The relationship between the severity of hemolysis, clinical manifestations and risk of death in 415 patients with sickle cell anemia in the US and Europe

被引：149

作者：

Nourale, Mehdi ^{[1
]}

Lee, Janet S. ^{[2
,3
]}

Zhang, Yingze ^{[2
]}

Kanias, Tamir ^{[2
,3
]}

Zhao, Xuejun ^{[4
]}

Xiong, Zeyu ^{[2
]}

Oriss, Timothy B. ^{[3
]}

Zeng, Qilu ^{[2
]}

Kato, Gregory J. ^{[4
]}

Gibbs, J. Simon R. ^{[5
]}

Hildesheim, Mariana E. ^{[3
]}

Sachdev, Vandana ^{[4
]}

Barst, Robyn J. ^{[6
]}

Machado, Roberto F. ^{[7
]}

Hassell, Kathryn L. ^{[8
]}

Little, Jane A. ^{[9
]}

Schraufnagel, Dean E. ^{[7
]}

Krishnamurti, Lakshmanan ^{[10
]}

Novelli, Enrico ^{[2
]}

Girgis, Reda E. ^{[11
]}

Morris, Claudia R. ^{[12
]}

Rosenzweig, Erika Berman ^{[6
]}

Badesch, David B. ^{[8
]}

Lanzkron, Sophie ^{[11
]}

Castro, Oswaldo L. ^{[1
]}

Goldsmith, Jonathan C. ^{[13
]}

Gordeuk, Victor R. ^{[7
]}

Gladwin, Mark T. ^{[2
,3
]}

机构：

[1] Howard Univ, Washington, DC 20059 USA

[2] Univ Pittsburgh, Vasc Med Inst, Pittsburgh, PA 15260 USA

[3] Univ Pittsburgh, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA 15260 USA

[4] NHLBI, Cardiovasc & Pulm Med Branch, Bethesda, MD 20892 USA

[5] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London SW7 2AZ, England

[6] Columbia Univ, New York, NY USA

[7] Univ Illinois, Chicago, IL USA

[8] Univ Colorado HSC, Denver, CO USA

[9] Case Western Reserve Univ, Cleveland, OH 44106 USA

[10] Childrens Hosp Pittsburgh, Pittsburgh, PA 15213 USA

[11] Johns Hopkins Univ, Baltimore, MD USA

[12] Childrens Hosp & Res Ctr Oakland, Oakland, CA USA

[13] NHLBI, NIH, Bethesda, MD 20892 USA

来源：

HAEMATOLOGICA | 2013年 / 98卷 / 03期

基金：

美国国家卫生研究院;

关键词：

HEMOGLOBIN OXYGEN DESATURATION; NITRIC-OXIDE BIOAVAILABILITY; PULMONARY-HYPERTENSION; PULSE OXIMETRY; MICROPARTICLE ENUMERATION; EXERCISE CAPACITY; CHEST SYNDROME; DISEASE; CHILDREN; ASSOCIATION;

D O I：

10.3324/haematol.2012.068965

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

The intensity of hemolytic anemia has been proposed as an independent risk factor for the development of certain clinical complications of sickle cell disease, such as pulmonary hypertension, hypoxemia and cutaneous leg ulceration. A composite variable derived from several individual markers of hemolysis could facilitate studies of the underlying mechanisms of hemolysis. In this study, we assessed the association of hemolysis with outcomes in sickle cell anemia. A hemolytic component was calculated by principal component analysis from reticulocyte count, serum lactate dehydrogenase, aspartate aminotransferase and total bilirubin concentrations in 415 hemoglobin SS patients. Association of this component with direct markers of hemolysis and clinical outcomes was assessed. As primary validation, both plasma red blood cell microparticles and cell-free hemoglobin concentration were higher in the highest hemolytic component quartile compared to the lowest quartile (P <= 0.0001 for both analyses). The hemolytic component was lower with hydroxyurea therapy, higher hemoglobin F, and alpha-thalassemia (P <= 0.0005); it was higher with higher systemic pulse pressure, lower oxygen saturation, and greater values for tricuspid regurgitation velocity, left ventricular diastolic dimension and left ventricular mass (all P<0.0001). Two-year follow-up analysis showed that a high hemolytic component was associated with an increased risk of death (hazard ratio, HR 3.44; 95% confidence interval, CI: 1.2-9.5; P=0.02). The hemolytic component reflects direct markers of intravascular hemolysis in patients with sickle cell disease and allows for adjusted analysis of associations between hemolytic severity and clinical outcomes. These results confirm associations between hemolytic rate and pulse pressure, oxygen saturation, increases in Doppler-estimated pulmonary systolic pressures and mortality

引用

页码：464 / 472

页数：9

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