Treatment with hydroxyurea in a patient compound heterozygote for a high oxygen affinity hemoglobin and β‐thalassemia minor

Abstract

Enhanced oxygen delivery to tissues has been shown to improve endurance performance [1]. This has led to widespread abuse of erythropoiesis-stimulating agents (ESA) in elite sport. It is conceivable that athletes have even learned how to continue illicit ESA doping [2]. This possibility has fuelled the search for novel methods to detect and deter ESA abuse using ''indirect'' markers. It is now widely accepted that drugs influence gene expression [3,4]. In this study, we envisage its use as a means to detect ESA doping. We obtained a global view of the transcriptome of total blood cells both before and after treatment with darbepoetin alpha using the serial analysis of gene expression (SAGE) method. In silico analysis identified 95 genes whose differential expression was subsequently tested by quantitative real-time polymerase chain reaction (PCR) in two athletes. The athletes were treated first with high doses of recombinant human erythropoietin (rHuEpo) to increase their hemoglobin concentration and then with microdoses to maintain the high concentration of hemoglobin. Significance analysis of microarrays (SAM) at a delta ratio greater than 1.5 indicated that 33 genes could be significant markers of ESA administration. Interestingly, when high and microdoses were taken into account together, five genes could still be considered as significant markers.

Symptomatic Erythrocytosis Associated with a Compound Heterozygosity for Hb Lepore-Boston-Washington (δ87-β116) and Hb Johnstown [β109(G11)Val→Leu,GTG>TTG]

“…However, a treadmill study showed no difference in exercise tolerance in the patient before and after reduction of PCV level (8). A patient with compound heterozygosity for Hb Regina [β96(FG3)Leu!Val, CTG>GTG] and β þ -thal, developed hepatosplenomegaly and renal vein thrombosis (9). This patient was treated with hydroxyurea resulting in an increase in Hb F, shift of p50 and a decrease in red cell volume, and the treatment led to an improvement in "general status."…”

“…There are a few exceptions including the patient with Hb Regina described above (9). Two of six patients reported by Percy et al (16) were said to have had thrombosis, but no details were given, thus it is unclear whether these patients had additional thrombophilic risks.…”

Ultra-rare Hb Regina (HBB:c.289C>G) with coinherited β-thalassaemia trait: solving the puzzle for extreme erythrocytosis

“…Hb Regina was first identified in a Canadian man in his late 20s of Scandinavian descent with erythrocytosis in 1985 8. Subsequently, a German family was described in 1991,9 and the third reported case was a Caucasian male in his late 30s who also had co-inheriting β-thalassaemia trait ( HBB :c.93–21G>A previously known as IVS1-110 G/A) 10. In the heterozygous cases, the variant constituted between 30% and 40% of the total Hb,8 while the double heterozygous case had the variant as the predominant Hb (85%) with absent HbA0 (10).…”