Effects of thalassemia and microcytosis on the hematologic and vasoocclusive severity of sickle cell anemia

Abstract

The characteristic clinical heterogeneity of sickle cell anemia (HbSS) may be, in part, a result of its interactions with alpha-thalassemia. Although alpha-thalassemia clearly affects some hematologic features of HbSS, its role in modulating the vasoocclusive severity of disease is not clear. To further explore this relationship, we examined the incidence of painful episodes, acute chest syndrome, aseptic bone necrosis, and leg ulcers in 3 patient groups with sickle cell disease: (1) 2,147 patients over age 2 yr, stratified according to mean corpuscular volume (MCV); (2) 183 patients selected on the basis of microcytosis and elevated HbA2, on whom globin biosynthesis studies were done; and (3) 125 patients who had alpha-globin genotype assigned by restriction endonuclease gene mapping. When patients were stratified by MCV, there was a reciprocal relationship between HbA2 levels and MCV, reflecting the presence of patients with beta o and alpha- thalassemia in the low MCV groups. The erythrocyte indices and HbA2 levels in patients classified as HbSS-alpha-thalassemia, by either globin synthesis studies or gene mapping, were very similar to those previously reported by others. Neither microcytosis, beta o, or alpha- thalassemia appeared to provide any clear protection from the vasoocclusive complication evaluated, and the prevalence of aseptic necrosis was increased in patients with microcytosis over age 20 yr and in groups with alpha-thalassemia. The effects of a reduced MCV and mean corpuscular hemoglobin concentration (MCHC), of possible benefit by themselves, when accompanied by a reduction in hemolysis and rise in hemoglobin concentration, as in HbSS-alpha-thalassemia, may cause sufficient rise in blood viscosity in critical vascular beds to impair blood flow and negate any amelioration of vasoocclusive complications in HbSS.

The genetics of hemoglobin A2 regulation in sickle cell anemia

“…α Thalassemia was associated with a reduction of MCV; (Figure S4). Increased HbA 2 in sickle cell anemia‐α thalassemia is a result α/δ‐globin dimerizing more readily than α/β S ‐globin . α Thalassemia modified the relationship between HbA 2 and MCV: without α thalassemia, a regression of HbA 2 on MCV yielded a slope of −0.028; with α thalassemia, the slope was −0.038 (a −33% change, P = 0.0339) (Table S2).…”

“…HbA 2 was measured by DEAE Cellulose column chromatography (CSSCD) or high performance liquid chromatography (Walk‐PHaSST, PUSH, β‐thalassemia cohort). HbF was measured by alkali denaturation (CSSCD) and HPLC (Walk‐PHaSST, PUSH, β‐thalassemia cohort).…”

Dificuldades na identificação laboratorial da talassemia alfa

“…Alguns autores descrevem interação de hemoglobinas variantes com talassemia alfa. Na anemia falciforme é descrita interação benéfica com talassemia alfa, ocorrendo diminuição da anemia hemolítica, inibição da polimerização intracelular da hemoglobina S e diminuição da intensidade de hemólise (18,19) .…”

Measuring success: utility of biomarkers in sickle cell disease clinical trials and care

“…In addition, frequent painful episodes and chronic pain significantly decrease the quality of life (QOL) in patients with SCD. Historically, it has been shown that advancing age, high hemoglobin, low fetal hemoglobin (HbF) 60 and coinheritance of a-thalassemia 61 are associated with increased number of VOCs in children and adults with SCD. Among the experimental biomarkers, elevated plasma thrombospondin 1, a secretory product of activated platelets that promotes sickle vascular adhesion, plasma levels 33,62 and imbalance of apelin (vasodilator) and endothelin 1 (vasoconstrictor) 63 are associated with a vasoocclusive phenotype.…”

“…119,120 Coinheritance of a-thalassemia has mixed effects on disease severity, as it decreases hemolysis 121,122 and risk of stroke 60,123 but increases the frequency of VOCs and avascular necrosis of bone. 61 Nongenetic factors such as environmental factors (eg, high wind speed, humidity, cold temperatures, and air pollution), infection, asthma, smoking, socioeconomic status, and access to care can adversely affect the disease course. 117,124,125 Unfortunately, there is no systematic way of accurately predicting which patient will have worse disease and die early preemptively by taking into account the factors listed above.…”