Decreased Hematocrit-To-Viscosity Ratio and Increased Lactate Dehydrogenase Level in Patients with Sickle Cell Anemia and Recurrent Leg Ulcers

Abstract

Leg ulcer is a disabling complication in patients with sickle cell anemia (SCA) but the exact pathophysiological mechanisms are unknown. The aim of this study was to identify the hematological and hemorheological alterations associated with recurrent leg ulcers. Sixty-two SCA patients who never experienced leg ulcers (ULC-) and 13 SCA patients with a positive history of recurrent leg ulcers (ULC+) - but with no leg ulcers at the time of the study – were recruited. All patients were in steady state condition. Blood was sampled to perform hematological, biochemical (hemolytic markers) and hemorheological analyses (blood viscosity, red blood cell deformability and aggregation properties). The hematocrit-to-viscosity ratio (HVR), which reflects the red blood cell oxygen transport efficiency, was calculated for each subject. Patients from the ULC+ group were older than patients from the ULC- group. Anemia (red blood cell count, hematocrit and hemoglobin levels) was more pronounced in the ULC+ group. Lactate dehydrogenase level was higher in the ULC+ group than in the ULC- group. Neither blood viscosity, nor RBC aggregation properties differed between the two groups. HVR was lower and RBC deformability tended to be reduced in the ULC+ group. Our study confirmed increased hemolytic rate and anemia in SCA patients with leg ulcers recurrence. Furthermore, our data suggest that although systemic blood viscosity is not a major factor involved in the pathophysiology of this complication, decreased red blood cell oxygen transport efficiency (i.e., low hematocrit/viscosity ratio) may play a role.

Elevated Low-Shear Blood Viscosity is Associated with Decreased Pulmonary Blood Flow in Children with Univentricular Heart Defects

“…These differences were statistically significant at all shear rates except for at 1000 s −1 , where ASD and Fontan were not significantly different. The hematocrit/viscosity ratio (HVR), a marker of RBC oxygen transport efficiency [5], was also calculated over the same range of shear rates; these curves are illustrated in Fig. 1b.…”

Critical Reviews: How we treat sickle cell patients with leg ulcers

“…The association of SCD leg ulcers with biomarkers of vascular dysfunction and pulmonary hypertension has been a recurrent theme [30,32,33]. Both conditions are associated with elevated plasma level of asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide (NO) synthase [34,35].…”

“…Genomics analyses have shown an association in both conditions with genetic polymorphisms in the BMP6, TGFBR3 and Klotho genes, important in vascular biology, including regulation of NO production [29,36]. There has been evidence of severely impaired red cell deformability, increased density and altered rheology [22,33,37]. SCD leg ulcers have been linked to venous incompetence and vasomotor alterations [13,38,39].…”

“…Alpha thalassemia trait has been protective [9,29], although this is not always consistent [13,23,40]. Elevated levels of fetal hemoglobin are generally protective [9,29,41], although this has not been true in all studies [33,42]. SCD ulcer patients have higher levels of soluble ICAM-1 and the key inflammatory cytokine IL-1beta [43].…”

Leg ulcers in sickle cell patients: management challenges

“…[2][3][4] Incidence of leg ulcers is highest among male adult patients from low socioeconomic backgrounds. 2,5,6 Ulcers in patients with SCD are considered a marker of disease severity, with problematic ulcers commonly occurring in association with pulmonary hypertension and priapism. 7 Ulcers normally occur in the lower extremities, in areas of thin skin, scarce subcutaneous fat, and low blood flow.…”