g(HbF): a genetic model of fetal hemoglobin in sickle cell disease.

Fetal hemoglobin (HbF) is a strong modifier of sickle cell disease (SCD) severity and is associated with 3 common genetic loci. Quantifying the genetic effects of the 3 loci would specifically address the benefits of HbF increases in patients. Here, we have applied statistical methods using the most representative variants: rs1427407 and rs6545816 in BCL11A, rs66650371 (3-bp deletion) and rs9376090 in HMIP-2A, rs9494142 and rs9494145 in HMIP-2B, and rs7482144 (Xmn1-HBG2 in the ß-globin locus) to create g(HbF), a genetic quantitative variable for HbF in SCD. Only patients aged ≥5 years with complete genotype and HbF data were studied. Five hundred eighty-one patients with hemoglobin SS (HbSS) or HbSß0 thalassemia formed the "discovery" cohort. Multiple linear regression modeling rationalized the 7 variants down to 4 markers (rs6545816, rs1427407, rs66650371, and rs7482144) each independently contributing HbF-boosting alleles, together accounting for 21.8% of HbF variability (r2) in the HbSS or HbSß0 patients. The model was replicated with consistent r2 in 2 different cohorts: 27.5% in HbSC patients (N = 186) and 23% in 994 Tanzanian HbSS patients. g(HbF), our 4-variant model, provides a robust approach to account for the genetic component of HbF in SCD and is of potential utility in sickle genetic and clinical studies.

Blood transfusion usage among adults with sickle cell disease - a single institution experience over ten years.

Transfusion of red blood cells is a major therapeutic option in sickle cell disease (SCD). There is strong evidence for its efficacy, particularly in primary and secondary stroke prevention in children, however, its use in other areas remains controversial. This study assessed the patterns of transfusion in the adult cohort attending King's College Hospital over a 10-year period, from 2000 to 2009. Total blood usage has increased significantly (P = 0·006) during this time, with 78% of the blood received by only 6% of the patients. The increase is explained by increased automated red cell exchange and increased usage for planned and acute transfusions for sickle-related complications.

Outcome of adults with sickle cell disease admitted to critical care - experience of a single institution in the UK.

Sickle cell disease (SCD) patients are perceived to have a high mortality when admitted to the Critical Care Unit (CCU). We performed a retrospective analysis of all adult sickle admissions to CCU at a single centre over an 8-year period (1 January 2000 to 31 December 2007). Thirty-eight patients (14 male) were admitted 46 times to CCU; the commonest reasons for admission were acute chest syndrome (14, 30%), multi-organ failure (8, 17%) and planned post-elective surgery (7, 15%). CCU mortality for SCD patients was 19.6%, comparable to a CCU-wide mortality of 17.6% during the study period in the same institution. Re-admission to CCU was high (16% over the 8-year period) but did not increase mortality risk.

Acute human parvovirus B19 infection and nephrotic syndrome in patients with sickle cell disease.

Acute Human Parvovirus B19 (HPV B19) infection is the major cause of transient red cell aplasia (TRCA) and acute anaemia in patients with sickle cell disease (SCD). We report three cases of patients who developed nephrotic syndrome (NS) with chronic sequelae after initially presenting with HPV B19-associated TRCA. There was no correlation between evidence of HPV B19 infection and impaired renal function in our cohort of adult sickle cell patients. This is consistent with a view that although NS is potentially a rare complication of symptomatic acute HPV B19 infection, exposure to HPV B19 is not associated with an increased risk of renal disease.