extracellular vesicles are small particles enclosed by a phospholipid bilayer. Vesicles deriving directly from the cellular membrane by an active budding process retain cell origin specific proteins and RNA. These vesicles carry pathophysiological information from their parental cell and hold the potential to allow analysis of organs without the need for a biopsy. We included in our study 27 patients undergoing bariatric surgery. Hepatic extracellular vesicles were determined by flow cytometry. mRNA specific for hepatic cellular origin was determined in the extracellular vesicle fraction using qPCR. Surgery led to a massive reduction of weight and overall hepatic stress as determined by alanine transaminase (ALT), aspartate transaminase (AST) and γ-glutamyltransferase (GGT). Total extracellular vesicle numbers were reduced after bariatric surgery. Liver specific vesicles identified by HepPar1 or asialoglycoprotein receptor (ASGPR) were significantly reduced after bariatric surgery in both AnnexinV+ and AnnexinV− subgroups. When analyzing circulating liver-specific mRNAs, we found reduced levels of these mRNAs after surgery even though total circulating RNA remained unchanged. We conclude that circulating hepatic extracellular vesicles are detectable in samples from patients undergoing gastric bypass surgery. These vesicles are reduced after a reduction of hepatic stress also observed with classic liver enzyme measurements. We conclude that ASGPR or HepPar positive vesicles hold the potential to serve as liver specific vesicle markers.

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Section: Introductionmentioning

confidence: 99%

Changes of Circulating Extracellular Vesicles from the Liver after Roux-en-Y Bariatric Surgery

Rega‐Kaun

Ritzel

Kaun

et al. 2019

IJMS

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“…Bariatric surgery has become an effective treatment for morbid obesity including an improvement in glucose metabolism, insulin resistance, and reduction of proinsulin levels [7][8][9][10]. In addition to changes in the metabolic syndrome, bariatric surgery is also associated with a reduced inflammatory profile and amelioration of coagulation [11,12].…”

Section: Introductionmentioning

confidence: 99%

Roux-en-Y-Bariatric Surgery Reduces Markers of Metabolic Syndrome in Morbidly Obese Patients

et al. 2019

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Background Obesity is closely linked to increased markers of metabolic syndrome and development of diabetes. Roux-en-Y bariatric surgery reduces hyperinsulinemia and improves insulin sensitivity and hence benefits morbidly obese patients. Aim To determine changes in markers of metabolic syndrome, pancreatic function, and hepatic insulin sensitivity in patients before and 1 year after undergoing Roux-en-Y gastric bypass surgery. Methods We enrolled 43 consecutive patients in a single center. Markers for metabolic syndrome included proinsulin, insulin, Cpeptide, liver enzymes, and serum levels of selected microRNAs hsa-miR-122, hsa-miR-130, hsa-miR-132, and hsa-miR-375. Results After surgery, all patients showed a significant 37% drop of body mass index (p < 0.001). Furthermore, proinsulin (59% reduction, p < 0.001), insulin (76% reduction, p < 0.001), and C-peptide (56% reduction, p < 0.001) were all reduced 1 year after surgery. Using the hepatic insulin clearance score, we determined a significant increase in hepatic insulin clearance after surgery (76% increase, p < 0.001). Especially diabetic patients showed a marked 2.1-fold increase after surgery. Hepatic enzymes ALT (35% reduction, p = 0.002) and γGT (48% reduction, p < 0.001) were significantly reduced in all patients with similar improvement in diabetic and non-diabetic patients. miRNAs hsa-miR-122, hsa-miR-130, and hsa-miR-132 were all significantly reduced whereas hsa-miR-375 was increased after gastric bypass surgery (p < 0.001 for all miRNAs). Conclusion Both liver and pancreatic stress parameters were reduced significantly 1 year after Roux-en-Y gastric bypass surgery suggesting an overall amelioration of the metabolic syndrome in all patients regardless of previous health status.

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“…Contrastingly, it has also been reported that 1 year after gastric bypass surgery, antithrombotic protein levels are also lower. 14 Future PK-pharmacodynamic (PD) studies should evaluate influence of obesity and weight loss on haemostatic balance to establish its relevance.…”

Section: Discussionmentioning

confidence: 99%

Impact of extreme weight loss on factor VIII concentrate pharmacokinetics in haemophilia

et al. 2021

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We explored the effects of extreme weight loss after gastric bypass surgery on factor VIII concentrate pharmacokinetic (PK) parameters in a patient with haemophilia A. We present a 32-year-old man with severe haemophilia A, with a body mass index (BMI) of 42.6 kg/m2 who underwent laparoscopic sleeve gastrectomy. We showed that a population PK model with ideal body weight as morphometric variable instead of bodyweight led to an adequate description of the individual PKs in this patient with a variable BMI. Strikingly, no differences were observed in the individual PK parameters after extreme weight loss. Therefore, the resulting extreme weight loss after surgery did not lead to prophylactic dose changes in this patient with severe haemophilia. We carefully conclude that population PK–pharmacodynamic models are still obligatory to give more insight into functional effects of significant weight loss on the haemostatic balance.

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Bariatric surgery in morbidly obese individuals affects plasma levels of protein C and thrombomodulin

Cited by 18 publications

References 33 publications

Changes of Circulating Extracellular Vesicles from the Liver after Roux-en-Y Bariatric Surgery

Changes of Circulating Extracellular Vesicles from the Liver after Roux-en-Y Bariatric Surgery

Roux-en-Y-Bariatric Surgery Reduces Markers of Metabolic Syndrome in Morbidly Obese Patients

Impact of extreme weight loss on factor VIII concentrate pharmacokinetics in haemophilia

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