Ulcers of the Leg in Thalassemia

Stevens, Dwight M.; Shupack, Jerome L.; Javid, Jamshid; Silber, Robert

doi:10.1001/archderm.1977.01640110078012

Cited by 28 publications

(16 citation statements)

References 18 publications

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“…1 These clinical features have also been reported in thalassemia intermedia, hereditary spherocytosis, and other forms of severe hemolytic anemia. [47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62] This suggests that sickling is not required for this subphenotype and instead implicates the severe hemolysis of sickle cell disease in its pathobiology. 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.…”

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

551

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

551

346

View full text Add to dashboard Cite

show abstract

“…Consequently, any trauma happened to the lower extremities results in their ulceration in 10-70% of sickle cell anaemia patients [19,20]. Further, in case of Thalassemia which is a quantitative disorder of haemoglobin synthesis, about 27% of the affected patients develop chronic ulcers [21] due to poor peripheral oxygenation resulting from the existing underlying haemolytic anaemia [22].…”

Section: Non-modifiable Risk Factorsmentioning

confidence: 99%

Impaired wound healing: facts and hypotheses for multi-professional considerations in predictive, preventive and personalised medicine

Avishai¹,

2017

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Whereas the physiologic wound healing (WH) successfully proceeds through the clearly defined sequence of the individual phases of wound healing, chronic non-healing wounds/ulcers fail to complete the individual stages and the entire healing process. There are many risk factors both modifiable (such as stress, smoking, inappropriate alcohol consumption, malnutrition, obesity, diabetes, cardio-vascular disease, etc.) and non-modifiable (such as genetic diseases and ageing) strongly contributing to the impaired WH. Current statistics demonstrate that both categories are increasingly presented in the populations, which causes dramatic socio-economic burden to the healthcare sector and society at large. Consequently, innovative concepts by predictive, preventive and personalised medicine are crucial to be implemented in the area. Individual risk factors, causality, functional interrelationships, molecular signature, predictive diagnosis, and primary and secondary prevention are thoroughly analysed followed by the expert recommendations in this paper.

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“…Die Patienten leiden unter einer hämo-lytischen Anämie, schwerer Hepatosplenomegalie und Knochenmarkshyperplasie; 27% aller Patienten mit β-Thalassä-mie entwickeln meist zwischen dem 20. und 30. Lebensjahr Ulzera insbesondere im Bereich des Malleolus medialis [46]. Ursächlich liegt diesen Ulzera vermutlich eine schlechte periphere Sauerstoffversorgung infolge der bestehenden hämoly-tischen Anämie zugrunde [38] Vaskulopathien Die Inzidenz tiefer Beinvenenthrombosen in der Bevölkerung wird auf 1:1000 geschätzt.…”

Section: Thalassämieunclassified

Genetische Ursachen schwerer Wundheilungsstörungen

Elsharkawi-Welt¹,

Hepp²,

Scharffetter‐Kochanek³

2008

Hautarzt

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Chronic leg ulcers affect about 1% of the German population. The intense search for the underlying cause of impaired wound healing is an essential requirement for successful therapy. The most common causes comprise chronic venous insufficiency (70%), peripheral arterial occlusive disease (10%) and diabetes mellitus. Besides vasculitis, infectious diseases and tumors, genetic diseases may constitute the underlying cause for impaired wound healing. In this review various rare genetic diseases causing chronic wounds like the Klinefelter-Syndrome, immunological diseases including the TAP-deficiency-syndrome and the leukocyte adhesion deficiency-syndromes, red blood cell disorders, thalassemia, thrombotic diseases, progeroid syndromes and inherited connective tissue disorders are presented.

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Ulcers of the Leg in Thalassemia

Cited by 28 publications

References 18 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

Impaired wound healing: facts and hypotheses for multi-professional considerations in predictive, preventive and personalised medicine

Genetische Ursachen schwerer Wundheilungsstörungen

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