Comparison of homozygous sickle cell disease in Northern Greece and Jamaica

Christakis, John; Hassapopoulou, Helen P.; Papadopoulou, Maria; Mandraveli, K.; Vavatsi, N.; Loukopoulos, Dimitris; Morris, J.N.; Serjeant, B. E.; Serjeant, G. R.

doi:10.1016/0140-6736(90)90419-6

Cited by 37 publications

(25 citation statements)

References 17 publications

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“…Consistent with this model, the Jamaican sickle cell population, characterized by severe hemolysis, has a much higher prevalence of leg ulcers and priapism than those in Greece and India, who have less severe hemolysis, but comparable rates of VOC pain crisis. [63][64][65] Recent analysis from the Cooperative Study of Sickle Cell Disease confirms the link of priapism to LDH and other markers of hemolytic severity. 66 It is interesting that LDH elevation also is associated with low transcutaneous oxygen saturation.…”

Section: Discussionmentioning

confidence: 99%

Lactate dehydrogenase as a biomarker of hemolysis-associated nitric oxide resistance, priapism, leg ulceration, pulmonary hypertension, and death in patients with sickle cell disease

Kato

McGowan

Machado

et al. 2006

Blood

561

346

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Pulmonary hypertension is prevalent in adult patients with sickle cell disease and is strongly associated with early mortality and markers of hemolysis, in particular, serum lactate dehydrogenase (LDH). Intravascular hemolysis leads to impaired bioavailability of nitric oxide (NO), mediated by NO scavenging by plasma oxyhemoglobin and by arginine degradation by plasma arginase. We hypothesized that serum LDH may represent a convenient biomarker of intravascular hemolysis and NO bioavailability, characterizing a clinical subphenotype of hemolysisassociated vasculopathy. In a cohort of 213 patients with sickle cell disease, we found statistically significant associations of steady-state LDH with low levels of hemoglobin and haptoglobin and high levels of reticulocytes, bilirubin, plasma hemoglobin, aspartate aminotransferase, arginase, and soluble adhesion molecules. LDH isoenzyme fractionation confirmed predominance of LD1 and LD2, the principal isoforms within erythrocytes. In a subgroup, LDH levels closely correlated with plasma cell-free hemoglobin, accelerated NO consumption by plasma, and impaired vasodilatory responses to an NO donor. Remarkably, this simple biomarker was associated with a clinical subphenotype of pulmonary hypertension, leg ulceration, priapism, and risk of death in patients with sickle cell disease. We propose that LDH elevation identifies patients with a syndrome of hemolysisassociated NO resistance, endothelial dysfunction, and end-organ vasculopathy. IntroductionPulmonary hypertension is an increasingly recognized complication of sickle cell disease and other chronic hereditary and acquired hemolytic anemias. Doppler echocardiography screening reveals a tricuspid regurgitant jet velocity (TRV) of 2.5 m/s or greater in 33% of adults with sickle cell disease, indicative of pulmonary hypertension. 1 Pulmonary hypertension in these patients is associated with a 10-fold increased risk for early mortality. Elevated pulmonary artery pressures in patients with sickle cell disease have been associated with low hemoglobin concentration, high levels of serum lactate dehydrogenase (LDH), elevated systolic systemic blood pressure, history of priapism, renal insufficiency, and markers of iron overload. Of the several independent epidemiologic factors associated with pulmonary hypertension, an elevated level of serum LDH has drawn particular interest and controversy. In addition to a link with pulmonary hypertension, we and others have observed a link between LDH and a generalized state of endothelial activation, reflected by elevated blood plasma levels of soluble adhesion molecules, especially vascular cell adhesion molecule (VCAM-1). 2-10 Both pathologic endothelial activation and pulmonary hypertension are associated with more severe hemolytic anemia, reflected by low hemoglobin levels and high reticulocyte counts. 1,2,8 These data begin to suggest that LDH elevation may be a marker of hemolysis-associated endothelial dysfunction and pulmonary hypertension.LDH has long been considered a useful c...

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Section: Discussionmentioning

confidence: 99%

Lactate dehydrogenase as a biomarker of hemolysis-associated nitric oxide resistance, priapism, leg ulceration, pulmonary hypertension, and death in patients with sickle cell disease

Kato

McGowan

Machado

et al. 2006

Blood

561

346

View full text Add to dashboard Cite

show abstract

“…Greece is the only population so far described in which SS disease is not associated with high frequencies of a-thalassemia, yet Greek patients were found to have significantly lower MCHC and features of milder disease compared with Jamaicans (Christakis et al 1990). The lowered MCHC in this population remains to be confirmed and the mechanism explored.…”

Section: Mchcmentioning

confidence: 99%

The Natural History of Sickle Cell Disease

Serjeant¹

2013

Cold Spring Harbor Perspectives in Medicine

215

159

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“…23 Comparing Greek and Jamaican SS disease, Greek subjects had higher hemoglobin levels and red cell counts and lower MCHC and reticulocyte counts. 28 The higher hemoglobin and lower reticulocyte counts are consistent with less hemolysis, but Greek subjects have neither of the genetic factors recognized to ameliorate hemolysis in patients of African origin, alpha thalassemia or high levels of HbF. Clinically, Greek SS subjects show persistence of splenomegaly, more normal body build, and less leg ulceration and priapism.…”

Section: Greecementioning

confidence: 86%

“…The only population in which sickle cell disease does not coincide with frequent alpha thalassemia is Greece. 28 In Saudi Arabia, deletional alpha thalassemia is common but nondeletional forms may also occur and coincide with SS disease.…”

Section: Alpha Thalassemiamentioning

confidence: 99%

The Geography of Sickle Cell Disease: Opportunities for Understanding its Diversity

Serjeant

1994

Annals of Saudi Medicine

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Comparison of homozygous sickle cell disease in Northern Greece and Jamaica

Cited by 37 publications

References 17 publications

Lactate dehydrogenase as a biomarker of hemolysis-associated nitric oxide resistance, priapism, leg ulceration, pulmonary hypertension, and death in patients with sickle cell disease

Lactate dehydrogenase as a biomarker of hemolysis-associated nitric oxide resistance, priapism, leg ulceration, pulmonary hypertension, and death in patients with sickle cell disease

The Natural History of Sickle Cell Disease

The Geography of Sickle Cell Disease: Opportunities for Understanding its Diversity

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