Bariatric patients have plasmatic hypercoagulability and systemic upregulation of heme oxygenase activity

Nielsen, Vance G.; Galvani, Carlos; Boyle, Patrick K.; Steinbrenner, Evangelina B.; Matika, Ryan W.

doi:10.1097/mbc.0000000000000194

Cited by 10 publications

(13 citation statements)

References 28 publications

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“…It would be expected that increased CO and iron would attenuated fibrinolysis in the absence of any other biochemical aberration [17]. Thus, the data of the present investigation support the concept that an endogenous fibrinolysin may have been present despite increased Hmox activity, as has been documented by us in the settings of obesity and cancer [33,34].…”

Section: Discussionsupporting

confidence: 77%

Carbon Monoxide and Iron Modulate Plasmatic Coagulation in Alzheimer’s disease

Nielsen¹,

Pretorius

Bester

et al. 2015

CNR

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Alzheimer's disease (AD) is a significant source of morbidity and mortality for millions of people worldwide, and multiple potential etiologies have been postulated to contribute to AD. Among these, spontaneous cerebral emboli and increased cerebral and circulating heme oxygenase (Hmox) activity in AD patients are of particular interest, as two of the products of Hmox activity, carbon monoxide (CO) and iron enhance plasmatic coagulation and modify the ultrastructure of thrombi. We hypothesized that patients afflicted with AD would have coagulation kinetics modulated by CO and iron. Using viscoelastic assessments of coagulation, it was determined with a small cohort (n=11) of AD patients that all had enhancement of coagulation by CO, iron, or both. In a complementary fashion, it was determined that a separate cohort (n=12) of AD patients had thrombi with ultrastructural features consistent with iron and CO exposure as assessed with scanning electron microscopy. Further, when stratified by normal or abnormally increased serum ferritin concentrations (which can be increased by Hmox), the AD patients with abnormal ferritin concentrations had significantly thinner fibrin fiber diameters, not unlike that noted when normal plasma is mixed with iron or CO. In sum, AD patients were noted to have plasmatic coagulation kinetic and thrombus ultrastructural changes consistent with exposure to CO and iron. Future investigation of CO and iron in the pathogenesis of Alzheimer's disease is warranted.

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Section: Discussionsupporting

confidence: 77%

Carbon Monoxide and Iron Modulate Plasmatic Coagulation in Alzheimer’s disease

Nielsen¹,

Pretorius

Bester

et al. 2015

CNR

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“…This approach was chosen because it took longer to reach a final clot strength in whole blood, presumably secondary to establishment of platelet-fibrin tension. The following elastic modulus-based parameters previously described [8] were determined: time to maximum rate of thrombus generation (TMRTG) [time interval (min) observed prior to maximum speed of clot growth]; maximum rate of thrombus generation (MRTG) [maximum velocity of clot growth observed (dynes/cm 2 /s)]; and total thrombus generation (TTG) [(dynes/cm 2 ) the final viscoelastic resistance observed after clot formation].…”

Section: Coagulation Kinetic Analysesmentioning

confidence: 99%

Effects of profound hypoxemia on coagulation & fibrinolysis in normal individuals

Redford

Paidy²,

Steinbrenner

et al. 2016

Blood Coagulation &Amp; Fibrinolysis

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Hypoxia has been proposed to enhance, diminish, or have no effect on laboratory measures of coagulation or clinical thrombosis. Further, there usually are significant pathological or environmental factors concurrently present with hypoxia. Thus, the goal of the present investigation was to determine whether whole blood or plasmatic coagulation and fibrinolytic kinetics would change in response to progressive hypoxia to a systemic oxygenation (SpO2) of 70%. Healthy, conscious volunteers (n = 9) breathing a hypoxic mixture of gases during an in-vivo validation of noninvasive cerebral oximetry had blood samples collected and assessed with thrombelastography at normoxia and after SpO2 of 70%. A mild release of endogenous heparin-like activity occurred that diminished plasmatic coagulation, and a mild increase in clot lysis time also was noted. Further investigation to determine whether these phenomena occur in more chronic, less hypoxic states as sources of hypocoagulation or thrombophilia is needed.

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“…Serendipitously, the small amount of hemolysis observed on our patients permitted the observation that Hmox-upregulating [27][28][29] comorbidities may play an important role in hypercoagulability in this clinical setting. The conditions of obesity, DM, and OSA are associated with thrombotic events and Hmox upregulation, [27][28][29] and not surprisingly patients that require LVAD support often are afflicted with such inflammatory disorders-especially those undergoing DT.…”

Section: Discussionmentioning

confidence: 69%

“…The conditions of obesity, DM, and OSA are associated with thrombotic events and Hmox upregulation, [27][28][29] and not surprisingly patients that require LVAD support often are afflicted with such inflammatory disorders-especially those undergoing DT. These comorbid states by themselves are thrombotic threats, but if device-derived substrate (hemolysis generated free heme) is introduced into the equation, then the summation of indolent Hmox upregulation and increased free heme may result in frank CO and ironenhanced coagulation.…”

Section: Discussionmentioning

confidence: 99%

“…Patients implanted with LVADs have been noted to be afflicted with diabetes mellitus (DM) and obesity, [1][2][3][4][5]13 and both of these conditions have been associated with enhancement of Hmox activity 27,28 and CO-mediated hypercoagulability. 28 Of interest, obstructive sleep apnea (OSA), a disorder often associated with obesity, has also been demonstrated to upregulate Hmox activity. 29 Consequently, although patient-device interactions are critical in the development of systemic hypercoagulability, comorbid conditions may further exacerbate Hmox-associated hypercoagulability via increased release of CO and iron into the circulation.…”

mentioning

confidence: 99%

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Left Ventricular Assist Device–Associated Carbon Monoxide and Iron-Enhanced Hypercoagulation

2015

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Left ventricular assist device (LVAD) therapy is associated with thrombophilia despite anticoagulation. Of interest, LVAD patients have increased carboxyhemoglobin, a measure of upregulated heme oxygenase (Hmox) activity that releases carbon monoxide (CO) and iron. Given that CO and iron enhance plasmatic coagulation, we determined if LVAD patients had hypercoagulability and decreased fibrinolytic vulnerability with measurable CO and iron-mediated effects. Blood samples were obtained a month or more after implantation of the LVAD. Thrombelastographic methods to assess coagulation kinetics, fibrinolytic kinetics, formation of carboxyhemefibrinogen, and iron-mediated enhancement of clot growth were utilized. Coagulation and fibrinolytic parameter normal individual (n = 30) plasma values were determined. Sixteen LVAD patients were studied. CO and iron enhancement of coagulation were observed in the majority of LVAD patients, contributing to hypercoagulation. However, most patients demonstrated abnormally increased rates of clot lysis. Critically, hemolysis as assessed by circulating lactate dehydrogenase activity was small in this cohort, and only four patients without comorbid states (e.g., obesity, diabetes, sleep apnea) were hypercoagulable with evidence of Hmox upregulation. However, seven patients with comorbidities were hypercoagulable with Hmox upregulation. Future investigation of CO and iron-related thrombophilia and comorbid disease is warranted to define its role in LVAD-related thrombosis.

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Bariatric patients have plasmatic hypercoagulability and systemic upregulation of heme oxygenase activity

Cited by 10 publications

References 28 publications

Carbon Monoxide and Iron Modulate Plasmatic Coagulation in Alzheimer’s disease

Carbon Monoxide and Iron Modulate Plasmatic Coagulation in Alzheimer’s disease

Effects of profound hypoxemia on coagulation & fibrinolysis in normal individuals

Left Ventricular Assist Device–Associated Carbon Monoxide and Iron-Enhanced Hypercoagulation

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