title: Chronic hyper-hemolysis in sickle cell anemia: association of vascular complications and mortality with less frequent vasoocclusive pain.
abstract: BACKGROUND
  Intravascular hemolysis in sickle cell anemia could contribute to complications associated with nitric oxide deficiency, advancing age, and increased mortality. We have previously reported that intense hemolysis is associated with increased risk of vascular complications in a small cohort of adults with sickle cell disease. These observations have not been validated in other populations.
  
  
  METHODS
  The distribution of serum lactic dehydrogenase (LDH) values was used as a surrogate measure of intravascular hemolysis in a contemporaneous patient group and an historical adult population from the Cooperative Study of Sickle Cell Disease (CSSCD), all with sickle cell anemia. Chronic hyper-hemolysis was defined by the top LDH quartile and was compared to the lowest LDH quartile.
  
  
  RESULTS
  Hyper-hemolysis subjects had higher systolic blood pressure, higher prevalence of leg ulcers (OR 3.27, 95% CI 1.92-5.53, P<0.0001), priapism (OR 2.62, 95% CI 1.13-6.90, P = 0.03) and pulmonary hypertension (OR 4.32, 95% CI 2.12-8.60, P<0.0001), while osteonecrosis (OR 0.32, 95% CI 0.19-0.54, P<0.0001) and pain (OR 0.23, 95% CI 0.09-0.55, P = 0.0004) were less prevalent. Hyper-hemolysis was influenced by fetal hemoglobin and alpha thalassemia, and was a risk factor for early death in the CSSCD population (Hazard Ratio = 1.97, P = 0.02).
  
  
  CONCLUSIONS
  Steady state LDH measurements can identify a chronic hyper-hemolysis phenotype which includes less frequent vasooclusive pain and earlier mortality. Clinicians should consider sickle cell specific therapies for these patients, as is done for those with more frequent acute pain. The findings also suggest that an important class of disease modifiers in sickle cell anemia affect the rate of hemolysis.
authors.affiliation: Pulmonary and Vascular Medicine Branch, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland, United States of America. jamesta@mail.nih.gov
authors.forename: James G
authors.initials: JG
authors.lastname: Taylor
authors.forename: Vikki G
authors.initials: VG
authors.lastname: Nolan
authors.forename: Laurel
authors.initials: L
authors.lastname: Mendelsohn
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Kato
authors.forename: Mark T
authors.initials: MT
authors.lastname: Gladwin
authors.forename: Martin H
authors.initials: MH
authors.lastname: Steinberg
mesh_terms: D000328:Adult; D000755:Anemia, Sickle Cell / Q000097:blood* / Q000150:complications / Q000401:mortality / Q000503:physiopathology; D006461:Hemolysis; D006801:Humans; D006976:Hypertension, Pulmonary / Q000453:epidemiology; D007770:L-Lactate Dehydrogenase / Q000097:blood; D007871:Leg Ulcer / Q000453:epidemiology; D009316:National Institutes of Health (U.S.); D010146:Pain / Q000503:physiopathology; D016019:Survival Analysis; D013789:Thalassemia / Q000150:complications; D014481:United States
chemical_list: D007770:L-Lactate Dehydrogenase