Developmental Pattern of Splenic Dysfunction in Sickle Cell Disorders

Abstract

Splenic function in sickle hemoglobinopathy syndromes was assessed to determine the developmental pattern of splenic dysfunction. Nonvisualization of the spleen using technetium-99 metastable (99mTc) spleen scans correlated strongly with pocked (vesiculated) RBCs ≥3.5%. Cross-sectional analysis of pocked RBC data from 2,086 patients showed differences in the developmental pattern of splenic dysfunction between several disorders. In hemoglobin SS disease (sickle cell anemia) and hemoglobin Sβ° thalassemia, splenic dysfunction (≥3.5% pocked RBCs) often occurred in the first 6 to 12 months of life. In hemoglobin Sβ+ thalassemia, splenic dysfunction occurred less frequently and later. Splenic dysfunction in hemoglobin SC disease (sickle cell-hemoglobin C) was intermediate. The level of pocked RBCs was inversely associated with fetal hemoglobin (P < .007) and directly associated with age (P ≤ .001). These patterns of splenic dysfunction reflect the known severity of hemolysis and intravascular sickling and are consistent with the epidemiology of severe bacterial meningitis and sepsis in these diseases. Serial measurement of pocked RBCs permits determination of the onset of splenic dysfunction and the time of increased susceptibility to severe bacterial infections.

Automating Pitted Red Blood Cell Counts Using Deep Neural Network Analysis: A New Method for Measuring Splenic Function in Sickle Cell Anaemia

“…Measuring splenic function is of clinical interest in multiple conditions, including sickle cell anaemia (SCA) ( Brousse et al, 2014 ). In SCA, spleen damage occurs in early childhood, leading to loss of function within the first years of life ( Pearson et al, 1969 ; Pearson et al, 1985 ; El Hoss et al, 2019 ).…”

“…Traditionally, both have been counted manually, HJBs in a May-Grünwald Giemsa-stained blood smear and pitted RBCs in an unstained wet preparation of fresh or fixed whole blood. Results of these splenic biomarkers have previously been compared to results of LS scans and both HJB and pitted RBC counts (PIT counts) correlate well with LS scan results ( Pearson et al, 1985 ; Rogers et al, 2011 ). However, both methods are user-dependent and time-consuming.…”

“…Thereby, the percentage of RBCs containing pits (the PIT count or %PIT) increases in individuals who have undergone splenectomy ( Holroyde and Gardner, 1970 ; Pearson et al, 1979 ), or in conditions where there is a loss of splenic function ( Casper et al, 1976 ). In SCA, early studies found that a PIT count of ≥3.5% indicated loss of splenic function ( Pearson et al, 1985 ). More recently, a PIT count of <1.2% was found to predict normal splenic function and a PIT count of >4.5% to predict absent splenic function in SCA ( Rogers et al, 2011 ).…”

A microfluidic-informatics assay for quantitative physical occlusion measurement in sickle cell disease

“…5 Patients with SC genotype experience reduced numbers of painful episodes 6 and lower incidence of vasculopathy-related complications. 7…”

“…5 Patients with SC genotype experience reduced numbers of painful episodes 6 and lower incidence of vasculopathy-related complications. 7 Clinical measurements such as complete blood count (CBC) and blood chemistry have indicated blood changes in sickle cell diseases, such as reduced lifespan of red blood cells (RBCs) 8,9 and increased white blood cells (WBCs). [10][11][12] However, clinical measurements are limited in reflecting factors directly related to vaso-occlusion, a life-threatening hallmark of SCD.…”