Biomarkers of splenic function in infants with sickle cell anemia: baseline data from the BABY HUG Trial
ABSTRACT We evaluated spleen function in 193 children with sickle cell anemia 8 to 18 months of age by (99m)Tc sulfur-colloid liver-spleen scan and correlated results with clinical and laboratory parameters, including 2 splenic biomarkers: pitted cell counts (PIT) and quantitative Howell-Jolly bodies (HJB) enumerated by flow cytometry. Loss of splenic function began before 12 months of age in 86% of infants in association with lower total or fetal hemoglobin and higher white blood cell or reticulocyte counts, reinforcing the need for early diagnosis and diligent preventive care. PIT and HJB correlated well with each other and liver-spleen scan results. Previously described biomarker threshold values did define patients with abnormal splenic function, but our data suggest that normal spleen function is better predicted by PIT of ≤1.2% or HJB ≤55/10(6) red blood cells and absent function by PIT ≥4.5% or HJB ≥665/10(6). HJB is methodologically advantageous compared with PIT, but both are valid biomarkers of splenic function. This trial was registered at www.clinicaltrials.gov as #NCT00006400.
Full-textDOI: · Available from: Russell Ware, Aug 27, 2015
- SourceAvailable from: Pierre A Buffet
[Show abstract] [Hide abstract]
- "Howell-Jolly bodies are small nuclear remnants from erythroblasts that cannot be removed from red blood cells if the spleen is absent. In sickle cell disease, there is a strong correlation  between the number of red blood cells harbouring Howell-Jolly bodies, or the number of “pitted cells” (i e, red blood cells containing small vesicles) in circulation and the intensity of functional hyposplenism. In Plasmodium infections, the spleen contributes to innate resistance and limits the magnitude of parasitaemia. "
ABSTRACT: Hyposplenism, due to splenectomy, inherited red blood cell disorders or acquired conditions such as celiac disease, has an important impact on the severity of malaria, especially in non-immune patients. Conversely, that malaria may reveal functional hyposplenism has not been described previously. A 31-year old gardener was diagnosed with an uncomplicated attack of Plasmodium malariae 11 years after leaving the endemic area. In addition to trophozoites and schizonts, thick and thin smears also showed Howell-Jolly bodies, pointing to functional hyposplenism. This was later confirmed by the presence of a calcified spleen in the context of S/beta + sickle-cell syndrome in a patient previously unaware of this condition. Malaria may reveal hyposplenism. Although Howell-Jolly bodies are morphologically similar to nuclei of young Plasmodium trophozoite, distinction on smears is based on the absence of cytoplasm and irregular size of Howell-Jolly bodies. In the patient reported here, hyposplenism was revealed by the occurrence of P. malariae infection relatively late in life. Timely diagnosis of hyposplenism resulted in the implementation of appropriate measures to prevent overwhelming infection with capsulated bacteria. This observation highlights the importance of diagnosing hyposplenism in patients with malaria despite the morphological similarities between ring nuclei and Howell-Jolly bodies on thick smears.Malaria Journal 08/2013; 12(1):271. DOI:10.1186/1475-2875-12-271 · 3.49 Impact Factor
[Show abstract] [Hide abstract]
- "The evaluation of splenic function still rests chiefly on indirect markers, such as the pitted erythrocyte count, Howell Jolly body count, and Tc99m uptake. These tools have produced robust data regarding spleen function in vast longitudinal cohort studies of SCD infants (Rogers et al, 2011). However, the correlation between the results and the vulnerability to infection remains indirect. "
ABSTRACT: Acute splenic sequestration crisis (ASSC) is an unpredictable life-threatening complication of sickle cell disease (SCD) in infants. Here, our objective was to update available clinical information on ASSC. We retrospectively studied the 190 patients who were diagnosed at birth with SS or Sbeta(0) in the Paris conurbation between 2000 and 2009 and who experienced ASSC. They had 437 ASSC episodes (0.06/patient-year). Median age at the first episode was 1.4 years (0.1-7) and 67% of patients had more than one episode. Age was the only factor predicting recurrence: the risk was lower when the first episode occurred after 2 years versus before 1 year of age (hazard ratio, 0.60; 95% confidence interval, 0.41-0.88; P=0.025). A concomitant clinical event was found in 57% of episodes. The mortality rate was 0.53%. The treatment consisted in watchful waiting without prophylactic blood transfusions or splenectomy in 103 (54%) patients and in a blood transfusion programme in 55 (29%) patients. Overall, splenectomy was performed in 71 (37%) patients, at a median age of 4.5 years (range, 1.9-9.4). In conclusion, aggressive treatment may be warranted in patients experiencing ASSC before 2 years of age. Randomized controlled trials are needed to define the best treatment modalities.British Journal of Haematology 03/2012; 156(5):643-8. DOI:10.1111/j.1365-2141.2011.08999.x · 4.96 Impact Factor
- "This is potentially a rapid way of assessing splenic function , and correlates closely with pitted red cell counts and functional spleen scans . Few laboratories currently offer this assay ( Rogers et al , 2011 ) . "
Article: Biomarkers in sickle cell disease[Show abstract] [Hide abstract]
ABSTRACT: More than 100 different blood and urine biomarkers have been described in sickle cell disease (SCD), with the number increasing rapidly as analytical techniques develop. Nearly all of these biomarkers are abnormal in the steady state, and become more so during complications. The range of abnormalities demonstrates the multisystem nature of SCD and the complex pathophysiology. Some biomarkers indicate damage to specific organs, such as urine albumin:creatinine ratio in nephropathy, whereas others indicate more systemic processes. Biomarkers have been useful in identifying various interrelated pathological mechanisms, including haemolysis, inflammation, hypercoagulability, oxidative stress, reperfusion injury, vasculopathy and endothelial dysfunction. However, most biomarkers correlate closely with other more routine measurements, and also with each other. It is not clear that any provide specific prognostic or clinical information beyond that given by the simple measurement of haemoglobin concentration. The identification of prognostically validated biomarkers in prospective clinical trials would be useful.British Journal of Haematology 11/2011; 156(4):433-45. DOI:10.1111/j.1365-2141.2011.08961.x · 4.96 Impact Factor