The Clinical Sequelae of Intravascular Hemolysis and Extracellular Plasma Hemoglobin

Rother, Russell P.; Bell, Leonard; Hillmen, Peter; Gladwin, Mark T.

doi:10.1001/jama.293.13.1653

Cited by 1,360 publications

(1,221 citation statements)

References 129 publications

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“…They found an increase in the NO levels of patients with hypertension and diabetes together, hence indicating that there is increased release of NO but maybe, low NO bioavailability. When the capacity of protective hemoglobin-scavenging mechanisms gets saturated, levels of cell free hemoglobin increase resulting in consumption of NO and clinical sequelae [7]. Increased plasma hemoglobin levels are responsible for impairment of EDRF (NO) function and may be the cause in setting up a disease process.…”

Section: Discussionmentioning

confidence: 99%

“…Intravascular hemoglobin limits the amount of endothelial-derived NO available for vasodilation. Hemolysis has recently been suggested to contribute to endothelial dysfunction based on a mechanism of NO scavenging by cell-free hemoglobin [7]. Plasma hemoglobin has the ability to scavenge NO while heme possesses multiple proinflammatory and prooxidant properties [7].…”

Section: Introductionmentioning

confidence: 99%

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Assessment of Endothelial Dysfunction in Health and Disease; Using Various Parameters

Jalali

Phadke

2011

Ind J Clin Biochem

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Conditions like hypertension, atherosclerosis and diabetes are known to be the result of endothelial dysfunction which could begin early in the life of an individual. The markers of endothelial dysfunction studied in the present work are plasma hemoglobin, serum high sensitivity C-reactive protein (hsCRP) and plasma nitrite and nitrate. We studied the onset of endothelial dysfunction with increase in age as well as in disease condition like newly detected hypertensives and of hypertensive diabetic patients. The mean plasma hemoglobin and hsCRP values were found to increase with age. hsCRP and plasma hemoglobin levels were significantly higher in patient groups as compared to aged-matched controls. On the other hand nitrate and nitrite was significantly higher in patients who suffered from both diabetes and hypertension together and nitrate values were significantly lower in patients who suffered from hypertensive alone. Plasma hemoglobin and hsCRP are associated with endothelial dysfunction and increases both with age as well as in disease condition.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Assessment of Endothelial Dysfunction in Health and Disease; Using Various Parameters

Jalali

Phadke

2011

Ind J Clin Biochem

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“…impaired regulation of smooth muscle tone, vascular constriction and intravascular thrombosis). 14 Although the exact mechanism by which hemoglobinuria causes kidney injury is unclear, heme proteins (e.g. hemoglobin and myoglobin) are thought to precipitate cast formation and obstruction of renal tubule, resulting in acute tubular necrosis of the proximal tubule cells.…”

Section: Hemolysis Caused By Thrombectomymentioning

confidence: 99%

Acute kidney injury caused by intravascular hemolysis after mechanical thrombectomy

et al. 2008

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Acute kidney injury caused by intravascular hemolysis after mechanical thrombectomy. Continuing Medical Education online Medscape, LLC is pleased to provide online continuing medical education (CME) for this journal article, allowing clinicians the opportunity to earn CME credit. Medscape, LLC is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide CME for physicians. Medscape, LLC designates this educational activity for a maximum of 0.5 AMA PRA Category 1 Credits TM . Physicians should only claim credit commensurate with the extent of their participation in the activity. All other clinicians completing this activity will be issued a certificate of participation. To receive credit, please go to http://www.medscape.com/cme/ncp and complete the post-test. Learning objectivesUpon completion of this activity, participants should be able to: 1 Describe the clinical features of pulmonary embolism in a pregnant woman. 2 Describe the clinical features of intravascular hemolysis. 3 Describe the mechanism of action of the AngioJet ® . 4 Review the management of acute kidney injury associated with hemolysis. Competing interestsThe authors, the Journal Editor C Harman and the CME questions author D Lie declared no competing interests. THE CASEA 43-year-old African-American female (gravida 5 para 0), with an intrauterine pregnancy of 8 weeks' gestation, presented to the emergency room with crampy abdominal pain, shortness of breath, and shoulder pain. The patient's medical history was notable for hypertension, uterine fibroids, one spontaneous abortion in the first trimester, and three elective therapeutic abortions. She was not taking any prescription medications and had no known drug allergies. The patient's history also indicated that she had smoked one pack of cigarettes per week for 25 years, but she denied alcohol or illicit drug use. On physical examination, the patient's temperature was 36.0 °C, and she had a pulse rate of 118 beats per minute and a blood pressure of 142/87 mmHg. Oxygen saturation was 100% on a nonrebreather mask. The patient was alert S u M M a rYBackground A 43-year-old African-American female (gravida 5 para 0) with an 8-week intrauterine pregnancy presented to the emergency room with crampy abdominal pain, shortness of breath, and shoulder pain. She had normal renal function on admission. CT angiography of the chest revealed bilateral pulmonary emboli; therefore, the AngioJet® (Possis Medical, Inc., Minneapolis, MN) device was used to perform mechanical thrombolysis. The patient subsequently developed hyperkalemia, red urine and anuria.

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“…However, the protective haptoglobin/hemopexin/Albumin/heme oxygenase (HO) systems can be overwhelmed in disease states, including hemolysis and inflammation, resulting in increased circulating levels of free Hb and free (or LDL bound) heme that can attack the endothelium and effect perfusion [6,43,69,70,81,97]. Such may be the case in AD when RBC fragility and lysis are increased.…”

Section: Discussionmentioning

confidence: 99%

“…Extracellular or free Hb released from lysed erythrocytes (oxyHb; Fe +2 ) causes injury to endothelial cells [5,59,81] and death of cultured neurons [24,77,83]. It also undergoes spontaneous oxidation to methemoglobin (metHb, Fe +3 ) which loses its heme group more readily than oxyHb [24,69].…”

Section: Oxidized Heme and Damage To Vascular Cellsmentioning

confidence: 99%

Hemoglobin binding to Aβ and HBG2 SNP association suggest a role in Alzheimer's disease

Perry

Gearhart

Wiener

et al. 2008

Neurobiology of Aging

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From a normal human brain phage display library screen we identified the gamma (A)-globin chain of fetal hemoglobin (Hb F) as a protein that bound strongly to Aβ1-42. We showed the oxidized form 1 These authors are co-corresponding authors for all stages of refereeing and publication and contributed equally to this work. Rodney T. Perry; Rm. 210H, 1665 University Blvd.; University of Alabama at Birmingham, Birmingham, USA; Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Disclosure Statement:I so state for myself and on behalf of the other authors on the manuscript, Hemoglobin binding to Aβ and HBG2 SNP association suggest a role in Alzheimer's disease, that we have no conflicts and sources of funding that influence the results of this paper, the data is not published or submitted elsewhere, and that appropriate approval and procedures were used concerning human subjects. I also verify that all authors on this manuscript have reviewed the contents of the manuscript, approve of its contents, and validate the accuracy of the data. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript of adult Hb (metHb A) binds with greater affinity to Aβ1-42 than metHb F. MetHb is more toxic than oxyhemoglobin because it loses its heme group more readily. Free Hb and heme readily damage vascular endothelial cells similar to Alzheimer's disease (AD) vascular pathology. The XmnI polymorphism (C→T) at −158 of the gamma (G)-globin promoter region can contribute to increased Hb F expression. Using family-based association testing, we found a significant protective association of this polymorphism in the NIMH sibling dataset (n=489) in families, with at least two affected and one unaffected sibling (p=0.006), with an age of onset >50 years (p=0.010) and >65 years (p=0.013), and families not homozygous for the APOE4 allele (p=0.041). We hypothesize that Hb F may be less toxic than adult Hb in its interaction with Aβ and may protect against the development of AD.

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The Clinical Sequelae of Intravascular Hemolysis and Extracellular Plasma Hemoglobin

Cited by 1,360 publications

References 129 publications

Assessment of Endothelial Dysfunction in Health and Disease; Using Various Parameters

Assessment of Endothelial Dysfunction in Health and Disease; Using Various Parameters

Acute kidney injury caused by intravascular hemolysis after mechanical thrombectomy

Hemoglobin binding to Aβ and HBG2 SNP association suggest a role in Alzheimer's disease

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